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Photochemistry within a Water-Soluble Organic Capsule Vaidhyanathan Ramamurthy Department of Chemistry, University of Miami, Coral Gables, Florida 33146, United States CONSPECTUS: Photochemistry along with life as we know it originated on earth billions of years ago. Supramolecular Photochemistry had its beginning when plants that sustain life began transforming water into oxygen by carrying out light initiated reactions within highly organized assemblies. Prompted by the efforts of J. Priestly (photosynthesis), F. Sestini, S. Cannizaro, and C. Liebermann (solid-state photochemistry of santonin, quinones, and cinnamic acid), orderly scientific investigations of the link between light absorption by matter and molecules and the chemical and physical consequences began in the mid-1700s. By 1970 when Molecular Photochemistry had matured, it was clear that controlling photochemical reactions by conventional methods of varying reaction parameters like temperature and pressure would be futile due to the photoreactions’ very low activation energies and enthalpies. During the last 50 years, the excited state behavior of molecules has been successfully manipulated with the use of confining media and weak interactions between the medium and the reactant molecule. In this context, with our knowledge from experimentation with micelles, cyclodextrins (CD), cucurbitruils (CB), calixarenes (CA), Pd nanocage, crystals, and zeolites as media, we began about a decade ago to explore the use of a new water-soluble synthetic organic cavitand, octa acid (OA) as a reaction container. The uniqueness of OA as an organic cavitand lies in that two OA molecules form a closed hydrophobic capsule to encapsulate waterinsoluble guest molecule(s). The ability to include a large number of guest molecules in OA has provided an opportunity to examine the excited state chemistry of organic molecules in a hydrophobic, confined environment. OA distinguishes itself from the well-known cavitands CD and CB by its active reaction cavity absorbing UV-radiation between 200 and 300 nm and serving as energy, electron, and hydrogen donor. The freedom of guest molecules in OA, between that in crystals and isotropic solution can be transformed into photoproducts selectivity. The results of our photochemical investigations elaborated in this Account demonstrate that OA with a medium sized cavity exerts better control on excited state processes than the more common and familiar organic hosts such as CD, CB, CA, and micelles. By examining the photochemistry of a number of molecules (olefins, carbonyls, aromatics and singlet oxygen) that undergo varied reactions (cleavage, cycloaddition, cis−trans isomerization, oxidation and cyclization) within OA capsule, we have demonstrated that the free space within the container, the capsule influenced conformation and preorientation of guest molecules, supramolecular steric control, and capsular dynamics contribute to the altered excited state behavior. In this Account, we have shown that photochemistry based on concepts of physical organic and supramolecular chemistry continues to be a discipline with unlimited potential. The future of supramolecular photochemistry lies in synthetic, materials, medicinal, and biological chemistries. Success in these areas depends on synthesizing well-designed water-soluble hosts that can emulate complex biological assemblies, organizing and examining the behavior of supramolecular assemblies on solid surfaces, rendering the photoreactions catalytic, and delivering encapsulated drugs in a targeted fashion. such as cyclodextrins,7 cucurbiturils,12 and Fujita’s Pd host,13 and micelles14 are directly relevant to the results reported here. All the above media provide an interface between external water and internal organic-like environment. In addition to preorganizing reactant molecules, the interface also allows the reactants and the reactive intermediates to escape the confined environment leading to poor product selectivity. One of the rare and appealing features of OA is the closed capsule it forms in the presence of a guest molecule. Most common hosts mentioned above neither are easily water-soluble nor form capsules. OA forms watersoluble capsular complexes (∼10−2 M) with a variety of organic molecules. Most of the recently reported covalently linked, hydrogen bonded and metal coordinated cages/capsules that can act as hosts are either soluble in organic solvents only or absorb
1. INTRODUCTION Pioneering work by several researchers that led to an understanding of “Molecular Photochemistry” shifted the focus of photochemical research in late 1970s to controlling and manipulating photochemical reactions.1−4 Due to the fact that photoreactions have very low activation energies temperature was not an option. This led to exploring the “medium”, especially the ones that offer a highly organized and confining environment, as a tool. In this context, diverse types of organized media in liquid, semisolid and solid forms have been explored to manipulate excited state processes.3,4 With interest in photoreactions in organized assemblies,5−10 we came across a new water-soluble organic cavitand known as octa acid (OA) whose synthesis and binding properties were reported by Gibb and Gibb.11 Our studies reported below demonstrate that OA exerts better control on excited state processes than hitherto known organic hosts. Photochemical studies in water-soluble cavitands © XXXX American Chemical Society
Received: August 2, 2015
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DOI: 10.1021/acs.accounts.5b00360 Acc. Chem. Res. XXXX, XXX, XXX−XXX
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Figure 1. (a) Molecular structure of OA. (b) Molecular structure of OA capsule; the gray rectangle represents guest. (c) CPK model of OA and with dimensions marked. (d) Cartoon representation of OA capsule.
the extent of 10−2 M. At concentrations above 10−3 M, OA molecules aggregate in solution as is evident from broad 1H NMR signals. In the presence of a guest molecule, formation of a 1:1 cavitandplex or 2:1 or 2:2 capsuleplex (ratio is expressed as host/guest and represented as guest@OA) results in sharpening of all host signals suggesting that the host−guest complexes are no longer aggregated.26 Generally amphiphilic molecules with an ionic (hydrophilic) head group and hydrophobic body (e.g., 1-adamantane carboxylic acid) form 1:1 cavitandplex and neutral hydrophobic molecules (e.g., adamantyl ester and adamantane) depending on their size, shape, and concentration form either a 2:1 or a 2:2 capsuleplex. A comparison of the complexing abilities of naphthalene, anthracene, tetracene, and pentacene reveals the role of the dimensions of the guest in controlling the ratio of the host−guest complex. Naphthalene and anthracene form 2:2 capsuleplexe while tetracene and pyrene form a 2:1 capsuleplex; long aromatic molecules like pentacene and bulkier benzpyrene do not complex with OA. Hydrocarbons with flexible methylene chain even up to 22 Å form 2:1 capsuleplexes (Figure 2). Photophysical data of probes such as of pyrene, pyrene aldehyde, 2-acetyl anthracene and coumarin-1 and measured EPR coupling constants of nitroxides reveal OA capsule to have internal polarity close to that of benzene with no water inside.27 Variable temperature 1H NMR experiments and molecular dynamics simulations point out that the confined guest molecules undergo tumbling and rotational motion along the X, Y, and Z axes in 2:1 complexes and sliding motion in 2:2 complexes (Figure 3b−d). The capsular complex also partially opens and closes as illustrated in Figure 3f.28−30 Confinement in OA capsule and placement of molecules in conformations/orientations different from those in solution provide opportunities to explore
light in the region where guest molecules do or the guest has to be introduced during the synthesis or too small to accommodate large molecules of photochemical interest.13,15,16 The results of our studies related to photoreactions within an OA capsule are highlighted in this Account. Aspects like the dynamics of OA and host−guest complexes, communication of molecules (spin-energy and electron transfer) across OA walls in solution, and photochemistry of OA−guest complexes aligned on surfaces have been reviewed by us recently.17,18 Our results in a broader context have been summarized in a recent review.19 For contributions by other groups on supramolecular photochemistry, recent reviews and monographs should be consulted.2−4,19−22
2. PROPERTIES OF OA AND ITS COMPLEXES The water-soluble cavitand with four carboxylic acid groups at the top and four at the bottom is generally known by the trivial name octa acid (OA) (Figure 1). OA has two openings: one at the top (11.4 Å) and one at the bottom (5.5 Å) (Figure 1). Constructed from methylenedioxy substituted phenyl bridges and benzoic acid units, it absorbs light up to 300 nm and emits weak fluorescence (310−420 nm). The S1 and T1 energies of OA were estimated to be ∼95 and ∼70 kcal/mol. Scheme 1a presents two examples where OA acts as the triplet sensitizer.23 From fluorescence quenching of a series of electron acceptors, OA is found to be a good electron donor with an estimated oxidation potential of ∼1.5 eV.23 The several benzylic hydrogens in the interior wall of OA can be abstracted by the reactive species generated upon excitation of guests. Two such examples are included in Scheme 1b.24,25 OA is sparingly soluble (∼10−5 M) in neutral water. However, under basic conditions (borate buffer, pH > 8.5), it is soluble to B
DOI: 10.1021/acs.accounts.5b00360 Acc. Chem. Res. XXXX, XXX, XXX−XXX
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Accounts of Chemical Research Scheme 1. Reactions Where OA Is (a) Triplet Sensitizer and (b) Hydrogen Donora
a
Two reactions at the top are the probes used to test the sensitizing ability of OA.
BB (1,2-ditolylethane) in solution in organic solvents suggested that OA is able to provide 100% cage effect. Such high cage effect is rarely achievable in any media except crystals. Based on the observed 100% cage effect we speculated that we could control the capsular free space and thereby the mobility of the intermediates and finally the products by varying the para-alkyl chain length in para-alkyl dibenzylketones. The structures of OA-guest complexes derived from 1H NMR and the products of photolysis of a few selected para-alkyl dibenzylketones of varying alkyl chain lengths are included in Figure 5.32,33 Based on these results, we believe that the longer alkyl chains of these guests are folded resulting in pushing the unsubstituted benzyl ring deeper into the narrower end of the capsule. This action reduces the cavity’s free space and restricts the rotation of the ketone (Figure 4). To our knowledge, this is the first example of “product distribution control” aided by a remote group within a restricted space in solution.
photochemistry under confined environment. This translates into selectivity in photoreactions as highlighted with examples in the following sections.
3. OA AS A PHOTOCHEMICAL REACTION CONTAINER Within the OA capsule the guest molecule(s) are held through weak interactions such as CH−π, van der Waals, and hydrophobic interactions.9 We highlight below with select examples from our studies OA capsule’s influence on the excited state behavior of included guest molecules. In each case the features that are likely responsible for the unique behavior within OA is highlighted. 3.1. Norrish Type I Reaction of Carbonyl Compounds: Cage Effect and Role of Capsular Free Space
Norrish type I (α-cleavage) reaction of dibenzylketones serves as a benchmark reaction to ascertain the confining ability of a medium during a photoreaction.1 The reaction sequence the excited dibenzylketone undergoes as sketched in Scheme 2 starts from the α-cleavage to yield the primary radical pair (RP-1), which loses CO to form a secondary radical pair (RP-2). In solution the products resulted from RP-2, for example, dibenzylketone, yielded 1,2-diphenylethane exclusively. Within OA capsule dibenzylketone gave the rearranged starting ketone p-RP from RP-1 in 56% yield.31 This unprecedented behavior suggested tumbling of the confined RP-1 (Figure 4) before recombining. The fact that para-methyl dibenzylketone gave 1-phenyl 2-tolylethane (AB) as the sole product within OA while yielding 1:2:1 mixture of AA (diphenylethane), AB, and
3.2. Norrish Type I and Type II Reactions of Carbonyl Compounds: Conformational Control
α-Alkyl dibenzylketones undergo both conformation-independent (Norrish type I) and dependent (Norrish type II) reactions in solution (Scheme 3).1 Photoproduct distributions of OA confined and free α-alkyl dibenzylketones presented in Scheme 4 reveal:34 (a) In solution, in the absence of OA, propyl- through octyl-alkyl substitutions resulted in the same product distribution with major products from type I (>80%) and minor ones from type II reactions. (b) While in solution, the type I reaction gave AA, AB, and BB products (Scheme 3) from RP-2 only, within OA C
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examined α-alkyl substituted dibenzylketones only the methyl to pentyl compounds gave rearranged starting ketones 1 and 2. (d) While smaller alkyl chains gave mostly ketone 2, the medium alkyl chains gave almost equal amounts of both ketones 1 and 2. (e) The ratio of type I to II products was very much dependent on the chain length of the α-propyl- through octyl-dibenzylketones varying from 89:11 (α-propyl) to 10:90 (α-octyl). One- and two-dimensional 1H NMR derived structures of the guests within the OA capsule (Scheme 4) help understand these spectacular product distribution dependence on the alkyl substituent’s length. The results and the guest structures within OA of three representative examples (α-methyl, α-pentyl, and α-octyl dibenzylketones) discussed below help grasp the role of confinement, free space and conformational control on photoreactions: (a) Low yield of type II products from α-pentyl dibenzylketone and their larger yield in α-octyl dibenzylketone are consistent with the conformation of the reactants within OA (Scheme 4). (b) The different amounts of the rearranged products from RP-1 in all three ketones are in accordance with the available free space required for rotation of benzyl radical intermediates within the OA capsule. The dearth of free space in α-octyl dibenzylketone around both the phenyl groups limits the rotation of the benzyl radicals resulting from α-C−C cleavage. In contrast, availability of free space in α-methyl and α-pentyl dibenzylketones permits rotation of the two benzyl radical intermediates resulting in rearranged ketones. (c) Finally, the conformation and the free space within the OA capsule in α-methyl and α-pentyl dibenzylketones rationalize the varied yield of 1 and 2 (Scheme 3). Of the available two α-C−C bonds in α-methyl dibenzylketone, the more readily cleavable alkyl substituted one leads to a major amount of 2. However, in the case of α-pentyl dibenzylketone, due to lack of free space, the 1-phenyl hexyl radical resulting from such a cleavage recombines without rearrangement of the RP-1 radical pair. Under such conditions, the less favored cleavage of the unsubstituted side competes to lead to the product 1. Regeneration of the reactant ketone from the return of RP-1 though not established in α-alkyl dibenzylketones it has been demonstrated in analogous α-alkyldeoxybenzoins by monitoring the optical purity of the reactant α−alkyldeoxybenzoins with irradiation time.35 The above results
Figure 2. Illustrations of types of complexes OA forms with organic molecules. Structures in (c) were generated by MD simulations.
products from both intermediates RP-1 (1 and 2; Scheme 3) and RP-2 (only AB and rearranged AB) were obtained; (c) Of the
Figure 3. Cartoon illustration of various motions of included guest molecule(s) and OA complexes as a whole: (a) axes representation; (b) rotation along the long axis; (c) tumbling along the short axis; (d) sliding motion in 2:2 complexes; (e) conformational equilibrium in cyclohexyl systems; and (f) capsule’s partial opening-closing. D
DOI: 10.1021/acs.accounts.5b00360 Acc. Chem. Res. XXXX, XXX, XXX−XXX
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Accounts of Chemical Research Scheme 2. Products and Intermediates during the Norrish Type I Reaction of Dibenzylketone
Figure 4. Importance of capsular free space during the formation of the rearranged ketone, p-RP.
(Figure 6a). Prolonged irradiation of either trans or cis isomer included in OA established a photostationary state consisting of 80% trans and 20% cis, distinctly different from the 17% trans and 79% cis in hexane.36,37 Importantly, the position and the number of methyl substituent affected the excited state behavior of methylated stilbenes within OA (Figure 6b). For example, in the series of 4,4′-, 3,3′-, and 2,2′-dimethylstilbenes, trans-4,4′-isomer was unique while the latter two behaved alike in OA and hexane. Monomethyl stilbenes, independent of the methyl group’s location, showed no difference in behavior between OA and hexane. Location of the methyl groups within OA of trans-4,4′dimethylstilbene explains its unique behavior (Figure 7a); its two methyl groups are anchored through C−H−π and van der Waals interaction at the two narrower ends of the OA capsule where the free space is small for the volume demanding trans−cis isomerization. The methyl groups at 3,3′ and 2,2′ positions localized at broader regions of the capsule experiencing lesser steric hindrance behaved like in an isotropic solution. The OA
highlight the determining role of a remote tether on the excited state chemistry of reactants in a confined space. 3.3. Geometric Isomerization of Olefins: Supramolecular Steric Effect
Geometric isomerization of olefins is one among the many crucial primary photoreactions in several biological events. In the protein environment, the isomerization is frequently siteselective and more efficient than that in an isotropic solvent. These features are attributed to intermolecular steric interaction (supramolecular steric effect) between the reactant and the surrounding protein during the volume demanding geometric isomerization. We show below that a similar effect operates within OA capsule leading to selectivity during isomerization of olefins. trans-4,4′-Dimethylstilbene which aggregated and exhibited a broad emission in water formed stable 4,4′-dimethylstilbene@OA2 capsular assemblies with OA. This complex emitted structured fluorescence with a lifetime of 1.5 ns (τ in hexane
