Surface Chemoselective Phototransformation of CâH Bonds on

Review pubs.acs.org/CR

Surface Chemoselective Phototransformation of C−H Bonds on Organic Polymeric Materials and Related High-Tech Applications Peng Yang‡ and Wantai Yang*,† †

The State Key Laboratory of Chemical Resource Engineering, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China ‡ Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, College of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062, China 3.5.1. Aryl Azides 3.5.2. Aryl Azides, Aryl Diazo, and Aryl Diazonium Salts 4. Phototransformation of C−H Bonds on Carbonaceous Material Surfaces 4.1. Photooxidation 4.2. Radical Transfer 4.2.1. Sulfur-Containing Compounds 4.2.2. Halide Compounds 4.3. Electron Injection 5. Summary and Outlook Author Information Corresponding Author Notes Biographies Acknowledgments Abbreviation List References

CONTENTS 1. Introduction 1.1. The Importance of Accurate Molecular Tailoring on Surfaces or Interfaces 1.2. C−H Bond Chemoselective Transformations: A New Direction in Surface Molecular Design 1.3. Why Photochemistry Is Chosen To Perform C−H Transformations 1.4. The Interaction between Photons and C−H Bonds: A Brief Outline 1.5. Overview of Related Fields 1.6. The Purpose of This Review 2. Outline 3. Phototransformation of C−H Bonds on Organic Surfaces 3.1. Direct Photoscission of C−H Bonds 3.1.1. Oxygen-Containing Polar Groups 3.1.2. Functional Groups Other Than OxygenContaining Structures 3.1.3. VUV-Induced Photo-cross-linking 3.1.4. VUV Emitted by Excimer Laser Sources 3.2. Photooxidation 3.2.1. Dry Photooxidation 3.2.2. Wet Photooxidation 3.2.3. Selected Applications 3.3. Radical Transfer 3.3.1. Organic Silanes 3.3.2. Halide Compounds 3.3.3. Sulfur-Containing Derivatives 3.3.4. Persulfate Salts 3.4. Hydrogen Abstraction 3.4.1. Gaseous Sulfur Dioxide 3.4.2. Acetone 3.4.3. Aryl Ketones 3.5. Direct Insertion by Reactive Intermediates © 2013 American Chemical Society

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1. INTRODUCTION 5550 5550 5550 5551

1.1. The Importance of Accurate Molecular Tailoring on Surfaces or Interfaces

Physical and chemical surface or interface properties play key roles in high-tech fields such as biotechnology,1 electronics,2 and photonics3 by virtue of the various kinds of physical and chemical interactions with adlayers such as covalent bonding, hydrophobic/hydrophilic interactions, hydrogen bonding, electrostatic interactions, charge-transfer-complex formation, van der Waals forces, and dipole−dipole interactions, as well as π−π interactions. The preparation of a functional or active surface has become an effective and economical way to integrate material bulk properties and new functionality.4 For instance, in the biological field, protein adsorption, cell growth, migration, and differentiation are strongly dependent on surface or interfacial properties. In electronic devices, physical and chemical surface structures affect organic semiconductor morphology and molecular ordering, and these have close relationships with the final electronic properties. Among various materials, synthetic organic substances prepared from oil, especially polyolefins, which exceed metal materials in volume produced, have become a dominant feature of modern life. In practical applications, most of these materials

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Received: June 18, 2012 Published: April 24, 2013 5547

dx.doi.org/10.1021/cr300246p | Chem. Rev. 2013, 113, 5547−5594

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Table 1. Typical Compounds Used in Photoaffinity Labeling (PAL)

bonds on their outermost surface18 to provide high-density reaction sites and final high-density group array. Second, the development of chemoselective C−H chemistry can avoid the use of backbone C−C or ester reactions for surface modification that may result in undesired surface degradation due to C−C or ester cleavage; these reactions often induce etching and degradation or the deterioration of bulk/surface properties such as the adhesion strength of a coating.19−21 Accordingly, new demands on polymer surfaces have led chemists to develop chemical systems that can directly convert C−H bonds on these soft organic material surfaces into functional groups or polymer chains in facile, efficient, specific, and selective ways. However, C−H activation on surfaces has been much less widely studied than the transformation of C−H bonds in molecules to other functional groups by organic chemistry, which is currently an active and frontier research field with far-reaching practical implications, ranging from highly efficient fine chemical synthesis to the replacement of current petrochemical feedstocks by less expensive and more readily available alkanes. Several methods have been established for C−H transformations in molecules during the past decades based on the use of different catalysts such as transition metal complexes,22 enzymes,23 and pure organic compound-catalyzed coupling methods.24 However, a similar portfolio of reactions for chemoselective activation of C−H bonds located on organic surfaces or interfaces has yet to be developed. The reactivity of C−H bonds on surfaces or interfaces might be different from that in molecules, because C−H bonds are “frozen” in a matrix, which changes their steric conformation and requires them to be closely adjacent to reactants on a surface to provide sufficient proximity to react. Therefore, the methods capable of tailoring C−H bonds on polymer surfaces or interfaces do not overlap well with the transformation chemistry of C−H bonds in molecules and mainly include mechanical treatment, blending,25 flame treatment,26 grafting,27 chemical wet oxidation,28 sequential surface chemical derivation,29 layer-by-layer (LbL) deposition,30 photooxidation,31 ion irradiation,32 vapor deposition,33 plasma treatment,34 ultrasound treatment,35 and electrochemistry,36 as well as enzymatic methods.4b,c Many of them often give rise to an uncontrolled dissociation of chemical bonds other than C−H and result in unnecessary physical or chemical changes such as the introduction of multiple functional groups, etching, and morphological alterations. For

suffer from serious problems due to their low surface energy and low surface reactivity. As a result, their surface modification and functionalization5 are of prime importance from both an academic and an industrial viewpoint, especially in efforts toward light, flexible, and disposable devices, as well as integrated molecular assemblies with other kinds of materials for use in, for example, antifouling coatings,6 platforms for biomolecule immobilization,7 microfluidic lab-on-a-chip devices,8 sensors,9 drug delivery scaffolds,10 tissue engineering,11 biomimetic self-assembly of inorganic and metal materials,12 smart responsive devices,13 optics,3 and adhesion,14 packaging,15 and lubrication.16 These advanced high-tech applications often demand that the modification possesses the ability for selective and controllable covalent bond transformation in order to provide pure functional molecular grafting layers. For example, in the field of immobilization of biomolecules on surfaces,17 the type and purity of the functional group is important for chemoselective immobilization of biomolecules in order to preserve the biological function and activity, since the binding site of biomolecules to >NH, −NH2, and amide groups differs from that for −OH, >CO, and ester groups. This difference may affect the function and activity of the immobilized biomolecules. Besides chemical purity, the introduction of functional groups should also result in only minor or no irregular etching of the soft polymer surfaces. Although such well-defined surface molecular engineering has been successfully accomplished on inorganic and metal substrates based on the use of selfassembled monolayers (SAMs), the methodology to form highquality functional group layers grafted on polymer surfaces has yet to be well established. 1.2. C−H Bond Chemoselective Transformations: A New Direction in Surface Molecular Design

Section 1.1 invites an important blueprint for the construction of well-defined functional group layers on a polymer surface. Obviously, this aim is closely related to the chemical nature of polymer substrate. The chemistry to convert oil to polymers (i.e., from refining to polymerization) mainly involves C−C bond chemistry (breaking and coupling), whereas in order to fundamentally resolve the surface problem and form welldefined functional group layers, novel efficient chemoselective surface C−H activation, especially saturated sp3 C−H σ bond transformation chemistry, is desirable. The reasons for this are twofold. First, most polymeric materials have abundant C−H 5548


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example, both corona and plasma treatments involve complex sources containing a variety of energetic components such as charged or neutral particles (electrons, ions, excited molecules, radicals, metastable species) and photons (infrared to soft Xrays), which easily give rise to multiple reaction pathways and products on soft matter surfaces. Alternatively, examples based on photochemistry have emerged to achieve chemoselective activation of C−H bonds, which thus become the emphasis of discussion and summary in this review. Nonetheless, photochemistry similarly suffers some drawbacks such as long modification time and deep modification depth, as well as wet chemical conditions frequently used, when compared with other methods, especially corona and plasma treatment.

Feature 3. Top-down techniques such as photochemistry, which facilitate the preparation of gradient surfaces, have found a wide range of applications in high-tech fields.42 A related gradient of functional group (e.g., grafting density, molecular weight, chemical composition) or physical topology feature size in 1D−3D space could provide a unique ability to create gradual changes in chemical or physical information on the target surface, which will generate gradually varying chemical or physical signals to communicate with the materials on such a surface and allow the development of smart functionality, as well as highly efficient parallel analytical methods. In terms of photochemical reactions, such a chemical or physical gradient could be conveniently obtained through deliberately changing the light intensity43 and exposure time,44 the two key factors that determine the extent of a photochemical reaction. For instance, VUV (vacuum UV)44a or UV/ozone43a,44b treatment of SAM-modified surfaces, as well as UV photooxidation of polymer surfaces followed by UV-induced photografting,44d,e have been used to induce gradient photolithography and phototransformation of hydrophobic alkyl groups to hydrophilic oxidized polar groups (e.g., −OH, −OOH, −COOH), and accordingly, gradients in wettability as well as chemical composition on the surface have been obtained. Such gradients have been used to produce patterning of target biomolecules and cells as well as directional water movement. The length scales that have been achieved using this method range from micrometers to milimeters.42−44 The formation of gradient structures is strongly related to the distribution profile of UV dosage (J/cm2) along the surface, which is determined by the product of the intensity (W/cm2) and exposure time (s). The light with a gradient of intensity imposed on the target surface can be obtained by making the light pass through a density filter43a or a photomask with gradient gray value.43b On the other hand, the exposure time of the target surface can be varied by moving the sample stage44a−d or the photomask44e,f over the sample with a predetermined direction and speed. The threshold for an effective UV dosage to initiate the formation of a gradient surface is dependent on the wavelength of UV light, the type of photochemical reaction, and the chemical structure of the target surface. For example, the threshold value for UV laser ablation on poly(ethylene glycol) (PEG) brush layers is 0.6−1 J/cm2 when using a 400 nm two-photon laser beam with different radii,42b while the threshold for UV photooxidation of the terminal oligo(ethylene glycol) tail of SAMs to form aldehyde groups is as low as 0.3 J/cm2 when a UV laser at 244 nm is used.42c In another case, the threshold for the surface photocuring process (frontal photopolymerization based on a thiol−ene photochemical reaction) is found to be around 0.01−0.1 J/cm2 when UV light at 365 nm is used.42e Feature 4. Another typical characteristic of photochemistry is the tunable input energy for C−H activation based on the selection of UV light with different wavelengths, intensities, and irradiation times as well as irradiation distance, a thickness of UV-absorbing material or solution. Longer wavelengths, lower intensities, shorter irradiation times, longer irradiation distance, or thicker UV-absorbing layer result in a lower input energy at the surface and vice versa. Some representative light ranges for photochemical reactions include visible light (>400 nm, 200 nm) usually leads to a common photooxidation process (section 3.2), which often introduces multiple functional groups such as hydroxyl or carbonyl on the surfaces, accompanied by undesired morphology changes. Alternatively, highly efficient chemoselective phototransformation of C−H bonds can be initiated by using photosensitizers, leading to three main kinds of reaction pathways. In route 1 (section 3.3), the photosensitizer is first dissociated under UV irradiation to give radical species that can abstract hydrogen atoms from C−H bonds, after which the resulting surface/interfacial radicals undergo radical coupling with functionality-containing radicals to complete the grafting of the functional monolayer. In route 2 (section 3.4), the photosensitizer is first activated by UV light giving a singlet state that subsequently transfers to a triplet state by intersystem crossing (ISC), and the resulting triplet can then abstract hydrogen from the C−H bonds on the surfaces to complete the grafting of the functional groups. In route 3 (section 3.5), instead of hydrogen abstraction from C−H bonds, direct insertion into C−H bonds is achieved by nitrene- and carbenegenerating compounds formed under UV irradiation. In section 4, the phototransformation of C−H bonds on carbonaceous materials is discussed; three possible routes are also involved photooxidation (section 4.1), radical transfer (section 4.2), and electron injection (section 4.3). Direct photoscission (section 3.1) and photooxidation (section 3.2) are nonchemoselective methods for C−H phototransformation, with complex reaction pathways generating heterogeneous chemical structures accompanied by physical changes. In contrast, the methods described in section 3.3−3.5 and section 4 can be generally considered as chemoselective C−H phototransformations where a well-defined chemically pure molecular layer is formed through specific C−H phototransformation reactions. Finally, in section 5, we give a summary and outlook for the photochemical transformation of C−H bonds on organic surfaces or interfaces and comment on the future direction of this field.

of C−H bond phototransformation infers the surface or interface at least from polymers, LB films, and SAMs. We expect this review to further stimulate the development of C− H phototransformations on organic surfaces or interfaces. Besides the activation of C−H bonds on synthetic organic surfaces or interfaces, there is another major class of C−H activation that can occur on surfaces or interfaces, namely, photochemical activation on hydrogenated carbonaceous materials, for example, diamond and amorphous carbon. The reactivity of C−H bonds on these carbon-based materials is different from that of synthetic organic polymers, due to their unique electronic properties in the bulk and at the surface. There have been some good reviews that have recently addressed this topic.48 Therefore, in this review, we will not place major emphasis on this field but would like to give a simple introduction for the sake of comparison and balance.

2. OUTLINE The structure of the review is categorized according to chemical reaction type (Figure 2) and following the description of each

Figure 2. The outline of phototransformation of C−H bonds.

kind of chemistry, related high-tech applications will be further incorporated into each section. Generally speaking, the phototransformation reactions of C−H bonds involve two aspects, the activation of a C−H bond and attachment of a functional group R. The activation of a C−H bond can be achieved through one of the following four ways: (a1) direct scission by exposure to short wavelength UV (200 nm) has a lower energy and can give more controllable C−H photochemical reactions without obvious side effects. In the absence of photosensitizers, the low-energy photons in long wavelength light result in low efficiency and rates with obvious morphology changes.125,126 The efficiency of phototransformation of C−H bonds by photooxidation can be enhanced by the addition of photosensitizers. As described in this section, one type of photosensitizer-mediated phototransformation is radical transfer by photofragmentation under UV light. During this process, the radicals are directly produced by the photodriven dissociation of the photosensitizer (P−R), and subsequently, the resulting radical can abstract hydrogen from the C−H bonds on a polymer surface. Consequently, a surface macroradical is formed that can further react with a surrounding functional molecular radical R•. Alternatively, the surface macroradical can directly react with the photosensitizer (P−R) to form C−R and another reactive P• radical, resulting in grafting of the functional R monolayer (Figure 8). In the following paragraph, we will discuss examples based on this mechanism including organic silanes, halides, and sulfur derivatives as well as persulfate salts.

Figure 9. Photoinitiated C−H activation on a PSt surface by trialkylsilanes.129

derivatized with alkenes under UV irradiation. Therefore, this approach opens up a new convenient way to functionalize polymer surfaces by using alkenes as anchoring linkers. 3.3.2. Halide Compounds. 3.3.2.1. Photochemical Reaction based on C-X Bond. Photoactivation of some halide compounds may induce the dissociation of C−X bonds, where the resulting X• radical is able to abstract hydrogen from C−H bonds resulting in functionalization. For example, simple irradiation of PSt in CCl4 can introduce chlorine atoms at αand β-sites along the chain and in the benzene rings in the later stages of the reaction.130 This photochlorination is accompanied by degradation of the polymer. Irradiation in 1,2,3,5tetrafluorobenzene has been used for the surface modification of PMMA.131,132 1,2,3,5-Tetrafluorobenzene has a strong absorption band in the UV spectrum at 252 nm and under KrF excimer laser (248 nm) irradiation dissociates to produce radical species that can subsequently attack C−H (I, II) and ester bonds (III) in the PMMA side chains of the polymer surface, leading to UV-photochemical fluorination (Figure 10).

Figure 8. Schematic reaction routes for phototransformation of C−H bonds by radical transfer. P−R, a photosensitizer; R, functional group; C−H, C−H bonds from molecular or matrix surfaces.

3.3.1. Organic Silanes. Under irradiation from a mercury lamp and a 193 nm ArF* excimer laser, vapor or liquid trialkylsilanes such as ethyldimethylsilane (EDMS) or trimethylsilane (TrMS) can undergo photofragmentation in two ways: cleavage of the Si−H bond (BDE, 380 kJ/mol) or the Si−C bond (BDE, 306 kJ/mol) (Figure 9). The resulting alkylsilyl radicals can initiate an addition reaction with vinyl bonds from an unsaturated polymer substrate (e.g., polybutadiene127) or abstract a hydrogen atom from the C−H bonds on a saturated polymer, for example, the benzylic αpositions in a PSt main chain to produce surface macroradicals. A possible side reaction is nucleophilic addition of silyl radicals to the aromatic ring in a PSt chain.128 The resulting surface radicals on the main polymer chain can further combine with alkylsilyl radicals to covalently graft silyl and Si−H groups without affecting the bulk properties.127,129 EDMS and TrMS are nontoxic and almost odorless. They also possess high vapor pressures and do not tend to self-ignite. The resulting Si−H functionality on the polymer surfaces can be further chemically

Figure 10. The reaction mechanism of UV-laser assisted photochemical fluorination on a PMMA surface by using 1,2,3,5tetrafluorobenzene: (a) the release of fluorine radicals by photodissociation of 1,2,3,5-tetrafluorobenzene; (b) substitution of hydrogen atoms by fluorine atoms in a PMMA molecule.132 5556


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Low laser fluence does not result in major surface defects on the sample, while a high fluence induces obvious surface cracks and even the formation of a carbonized surface. In addition to fluorine groups, oxygen functionalities are also found on the modified surfaces. The modification results in the formation of a water-repelling (hydrophobic) fluorinated polymer surface. Another kind of C−X-type halide derivative is oxalyl chloride, which can be photolyzed under UV irradiation (e.g., 254 nm) to produce chlorocarbonyl and chlorine radicals. The resulting chlorocarbonyl radicals can abstract hydrogen atom from C−H bonds (Figure 11). Consequently, alkyl radicals are

(Figure 12).142a The photodissociation of X−CN yields both reactive halogen and CN radicals that can abstract hydrogen

Figure 11. The proposed reaction mechanism for C−H activation by oxalyl chloride.133,134 Figure 12. The reaction mechanism for UV-laser assisted photochemical modification on a PSt surface by using cyanogen bromide: (1) the release of Br and CN radicals from BrCN by photodissociation; (2) hydrogen abstraction from a C−H bond by Br and CN radicals to form macroradicals; (3) radical recombination between the macroradicals and Br/CN radicals. As an alternative to step 3, the macroradical may directly react with Br−CN to incorporate Br/CN groups.142a

formed that can further undergo radical transfer by reaction with another oxalyl chloride molecule to give functional groups such as acid chlorides.133 By this method, a 1-decene layer grafted on a polished glassy carbon (GC) or a pyrolyzed photoresist film (PPF) was functionalized to introduce reactive acid chloride groups,134 which can further be chemically derivatized with ethylenediamine and 4-nitro-4-aminoazobenzene to incorporate amines via amide bond formation. The resulting aminated films could induce the surface assembly of citrate-capped gold nanoparticles. 3.3.2.2. Photochemical Reaction Based on R-X Bond (R = X or Other Non-C Group). Vapors of halogens such as bromine (Br2), chlorine (Cl2), and pseudohalogens such as cyanogen halides (X−CN, X = F, Cl, Br) can also be dissociated under UV irradiation to form the corresponding radical species, which abstract hydrogen from C−H bonds on polymer surfaces.135 Irradiation in bromine or chlorine leads to bromination136 or chlorination137 on the polymer surface. Bromination is more regioselective than chlorination, with substitution mainly occurring at the carbon atom adjacent to the carbon atom containing bromine138 because of the neighboring group mechanism139 in which the abstraction of a hydrogen atom by a bromine radical is assisted by a neighboring bromine atom.140 Because of the better leaving group ability of bromide compared with fluoride and chloride, bromine atoms grafted by bromination possess higher reactivity than other grafted halides toward nucleophilic substitution, allowing C−Br group to be converted to a variety of functional groups.136b The incorporated bromine atoms can also be used as a radical generator under UV irradiation to initiate UV-induced graft polymerization with acrylic monomers.141 Bromination has two obvious drawbacks. The first is undesired morphology changes after bromination such as bubbles, blisters, holes, or even fragmentation. The other is that if the bromination is performed for a relatively long time (e.g., >1 h), dehydrobromination results in the formation of conjugated polyene structures. Cyanogen halides have been used to graft both X and CN atoms onto a PSt surface through UV irradiation at 254 nm

atoms from alkanes to afford alkyl bromides and cyanides.143 The CN formed on the surface by this method can be easily converted to other functional groups such as amides, carboxylic acids, and amines for target interface-supported applications. Although the use of gaseous X−CN facilitates the dry modification process, the serious health risk and explosive dangers associated with this gaseous compound demand a more manangeable/safe method involving an alternative compound in a liquid phase. For example, chlorine/bromine and CN radical sources can be also produced by irradiating benzyl chloride/bromide and selenocyanate in solution,142b and this mixture has been used to abstract hydrogen from C−H bonds toward photo-cross-linking of polymeric materials. 3.3.3. Sulfur-Containing Derivatives. Dithiocarbamate or xanthate can dissociate under UV irradiation to form radical species (Figure 13) that are able to abstract hydrogen atoms from C−H bonds in organic substrates. This reaction has been

Figure 13. The formation of radicals by photodissociation of dithiocarbamate and xanthate under UV irradiation. 5557


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1). After UV irradiation for a certain time (∼12 h) at 50 °C, multiple functional groups including carbonyl and hydroxyl were introduced through a classical photooxidation of organic C−H bonds by persulfate ions. Yang et al.148 improved this method to obtain a pure sulfategroup-grafted surface by developing a new reaction model: “confined photochemical reaction” (CPR). Rather than employing a thick layer of solution as in traditional organic photochemical reactions, the concept of CPR is as follows: a very thin (micrometer) layer of a photosensitive solution is deposited on a polymer surface through a sandwiching setup or common coating technique. The sandwiching setup comprises a top and bottom polymer substrate with photosensitive solution in between (Figure 16). The ultrathin layer of solution

used for a photoinduced surface hydrogelation with regional precision. A photoreactive hydrophilic polymer containing dithiocarbamate or xanthate groups144 is first synthesized by radical copolymerization of N,N-dimethylacrylamide with vinylbenzyl N,N-diethyldithiocarbamate or 2-(ethylxanthate)ethyl methacrylate. The dithiocarbamate moieties and xanthate groups dissociate to highly reactive radical pairs under UV illumination and are able to abstract hydrogen atoms from C− H bonds on both the hydrophilic polymer chains and PET substrates. As a result, a film based on such a photoreactive polymer can be converted to a water-absorbable cross-linked gel and fixed onto substrates through radical recombination (Figure 14). A higher percentage of photoreactive groups and

Figure 16. The proposed confined photocatalytic oxidation (CPO) by persulfate and subsequent hydrolysis. Reprinted with permission from ref 148. Copyright 2003 Elsevier. Figure 14. The proposed mechanism for hydrogel formation from photoreactive copolymers with simultaneous surface fixation onto a PET substrate by radical recombination. “Polymer” and “P” show the photoreactive copolymer and photoreactive groups (dithiocarbamate and xanthate), respectively.144.

on the polymer surface effectively shortens the propagation length of the irradiation pathway and enlarges the contact area. Consequently, under UV irradiation, the rate and extent of photochemical reactions and even the reaction route and products formed differ greatly from those in conventional photochemical reactions. By use of different types of photosensitive solution, this concept has been used to develop a series of photochemical methods and chemical principles to introduce versatile groups such as sulfate anions, sulfonate, hydroxyl, amine, thiol, and carboxyl groups on polymer surfaces (see this section and section 3.4.2). In the case of a persulfate salt, a very thin layer (micrometer) of a persulfate salt aqueous solution is sandwiched between two polymer films, and this assembly is irradiated by strong UV light from the side that is transparent to UV light. In such a sandwiching setup, a new reaction pathway is followed whereby persulfates dissociate directly to form sulfate anion radicals under short UV irradiation periods (∼120 s), the resulting sulfate radicals quickly oxidize the polymer surface by abstracting hydrogen atoms from it, after which the surface radicals couple with other sulfate anion radicals creating an array of sulfate anion groups covalently attached to the outermost surface (Figure 16). This reaction model is termed as “confined photocatalytic oxidation” (CPO). The resulting surface has high hydrophilicity (Figure 17), and can be further converted to a hydroxylated surface through the hydrolysis of grafted sulfate anion groups by immersing the surface in water for tens of hours. The modification is rapid and efficient without any discernible morphology changes. The sandwich setup used in this experiment, as the key to provide a confined reaction space, plays an important role in successful CPO, because it is found that when the sandwich setup is replaced with a conventional photochemical reaction setup where film samples are put (floating) onto the surface of the reaction solution, the surface hydrophilicity of the modified samples is much lower than that of the modified samples obtained using the sandwich setup (Table 3). In the sandwich setup used in CPO, since there is a large difference in polarity

longer irradiation times resulted in higher gel yields and reduced swellability. Doping the pregel polymer with bioactive substances such as heparin and urokinase resulted in prolonged whole-blood-coagulation times for heparin-immobilized surfaces and fibrinolysis for urokinase-immobilized surfaces. Furthermore, a micropatterned hydrogel array could be fabricated by applying a photomask. 3.3.4. Persulfate Salts. Persulfate salts such as ammonium persulfate (APS) and potassium persulfate (KPS) are photosensitive to UV light. The maximum absorption of persulfate salts is at 200 nm, while the quantum efficiency has a maximum value at 254 nm of around 0.6.145 The molecule dissociates to form a persulfate radical ion that can oxidize surrounding substances and surfaces by hydrogen abstraction. The resulting radicals can then undergo typical radical-related processes such as radical coupling and oxidation. Specifically, water molecules are first oxidized by persulfates to form hydroxyl radicals, which further oxidize organic substances.146 The reaction usually results in a surface array of complex reaction products such as hydroxyl and carbonyl groups (Figure 15). For example, Kubota et al.147 studied a UV-assisted surface oxidation method where a low-density PE (LDPE) film was put in a rotary Pyrex glass tube containing a KPS aqueous solution (0.01−0.30 mol/

Figure 15. The conventional photochemical route for C−H activation on polymer surfaces by persulfate salts. 5558


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fast, mild (to the environment and the substrate), facile, and low-cost technological process. Based on CPO, it has been possible to develop a universal method to create hydrophilic/hydrophobic hybrid polymer surfaces, by regional control using a photomask. The resulting wettability or surface sulfate anion and hydroxyl template patterns have been used to support the growth and patterning of various functional inorganic and organic materials,149−153 water droplet transportation,149b chemical bond assembly,154 and inkjet printing for the preparation of flexible soft photomasks.152a,155 Previously, similar work was developed on SAMs-modified substrates. However, since the construction of SAMs is mainly limited to inorganic and metal materials, the methodology based on CPO provides a promising and general means of fabricating versatile materials and patterning on flexible plastic substrates, which are difficult to achieve using the SAMs-based method. For example, an effective conductive polyaniline (PANI) micropattern could be fabricated on such a wettabilitypatterned surface (Figure 18).149a The resulting pattern is

Figure 17. Water contact angles on a variety of polymeric substrates after CPO modification. HDPE, high-density polyethylene; LDPE, low-density polyethylene; CPP, cast polypropylene; BOPP, biaxially oriented polypropylene; PET, polyethylene terephthalate; PVC, polyvinyl chloride; PC, polycarbonate; Nylon, polyamides; TPX, poly(4-methyl-1-pentene); PVF, polyvinyl fluoride; NBR, acrylonitrile−butadiene rubber; EPDM, ethylene−propylene−diene−terpolymer rubber; SBR, styrene butadiene rubber. Reprinted with permission from ref 148. Copyright 2003 Elsevier.

Table 3. The Surface Water Contact Angles of Polymer Films Modified Using Two Different Setupsa substrate

setup

reaction time (s)

water contact angle (deg)

LDPE LDPE CPP CPP LDPE CPP

conventional conventional conventional conventional sandwich sandwich

90 240 90 240 90 90

76 75 83 76 44 56

a

The results are taken from ref 148.

between the persulfate salt aqueous solution and a polymeric substrate, the solution does not diffuse into the substrate but maintains a continuous phase with micrometer thickness. This setup not only brings the reaction solution and polymer surface into the most intimate contact, which maximizes the relative concentration of C−H groups on organic substrates, but also minimizes the attenuation of UV intensity in the solution due to its thinness. Accordingly, under strong UV irradiation, a great large number of sulfate anion radicals are produced in a very short time. Since the rate of reaction of sulfate anion radicals with organic substrates is much higher than that with H2O, the reactions of sulfate anion radicals with the polymer surface dominate the whole reaction course: some of the sulfate anion radicals abstract surface hydrogen atoms and produce surface free radicals, while others couple with the surface free radicals, eventually forming surface SO4− groups as shown in Figure 16. Obviously, a conventional setup where a thick solution layer (tens of millimeters to centimeters) is used could not provide such confinement during the oxidative photochemical reaction, and accordingly, conventional reaction routes (Figure 15) only afford moderate improvements in wettability. The CPO method is an important step toward chemoselective surface modification with the advantages of a

Figure 18. The schematic process of PANI pattern fabrication on polymer substrates. By use of a photomask, a PANI pattern is deposited on hydrophobic regions of PET (strategy I) (a−c) or obtained on hydrophilic regions of BOPP (e, strategy II) by the adhesive peeling of the deposited film (d).

dependent on the type of polymeric substrate. For PP or PI, the direct deposition of PANI is nonselective. Nevertheless, the PANI layer can be made to remain preferentially on the hydrophilic regions by peeling off the PANI layer on the hydrophobic region thus forming a positive micropattern that is consistent with the exposed regions. For PET, a stable negative micropattern comprising complementary areas to the exposed regions could be formed directly by the selective deposition of PANI onto the hydrophobic region. It was further found that the grafted sulfate groups improved the adhesion of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) when deposited on BOPP substrate via static interactions and also induced polymerization of EDOT onto 5559


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Figure 19. Schematic illustration of the processes of fabricating positive and negative TiO2 micropatterns on BOPP films. (a, b). A wettabilitypatterned surface is formed by CPO through a photomask, which is further utilized to fabricate a positive (I) pattern where the deposition occurs on the hydrophilic area and a negative (II) pattern where the deposition occurs on the hydrophobic area. LPD: Liquid Phase Deposition. Adapted with permission from ref 150. Copyright 2007 American Chemical Society.

the substrate surface generating the primary dopant of the deposited PEDOT.149c The conductivity of the resulting transparent PEDOT−BOPP composite film was as high as 300 S/cm. Besides organic polymers, high-quality metal, as well as inorganic oxide, patterning and films can also be achieved on CPO-treated polymer surfaces by combining the use of functionalized surfaces with the liquid phase deposition technique (LPD). In a typical LPD process, the reactive precursors to metal oxide particles are codissolved in an aqueous solution and then the resultant supersaturated solution is incubated at certain pH and low temperature to initiate the particle growth, condensation, and finally ripening to form a continuous film on a substrate with a predetermined morphology. The surface properties of the substrate play a key role during the film deposition and growth process. For instance, it is found that hydrophilic regions of certain films have an affinity for TiF62−, which results in the deposition of a titanium dioxide film with strong adhesion. In contrast, the hydrophobic regions repel the aqueous solution, resulting in either a total lack of deposition or a deposit so weakly attached that it can be peeled off from the surface by an ultrasonic liftoff. Conventionally, such wettability-patterned surfaces are provided by SAM-modified inorganic and metal substrates. By the CPO method; however, it has been successfully demonstrated that LPD can be effectively extended to polymer substrates. For example, although it is found that an anatase TiO2 film could be selectively deposited on the hydrophilic regions of a substrate, giving rise to a positive pattern with significant bonding strength and good line edge acuity,150 by simply adjusting the reaction conditions, TiO2 could also be selectively retained on hydrophobic regions to form a negative pattern (Figure 19). Such negative patterns can be used to fabricate large areas (mm2) of interconnected TiO2 micronetworks for flexible photomasks and macro/mesoporous TiO2 films. By employing an as-prepared negative TiO2 film as a polymer-based photomask, the patterned photografting of PAA on the surface of BOPP has been achieved (Figure 20). The innovativeness of this method arises from its ability to provide both positive and negative patterning of metals and inorganic oxides without the use of complex photolithography and

Figure 20. Micropatterning of a BOPP surface using the negative TiO2 pattern on the BOPP film as a photomask: (a) phase contrast microscope image of the negative TiO2 pattern on the BOPP film; (b) optical microscope image of the patterned PAA grafts on the BOPP surface after staining with toluidine blue; (c) phase contrast microscope image of the patterned PAA grafts on the BOPP surface; (d) 3D AFM image of a circle from the PAA grafted region on the BOPP surface. The scale bars in images a−c are 80 μm. Adapted with permission from ref 150. Copyright 2007 American Chemical Society.

cleanrooms, thereby providing a simple, fast, and low-cost method for fabricating macroelectronic components on flexible plastic. The approach has further been demonstrated for the growth of ZnO151 and SiO2152b,153 on polymer substrates. A ZnO film made of arrayed rods, typically 500−750 nm in diameter and 2.5 mm in length, is selectively obtained on sulfated and hydroxylated regions of BOPP, giving rise to positive patterns. For reactive polyesters such as PET, on the other hand, the ZnO rods selectively remain on the unmodified original regions, creating negative patterns (Figure 21). Standard silanization152b and sol−gel153 treatments are also successfully performed on such kinds of hydroxylated surface where surfacegrafted hydroxyl groups serve as condensation sites to initiate 5560


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wrapping with the flexible polymeric photomask.155a This approach constitutes a low-cost method for the preparation of printed flexible soft photomasks for use in prototype microfluidics, microsensors, optical structures, and any other kind of microstructures. A similar approach was originally developed based on the use of SAM-modified substrates.156 The method based on CPO provides an effective alternative to achieve such a goal with flexible polymeric materials. For example, a gradation photomask with printed gradient black level has been successfully prepared on a BOPP−SiOx hybrid film.155b The printed gradient black level can provide the photochemical system with gradient change of phototransmittance intensity from 0 to 100% at both 254 and 365 nm. Consequently, by combination of this gradient photomask with photoinduced reactions, such as CPO and photografting polymerization, a functionalized polymer surface with gradient distributions of surface energy, grafting layer thickness, and grafting chain density can be obtained. Well-defined hydroxylated surfaces obtained by CPO modification also support high-quality LbL self-assembly at a molecular level to form self-assembled organic multilayers. A chemical bonding assembly (CBA) based on surface hydroxylinitiated alternate reactions with the bifunctional linkers terephthalyl chloride (TPC) and bisphenol A (BPA) has been successfully achieved on a hydroxylated surface (Figure 23).154 As revealed by UV−vis spectra, a stable and well-defined multilayer film is thus fabricated via the CBA method in a strict LbL growth mode.

Figure 21. The growth scheme of a ZnO layer on patterned functionalized polymer surfaces: (a−c) a wettability-patterned surface with grafted patterned sulfate anion groups or hydroxyl groups is obtained by CPO through a photomask. The positive pattern of the ZnO layer selectively remains on the sulfated and hydroxylated regions of the BOPP film (d, g), whereas for PET, the ZnO layer selectively remains on the unirradiated regions (e, h) to produce a negative pattern. The corresponding SEM images for positive and negative ZnO patterns are shown on the right.151

the surface silanization and sol−gel processes. Patterned hydroxylation regions can be easily utilized to induce the formation of a patterned silane-based SAM, which is used to conjugate with immunoglobulin G (IgG).152b By combination of spin-coating with the interface-directed sol−gel process, very smooth silica surfaces with RMS (root-mean-square) values lower than 9 Å are obtained on flexible plastics, and the thickness could be well controlled by the varying the concentration of tetraethylorthosilicate (TEOS). The resulting silica surface has excellent gas barrier properties and can support further chemical derivatization allowing immobilization of proteins.153 By combination of the inkjet-printing technique with a hydrophilic BOPP film152a or a BOPP film coated with silica oxide (BOPP−SiOx),153 a flexible photomask can be further fabricated, which in turn is used to develop micropatterning of various functional organic and inorganic materials. For example, a novel photochemical reaction termed UV-induced surface aminolysis reaction (USAR) is performed on a PET substrate under a BOPP-based soft photomask to create an arbitrary IgG pattern (Figure 22).152a Conductive PANI film and PAA brushes have also been fabricated on curved substrates by

Figure 23. UV−vis absorption spectra of the CBA film with various numbers of layers. The number of layers is 1, 2, 4, 8, 12, and 16 (from bottom to top). (Inset) Increase in absorbance at 246 nm as a function of the layer number. Adapted with permission from ref 154. Copyright 2007 American Chemical Society.

Recently, the CPO method has been used to create the first example of a π-conjugated polymer-based water transportation vehicle (Figure 24).149b The surface of poly(2-methoxy-5-(2′ethyl-hexyloxy)-1,4-phenylene vinylene) (MEH-PPV) is modified by the CPO method to introduce a monolayer of sulfate anion (SO4−) groups. After the functionalization, the surface water contact angle of MEH-PPV decreases to 82.1° from the initial 95.5° without its optical properties being influenced. Water transport tests show that the modified MEH-PPV surface could adsorb water droplets from the pristine MEHPPV surface, and the adsorbed water droplet could be kept stable without sliding even at substrate tilt angles of 90° and 180°. Photo-cross-linking is also possible after hydrogen abstraction from C−H bonds by persulfate salts. As a result,

Figure 22. Schematic etching process of a “T”-type microchannel (left picture) and the corresponding practical fluorescence image after incubation of the structure in a FITC−IgG solution for a given time (right image). The “T” pattern was designed via computer and printed onto a hydrophilically modified BOPP surface by CPO through an office laser printer (1200 dpi). Adapted with permission from ref 152a. Copyright 2006 American Chemical Society. 5561


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monolayer. Alternatively, functional molecular R groups can also be attached to the surface by a heterofunctional linker that contains both a photosensitizer and R groups. In this case, the photochemical reaction is conducted without addition of exogenous functional molecules. Similarly, the triplet state of the R-containing photosensitizer can abstract hydrogen atoms from C−H bonds on the polymer surface or another molecule, and thus be converted to a radical. Both the surface radical and the photosensitizer radical then recombine to graft R onto the surface. The third way is to preinstall the photosensitizer on a surface, and then utilize it to attach functional R group onto the surface through C−H phototransformation. In the following paragraph, we discuss examples based on this mechanism including sulfur dioxide, acetone, acetophenone, isopropyl thioxanthone, benzophenone, binaphthyl ketone, anthraquinone, and phthalimide. 3.4.1. Gaseous Sulfur Dioxide. The vapor of sulfur dioxide (SO2) absorbs in the UV region 240−320 nm with a maximum peak at 285 nm. Under UV irradiation, ground state SO2 is first activated to an excited singlet state, which is converted to the triplet state through ISC. The excited SO2 molecule in the triplet state can abstract a hydrogen atom from the C−H bond at the polymer surface (eqs 1 and 2 in Figure 26), and as a result, a surface macroradical is formed that can

Figure 24. Water droplet transportation using a CPO-modified MEHPPV surface. Adapted with permission from ref 149b. Copyright 2012 Elsevier.

superabsorbent polymer particles, consisting of partly neutralized, slightly cross-linked PAA are obtained by surface photocross-linking under UV irradiation (200−300 nm) with APS dopant as a photoactivated cross-linking agent.157 This new photochemical method generates superabsorbent materials with superior properties, such as improved flow of liquid through the gel bed and an elevated water absorption capacity. 3.4. Hydrogen Abstraction

This section discusses the second type of photosensitizermediated phototransformation, that is triplet state formation by photoactivation. Depending on the location of the photosensitizer and functional group R, there are three approaches to achieve this aim (Figure 25). In the first approach, a free

Figure 26. The photoactivation of SO2 and subsequent reaction with alkyl C−H bonds.158

further undergo a series of chain propagation steps as shown in eqs 3−7 with persulfonic acid as an intermediate. Finally, sulfonic acid groups can be introduced on the surface, and the surface hydrophilicity is increased.158 3.4.2. Acetone. Acetone (AC) is a simple compound belonging to the class of carbonyl derivatives. The photochemical performance of carbonyl derivatives has been widely studied due to the photosensitivity of the carbonyl groups contained in these structures. Yang and Rånby159 pointed out that some ketone derivatives could be decomposed under UV irradiation to yield fragment radicals (Norrish type-I); on the other hand, these ketones are activated by UV to form a triplet state, which can abstract hydrogen from a polymer surface (Norrish type-II). Either way, the final result is the production of activated surface radicals capable of photoinitiated polymerization. The idea of phototransformation of C−H bonds using carbonyl-containing derivatives is thus based on a radical coupling mechanism. The surface radical is produced by hydrogen abstraction of activated carbonyl-containing derivatives (radical species or triplet state), which then react with functional molecular radicals to terminate the phototransformation.

Figure 25. Three typical routes for photochemical transformation of C−H bonds by triplet states of a photosensitizer (P).

photosensitizer in the ground state is activated to an excited singlet state. If the singlet state has a sufficient lifetime, it can subsequently transit to the n,π* triplet state with much longer lifetime by ISC, which can then abstract hydrogen atoms from C−H bonds both on the polymer surface and in exogenous functional molecules. Consequently, surface alkyl and functional molecular radicals R• are formed, which can couple with each other to achieve the grafting of the functional R 5562


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Figure 27. The proposed reaction routes for phototransformation of C−H bonds by acetone and the subsequent use of the product as a polymersupported inhibitor. Reprinted with permission from ref 160a. Copyright 2004 WILEY-VCH Verlag GmbH & Co. KGaA.

Table 4. The Aryl Ketones Used in the Phototransformation of C−H Bonds on Surfaces or Interfaces

large amount of AC can be photoexcited in a short time and abstract hydrogen atoms from the polymer surface and the phenolic hydroxyl groups of HQ. As a result, HQ is grafted on the polymer surface without any obvious side reactions. By using a HQ derivative with a para-substituent R group, a strategy has been further developed to incorporate a broad range of functional R groups onto the polymeric surface.161 Eventually, a series of R groups, including SO3H, NH2, SH, and COOH were grafted onto the polymer surface with an R spacer. Improved hydrophilicity and self-assembly of gold nanoparticles are achieved on modified surfaces on which different functional groups have been grafted. 3.4.3. Aryl Ketones. Aryl ketones contain a benzene ring connected to a carbonyl group. Aromatic ketones have been the subject of numerous photochemical studies. Some typical compounds that have been used for C−H phototransformation on surfaces or interfaces are listed in Table 4. The presence of a carbonyl group induces Norrish II type photochemical reactions162 under UV irradiation. As a result, the n,π* triplet state is formed by ISC of the singlet state, and this has been recognized as a highly active biradical intermediate with a lifetime on the order of 10−7 to 10−8 s. It should be noted that

The photochemical behavior of AC under UV irradiation mainly involves one of two routes: it can either be activated to a singlet state followed by ISC to a triplet state, or it can be directly dissociated under UV irradiation to form methyl and carbonyl radicals. Yang et al. proposed a method to immobilize hydroquinone (HQ) and short polymer chain monolayers on propylene surfaces by AC-induced phototransformation of C− H bonds.160a A thin film of HQ/AC solution is sandwiched between two polymer films. Under UV irradiation, the triplet state of the excited acetone can either abstract surface H atoms from the polymer substrate to generate carbon-centered surface radicals or abstract H from OH groups of HQ to produce oxygen-centered phenoxy radicals, which predominately couple with the surface radicals to form a stable surface-grafted HQ (Figure 27). The resulting functional film can be used as a polymer-supported inhibitor (PSI) to inhibit the thermal polymerization of styrene and methyl methacrylate and a free radical trap to capture PAA chain radicals to form a polymer monolayer.160b Similarly to CPO discussed in section 3.3.4, a confined reaction space also plays a key role during this reaction. Although AC is not an effective photoinitiator, in such a setup a 5563


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Figure 28. The reaction mechanism for AcP-mediated phototransformation of C−H bonds on surfaces: (A) hydrogen abstraction by the AcP triplet state; (B) hydrogen abstraction through energy transfer from the AcP triplet state to other molecules.

macroradicals and is itself converted to the corresponding radical intermediate. Photo-cross-linking has also been achieved on LDPE films by using molecules containing one or two AcP groups and their precursors.168 3.4.3.2. Isopropyl Thioxanthone. Isopropyl thioxanthone (ITX) is a xanthone (XT) derivative where an oxygen atom in the ether bridge is replaced by sulfur atom and the aromatic ring is functionalized with an isopropyl group (Chart 1). XT

such a lifetime value of the photoexcited state can be affected markedly by some solution parameters such as concentration, the type of media, pH, and other secondary interactions in solution. This intermediate can behave like alkoxy radicals162a and abstract hydrogen from C−H bonds. Aryl ketones are first used in biomimetic chemistry in the 1970s,163 including the first quantitative inactivation of chymotrypsin.164 The benzene ring in aryl ketones can be conveniently functionalized to attach a variety of functional groups or molecular linkers through specific reactions such as Friedel−Crafts acylation or alkylation. 3.4.3.1. Acetophenone. Although acetophenone (AcP) has an unpleasant odor and more volatility than the benzophenone, it possesses similar photochemical reactivity to benzophenone in solution.165 AcP has a weak n−π* transition at 315−320 nm and a π−π* transition at 280 nm. This molecule has a molar absorption coefficient of 1.5 × 103 mol−1 cm−1 at 254 nm, the wavelength of a commonly used UV source.166 Successful applications of AcP as a PAL reagent have been achieved under UV irradiation at 320 nm. By UV irradiation, AcP is activated to its excited singlet state, followed by ISC to its triplet state, which can subsequently abstract hydrogen atoms from C−H or N−H bonds from organic substances and functional molecules. Finally, the resulting surface radicals couple with surrounding functional molecular radicals to complete the grafting (Figure 28A). With this method, biologically active molecules including 2-aminopyridine (AP), N′-(2-pyridylaminomethyl)-1,2,4-triazole (TA),and benzocaine (BC) have been implanted on HDPE surfaces to enhance the surface hydrophilicity.167 The modified HDPE surface grafted with TA has a substantially decreased water contact angle below 20°. Besides the normal reaction routes observed in the case of grafting AP and TA, it is found that in the case of grafting BC, the reaction mechanism is based on the energy transfer from the triplet state of AcP to BC due to the photosensitivity of the carbonyl group contained in BC molecules (Figure 28B). Such energy transfer first converts the ground state of BC to a triplet state, which can further react with C−H bonds from the HDPE surface to form surface

Chart 1. The Molecular Structure of XT and ITX

has a structure quite similar to benzophenone and a typical triplet energy almost identical to that of AcP.169a Nonetheless, XT does show some interesting differences from other aromatic ketones. For example, it has been found that the nature of the lowest lying triplet state has a strong dependence on the temperature and polarity of the media;169b−f the reaction rate with hydrogen donor in solution and self-quenching rate are markedly correlated to the hydrogen-bonding properties of the solvent, showing an extremely enhanced reaction rate for hydrogen abstraction in nonpolar solvents.169g From the viewpoint of molecular structure and thermodynamics, the high self-quenching and hydrogen abstraction rates in nonpolar media are due to the reactivity at the ether bridge of XT and a combination of increased electrophilic character of the triplet state as well as a more favorable enthalpy change.169g In the report on the use of ITX for surface C−H bond transformation,169h activated ITX is first formed under UV irradiation (e.g., 254 nm), which then can abstract hydrogen from C−H bonds on polymer surfaces after ISC from a singlet to a triplet state. If exogenous reagents are not added, the resulting surface radical can couple with ITX-semipinacol 5564


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Figure 29. A mechanism and schematic illustration of the reaction process introducing ITX as “dormant” groups onto a LDPE film by ITX-mediated phototransformation of C−H bonds. The grafted ITX further undergoes reversible photosensitive dissociation to initiate free radical polymerization of GMA by visible light irradiation.171.

using free BP to form surface radicals that can subsequently react with the surrounding reactive groups to give functionalization (II); the final one entails attaching the benzene ring of BP onto surfaces and then using this immobilized BP to attack molecules carrying the functional R groups (III) (Figure 30).

(ITXSP) to obtain a functionalized surface grafted with ITXSP. The grafted ITXSP structure has a large stereohindrance and has a maximum absorption in the range from 380 to 420 nm (in the visible region),170 and it thus can further undergo a novel visible light-induced living surface grafting polymerization171 through reactivation under visible light (Figure 29). With glycidyl methacrylate (GMA) and LDPE films as models, this green living chemical process has been demonstrated to show a linear dependence on monomer concentration in both the surface grafting chain length and the grafting polymerization rate. It is therefore possible to accurately control the thickness of the grafted layer by simply altering the irradiation time and using environmentally friendly, energy-saving green chemistry. This visible light-induced living surface grafting polymerization can be used for biosensitive material systems where UV light cannot be used because of its strong denaturing action on biospecies.172 3.4.3.3. Benzophenone. Because of its high chemical stability, commercial availability, and photochemical properties, benzophenone (BP) has been widely used in photopolymerization173a and PAL173b where H-abstraction from C−H bonds is utilized to produce active radical species for further radical polymerization of monomers or radical coupling-based molecular conjugation. BP has an n−π* transition near 330− 360 nm that is well-separated from the π−π* transition, and the resultant triplet state formed from the singlet state is responsible for hydrogen abstraction from C−H bonds. The excitation occurs with long wavelength UV (typically 365 nm), which is favorable for biomolecule immobilization because of low UV damage to biological substances with long wavelength UV. Except having a shorter triplet lifetime in organized media (e.g., 10−100 ns in cyclodextrin complexes), BP (and also ITX mentioned in section 3.4.3.2) normally can afford a long lifetime (7.7 × 10−3 s for BP and 8.0 × 10−3 s for ITX).173c,d The chemoselective modification of C−H bonds mediated by BP can be divided into three main routes. The first one involves attaching a functional R group onto the benzene ring of BP and then introducing R onto the polymer surface by the coupling of BP onto the surface (I); the second route involves

Figure 30. Three typical reaction routes to convert C−H to C−R bonds by BP-mediated photochemical transformation.

Here, R can be a variety of structures ranging from small functional groups to amino acids, lipids, peptides, or macromolecules. The polymer radicals generated by BP photochemistry also probably undergo photodegradation through radical-initiated chain scission,174 and such photodegradation can result in advanced applications in for instance the field of liquid crystal alignement.175 3.4.3.3.1. Small Molecular Groups. BP itself can be used to convert C−H to C−BP by a radical coupling process, and the resulting BP-terminated surface has been used to develop photolamination, photo-cross-linking, and hyperbranched polymer synthesis, as well as living photoinitiated or thermally initiated radical surface graft polymerization.176,177 For example, when BP is conjugated onto a surface by route I, the resulting 5565


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Figure 31. Schematic diagram of living surface graft polymerization by immobilized BP via phototransformation of C−H bonds on surfaces. Adapted with permission from ref 177a. Copyright 2000 American Chemical Society.

Figure 32. Phototransformation of C−H bonds on PE film to graft succinic anhydride groups by BP-mediated photochemistry and subsequent sequential chemical derivatization to introduce various functional groups.180

with the local polymeric substrates for further photografting. By this method, the polymer surface modification method could technically be denoted as a photoactivated quasi-plasma technique with a potential to be applied in the surface modification (outer and inner) of organic polymeric material devices with complex shapes. Besides conjugation onto the surface itself, another important application is to use BP to introduce functional R groups onto irradiated surfaces by preattaching functional R groups onto the benzene ring of BP followed by photoabstraction. Consequently, functional R groups can be introduced onto the surface leading to improved adhesion.178 This also makes it possible to achieve good wettability, lubricity, passivation, and immobilization of other molecules, as well as initiating sites for further living surface grafting polymerization179 on a wide range of organic materials, thus offering a tremendous flexibility to tailor surface properties for a broad range of applications.

grafted BP can develop a reversible dissociation/recombination equilibrium with surface macroradicals under thermal or UV stimulation. This reversible balance can allow the continuous insertion of vinyl monomers to initiate a living surface graft polymerization with semipinacol as the living dormant end group (Figure 31). Not only does this procedure have the advantages of traditional UV-grafting polymerization, it also demonstrates a control of the grafting density and grafting polymer structure because of its living polymerization features. Yang et al. have recently reviewed this topic.27e,f In a series of recent reports,176b−d the relatively high stability of BP triplet has been utilized to achieve a nonconventional photochemical reaction where photoinitiated surface graft polymerization is well separated by space and time. The key novelty is that the target substrate for the modification does not need to be exposed to UV irradiation. Alternatively, the relatively stable BP triplets in vapor or liquid can be transported to remote (∼2 m) positions from the UV source and then react 5566


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biomolecules and polymers are minimized.181 Even so, the radical processes during photoactivation of BP and subsequent reaction with C−H bonds still carry a certain risk of radicalbased damage to biomolecules due to the nonspecificity of the BP-ketyl radical in reaction with C−H bonds, with the potential to weaken the biological function. For example, when a biomaterial surface is synthesized by immobilizing phospholipid polar units and functional peptides via BP photochemistry, it is found that cell attachment is nonspecific with respect to the peptide sequence used,182 because the nonspecificity of the attack of the BP-ketyl radical on C−H bonds along the peptide sequence induces the formation of a branched structure of the peptide sequence that enabled cells to overcome the nonpermissive properties of synthetic polymers with respect to nonspecific cell attachment. The combination of a hydrophilic spacer with the use of a smaller biomolecule concentration can help enhance the receptor-specific cell attachment property of the surface. Second, instead of random protein ligation through BP photochemistry, site-specific immobilization of proteins is desirable. For this purpose, BP-specific proteins in which the protein surface can bind with BP have thus been thus screened183 through chirality recognition in their surface pockets by using two pairs of diastereomeric probes containing BP and biotin. Based on these findings, selective labeling of BPbinding proteins in complex proteomes (e.g., cell lysate) has been achieved and shows great potential for applications such as protein ligation, protein cross-linking, biomarker discovery, and drug screening. In route 1, BP is preincorporated into recombinant proteins by combining gene engineering and chemically modified unnatural amino acids, for example, the photo-cross-linkable amino acid p-benzoyl-L-phenylalanine (pBpa).184,185 Obviously, route 1 renders it possible to immobilize directly various recombinant proteins on surfaces through BP-mediated C−H phototransformation with surfaces. Chin et al. utilize two kinds of plasmids in a single expression system (Figure 34).184 One

In the absence of prelabeling of the BP molecule, the functional R group can also be implanted by using a mixture containing BP as a photosensitizer and a functional molecule carrying R groups. For example, succinic anhydride groups could be grafted onto a PE film surface by BP-mediated photochemical reaction,180 and then these highly reactive anhydride groups can be further converted to a variety of chemical structures such as acids, esters, or amides by reaction with water, amine compounds, or poly(ethylene glycol) (PEG). In this phototransformation reaction, the surface macroradicals formed by hydrogen abstraction by the BP triplet can add to maleic anhydride to generate a new carbon-centered radical. The grafting of functional groups is finally achieved by radical termination with a hydrogen donor reagent, either the diluent or the polymer. By means of the reaction between the anhydride and 4-aminoazobenzene, photosensitive azobenzene groups could be further grafted onto the surface (Figure 32) and show interesting responses to external stimuli, such as photoinduced or thermally induced E/Z isomerization. Reversible changes in the UV absorbance and surface wettability due to this reversible E/Z isomerization are observed through the switching from UV to visible irradiation (Figure 33).

Figure 33. Photoinduced changes in the UV absorbance at 342 nm and wettability of the film monofunctionalized with azobenzene. Reprinted with permission from ref 180. Copyright 1997 American Chemical Society.

3.4.3.3.2. Biomolecules. Nucleic acids, peptides, or proteins can be grafted onto a surface by the photochemical reaction between BP and sterically accessible C−H bonds on these biomolecular surfaces, for example, backbone and side chain C−H bonds in amino acids. Based on the immobilized biomolecules, further functionality could also be incorporated in devices, such as DNA hybridization, protein interaction studies, and immunoassays. This process can be achieved by either of two routes. Route 1 involves incorporating BPcontaining unnatural amino acids in biomolecules, first through gene engineering and then by performing biomolecule ligation. Route 2 involves using BP molecules as special heterofunctional molecular linkers to graft biomolecules. However, some concerns have to be considered with both routes. First, the UV damage to biomolecules has to be considered. Since BP has an n−π* transition near 330−360 nm, this concern can be partially addressed by irradiation in the UVA range (e.g., 365 nm) where photochemical damage of

Figure 34. Structure of pBpa (a) and a schematic view of the pDULE plasmid (b). Reprinted with permission from ref 184. Copyright 2005 Nature Publishing Group.

plasmid is based on p15A to express the orthogonal aminoacyl tRNA synthetase (pDULE)−tRNACUA pair that incorporates pBpa at the position encoded by the amber codon (UAG), and the other is an amber mutant of the gene of interest. The culture of Escherichia coli carrying both plasmids in the presence of pBpa results in the incorporation of the BP-amino acid into the target protein. The incorporated pBpa in recombinant proteins could be consequently immobilized onto a C−Henriched surface through BP-mediated hydrogen abstraction and conjugation. For example, a protein carrying pBpa is first docked into the hydrophobic cavity of β-cyclodextrin (β-CD) through noncovalent interaction between pBpa and β-CD, after which the BP moiety in pBpa abstracts the hydrogen atom from 5567


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β-CD to terminate the covalent coupling process upon UV irradiation (Figure 35).185

A risk for BP-mediated protein conjugation is possible nonspecific reactivity toward sequences. A sequence-specific chemoselective immobilization strategy is thus developed by combining affinity binding and BP photoconjugation. For example, the minimal Fc-binding domain (FcBD) of protein G, a widely used antibody binding protein, is labeled with BP through a Michael addition between the free thiol group on the surface of protein G and the maleimide group of the BPcontaining linker (Figure 36).187 This small protein is then cross-linked only to the Fc region of the antibody without any nonspecific reactivity. Further UV irradiation enables lightinduced covalent immobilization of antibodies directly on various solid surfaces (Figure 37). Antibody coupling via photoactivable antibody-binding proteins overcomes several limitations of conventional approaches, for example, random chemical reactions or reversible protein binding, and offers a versatile tool for fabricating immunosensors. The strategy to construct BP-terminated surface is relatively versatile. First, well-defined BP-terminated SAMs can be formed on surfaces with BP exposed outward for subsequent photoimmobilization of proteins. For example, two kinds of BP-terminated silanes (BP-silanes) have been synthesized and grafted by regular hydrosilation procedures onto a fiber-optic silica surface to form BP-terminated silane SAMs (Figure 38). The functionalized fibers are then used to immobilize cholera toxin B (CTB) subunits by UV light in order to detect cholera antitoxin antibodies. The immunosensor system shows good specificity and sensitivity, exhibiting a rabbit serum titer of 1:1 700 000.189 Besides BP-silanes, BP-terminated thiol SAMs have also been constructed on a gold surface through the use of a bifunctional peptide carrying a cysteine for binding with a gold substrate and a BP terminus. The resultant immobilized BP is used to photochemically conjugate the chymotrypsin.190 Instead of synthesizing BP-decorated silane or thiol, BP can also be grafted in situ on the surface through sequential chemical derivatization. For instance, BP-terminated thiol SAMs can be constructed step-by-step on a gold surface for IgG immobilization by a sequential two-step chemical reaction

Figure 35. Schematic illustration of the Dock’n’Flash method. In this method, a pBpa-tagged protein is loaded onto a β-CD functionalized surface (1). Consequently, the BP group on the protein surface can dock with the CD cavity to achieve physical binding (2). Such a complex is further covalently connected by irradiation from a focused beam of UV-A light (360 nm) (3). After washing to remove noncovalently bound protein molecules on nonirradiated regions (4), the immobilization of the target protein is achieved. The entire process can be repeated to immobilize multiple proteins. Reprinted with permission from ref 185. Copyright 2010 American Chemical Society.

Besides the utilization of gene engineering to express directly proteins tagged with unnatural amino acids, route 2 shows that BP can also be attached onto proteins or surfaces by postexpression chemical conjugation.186−195 Through the use of a model protein, ovalbumin, and agarose gel as the substrate, it has been found that attaching BP directly on the substrate shows a higher immobilization efficiency for biomolecules than that obtained by first attaching it to target molecules,186 probably due to inherent steric hindrance and embedding of biomolecules toward small molecular group.

Figure 36. The preparation of a photosensitive antibody tagged with BP and photo-cross-linking to the antibody: (A) The Fc binding domain (FcBD) is first modified by BP through a Michael addition; (B) the modified FcBD is treated in order to recognize the corresponding binding site on an antibody, followed by irradiation at 365 nm to further obtain covalent bonding. Reprinted with permission from ref 187. Copyright 2009 American Chemical Society. 5568


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conductive and photoactivable polymer films on thin layers of indium tin oxide (ITO) coated on the silica surface of optical fiber (Figure 40).193−195 Hepatitis C virus-E2 (HCV-E2) envelope protein antigen is subsequently immobilized under illumination by UV light.193 As a result, the diagnosis of HCV could be achieved by using the antigen surface to detect the anti-E2 protein antibody analyte via a standard immunoassay method. This approach could significantly improve HCV serological standard testing and be used for HCV screening in blood banks. A similar strategy has been used to create a pattern array of antigen staphylococcal enterotoxin B (SEB) for anti-SEB detection.194 More than one bioreceptor can also be immobilized by this strategy for simultaneous detection of several analytes including surface and core protein antibodies of anti-cholera toxin B and anti-hepatitis B virus.195 3.4.3.3.3. Synthetic Polymers. BP has also been utilized to immobilize polymers including linear polymers, dendrimers, and hydrogels, as well as biopolymer conjugates, through phototransformation of C−H bonds on surfaces or interfaces. The covalent attachment of polymer layers on a surface offers many advantages such as corrosion protection, biocompatibility, and adhesion improvement for biomedical devices and sensors, as well as better lubrication properties. The methods for grafting of polymers mainly comprise grafting-from and grafting-to strategies. Grafting-from involves a photogenerated surface radical formed by BP photoabstraction or BP dissociation that can further initiate radical graft polymerization, and this topic has been reviewed recently.27e,f We herein mainly concentrate on the grafting-to strategy. BP photochemistry has been successfully combined with well-established surface coating and self-assembly techniques such as chemical vapor deposition (CVD) and SAMs to achieve satisfactory polymer grafting. CVD has been used to deposit a BP-containing photoactive thin layer, poly(4-benzoyl-p-xylylene-co-p-xylylene), on the inner surface of a microfluidic device (Figure 41).196 By patterning irradiation via a photomask, BP could capture PEO molecules (linear or star) adjacent to the surface. These patterned PEO-grafted areas result in spatially controlled, bioinert surfaces, so that spatially controlled protein immobilization can be achieved. The combination of SAMs and BP has led to a series of techniques to attach fluorinated 197 and nonfluorinated polymers198,199 onto substrates. BP-terminated SAMs, for example, BP-silanes, are first formed on substrates, and a polymer layer is then grafted to the substrates through BPmediated phototransformation of C−H bonds on the polymer chain (Figure 42). Surfaces modified by different polymers exhibit various useful properties, for example, spatially controlled ultraphobicity with patterned fluoropolymers and cell-adhesion with polyethyloxazoline (PEtOx), as well as nonattraction to cell adhesion with polyacrylamide (PAm) (Figure 43). Peptide−polymer conjugates can also be attached by this method and used to control cell adhesion. Poly(dimethylacrylamide) (PDMAA) glycine arginine glycine aspartic acid serine proline (GRGDSP) is immobilized on a glass substrate by BP-silane SAMs.200 In this hybrid molecule, the PDMAA part prevents cell adhesion while GRGDSP is known as a cell adhesion promoter. Therefore, the resulting micropatterned peptide polymer films can afford a spatially controlled adhesion of living cells, thus showing potential for the fabrication of live-cell biochips (Figure 44).

Figure 37. Surface plasmon resonance (SPR) and fluorescence images of an antibody array on solid surfaces obtained by photoactivable FcBD: (A) immobilization of the Cy3-labeled antibody by BPmodified FcBD and control samples without a BP tag, UV irradiation, or FcBD structures (replacing FcBD with bovine serum albumin, BSA). (B) A patterned antibody array is further achieved through irradiation controlled by a 300 μm mask, as revealed by SPR and fluorescence imaging on glass and gold surfaces. Reprinted with permission from ref 187. Copyright 2009 American Chemical Society.

Figure 38. A schematic illustration of the immobilization of cholera toxin B (CTB) subunits on BP-terminated silane SAMs.189.

to convert the terminal N-hydroxysuccinimide (NHS) ester to a BP moiety, which involved the hydrolysis of the NHS ester to release free amines followed by conjugation with NCSdecorated BP (BP-NCS) (Figure 39).191 A similar strategy has been used to modify the inner surface of a fused silica capillary by standard silanization with 3-aminopropyltriethoxysilane (APTES) to form an amine-terminated surface, which is subsequently reacted with BP-NCS to form a surface-grafted BP monolayer for the immobilization of oligonucleotides or proteins.192 In addition to the use of SAMs, electropolymerization of pyrrole tagged by BP (pyrrole-BP) has been found to form 5569


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Figure 39. A schematic illustration for preparing BP-terminated SAMs on a gold surface through sequential chemical reactions and subsequent immobilization of an antibody IgG by BP-mediated photochemistry. Reprinted with permission from ref 191. Copyright 1996 American Chemical Society.

control cell shrinkage and attachment by varying the temperature. Just like other photoinitiated radical reactions, BP-mediated C−H phototransformation can also lead to photo-cross-linking under certain conditions through certain radical coupling. Such a photo-cross-linking has great industrial and academic importance because it can afford substantial changes in material properties and create new functional materials. The photocross-linking can result in the formation of gels grafted on surfaces for various advanced applications, especially in the biomedical field. Gelation and immobilization on substrates can be achieved by two strategies. First, surface-grafted BP can be used to photochemically react with vinyl bond-terminated polymers (macromers). For this aim, a thin layer of poly[(4-phenylacetyl-p-xylylene)-co-(pxylylene)] is first deposited on substrates by CVD, and the resulting exposed BP groups can further photoinitiate the crosslinking and gelation of the macromer, poly(ethylene glycol)dimethacrylate (PEG-DMA).207 The resulting PEG hydrogel array can directly serve as a nonfouling substrate or be further chemically derivatized for protein conjugation. Instead of preattaching BP onto surfaces for surface-initiated gelation (photopolymerization with vinyl bonds), BP can also be incorporated into polymer chains through chemical modification or copolymerization with vinyl monomers carrying BP groups. Consequently, the polymers with BP attached can be photo-cross-linked through BP mediated C−H photoactivation (Figure 46).198 A variety of polymer gel materials have been synthesized on substrates by this strategy that are used for rapid screening on which polymers are expected to have favorable interactions with cells. The selected PEtOx gel has been used as a repair material for a porcine heart valve device (Figure 47). Through incorporating biological substances, BP-mediated photo-cross-linking has been further used to immobilize functional probe proteins onto unmodified plastic chip surfaces by automatic spotting (Figure 48).208 A printing solution containing polymer/protein mixtures is spotted on substrates and during subsequent UV irradiation, three reactions occur

In addition to materials for biological applications, the patterning of thin chromium and copper films on SiO2/Si substrates has been achieved by using patterned PSt layers as etching resist material.201 Since the chlorosilanes often used in silanization require rather stringent exclusion of moisture during self-assembly, an alternative (hydridosilanes) has also been developed.202 These hydridosilanes are rather robust, and functional monolayers can be formed even under ambient conditions, which in turn allows the use of silanes in standard printing processes without the requirement of strictly anhydrous conditions. In addition to silanization on SiO2, polymer films can also be attached onto aluminum surfaces by phosphoric acid-mediated SAMs.203 In this way, an Al surface is first modified by a phosphoric acid anchor to form BP-terminated SAMs. Then, these grafted BP can capture polymer molecules onto the Al surface under UV light illumination at 365 nm. A technique to combine SAMs on a gold surface with BP photochemistry has also been reported.204 In this method (Figure 45), a BPterminated thiol, 4-((10-mercaptodecyl)-oxy)benzophenone, is first formed on the gold surface, after which the BP exposed under UV irradiation can covalently capture PSt films coated on the SAM-modified surface. Such a photochemical grafting reaction suppresses the thermally induced dewetting of a PSt thin film on the modified gold surface, and the grafted PSt film can serve as a resist layer for wet etching.205 In this way, 100nm patterns of a gold thin film can be prepared simply by thermal nanoimprint lithography. In addition to linear simple polymers, more complex polymers can also be grafted by this strategy. For example, the star polymers consisting of 2-(2-methoxyethoxy)ethyl methacrylate and oligo(ethylene glycol) methacrylate (OEGMA) as arms and terminal BP as the star periphery are synthesized via atom transfer radical polymerization (ATRP).206 This type of polymer can be photografted onto commercially available tissue culture grade PSt surface under UV irradiation, and finally a thin film of star polymers is covalently attached, rendering the hydrophobic surface able to 5570


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Figure 42. Polymer thin films attached on BP-terminated silane SAMs: (a) a schematic view of the immobilization process; (b) the structures of polymers immobilized on surfaces by this method. Reprinted with permission from ref 198. Copyright 2004 Elsevier.

Figure 43. The difference in adhesion of human umbilical vein endothelial cells (HUVECs) on (a) PEtOx and (b) PAm layers deposited onto glass fabricated by BP-terminated silane-based SAMs. Reprinted with permission from ref 198. Copyright 2004 Elsevier.

Figure 40. The fabrication of BP-terminated surfaces through electropolymerization of pyrrole-BP monomer on ITO coated on the silica surface of optical fibers. The exposed BP groups can capture HCV-E2 protein in human sera samples through photochemical reaction, and the immobilized protein can function in immunoassay through sequential recognition with anti-E2 and anti-human IgGHRP.193

simultaneously: transformation of the polymer into hydrogel dots, covalent binding of the resulting gel to the substrate, and covalent immobilization of the proteins to a three-dimensional hydrogel scaffold. By use of anti-bovine serum albumin (antiBSA) as the model protein, a water-swellable polymer network

Figure 41. Patterned protein deposition controlled by photopatterning of nonfouling PEO coating within microchannels. A BP-terminated coating is first deposited via CVD polymerization, and then photocapturing of PEO molecules by BP is subsequently achieved by UV irradiation.196 5571


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Figure 46. A schematic illustration of the preparation of surfaceattached polymer hydrogels by using polymers containing BP groups. Reprinted with permission from ref 198. Copyright 2004 Elsevier. Figure 44. Spatial control of cell adhesion on a PDMAA substrate with a patterned GRGDSP layer: (a) schematic mask layout with four individual squares that represent the mask with different feature sizes of 1000 μm (red, lower left), 500 μm (violet, lower right), 300 μm (gray, upper left), and 150 μm (green, upper right); (b−d) selective adhesion of cells on GRGDSP-grafted areas while no cells adhere to the surrounding PDMAA background monolayer. Reprinted with permission from ref 200. Copyright 2008 American Chemical Society.

Figure 47. The use of PEtOx hydrogel formed by BP-mediated crosslinking and immobilization on a porcine heart valve. Upon UV irradiation, only the polymer containing the BP group undergoes cross-linking and forms a stable surface-attached hydrogel. As a control sample, the polymer without BP could not be gelated. Reprinted with permission from ref 198. Copyright 2004 Elsevier.

microarrays with a large amount of probes per spot in a very simple way, and the resulting captured proteins in the printed hydrogels retain their accessibility and functionality. In addition to planar chip surfaces, gel arrays can also be fabricated on polymer-based microfluidic devices.209 Thin films of different polymers containing photoactive BP units have been photochemically grafted onto the surfaces of compact disk-based microfluidic devices made from PMMA and PE− conorbornene. The modified microfluidic channels coated with hydrophilic PEtOx layers could be filled in a straightforward manner with water by capillary forces and show complete resistance to nonspecific protein binding. The generation of hydrophobic patches inside the modified microfluidic channels using BP-containing fluoropolymers allows the generation of passive microfluidic valves, which direct fluid motion in these compact disk-based devices. Gelation has also been used to prepare enzymatic sensors and biofuel cells.210 A photoreactive ferrocene redox polymer containing BP moieties has been cross-linked on the surface of glassy carbon electrodes. By encapsulating the enzyme glucose oxidase in this step, functional electrodes are obtained that yield electrical power upon addition of glucose. Stimuli-responsive films,211−213 surface gratings,212 and actuators214 can also be prepared by BP-mediated photocross-linking. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and salt concentration-responsive acidic polymers are combined into a terpolymer consisting PNIPAAm

Figure 45. A schematic view of the process to attach a PSt film on a gold surface by BP-terminated thiol-based SAMs. The corresponding SEM images of the patterned PSt film (a) and Au lines (b) prepared by using the patterned PSt film as a resist layer during Au and Cr wet etching are shown at the bottom. Reprinted with permission from ref 204. Copyright 2009 American Chemical Society.

based on polydimethylacrylamide as a scaffold and BP as a cross-linker, this method makes it possible to achieve 5572


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upon volume phase transition. Liquid crystalline actuators have also been prepared through the incorporation of BP into polymalonates for photochemical cross-linking.214 The crosslinked fibers (monodomains) show the potential of the smectic LC main-chain elastomers for use as actuators (Figure 51). In combination with electrostatic LbL deposition, BPmediated photo-cross-linking has been further used to prepare pH-sensitive bipolar ion-permselective polyelectrolyte multilayer films for ion separation.215 In this approach, two kinds of classical polyelectrolytes used in LbL assembly, PAA and poly(allylamine hydrochloride) (PAH) are prelabeled with BP moieties. As a result, the structure and composition of the resulting LbL film can be preserved by photo-cross-linking to form highly stable membrane films. Ion permselectivity can be regulated by changing the pH to control the extent of ionization of carboxyl and amine groups in the membrane. For example, at pH 10 the film shows permeability to the cationic probe Ru(NH3)3+ and impermeability to the anionic probe Fe(CN)63−, while the reverse permeability is observed at pH 3.2 (Figure 52). BP-mediated photo-cross-linking has also been used to improve the performance of sulfonated poly(ether ether ketone) (SPEEK) proton exchange membranes for direct methanol fuel cell applications.216 Instead of the above-mentioned chemical conjugation of BP prior to photo-cross-linking, even simple physical doping of BP into polymers could result in effective postpolymerization cross-linking. For example, photo-cross-linking on PE can be achieved by doping with BP and its derivatives, for example, anthrone, xanthone, thioxanthone, etc.217 Doping with BP has also been used with other polymer materials such as inorganic polymers, polyphosphazene membranes218 and polymer electrolyte membranes such as PSt−ethylene−butylene sulfonate (PSEBS) used for fuel cells.219 The photochemically crosslinked PSEBS membranes show a lower water swelling, lower proton conductivity, and higher chemical stability than noncross-linked PSEBS.219 Obviously, compared with its counterpart mentioned above, this method has a drawback in the lack of fine controllability of the chemical and physical structure at the molecular level and of the final properties of the resultant photo-cross-linked materials. 3.4.3.4. Binaphthyl Ketone. The photochemical excitation of binaphthyl ketone shows the absorption peaks between 320 and 356 nm due to the π−π* and n−π* transitions. It generally

Figure 48. Formation of a protein microarray by BP-mediated photocross-linking. Target proteins are conjugated with the epoxide side groups along polymer chains in solution, and then the solution of polymers with proteins and photoreactive BP moieties is printed on unmodified plastic slides. Under subsequent UV irradiation, the BPmediated photo-cross-linking is initiated, resulting in covalent attachment of a polymer network with proteins encapsulated on the substrate. Reprinted with permission from ref 208. Copyright 2010 Elsevier.

blocks, polymethylacrylic acid blocks, and PAA blocks, where the carboxyl groups are conjugated with BP units.211 Due to stimuli-responsive phase transition, the thickness and refractive index of the resulting film show corresponding changes to temperature and salt concentration (Figure 49). If the photocross-linking is performed in a photodefinable mode through photomask-controlled irradiation, a surface grating consisting of micropatterned hydrogel structure is formed (Figure 50).212 By surface plasmon diffraction (SPD) techniques, a weak diffraction intensity of the hydrogel grating is observed in the swollen state, while high intensity peaks are seen for the collapsed state, owing to the large change in optical contrast

Figure 49. Temperature- and salt concentration-dependent swelling behavior of a PNIPAAm terpolymer film synthesized by BP-mediated photocross-linking. Reprinted with permission from ref 211. Copyright 2007 American Chemical Society. 5573


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Figure 50. Schematic illustration of the process to prepare a hydrogel grating by BP-mediated photo-cross-linking of polymers. The optical microscopy image of a hydrogel grating film layer is shown on the right. Reprinted with permission from ref 212. Copyright 2009 American Chemical Society.

containing C−H or C−F bonds. AQ is nontoxic, water-soluble, and highly reactive under irradiation from light in the UV-A range, where photochemical damage of biomolecules and polymers is minimized. In C−H phototransformation by AQ (Figure 54), the carbonyl group in AQ (I) is first activated to the lowest excited n,π* triplet state via the formation of the singlet state and subsequent ISC. The resulting triplet state then abstracts hydrogen from C−H bonds on the polymer substrate to form a semiquinone radical (II)222 with a new surface macroradical being produced. The semiquinone radical can recombine with the surface macroradical (III) or abstract another hydrogen (IV) from a hydrogen donor reagent or the substrate. In contrast to the above-mentioned aryl ketones where the conjugation of the photosensitizer usually results in a C−C bond, the conjugation of AQ onto a C−H surface leads to a C−O linkage. By decoration of the benzene ring of AQ with a molecular linker,223 two kinds of AQ derivatives, AQ-E and AQ-NH2, have been used to functionalize the surface of a Novolac A derivative polymer (SU-8) (Figure 55). In AQ-E, an electrophilic group is able to further react with amino and thiol groups in other molecules at different pH. The ethylene glycol units in AQ-E further provide the AQ-E modified surfaces with antifouling properties, which minimize nonspecific adsorption. With AQ-NH2, reactive amine groups can be grafted onto the SU-8 surface through the photochemical immobilization of AQ and can further react with phosphate- or carboxylic acidcontaining biomolecules such as DNA, polysaccharides, and proteins. By means of these two kinds of AQ photolinkers, fluorescein-conjugated diamine (Alexa 647−cadaverine) and amino-modified biotin (biotin-NH2) have been covalently immobilized onto AQ-E and AQ-NH2 modified SU-8 surfaces, respectively. The feature resolution limit is compatible with state-of-the-art standard photolithography: 20 μm under irradiation from uncollimated light and 1.5 μm when a collimated light source is used (Figure 55). This micropatterning process on SU-8 substrates can be conveniently integrated with standard microfabrication in a cleanroom and therefore has great importance in the functionalization of MEMS-based biosensors. 3.4.3.6. Phthalimide. Under UV irradiation (typically 300 nm), phthalimide derivatives can be excited to form an n,π* triplet state that subsequently abstracts hydrogen atom from an adjacent C−H bond (Figure 56).224 The resulting two radicals

Figure 51. The uniaxial orientation of the photo-cross-linked oriented LC fiber observed under crossed polarizer microscopy and its thermal deformation upon heating from the liquid crystalline (95 °C) to the isotropic (102 °C) phase. Reprinted with permission from ref 214. Copyright 2007 WILEY-VCH Verlag GmbH & Co. KGaA.

Figure 52. The pH-switchable on/off function of a multilayer film prepared by BP-mediated photo-cross-linking of an LbL polymeric membrane composed of PAA/PAH. Reprinted with permission from ref 215. Copyright 2004 American Chemical Society.

shows a lower reactivity than BP in hydrogen abstraction reactions.220 By use of a silane carrying a binaphthyl ketone moiety (Chart 2), binaphthyl ketone can be immobilized on a target substrate, which is subsequently used as a surfaceconfined photochemical radical generator (PRG) to capture a variety of polymers onto silicon surfaces, and micropatterned immobilization of polymers is thus obtained (Figure 53).221 3.4.3.5. Anthraquinone. Anthraquinone (AQ) photochemistry is suitable for any type of organic surface/interface 5574


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Chart 2. The molecular structure of binaphthyl ketone and its photochemical behavior in transforming C−H to C−R bonds

Figure 53. A silane molecule carrying a binaphthyl ketone moiety and the grafting of a patterned polymer film on binaphthyl ketoneterminated silane SAMs as revealed by the subsequent fluorescence labeling seen under a fluorescence microscope. Reprinted with permission from ref 221. Copyright 2004 WILEY-VCH Verlag GmbH & Co. KGaA.

Figure 55. The chemical structure of AQ derivatives, AQ-E and AQNH2, used and the resulting fluorescence micrograph for patterned Alexa 647−cadaverine on AQ-E modified SU-8 (a), biotin-NH2 Cy3streptavidin on AQ-NH2-modified SU-8 (b), and Alexa 647− cadaverine resolution indications (c). Adapted with permission from ref 223. Copyright 2008 American Chemical Society.

detection of Bacillus anthracis spores and the development of novel vaccines that target anthrax spores, through a highthroughput characterization of synthetic carbohydrates for their antigenic reactivities with pathogen-specific antibodies.225b

Figure 54. The schematic route for photochemical activation of C−H bonds by AQ derivatives.

3.5. Direct Insertion by Reactive Intermediates

can then recombine to form a covalent linkage. By this method, unmodified carbohydrates have been immobilized onto silanebased SAM-modified glass, quartz, or silicon surfaces with phthalimides as terminal groups in SAMs.225a With control by a photomask, micropatterned mono-, oligo-, and polysaccharides can be formed on the surface (Figure 56). Carbohydrate arrays have also been achieved by using commercial robotic microspotting and display well-defined antigenic determinants for antibody recognition. Photogenerated carbohydrate microarrays have been successfully used to screen a biomarker for

As an alternative to processes that rely on hydrogen abstraction from C−H bonds by radical or triplet species, such as radical transfer (section 3.3) or hydrogen abstraction by a triplet state (section 3.4), this section describes another class of photochemical reactions involving direct insertion into C−H bonds by reactive nitrene- and carbene-generating compounds. Two typical examples are discussed in this section, namely, aryl azides and their derivatives (aryl diazirine, aryl diazo, aryl diazonium salts). 5575


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Figure 56. The mechanism of phototransformation of C−H bonds by phthalimides, and a schematic view of the process to fabricate carbohydrate patterns by phthalimide photochemistry. In this case, phthalimides are preimmobilized on the terminus of silane-based SAMs on glass substrates. Reprinted with permission from ref 225a. Copyright 2006 American Chemical Society.

3.5.1. Aryl Azides. Aryl azides possess a strong ability to tune a variety of carbon-based materials including polymer- and graphene-based structures.226 Fleet et al. pioneered this research by using aryl azide and derivatives as PAL reagents.227 Based on the type of substituent on the phenyl ring of an aryl azide, four basic forms of aryl azides exist: plain phenyl azides (no substituent), hydroxyphenyl azides, nitrophenyl azides, and perfluorophenyl azides (PFPA).228 Generally, these substituents affect greatly the light range needed for effective photoactivation: short-wavelength UV light (typically 254 nm) is needed for plain phenyl azides and hydroxyphenyl azides, while effective photolysis can be obtained under UV light with longer wavelength (typically 365 nm) for nitrophenyl azides and PFPA, which contain electron-withdrawing groups in the benzene ring. Therefore, in order to minimize the UV damage of molecules, especially biological substances, nitrophenyl azides and PFPA are preferable. The use of PFPA has recently been reviewed by Yan et al. with regard to various surface and interface activation and material applications.226b During ultraviolet (UV) photolysis, the photochemical reaction of phenyl azide is not a simple insertion process, but a complex procedure involving two parallel routes and utilizing nitrenes formed in situ under UV irradiation as reactive intermediates. Under UV excitation, the aromatic nucleus absorbs light, followed by vibrational transmission to the azide group.229 A reactive, uncharged singlet or triplet nitrene is subsequently formed through elimination of nitrogen.230 On the one hand, the singlet state can directly insert into a C−H bond. On the other hand, the singlet state can be subsequently converted to a triplet state through ISC, which will then abstract hydrogen from the C−H bond to form a phenyl azide radical and a surface alkyl radical. These two radicals further undergo radical coupling to complete the pseudoinsertion of phenyl azide into the C−H bond (Figure 57). The ISC is favored at low temperature because it is a barrierless process and can be catalyzed by heavy atoms or alcohols, while high temperature induces a greater contribution from the singletmediated process.231

Figure 57. Reaction mechanism of phototransformation of C−H bonds by phenyl azides.

The azide photochemical reaction does not require C−H bonds, and other hydrogen-containing bonds such as O−H, N−H, or S−H or even bonds without hydrogen can also undergo the reaction. It has been suggested that singlet nitrenes react preferentially by insertion into O−H or N−H bonds while triplet state nitrenes favor insertion into a C−H bond to form a secondary arylamine.232 Because of the high reactivity of nitrenes, the photoactivated phenyl azides sometimes undergo intramolecular rearrangement to give keteimines as undesired side products. The introduction of electron-withdrawing groups such as nitro (NO2) or fluoro (F) can stabilize the reactive intermediates, resulting in improved photoactivation performance as observed in the case of PFPA.228 There are two main routes for converting C−H to C−R bonds, based on the location of the azide (Figure 58): route I involves the incorporation of an azide decorated with a functional group R onto the surface, whereas route II involves the grafting of functional molecules carrying R groups by a surface-immobilized azide. R can be a small molecule, lipid, nucleic acid, peptide, protein, or polymer, as well as a carbohydrate. 3.5.1.1. Simple Functional Groups. If no special groups are conjugated on the benzene ring of phenyl azide, the introduction of a benzene ring or pentafluoro-substituted 5576


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Figure 58. Two typical routes for phenyl azide mediated photochemical surface functionalization.

benzene ring onto surfaces will cause an increase in surface hydrophobicity. For example, the photolysis of PFPA on the surfaces of PET films and alkylthiol monolayers is used to improve the surface hydrophobicity by virtue of the introduction of the fluorinated group in PFPA.233 Furthermore, simple functional groups such as carboxyl,234 amine,235 aldehyde,235 amide, and sulfonamide236 can be conveniently grafted onto C−H-rich polyolefin surfaces by preincorporation of these groups on the benzene ring of phenyl azide or reaction between grafted phenyl azide and the corresponding functional reagent. For instance, the surface chemistry of cyclic olefin copolymer (COC) and PMMA surfaces is tailored by PFPA carrying quaternary amine or aldehyde functional groups.235 After introduction of these functional groups, the patterned immobilization of a trypsin enzyme is achieved through the aldehyde−amine condensation reaction between the surface aldehyde groups and amine groups in the enzyme (Figure 59). Figure 60. Chemical structures of tree-type molecules and their immobilization on PE surfaces through molecular self-assembly followed by azide-induced photoimmobilization.237

Similarly, a molecule containing theophylline with a 4azidobenzoyl group separated by a short spacer chain240 has been synthesized and used to modify PU sheets under UV illumination. The modified surface grafted with theophylline shows a significant increase in lag-time for surface-induced thrombin formation and adhesion of a few platelets with nearly unchanged morphology, whereas a control sample without modification shows extensive adsorption of activated platelets on the surface. 3.5.1.2. Lipids. Phosphorylcholine-terminated phenylazide molecules can be photoimmobilized on organic surfaces through C−H phototransformations.241−243 For instance, a photoreactive polymer having a 2-methacryloyloxyethyl phosphorylcholine (MPC) group and an azide group is photoimmobilized onto polymeric surfaces such as PE and PP.243 The biomimetic MPC polymer is well-known for its ability to suppress nonspecific protein adsorption, platelet adhesion, activation, and aggregation. Consequently, the MPC-immobilized regions induce the inhibition of mammalian cell adhesion by the formation of aggregates on the immobilized regions. Tethered bilayer lipid membranes (tBLMs) have also been prepared on surfaces by using lipoglycopolymers (LGP) together with azide photochemistry (Figure 61).244 Reactive SAMs are first formed on a gold surface where a phenyl azide group is exposed outward from the surface. Subsequently, an LB monolayer of LGP is transferred onto this surface, followed by photochemical immobilization to form a stable lipid modified surface. The resulting substrate is used as a platform for vesicle fusion to form tBLM. Valinomycin, a cyclic peptide ion carrier, is embedded in tBLM to mimic the ionic conduction in biological membranes.

Figure 59. The fluorescence confocal microscopy images of patterned trypsin on modified PMMA surfaces. The immobilized trypsin is tagged by 5-(aminoacetamido)fluorescein. Reprinted with permission from ref 235. Copyright 2008 American Chemical Society.

Besides simple functional groups as mentioned above, larger and more complex molecular structures can also be grafted, for example, biologically active molecules and synthetic complex molecular structures. For instance, a tree-type molecule has been synthesized that includes a phenylazide group as the root, an aliphatic hydrocarbon chain as the stem, and two or three tris(hydroxymethyl)aminomethane groups as leaves (Figure 60).237 By combination of molecular self-assembly with the azide photochemical reaction, a well-defined molecular layer could be fixed on a PE surface with a high degree of packing. The construction of complex molecular structures can impart certain functions on the modified polymers. For example, polyolefin surfaces are grafted with hindered amine light stabilizers (HALS)238 to enhance their light stability, and the resulting photostability is comparable to that of polymers stabilized by Tinuvin 770. Dipyridamole, a well-known nontoxic vasodilator and inhibitor of activation and aggregation of blood platelets is photografted onto PU surfaces to enhance thromboresistance in clinical anti-coagulation fields, for example, pre- and postcoronary angioplasty procedures.239 5577


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biomedical applications, other applications have also appeared: for instance, PVC sheets have been modified by poly(azido acrylate)s via UV irradiation to inhibit the migration of the plasticizer.252 The second process involves the preparation of an azidedecorated surface and the capture of polymers by surfaceconfined azide photochemistry. The advantage of this method is the absence of any requirement to prelabel functional groups specific for the target polymers. A heterofunctional linker is often used that contains both photoactive azide and another anchoring group. The anchoring group in this molecular clip first binds with the substrate, resulting in the formation of surface-immobilized azide groups, which undergo further photochemical reaction with target polymers. For example, an alkanethiol with a terminal phenylazide group has been used to form SAMs on a gold surface, and the resulting azideterminated surface can be used to photochemically capture conductive polymers with regional selectivity.253 Silane-based phenyl azides that combine silane and phenyl azide in one molecule have also been developed to form azide-terminated silane SAMs on a SiO2 substrate through silanization process. Based on this strategy, Yan et al. covalently attached PEtOX and PSt thin films,254 as well as antibacterial furanone molecules,255 onto SiO2 surfaces by using PFPA−silane. Because of the quantitative nature of azide photochemistry and the use of azide−silane SAMs, the surface density of the immobilized furanone molecules can be adjusted by simply changing the concentration of PFPA−silane solution during the fabrication of silane SAMs. Photo-cross-linking can be also achieved by azide-induced phototransformation. For example, a LbL polyelectrolyte multilayer (PEM) film has been stabilized by such photocross-linking giving an easy and versatile method for cell patterning (Figure 62).256 The key to this is to mix PAA conjugated with 4-azidoaniline into a PAA/PAm multilayer film. Subsequently, a patterned photo-cross-linking reaction occurs under UV irradiation through a photomask. After rinsing, the resulting patterned PEM array can support a cell pattern since the cell adhesion is selectively limited to within the base substrate without a PEM coating. After conjugation of collagen onto the patterned PEGylated PEM film, the cytophobic PEM surface becomes cytophilic, resulting in selective seeding of C3A cells. Further L929 cell seeding on

Figure 61. The grafting of lipoglycopolymers by phenyl azide photochemistry onto gold sensor surfaces after Langmuir−Blodgett (LB) transfer.244

3.5.1.3. Synthetic Polymers. The first method is the synthesis or decoration of a polymer with azide groups followed by conjugation of the azide-decorated polymer on the surface or interface. Such modified surfaces have been widely used as antifouling coatings, immunoassay chips or cell culture platforms as well as in other applications. For example, the biocompatibility of PU and poly(vinyl chloride) (PVC) surfaces is improved through photografting of azide-based polymers such as PEO245 and poly(N-vinylpyrrolidinone).246 The cell adhesion, spreading, and differential behavior can be regulated by photografting and patterning of a variety of polymers containing hydrocarbon or fluorocarbonalkyl, sulfonato, amino, or hydroxyl groups or PSt, PAm, histidinecontaining polymers,247 and PEG blocks248,249 as well as thermo-responsive PNIPAAm250 and pH-responsive PAA.251 It has been found that endothelial cells will adhere on (fluoro)alkyl, phenylsulfonato, and phenylamino groups as well as on PSt-modified hydrophobic surfaces, while the adhesion is unfavorable on a hydroxyl group-bearing hydrogel-like PAm and PEG, as well as on a histidine-containing polymer grafted hydrophilic surface.247 In addition to the above

Figure 62. Cell patterning based on a photo-cross-linked PAA/PAm PEM film array on surfaces. C3A cells are first attached to the collagenimmobilized PEM regions. After rinsing away unattached cells, L929 cells are seeded under serum-containing conditions. After culture for 3 days, the cell morphology, staining of cell nuclei by DAPI, and albumin synthesis in C3A cells by immunofluorescent staining are shown in panels B−D. Scale bar, 100 μm. Reprinted with permission from ref 256. Copyright 2009 Elsevier. 5578


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the bare regions induces the formation of the hybrid cell patterning. 3.5.1.4. Nucleic Acids. Similar to the above-mentioned cases for polymer immobilization, the grafting of nucleic acids (also peptides, proteins, and carbohydrates, see below) has been achieved by use of various heterofunctional molecular linkers, showing promise for cost-effective DNA-based biosensors, biochips, and microtiter plate-based assay systems. The linker can bridge between functional target molecule and surfaces through covalent/noncovalent bonding formed by the binding of the extra functionality in the linker onto surfaces (then the azides bonding with target biomolecule) or the azides onto surfaces (then the extra functionality bonding with target biomolecule). For example, a photoreactive biotin derivative, photobiotin (PHB) (Chart 3),257 carrying a phenyl azide group

Chart 4. The Molecular Structure of FNAB

oligonucleotide probe to terminate the grafting for further hybridization. A high selectivity could be achieved during the hybridization processes with the covalently immobilized oligonucleotide probe, clearly discriminating a single-base mismatched oligonucleotide target (Figure 64). Besides

Chart 3. The Molecular Structure of Photobiotin (PHB)

Figure 64. Hybridization tests on an oligonucleotide probe immobilized on a PSt microtiter plate by using complementary (PM), single-base mismatch (MM-1), three-base mismatch (MM-2), and noncomplementary (random) target oligonucleotides. Reprinted with permission from ref 262. Copyright 2010 The Royal Society of Chemistry.

for photoreactions and a biotin moiety for further biological interaction with a tetrameric avidin,258 has been employed to immobilize various biomolecules such as antibodies,259 enzymes,260 and nucleic acids261 on organic surface. As one typical example, PHB is photoimmobilized onto a PSt film deposited on a silver-coated quartz crystal microbalance (QCM) for DNA grafting.261 After recognition with avidin, a surface with immobilized free avidin pockets is obtained that could interact with a biotin-labeled DNA probe allowing the final immobilization of the DNA probes (Figure 63). A DNA hybridization assay is achieved on the QCM by sampling a 70mer single-stranded DNA fragment containing complementary or noncomplementary sequences. Another typical example involves using l-fluoro-2-nitro-4azidobenzene (FNAB) as the linker (Chart 4). In this case, FNAB is first photoimmobilized on the PSt surface through azide photochemistry.262 The resulting exposed phenylfluoro group reacts further with a protonated amine-modified

amine-modified oligonucleotides, this method is also applicable for the immobilization of thiol-modified oligonucleotides through the reaction between phenylfuoro group and thiol. 3.5.1.5. Peptides. Two kinds of typical functional peptides, namely, the cell adhesive sequence Arg−Gly−Asp (RGD) and epidermal growth factor (EGF) polypeptide, have been grafted by azide-induced phototransformations as reported in several studies. RGD is conjugated with an NHS ester-based heterofunctional linker 4-azidobenzoyloxysuccinimide at its N-terminal end to form a photoreactive peptide containing RGD,263 which could subsequently be photoimmobilized onto

Figure 63. Schematic illustration of the procedures to functionalize a PSt coating on a QCM by photochemical immobilization of PHB and subsequent recognition with biotin−ssDNA immobilization through biotin−avidin−biotin bridges and subsequent DNA hybridization. Reprinted with permission from ref 261. Copyright 2002 Elsevier. 5579


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a poly(vinyl alcohol) (PVA) surface. Bovine endothelial cells (ECs) could adhere and spread well on the RGD peptidederivatized surfaces in a biologically specific manner. The use of a photomask during UV irradiation can induce the formation of a two-dimensional micropattern of ECs (Figure 65).263

Figure 66. The photochemical immobilization of RGD peptide by using sulfo-SANPAH.266 Adapted with permission from ref 266. Copyright 2006 WILEY-VCH Verlag GmbH & Co. KGaA.

Figure 65. Phase-contrast images of area-selective adhesion and spreading of ECs on a PVA substrate with patterned immobilization of RGD peptides: (a) honeycomb pattern; (b) stripe pattern. Reprinted with permission from ref 263. Copyright 1995 WILEY-VCH Verlag GmbH & Co. KGaA.

For example, APG is used to obtain an azide-decorated surface through the reaction between glyoxyl in the linker and guanidino groups on the SAM-modified gold surface,273 while NHS-functionalized PFPA has been widely used to immobilize proteins on various substrates, for example, polymer, silica, and graphite.274 The corresponding photolithography process can produce a pattern with micrometer-sized features (Figure 67).

Another NHS-based phenylazide linker is the commercially available sulfo-SANPAH (sulfosuccinimidyl-6-(4′-azido-2′-nitrophenyl-amino)hexanoate) (Chart 5), which has been used Chart 5. The Molecular Structure of Sulfo-SANPAH

to label the C-terminus of RGD264 and EGF265 for subsequent photochemical immobilization on a chitosan membrane surface. The EGF-modified surface shows a stimulated fibroblast growth and a considerable difference in cell proliferation. The above-mentioned heterofunctional linkers have also been used to immobilize label-free peptides on organic surfaces. In this way, a photoreactive azide is first inserted into a C−H bond on a polymer surface, resulting in the grafting of NHS groups that can subsequently react with amine-terminated (usually at the N-terminus) functional peptides through NHS displacement.266−268 For example, PDMS surface has been modified through phenylazide-induced C−H phototransformation to introduce NHS ester groups (Figure 66), and then RGD peptides are conjugated on the reactive surface allowing a promotion of the adhesion, proliferation, and collagen production of human skin fibroblasts (HSFs).266 In another approach, the linker is used to photochemically immobilize RGD in a thermosensitive hydrogel formed by copolymerization of ethylene glycol vinyl ether and butyl vinyl ether.268 The thermoresponsive character of the hydrogel enables this material to recover the attached viable cells from the surface of the hydrogel by a simple low-temperature treatment without the use of trypsin. 3.5.1.6. Proteins. Similar to peptides, the strategies to immobilize proteins on organic surfaces can also be grouped into label-free and label-based methods.269 Several heterofunctional linkers have been used in these two protocols such as PHB,257−260 FNAB,270−272 p-azidophenyl glyoxal (APG),273 and NHS-PFPA.274 The azide in the linker is used to attach it to the surface or proteins, and the other reactive group in another portion is utilized to react with the proteins or surfaces.

Figure 67. The patterned immobilization of fluorescent proteins on a PSt surface using a NHS-PFPA bifunctional linker. Reprinted with permission from ref 274a. Copyright 1993 American Chemical Society.

Kinds of proteins such as horseradish peroxidase (HRP) and alkaline phosphatase,275 albumin and gelatin,269 insulin,276 and some growth factors277,278 as well as BSA and glucose oxidase (GOD)279,280 have been grafted by this strategy on a variety of polymeric substrates, for example, polymer microchannels,280 conductive polypyrrole films,278 and PEG hydrogels.279 The unique feature of this photochemical method, spatial addressing capability, further enables this approach to graft multiple proteins in a determined array. Such a sequential pattern allows a sequential cascade detection of biochemical product, providing a potential tool as microfluidic bioreactor or sensor. For example, GOD and HRP are sequentially patterned both in a single microchannel by using NHS-functionalized 5580


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Figure 68. The strategy for glucose analysis by cascade arrangement of GOD and HRP on a microchip through regioselective illumination of a conjugate solution. Reprinted with permission from ref 280a. Copyright 2006 Elsevier.

PFPA as a bifunctional linker.280 The light-induced spatial addressable immobilization can be achieved by regioselective illumination of a conjugate solution containing the linker and target enzymes (Figure 68). The final immobilization features a sequential pattern where the location of the HRP zone is downstream from the GOD zone. This arrangement allows a sequential cascade detection of the oxidation product of glucose by GOD, since the oxidation product, H2O2 produced in GOD regions, can be subsequently recognized by HRP using resorufin for fluorescence detection. Compared with the traditional method based on a 96-well microtiter plate, the technique on the microchip significantly decreases the reaction time from 30 min to 4.8 s. 3.5.1.7. Carbohydrates. Carbohydrates such as glucose,238 sucrose,238,281 dextrine,238 dextran,282,283 chitosan,284−287 lactose, α-D-mannopyranoside,288,289 heparin,290,291 and hyaluronic acid292 as well as dextran sulfate, dermatan sulfate, and endothelial cell surface heparan sulfate291 have been immobilized on polymer membrane or fiber surfaces in order to improve their hydrophilicity and hemocompatibility,238,281,285 as well as for specific cell or protein recognition.287−289 Both label-based and label-free methods have been employed. In a typical label-based example, a cellulose membrane surface is grafted by O-butyrylchitosan (OBCS) through prelabeling a phenylazide functionality in OBCS and subsequent photochemical immobilization.287 The resulting cross-linked OBCS film shows good blood compatibility and is potentially promising for application in blood-contacting devices. Azide−chitosan has also been photochemically immobilized onto a biodegradable poly(lactide-co-glycolide acid) (PLGA) surface.286 The grafted chitosan layer facilitates further grafting of gelatin through the active amine groups on chitosan allowing control of the initial cell deformation rate, degree of cell spreading, and adhesion kinetics. Photo-crosslinked carbohydrate gel coatings can also be obtained using azide-labeled glycopolymers. For example, dextran carrying a phenyl azide moiety can be photo-cross-linked to prepare dextran hydrogel films on PET surfaces in order to create protein-rejecting and cell-repelling coatings as well as multivalent sites to further graft biologically active molecules.283 Alternatively, in a typical label-free method, PCL−PEG amphiphilic copolymers are decorated with pendent NHS esters by photochemical attachment of the bifunctional molecular linker O-succinimidyl-4-(p-azido-phenyl)butanoate.288 The resulting NHS groups are further used to couple with a 2-aminoethyl α-D-mannopyranoside ligand that can be recognized by a receptor in dendritic cells. The PCL−

PEG copolymer with immobilized mannose ligand can thus be used as a nanocarrier for oral delivery, for example, in oral vaccination. Besides the NHS-mediated conjugation, Cucatalyzed azide/alkyne cycloaddition (CuAAC, click chemistry) has also been combined with PFPA photochemistry to develop rapid and efficient photoclick methods for carbohydrate capture on a polymer surface. For example, a bifunctional linker containing an alkyne and PFPA as the two termini has been synthesized and photoimmobilized onto a PSt surface through PFPA-mediated photoligation, after which α-D-mannopyranosides with an azide moiety undergo CuAAC to achieve the immobilization.289 Another bifunctional linker used for such purposes is FNAB. For example, the phenylfluoro group in FNAB can react preferentially with protonated amines on the substrate to conjugate itself on the surface. As a result, phenyl azide is implanted and exposed outward for further reaction. A series of glycopolymers including heparin, dextran sulfate, dermatan sulfate, and endothelial cell surface heparan sulfate have been immobilized on cellulose membranes by this method.291 These matrices show different platelet adhesion performance based on the type of carbohydrate grafted, and endothelial cell surface heparan sulfate modified membranes show no platelet adhesion. 3.5.2. Aryl Azides, Aryl Diazo, and Aryl Diazonium Salts. In addition to phenylazides, other azide derivatives such as aryl diazirine (λmax 350 nm), aryl diazo (λmax 250−260 nm), and aryl diazonium salts (λmax 270−450 nm) can also function as photosensitizers in a similar way. Diazirines have been widely used in PAL for intermolecular cross-linking.293 For C−H phototransformation on macroscopic surfaces, aryl diazirine and aryl diazo moieties can be converted to carbenes, while aryl diazonium salts can be converted to carbocations under UV irradiation (Figure 69). These highly reactive intermediates rapidly become inserted into C−H, CC, N−H, O−H, or S− H bonds.294 As a result, functional molecular structures carrying these reactive groups can be photochemically fixed onto organic surfaces or interfaces. For example, synthetic polymers bearing these functional groups by copolymerization of N,N-dimethylacrylamide and styrene derivatized with aryl diazo and aryl diazonium moieties can be grafted onto a PET surface under UV irradiation.295 Besides polymers, biomolecules such as peptides,267a,296 proteins,297−300 and carbohydrates301 have also been immobilized on polymer surfaces in order to function as passivation layers for further antibody immobilization, immunoassay, platforms for enzyme immobilization, and selective cell attachment, as well as in biomolecular interaction studies. 5581


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reaction, single-walled carbon nanotubes304 and diamond films305 have been modified by introduction of sulfurcontaining functionalities. The resulting free thiol groups on the diamond film surface can further support self-assembly of gold nanoparticles (Figure 70).

Figure 69. Schematic mechanism of the photochemical activation of C−H bonds by using aryl diazirine, aryl diazo, and aryl diazonium salts.

4. PHOTOTRANSFORMATION OF C−H BONDS ON CARBONACEOUS MATERIAL SURFACES Carbonaceous material is the general name for a substance rich in carbon. Some important types include diamond, amorphous carbon, glassy carbon, carbon nanotube, and graphene, and these have been utilized in modern material science and technology such as for electrodes, capacitors, semiconductors, hydrogen storage, and biosensors. For instance, diamonds are excellent substrates due to their outstanding stability in biological and aqueous environments, biocompatibility, and large electrochemical potential window. Surface activation on these materials is thus important in order to combine the outstanding bulk properties with functional surface molecular structures. Among various modification methods, techniques involving C−H phototransformation have mainly concentrated on photochemical reactions of hydrogen-terminated diamond and amorphous carbon. Generally, such hydrogen-terminated surfaces have an array of sp3 C−H bonds that resembles a saturated hydrocarbon. However, these C−H bonds are more susceptible to photochemical reactions than alkanes because of the unique electrochemical properties of the materials. For instance, the presence of C−H bonds on a hydrogenterminated diamond surface induces the condition of negative electron affinity (NEA), which makes hydrogenated diamond a good electron donor to facilitate the phototransformation of surface C−H bonds.

Figure 70. The phototransformation of C−H bonds on a diamond surface by cyclic disulfides and subsequent application to support the deposition of Au colloids. Reprinted with permission from ref 305. Copyright 2007 The Japan Society of Applied Physics.

Dithio-radicals can also be formed by the photoinduced ring cleavage of elemental sulfur (S8) under UV irradiation.306 One of two thio radical sites can then be deactivated through hydrogen abstraction from the C−H bond on hydrogenated diamond powder and as a result, a surface carbon radical is formed. The other remaining thio radical combines with the surface carbon radical to form a thiol-terminated polysulfide (−Sn−) layer. Under UV irradiation, the polysulfide bonds are easily cleaved to form new thio radicals and are finally converted to thiol and thiocarbonyl groups on the surface (Figure 71).307 The diamond powder with free thiol capping groups can be thereby attached to a patterned gold film coated on a Si substrate to produce a site-selective deposition of the diamond particles (Figure 72).307 4.2.2. Halide Compounds. It has been found that a perfluorooctyl (C8F17) radical, generated by photolysis of an azo-containing perfluorooctane under 185 nm UV via elimination of a nitrogen molecule, can abstract a hydrogen atom or react with a CC bond on a diamond surface to produce surface radical sites. The resulting surface carbon dangling bond (radical) then recombines with another remaining C8F17 radical to give perfluorooctyl groups grafted on carbonaceous substrates including diamond powder, film, or coating and single-walled carbon nanotubes (Figure 73).308−312 The surface morphology does not change after the introduction of C8F17 moieties, and the modified surface shows water repellency and low friction coefficient. The surface water contact angle on the modified surface changes little even upon storage of the substrate in air for 60 months, indicating the high stability of the surface properties. Furthermore, the modification does not significantly influence the optical transparency of the final material. For example, in the case of modification of a nanodiamond-coated glass substrate, the functionalized substrate shows >87% transmittance in the >400 nm wavelength region. In another approach, the photolysis of C4F9I under UV irradiation (

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