Mild and Modular Surface Modification of Cellulose via Hetero Diels

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Mild and Modular Surface Modification of Cellulose via Hetero Diels-Alder (HDA) Cycloaddition Anja S. Goldmann,† Thomas Tischer,† Leonie Barner,‡ Michael Bruns,§ and Christopher Barner-Kowollik*,† †

Preparative Macromolecular Chemistry, Institut f€ur Technische Chemie und Polymerchemie, Karlsruhe Institute of Technology (KIT), Engesserstr. 18, 76128 Karlsruhe, Germany ‡ Fraunhofer Institut f€ur Chemische Technologie, Umwelt-Engineering, Joseph-von-Fraunhofer-Str. 7, 76327 Pfinztal, Germany § Institute for Materials Research III and Karlsruhe Nano Micro Facility (KNMF), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany

bS Supporting Information ABSTRACT: A combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and hetero DielsAlder (HDA) cycloaddition was used to effect, under mild (T ≈ 20 °C), fast, and modular conditions, the grafting of poly(isobornyl acrylate) (Mn = 9800 g mol-1, PDI = 1.19) onto a solid cellulose substrate. The active hydroxyl groups expressed on the cellulose fibers were converted to tosylate leaving groups, which were subsequently substituted by a highly reactive cyclopentadienyl functionality (Cp). By employing the reactive Cp-functionality as a diene, thiocarbonyl thio-capped poly(isobornyl acrylate) synthesized via RAFT polymerization (mediated by benzyl pyridine-2-yldithioformiate (BPDF)) was attached to the surface under ambient conditions by an HDA cycloaddition (reaction time: 15 h). The surface-modified cellulose samples were analyzed in-depth by X-ray photoelectron spectroscopy, scanning electron microscopy, elemental analysis, Fourier transform infrared (FT-IR) spectroscopy as well as Fourier transform infrared microscopy employing a focal plane array detector for imaging purposes. The analytical results provide strong evidence that the reaction of suitable dienophiles with Cp-functional cellulose proceeds under mild reaction conditions (T ≈ 20 °C) in an efficient fashion. In particular, the visualization of individual modified cellulose fibers via high-resolution FT-IR microscopy corroborates the homogeneous distribution of the polymer film on the cellulose fibers.

’ INTRODUCTION The modification of cellulose in both the solid state as well as in solution for altering its chemical and physical properties is a widely studied field.1 Because of the inherent attributes of cellulose as an inexpensive, biocompatible, thermally and mechanically stable as well as sustainable resource, cellulose is itself an important polymeric product.2 Nevertheless, cellulose lacks the versatile and tunable properties of synthetic polymers.3 To control the properties of cellulose such as wettability, adhesion, or hydrophobicity, its efficient modification with synthetic polymers is an important synthetic endeavour.4 A common route to modify cellulose, whether under heterogeneous conditions as in the present contribution or in homogeneous solution, are grafting approaches,4,5 where synthetic polymer strands are covalently tethered to the biopolymer’s surface via a range of different approaches (see below). Several methods exist and have been extensively studied for the modification of cellulose (and other) surfaces, typically achieved by the formation of grafts of synthetic polymers that implement specific properties while at the same time keeping the intrinsic properties of the biopolymeric material intact.3,6 Variable grafting approaches exist for surface modification, that is, ‘grafting-to’ (where a preformed functional surface is reacted r 2011 American Chemical Society

with a functional polymeric material)7 and ‘grafting-from’ (where synthetic polymer chains are grown directly from the surface via a suitable (often living/controlled radical) polymerization process).8 Of these grafting approaches, the ‘grafting-from’ approach is the most commonly employed technique because it can lead to high grafting densities.4,8a,8b,8d,9 Nevertheless, a range of efficient reactions (some of which adhere to the criteria defined for Click chemistry,10 for example, copper-catalyzed Huisgen [2 þ 3] cycloadditions, Michael additions, as well as (hetero) Diels-Alder cycloadditions when employed in a ‘grafting-to’ approach can lead to comparable grafting densities as ‘graftingfrom’ approaches.11 The fact that reactions falling under the Click chemistry criteria show (ideally) quantitative conversions makes them a particularly attractive reaction class to be employed for the orthogonal modification of variable surfaces. Interestingly, the ‘grafting-to’ approach as an efficient means of modifying cellulose fibers in their solid state with well-defined synthetic macromolecules has obtained little attention to date. In the majority of the few literature reported cases, the coupling was Received: December 3, 2010 Revised: January 28, 2011 Published: March 02, 2011 1137

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Biomacromolecules accomplished with a premade polymer generated by anionic or cationic polymerization. For example, Mansson and Westfelt7a grafted anionically prepared low-molecular-weight polystyrene onto cellulose acetate. A grafting yield of up to 83% (the grafting yield is defined as the percentage of added PSCOCl which was attached) was obtained under strictly anhydrous conditions employing high concentrations of esterification catalysts such as 4-(dimethylamino)-pyridine over extended periods of reaction time (up to 3 days). Furthermore, Biermann et al.7b likewise grafted polystyrene onto mesylated cellulose acetate by reacting it with polystyrylcarboxylate. In such an approach, the polystyrylcarboxylate anion displaces the mesylate groups via a SN2 nucleophilic reaction, which occurs almost quantitatively at 75 °C after 20 h in a homogeneous phase reaction. Aminofunctionalized cellulose was modified by a ‘grafting-to’ approach by Takayama and coworkers.7c In here, poly(2-methyl-2oxazoline) and poly(isobutyl vinyl ether) were prepared via a living polymerization technique. The introduction of amino groups onto a cellulose powder surface was achieved by the treatment of cellulose powder with isatoic anhydride. It was found that cellulose powder having amino groups is readily reacted with living poly(2-methyl-2-oxazoline) (polyMeOZO) cation, which was generated by ring-opening polymerization. By the termination of living poly(isobutyl vinyl ether) (polyIBVE), which was generated by the polymerization with a HCl/ZnCl2 initiating system, with amino groups on cellulose powder, polyIBVE was also grafted onto the surface. Cordova and coworkers12 demonstrated the modification of solid polysaccharides by a combination of organocatalysis and thiol-ene reaction under environmental friendly reaction condition. However, only limited characterization methods have been employed to prove the successful grafting. In our group, the hetero Diels-Alder reaction (HDA) between reactive dienes and highly electron deficient thiocarbonyl thio compounds was developed as a fast and efficient Click reaction10a,13 and successfully applied for the surfacemodification of poly(divinyl benzene) microspheres14 as well as silicon surfaces.15 We demonstrated a dramatic reaction rate improvement of the HDA Click reaction through the use of Cp-functionalized polymers.13a Within the present contribution, the effective application of the RAFT-HDA concept for the rapid surface modification of cellulose is outlined. Cp-functional polymers of narrow polydispersity can be readily prepared by reacting bromine terminal polymers (accessible via ATRP) with nickelocene under mild conditions.13b This functionalization approach, being applicable to all ATRP-derived polymers, provides ready access to highly DA reactive macromolecules. Guided by the same principal idea of generating highly DA reactive Cpfunctional materials, the present study follows the idea to generate Cp functional cellulose surfaces, which are later employed as a reactive scaffold for polymer-surface conjugation reactions. The chemical reaction sequence is based on the transformation of the cellulose intrinsic OH groups into tosylate moieties as good leaving groups and their subsequent substitution with a Cp functionality. RAFT-HDA cycloaddition with poly(isobornyl acrylate) as dieneophile synthesized via RAFT polymerization was then employed to modify the surface at ambient temperature in an efficient polymer-surface covalent conjugation in dip-coat style procedure. On a more general level, Cp-functionalized cellulose can be seen as a versatile template for the modular and rapid functionalization with several functional polymers, biopolymers, and other interesting compounds that

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present dienophiles that can undergo hetero Diels-Alder cycloadditions.

’ EXPERIMENTAL SECTION Materials. Isobornyl acrylate (Alfa Aesar, techn.), was destabilized by percolating over a column of basic Al2O3 and stored at -19 °C. Acetone (Normapur), chloroform (Normapur), methanol (Normapur), sodium hydroxide (Roth, >99%), sodium iodide (Fluka, >99%), pyridine (Acros, 99.5% extra dry), tetrahydrofuran (Acros, 99.5%), p-toluene sulphonyl chloride (Acros, 99þ%), trifluoro acetic acid (Acros, 99%), triphenylphosphine (Merck), ethylenediaminetetraacetic acid (EDTA, Acros, 99%), nickelocene (ABCR, 99%), and N-(1-pyrene)maleimide (TCI Europe, >99%) were used without further purification unless otherwise stated. Characterization. SEC measurements were performed on a Polymer Laboratories (Varian) PL-GPC 50 Plus Integrated System, comprising an autosampler, a PLgel 5 μm beadsize guard column (50  7.5 mm), followed by three PLgel 5 μm Mixed-C columns (300  7.5 mm), and a differential refractive index detector using THF as the eluent at 35 °C with a flow rate of 1 mL min-1. The SEC system was calibrated using linear poly(styrene) standards ranging from 160 to 6  106 g mol-1 and linear poly(methyl methacrylate) standards ranging from 700 to 2  106 g mol-1. Molecular weights relative to PMMA are reported in the current contribution. Calculation of the molecular weight of poly(isobornyl acrylate) proceeded via the Mark-Houwink parameters for this polymer (K = 5.0  10-5 dL g-1 and R = 0.75).37 Fluorescence Spectroscopy. Fluorescence images were recorded on a LSM 510 META apparatus with an excitation wavelength of 405 nm. Scanning Electron Microscopy and EDX Measurements. SEM images and EDX measurements were performed on a Zeiss Supra 40 VP with an accelerating voltage of 10 kV. EDX measurements were captured with a Sapphire Si(Li)-detector PV7715/89 (EDAX, Inc.). Elemental Analysis. The elemental composition of the cellulose samples was analyzed using an automatic elemental analyzer Flash EA 1112 from Thermo Scientific, which was equipped with a MAS 200R auto sampler. XPS Investigations were performed on a K-Alpha spectrometer (ThermoFisher Scientific, East Grinstead, U.K.) using a microfocused, monochromated Al KR X-ray source (200 μm spot size). Up to 30 separated spots were measured to prevent the samples from X-ray damage, each at minimum acquisition time. All spectra were finally collapsed to one single spectrum with a sufficient signal/noise ratio. The kinetic energy of the electrons was measured by a 180° hemispherical energy analyzer operated in the constant analyzer energy mode (CAE) at 50 eV pass energy for elemental spectra. The photoelectrons were detected at an emission angle of 0° with respect to the normal of the sample surface. The K-Alpha charge compensation system was employed during analysis, using electrons of 8 eV energy and low-energy argon ions to prevent any localized charge build-up. Data acquisition and processing using the Thermo Avantage software is described elsewhere.16 The spectra were fitted with one or more Voigt profiles (BE uncertainty: (0.2 eV). The analyzer transmission function, Scofield17 sensitivity factors, and effective attenuation lengths (EALs) for photoelectrons were applied for quantification. EALs were calculated using the standard TPP-2 M formalism.18 All spectra were referenced to the C1s peak of hydrocarbon at 285.0 eV binding energy controlled by means of the well-known photoelectron peaks of metallic Cu, Ag, and Au, respectively. FT-IR Measurements and FT-IR Microscopy Imaging. Infrared measurements of the cellulose samples have been performed using a Bruker FT-IR microscope HYPERION 3000 coupled to a research spectrometer VERTEX 80. The HYPERION 3000 microscope is 1138

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Biomacromolecules equipped with two types of detector: a single element MCT-detector (Mercury Cadmium Telluride) for the conventional mapping approach and a multi-element FPA-detector (focal plane array) for imaging. The single element MCT-detector has been used for nonlaterally resolved measurements and the FPA-detector for the laterally resolved measurements. The multielement FPA-detector consists of 64  64 elements. This allows for the simultaneous acquisition of 4096 spectra covering a sample area of 32  32 μm (for ATR detection). With the FPA-detector in combination with the 20 Germanium ATR-lens, a lateral resolution of 0.25 μm2 per pixel is achieved. This high-resolution is needed for the analysis of single fibers within the cellulose matrix to examine the homogeneity of the covalent functionalization applied on the cellulose. Besides the high lateral resolution, the extremely short measurement time (< 2 sec/scan) is another significant benefit of the FPA-detector. With the FPA-detector, 4096 spectra are acquired simultaneously within a few seconds. For postprocessing baseline correction and atmospheric compensation were used. Synthesis of the RAFT Agent. Benzyl pyridine-2-yldithioformiate (BPDF) was synthesized according to a procedure described by Abrunhosa et al.19 RAFT Polymerization of Isobornyl Acrylate. The polymerization method was adopted from a procedure described by Inglis et al.13c Destabilized isobornyl acrylate (50 mL, 0.24 mol) was mixed with 290 mg benzyl pyridine-2-yldithioformiate (1.18 mmol) and 29 mg 2,20 -azo(bisisobutyronitrile) (0.18 mmol) in a dried Schlenk flask, and the oxygen was removed by percolating with nitrogen for 45 min. The mixture was stirred for 15 h at 60 °C and subsequently precipitated in ice-cold methanol (Mn = 9800 g mol-1, PDI = 1.19 with K = 5.0  10-5 dL g-1 and R = 0.75). Cellulose Pretreatment. Whatman No. 5 filter paper was cut into round pieces with a hole puncher featuring a diameter of close to 1 cm 0.5 g of cellulose was immersed in an aqueous solution of 10 wt % NaOH (150 mL) for 18 h. The swollen cellulose samples were repeatedly washed with absolute ethanol until a neutral solution was obtained. The cellulose sheets were directly used without any drying and employed for further reactions. 50 mg of pretreated cellulose (Whatman No. 5) contains 0.91 mmol of active hydroxyl groups.8d Tosylation of Cellulose. Pretreated cellulose (0.2 g, 3.64 mmol of active OH-groups) was dispersed in 7.5 mL of dry pyridine, and 2.35 g p-toluene sulfonic acid chloride (12.33 mmol, 3.4 equiv) was added. The reaction mixture was kept on a shaker overnight. The reaction was stopped by the addition of an ice-cold acetone/H2O mixture (15 mL, 1:1), and the product was washed thoroughly with distilled water and stored in THF. Cp-Functionalization of Cellulose. 30.6 mg of tosylated cellulose were suspended in 6 mL of anhydrous THF. 528 mg NaI (3.52 mmol, 6.3 equiv) and 308 mg of triphenyl phosphine (1.176 mmol, 2.1 equiv) were then added. Subsequently, the solution was freed from oxygen with a nitrogen stream. Nickelocene (222 mg, 1.176 mmol, 2.1 equiv) was dissolved in 6 mL of anhydrous THF under N2 and added to the solution. The reaction mixture was stirred for 15 h at ambient temperature. The cellulose was washed thoroughly with distilled water and submersed under agitation for 15 h in 50 mL of EDTA solution (0.1 molar). Subsequently the filter paper was suspended in 100 mL of distilled water overnight. The rinsed cellulose was stored in THF.

RAFT-HDA Modification of Cellulose with piBoA-BPDF. Cp-functionalized cellulose (2 mg) was suspended in 0.5 mL of CHCl3 with 201.9 mg piBoA-BPDF (Mn = 9800 g mol-1, PDI = 1.19), and 15 mL of trifluoroacetic acid (TFA) was added. The reaction mixture was shaken for 15 h at ambient temperature. Subsequently, the cellulose was subjected to the following washing procedure: 15 min in 5 mL of CHCl3, 15 min in 10 mL of CHCl3, 15 min in 5 mL of THF, and 15 min in 10 mL of CHCl3. The functional cellulose sheets are left to dry.

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Fluorescence Labeling of Cellulose. Cp-functionalized cellulose (19 mg) was mixed with 14.8 mg of N-(1-pyrene)-maleimide (49.4 μmol, in 5 mL CHCl3) and stirred for 62 h at ambient temperature and subsequently washed for 30 min in 10 mL of CHCl3 and dried in air.

’ RESULTS AND DISCUSSIONS Cellulose Pretreatment. Cellulose consists of D-anhydroglucose units joined together by β-1,4-linkages.20 In its native state, cellulose chains feature strong intermolecular hydrogen bonding due to the hydroxyl groups. Prior to surface modification, cellulose substrates were thus subjected to a pretreatment to increase its ability to react: The cellulose sheets were immersed in an aqueous solution of 10 wt % NaOH to break down the extensive hydrogen bonding between the OH groups of cellulose and to open up the ordered regions so that the reagents can penetrate more readily into the cellulose substrate and render it accessible for further modification. The coupling reaction between the (pretreated) cellulose surfaces modified with a Cpfunctionality and poly(isobornyl acrylate) (PiBoA-BPDF) was performed at ambient temperature in chloroform within 15 h. The conjugation leads to the formation of a thionorbonene linkage. The stability of related thiopyrane linkages has been previously investigated and found to be withstanding relatively harsh conditions of pH (between 0 and 14 at ambient temperature) and temperatures of up to 100 °C.21 The reversibility of thionorbonene linkages was also previously explored: Upon thermal treatment, the reversibly stimuli-responsive crosslinked polymeric network showed that debonding takes place at temperatures close to 80 °C.22 For single-chain coupling, our group investigated the reversibility and therefore stability of the Diels-Alder chemistry as a modular polymeric color switch.23 In this case, the stability of the thiopyran-ring from single-chain coupling was found to undergo retro Diels-Alder reaction at temperatures of ∼100 °C. Recently, we have shown the reversibility of the Diels-Alder reaction for PS-b-PEO copolymers synthesized via the RAFT-HDA approach, which can subsequently undergo a quantitative cleavage into the constituent blocks in the solid state under mild heating conditions (90 °C) to form nanoporous polystyrene films.24 The conjugation of polymer chains to the cellulose is achieved via a HDA cycloaddition, thus following a ‘grafting-to’ approach. As noted in the Introduction, ‘grafting-to’ approaches have been noted as affording lower grafting densities compared with ‘grafting-from’ approaches,4,25 although recently ‘grafting-to’ systems have also been reported of leading to high substrate loading capacities.11b A clear advantage of the ‘grafting to approach’ offers the advantage of using tailor-made polymer strands, which can be well-characterized before the surface modification sequence. In the case of employing the RAFTHDA technique for grafting, an especially mild, effective, and fast reaction is utilized. In the present study, the successful conjugation of piBoA-BPDF to the cellulose surface is evidenced by several surface analysis techniques, including FT-IR spectroscopy, high-resolution FT-IR microscopy, as well as XPS measurements supported by elemental analysis and EDX spectroscopy. Scheme 1 illustrates the synthetic strategy for surface modification of cellulose via the RAFT-HDA concept. Prior to the insertion of the cyclopentadienyl group, the active hydroxyl groups were transferred into a good leaving group. In general, bromide and tosylate groups are suitable candidates that facilitate 1139

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Scheme 1. Strategy for Surface Modification of Cellulose via RAFT Hetero Diels-Alder Cycloaddition

Figure 1. S 2p XPS spectrum of the tosylated cellulose (Cel-OTos). The S 2p3/2 peak at 168.7 eV corresponds to sulfur in the oxidation state þ6, and the weak component at 166.8 eV is probably due to X-rayinduced reduction.30

an easy transfer to a Cp functionality.13a In this work, tosylate was chosen as leaving group. The Cp-functionality acts as diene for further conjugation with RAFT-synthesized polymers such as piBoA-BPDF. Polymers synthesized via RAFT polymerization can undergo (rapid) hetero Diels-Alder cycloaddition if the RAFT agent carries a highly electron-deficient Z-group such as benzyl pyridine-2-yldithioformiate (BPDF). Therefore, the RAFTHDA approach provides a convenient methodology for the surface modification of cellulose employing RAFT generated polymers directly and without any further modification as a reactive hetero dieneophile. Moreover, it should be explicitly noted that all reaction steps are carried out at ambient temperature and under mild reaction conditions. Owing to the higher reactivity of the OH-group in C6-position (primary alcohol), the majority of tosylate- and subsequent Cp-functionalization will take place at this position.26 Therefore, for reasons of clarity, the functionalization at position C6 is shown in Scheme 1. Initially, the tosylation of the cellulose sheets needs to be established, although such transformations have been known to operate efficiently.26 The heterogeneous tosylation of cellulose with p-toluene sulfonic acid chloride is verified by elemental analysis, EDX (energy-dispersive X-ray spectroscopy), XPS (X-ray photoelectron spectroscopy), and FT-IR (Fourier transform infrared) spectroscopy. As expected, the sulfur content correlates with reaction time, even if a regiospecific tosylation of the hydroxyl group C6 cannot be ensured. Nevertheless, C6 achieves a higher functionalization compared with the hydroxyl groups at positions C2 and C3 because of its higher reactivity. The hydroxyl groups at the two and three positions behave as secondary alcohols, whereas the hydroxyl groups in the six

position act as a primary alcohol and are mainly responsible for the reactions of cellulose. EDX (Supporting Information, Figure S1), XPS, and FT-IR spectroscopy give qualitative evidence of the tosylate modification, whereas elemental analysis provides quantitative information of the functionalization. The results of the elemental analysis of pretreated and tosylated cellulose are shown in Table S1 of the Supporting Information. After tosylation, sulfur can be detected, which correlates with a successful reaction. Concomitantly an increase in the carbon content and a decrease in the oxygen content can be observed. The effectiveness of the reaction was calculated and gives a yield of 14.4% of the hydroxyl group at the position C6 (L = 2.61 mmol tosylate g-1 cellulose). Whereas a loading capacity can be readily provided, it is not possible to provide the number of tosylate moieties (or indeed Cp entities and polymer chains) grafted per unit of surface area of cellulose because the true surface area is unknown. In principle, a loading capacity may also be provided for Cp (L = 1.23 mmol Cp g-1 cellulose); however, it has to be kept in mind that the mass balance in the elemental analysis is less than 100% and thus the above value is beset with a considerable uncertainty. Most likely, the remaining mass (4.41 wt %) is due to nickel still embedded in the material. Whereas elemental analysis provides a clear indication that the transformation of the hydroxyl groups to tosylate entities was successful, further analytical proof is required. Figure 1 shows the S 2p XPS spectrum of tosylated cellulose. The main S 2p3/2 signal at 168.7 eV corresponds to sulfur in the oxidation state þ627 and indicates the coupling of the tosyl group. The weak component at 166.8 eV is probably due to X-ray induced reduction.28 FT-IR-ATR measurements of the tosylate functional cellulose show the characteristic vibration bonds ν(CdC) at 1600 cm-1, νas(SO2) at 1367 cm-1, and ν(dCH) at 810 cm-1.29 For the subsequent Cp-functionalization (i.e. substitution of the tosylate groups), a mild conjugation method was utilized to 1140

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Figure 3. Dependence of the effectiveness of HDA Click reaction of Cel-Cp with piBoA-BPDF on the TFA concentration used in the RAFTHDA cycloaddition.

Figure 2. Fluorescence spectroscopy images of Cel-g-N-(1-pyrene) maleimide and a blank sample at an excitation wavelength of 405 nm: (a) emission image at 513 nm of Cel-g-N-(1-pyrene)-maleimide, (b) transmission image of Cel-g-N-(1-pyrene)-maleimide, (c) emission image at 513 nm of blank sample, and (d) transmission image of blank sample.

ensure that the structural integrity of the cellulose sheets is kept intact. Nickelocene (NiCp2) as a cyclopentadienyl source is particularly suitable and has been demonstrated to effect a mild introduction of Cp without leading to side reactions with electrophilic positions.13b The effective Cp-functionalization can be verified via elemental analysis, whereby a decrease in the sulfur content is characteristic for a successful substitution reaction. (See Table S1 in the Supporting Information.) Inspection of Table S1 in the Supporting Information indicates that the sulfur content of Cel-OTos (8.36 ((0.04)) decreases significantly when functionalized with NiCp2 as a Cp-source (Cel-Cp 4.41 ((0.16)). At the same time, the carbon content is increasing (Cel-OTos: 47.96 ((0.11); CelCp: 49.40 ((0.12)), which can be attributed to the shift of the carbon/oxygen-ratio when introducing a Cp-functionality. From these numbers, it can be concluded that ∼50% of the tosylate units have been replaced by Cp. Leadbeater demonstrated that a Cp-functionalization of Merrifield resins with NiCp2 with reaction times >18 h at ambient temperature leads to chemically bound nickel.31 Here the desired Cp-functionalized product was observed to undergo partial reaction with the NiCp(PPh3)I in solution, giving a small quantity of a resinbound nickel complex. Considering these observations, reaction times