Exploring Versatile Sulfhydryl Chemistry in the Chain End of a

Oct 29, 2012 - Further atomic force microscopic (AFM) studies revealed NDI-functionalized polymer formed uniform spherical aggregates upon drying of a...
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Exploring Versatile Sulfhydryl Chemistry in the Chain End of a Synthetic Polylactide Mijanur Rahaman Molla and Suhrit Ghosh* Polymer Science Unit, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India S Supporting Information *

ABSTRACT: Synthesis of an end-functionalized polylactide by ring-opening polymerization of lactide monomer using a functional initiator containing pyridyl disulfide group is reported. Molecular weight of the polymer determined by GPC matched very well with that determined by end-group analysis using the UV/vis method, suggesting survival of the end-group functionality during polymerization. DTT-induced reduction of the pyridyl disulfide group produced free sulfhydryl group quantitatively which was utilized for versatile chain-end modifications using various thiol-mediated high-yielding chemical transformations including thiol−ene, thiol− maleimide, and thiol−acrylate “click” reactions. This strategy was further extended to link two macromolecules by reaction of sulfhydryl-functionalized polylactide and acrylate-terminated poly(ethylene oxide) (PEO) which produced a block copolymer with an acid-labile β-thiopropionate linker between the two constituent blocks. This functional group could be cleaved under mild acidic condition to produce the individual parent polymers. Further as-synthesized pyridyl disulfide-terminated polylactide was treated with thiol-functionalized sugar moiety and n-type semiconducting naphthalene diimide (NDI) chromophore which also generated quantitative chain-end functionalization by thiol−disulfide exchange reaction. NDI-functionalized polylactide showed white light emission due to mixed emission from monomeric and excimer-type species. Further atomic force microscopic (AFM) studies revealed NDI-functionalized polymer formed uniform spherical aggregates upon drying of a drop-casted film on silicon surface possibly due to solvent-evaporation-induced defined organization of the polymer chain dictated by strong πstacking interaction among the NDI chromophores.

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INTRODUCTION Synthetic polymers that contain highly reactive functional groups1 either as pendant2 or in the chain end3 have been studied extensively in the recent past owing to the possibility of generating structurally diverse functional polymers and various polymeric conjugates by high-yielding postpolymerization chemical transformations. Postpolymerization end-group modification is particularly challenging because it demands survival of the chain-end functional group during polymerization condition, and at the same time the reactivity of the functional group should be high to allow quantitative transformation after polymerization. However, this has been successfully achieved4 in various controlled chain polymerization reactions by utilizing suitably designed functional initiators. In this context sulfhydryl group has been studied extensively owing to its well-established high fidelity reactions5 with number of functional groups such as maleimide, isocyanate, alkene, alkyne, acrylate, halogenated alkane, disulfides, and so forth. Mainly two different strategies have been adopted for chain-end modifications using sulfhydryl chemistry. One is to generate a thiol group in the terminal of a polymer synthesized by mostly RAFT route by postpolymerization reduction of the macro-chain-transfer agent using suitable reagents6 and subsequently utilizing the free sulfhydryl functionality for conjugation with various small molecules and macromolecules by different thiol-mediated reactions. The © 2012 American Chemical Society

other approach includes controlled/living chain polymerization using functional initiators containing a thiol-reactive functionality such as maleimide or derivatives7 in protected form and modification of chain end by postpolymerization reactions with desired molecules, macromolecules, or biomacromolecules containing free thiol functionality. Pyridyl disulfide is an interesting option in this context because of the following: (i) It can react with sulfhydryl groups quantitatively under very mild conditions in range of solvents starting from chloroform to water and generates a redox-sensitive disulfide bond.8 (ii) It can also quantitatively and spontaneously generate a thiol group in the presence of a reducing agent such as dithiothreitol (DTT). It is noteworthy that generation of thiol functionality by reducing macro-CTA in RAFT-generated polymers often leads disulfide bond formation during the course of the reaction itself.6 But generating thiol by cleavage of pyridyl disulfide functionality is not associated with this problem due to the presence of DTT in the reaction mixture. (iii) The byproduct of both these above-mentioned reactions, 2-pyridinethione, is highly water-soluble and thus can be removed easily from reaction medium. Further, it also exhibits a signature absorption Received: October 11, 2012 Revised: October 20, 2012 Published: October 29, 2012 8561

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Scheme 1. Schematic Presentation Showing Various Chain-End Modifications of a Synthetic Polylactide Using Different ThiolMediated Chemical Transformations

polymer was first structurally characterized by 1H NMR spectrum (Figure 1a).

band in the visible region which allows one to monitor the proceeding of the reaction quantitatively. (iv) Pyridyl disulfide is also unique in a sense that it is highly reactive toward thiol or reducing agents while remarkably stable in a wide range of pH and temperature and also inert to other functional groups such as amine or alcohols. Considering these attractive features, it is not surprising that several reports have appeared,9 demonstrating the utility of pyridyl disulfide-functionalized initiators or chain transfer agent (CTA) for ATRP and RAFT polymerizations, respectively. However, to date, to the best of our knowledge no such report is available for polylactides, which are an important class of polymers synthesized by ring-opening polymerization of lactide monomers and have tremendous applications in engineering plastics, biomedical field, and tissue engineering.10 We envisaged that establishing a synthetic protocol to produce pyridyl disulfide end-functionalized polylactide would be highly interesting in terms of generating functional polylactides and their conjugates. In this report we demonstrate synthesis of a polylactide using a structurally simple initiator (1, Scheme 1) containing pyridyl disulfide group and show its utility to produce number of chain-endfunctionalized polymers (Scheme 1) using different thiolmediated reactions. We further demonstrate synthesis of an acid-labile block copolymer (P7, Scheme 1) by reacting a free sulfhydryl group of the polylactide with an acrylate endfunctionalized poly(ethylene oxide). We also show endfunctionalization by thiol−disulfide exchange between the pyridyl disulfide-containing polylactide and free-thiol-containing functional groups and utility of such chain-end functionalization in modulating the photophysical properties and macroscopic phase behavior of the parent polylactide.

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RESULTS AND DISCUSSION Synthesis and Characterization. Initiator 1 (Scheme 1) was synthesized in a single step starting from commercially available Aldrithiol-2 with 2-mercaptoethanol by maintaining a proper stoichiometric control of the two reactants and was isolated in 72% yield. It was used as the initiator for ringopening polymerization11 of commercially available cyclic lactide monomer in presence of tin(II) 2-ethylhexanoate (Sn(Oct)2) catalyst in dry toluene at 120 °C under an inert atmosphere for 48 h using the ratio of [monomer]/[initiator]/ [catalyst] = 60:1:0.75 and was isolated as a white powder in 70% yield by precipitation from cold methanol. The resulting

Figure 1. (a) Selected region of 1H NMR spectrum of P1 in CDCl3 (asterisk indicates peaks coming from the solvent). (b) UV/vis spectra of P1 in THF (C = 0.5 mg/mL) before (black line) and 30 min after addition of DTT (0.5 mg/mL).

In the proton NMR spectrum of P1 two major peaks appeared at 1.54 and 5.21 ppm for Ha and Hb, respectively. Peaks corresponding to the chain-end functionalities (Hc and Hd and aromatic protons from pyridyl disulfide ring) could be also detected. GPC analysis (Figure S1) revealed numberaverage molecule weight (Mn) to be 7200 (PDI = 1.2). The 8562

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Scheme 2. Schematic Presentation Showing Various Thiol-Mediated Transformations of P2

conjugated chromophores so that their attachment to the polymer chain could be traced by optical spectroscopic studies even at relatively low concentration. First, thiol−acrylate Michael addition reaction was attempted with P2 and compound 2 (Scheme 2) using Me2PPh as catalyst. The resulting polymer P3 (Scheme 2) was isolated by precipitation from cold diethyl ether to ensure complete removal of any unreacted/excess compound 2 or catalyst and was isolated in almost quantitative yield. 1 H NMR of P3 (Figure 2a) revealed peaks in the aromatic region (7.2 −8.0 ppm) indicating incorporation of the naphthyl group. The UV/vis absorption spectrum of P3 was compared with that of compound 2 while a sharp absorption band with λmax = 323 nm (Figure 2b) was noticed for both samples further confirming attachment of the naphthyl chromophore in the polymer chain. Photoluminescence spectrum of P3 (Figure 2b) also showed characteristic emission of naphthyl chromophore. To estimate the extent of functionalization, molecular weight of P3 was calculated by end-group analysis using UV/vis data shown in Figure 2b. The extinction coefficient of 2 in THF was independently estimated to be 3536 M−1 cm−1, which indicated concentration of naphthyl chromophore was 0.053 mM in the polymer solution. Assuming that each polymer chain contains one naphthyl group, it can be stated that [naphthyl] = [polymer]. It means 0.5 mg/mL = 0.053 mM, which corresponds to a molecular weight of 9363 for P3, which corroborates well with its theoretically calculated molecular weight of 8987 (molecular weight of P1 by UV/vis − pyridinethione + 2). One can expect this to happen only if conversion of P2 to P3 is quantitative. Further thiol−ene and thiol−maleimide reactions were also tested with P2 with compounds 3 and 4 (Scheme 2) which generated two more end-functionalized polymers P4 and P5, respectively. In both occasions incorporation of the naphthyl chromophore was confirmed by detecting aromatic signals in their proton NMR (Figures S4 and S5) and also by UV/vis and emission spectroscopy (Figure S6). Molecular weights of P4 and P5 were estimated to be 9487 and 9074, respectively, by end-group analysis using the same method described above for P3. In both cases they nearly matched with theoretically calculated values of 8973 (molecular weight of P1 by UV/vis − pyridinethione + 3)

polymer was also characterized by FT-IR spectra (Figure S2) wherein a characteristic sharp peak was noticed at 1752 cm−1 due to the carbonyl stretching of the backbone ester in contrast to the peak at 1765 cm−1 for the carbonyl of the cyclic ester monomer. To generate free thiol group in the chain end P1 was treated with a reducing agent DTT, and the reaction was monitored by UV/vis spectroscopy (Figure 1b). The absorption spectrum of P1 in THF showed a peak at 280 nm, confirming the presence of the pyridyl disulfide functional group.9b It was then added with DTT and stirred for 30 min while a yellow color appeared, suggesting generation of 2-pyridinethione (Figure 1b) which is the byproduct of the cleavage reaction. Consequently, in the UV/vis spectrum of the reaction mixture a new peak appeared with λmax = 380 nm due to 2-pyridinethione. The extinction coefficient of 2-pyridinethione in THF was independently estimated to be 900 M−1 cm−1 at 380 nm (Figure S3), which was used to estimate the concentration of released 2pyridinethione during conversion of P1 to P2 (Figure 1b). Utilizing this data and assuming DTT induced cleavage reaction to be quantitative, the molecular weight of the polymer which was estimated to be 8900, which is in reasonable good agreement with that found from the GPC analysis and provides further strong support in favor of survival of the chainend functionality (unsymmetrical pyridyl disulfide) during the polymerization reaction. As the GPC analysis was done using a conventional calibration curve with respect to PMMA standard, it may not provide most accurate data for the molecular weight. Thus, for all studies polymer concentration was calculated using molecular weight determined by end-group analysis using the UV/vis method as described above. Chain-End Modification of P2 Using Various ThiolReactive Chromophores. To test the possibility of various chain-end modifications, trademark thiol-mediated reactions (Scheme 2) were attempted with polymer P2 which contains a free sulfhydryl group in the chain end. Quantification of functional groups present in the terminal of a polymer chain with reasonably high molecular weight is always a difficult task due to lack of appropriate experimental tool. To overcome this problem in this study, we intentionally synthesized various thiol reactive building blocks containing π8563

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Figure 2. (a) Selected region of 1H NMR spectra of P2, 2, and P3 in CDCl3 (∗ peaks coming from solvent). (b) UV/vis absorption spectra (l = 1 cm) of P3 (0.5 mg/mL) and compound 2 (0.1 mM) and photoluminescence spectra (λex = 280 nm) of P3 (0.5 mg/mL) in THF. T = 25 °C.

and 9012 (molecular weight of P1 by UV/vis − pyridinethione + 4) for P4 and P5, respectively, suggesting quantitative chainend modifications. Synthesis of Acid Labile Block Copolymer. Having established very efficient chain-end modifications with small molecules, we extended this synthetic approach to synthesize a block copolymer (Scheme 3).

For this purpose we choose thiol−acrylate Michael addition reaction because it also offers an additional advantage of generating an acid-labile β-thiopropionate linker (Scheme 3).12 Commercially available PEO (Mn ∼ 2000) was reacted with acryloyl chloride to generate acrylate-terminated PEO (P6, Scheme 3) which was treated with thiol-terminated polylactide P2 in presence of catalytic amount Me2PPh to produce desired 8564

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was carried out with P2 before it was coupled to the P6, intense absorption bands appeared with λmax = 440 and 510 nm due to the presence of free thiol in the chain end. GPC analysis (Figure 4) revealed molecular weight of block copolymer P7 to be 9200 (Mn), which was an excellent match

Scheme 3. Synthesis of Block Copolymer by Michael Addition and Acid-Induced Cleavage

block copolymer P7. It was purified by repeated precipitation from H2O and isolated in ∼90% yield. The 1H NMR spectrum of P7 (Figure 3) showed intense peaks in the region of 5.2−5.5

Figure 4. GPC traces of various polymers in THF.

with the summation of the molecular weight of P2 [(Mn of P1) − pyridinethione ≈ 7100) and P6 (Mn = 2100). Further it has been reported by us as well as others12 that β-thiopropionate linker undergoes hydrolysis in acidic condition. The block copolymer P7 interestingly contains such a linker in-between the two blocks. Thus, to test whether it can be disintegrated to two parent polymers,14 P7 was treated with TFA and after removal of all the volatiles from the reaction vial solid polymer was redissolved and sample was directly injected to the GPC which now showed (Figure 4) two distinct peaks corresponding to the two parent polymers (Scheme 3). Implications of such disintegration of two constituent blocks can be manyfold including stimuli-responsive assemblies15 and generating porous membrane,16 which are the topics of our interest in the not too distant future. Chain-End Modification by Thiol−Disulfide Exchange Reactions. In the forgone discussion we have demonstrated various synthetic pathways for chain-end modification involving the free sulfhydryl group in the terminal of the polymer chain. In this section we show a complementary approach for attaching various functional moieties containing a free sulfhydryl group by thiol−disulfide exchange with the pyridyl disulfide moiety in the chain end of P1 (Scheme 1).17 First, polymer P1 was treated with commercially available 1-thio-β-Dglucose tetraacetate (5, Figure 5). In this case the proceedings of the reaction could be followed by UV/vis spectroscopy by monitoring absorption at 378 nm corresponding to the 2pyridinethione as a function of time (Figure 5a) which indicated the reaction was over in 1 h. Subsequently, the polymer was precipitated out and analyzed by 1H NMR (Figure 5b) which clearly showed additional peaks in the region of 5.0− 4.0 ppm, confirming incorporation of the carbohydrate moiety. The UV/vis spectrum of the precipitated polymer P8 (Figure 5a) did not show any peak around 280 nm, further confirming the absence of any pyridyl disulfide group. Further, we tested thiol−disulfide exchange between P1 and thiol-functionalized naphthalene diimide (NDI-SH, Figure 6a) chromophore which is well-known for its strong π−π interaction and rich photophysical properties. 18 The resulting polymer was characterized by UV/vis spectroscopy which showed (Figure 6b) distinct absorption bands in the range of 300−400 nm

Figure 3. Top: synthesis of the block copolymer. Bottom: 1H NMR spectra (selected region) of two constituent blocks (P2, P6) and the final block copolymer (P7).

ppm as well as in 3.7−3.3 ppm for the polylactide backbone protons and the methylene protons of the PEO block, respectively. Further the acrylate protons for polymer P6 could not be traced, confirming that the excess P6 could be completely removed while precipitation from water. On the other hand, to test the presence of even a trace amount of thiolterminated polylactide P2 Ellman’s test was carried out (Figure S7) which is highly sensitive to free thiol group.13 A solution of the block copolymer P7 was treated with Ellman’s reagent where no peak appeared at 440−510 nm, confirming the absence of free thiol functionality. Note that when the same test 8565

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Figure 5. Top: synthesis of P8 from P1. Bottom: (a) UV/vis spectra of the reaction mixture at different time interval. Concentration of P1 = 5.0 mg/mL, 5 = 1.0 mg/mL, solvent = THF, T = 25 °C. (b) 1H NMR spectra (selected region) of P1 and P8 in CDCl3 (∗ indicates solvent peaks) showing appearance of carbohydrate protons in the latter case.

which perfectly matched with NDI-SH, confirming its attachment to the polymer chain. Based on the extinction coefficient of NDI-SH at λ = 378 nm and the absorption intensity of the peak at 378 nm in P9, the molecular weight of the NDIattached polymer P9 was estimated to be 9727, which excellently matched with theoretically calculated value 9284 (molecular weight of P1 by UV/vis − pyridinethione + NDISH), indicating quantitative incorporation. Incorporation of NDI was also confirmed by 1H NMR where a peak at 8.8 ppm could be detected for the chromophore (Figure S8). Further, the photoluminescence spectrum of P9 was compared with that of NDI-SH (Figure 6b). For NDI-SH the emission spectra revealed perfect mirror-image relationship with the absorption spectra and showed fine structure (Figure 6b), suggesting monomeric blue emitting species. However, for the P9 the monomer emission reduced, and in turn a broad structureless intense emission band appeared (Figure 6b,c) in the range of 500−650 nm. Concentration normalized emission spectra of NDI-SH and P9 are compared in Figure 6c. For P9 two distinct components of the emission spectrum are clearly visible. In the 360−490 nm range the spectrum obeyed a mirror-image relationship with the absorption bands and also exhibited vibrational fine structure, suggesting monomeric emission, while the broad additional band in the range of 500−650 nm can be attributed to excimer type species which was absent for NDI-SH. Thus, this can be attributed to attachment of this chromophore to a macromolecule scaffold which probably enhances the possibility of excimer formation for reasons not fully understood. However, it is noteworthy that such excimer type emission for NDI chromophore has been ascribed to excitation of loosely packed ground state aggregates.19

Remarkably simultaneous emission from monomer and excimer (Figure 6c) covered almost the entire visible range, resulting in almost pure (Figure 6d) white light emission (inset, Figure 6b) with CIE coordinates (0.27, 0.33) from a single emitter which is rarely achieved.20 We also tested the morphology of drop-casted film from P1 and P9 by atomic force microscopic (AFM) studies (Figure 7). To our surprise, we found (Figure 7, top image) even polylactide P1 showed uniform spherical morphology (height = 120 ± 2 nm, width = 422 ± 5 nm) just by drop-casting from THF and air-drying at ambient conditions. This can be related to a very recent report21 which suggests in such polymer films when solvent evaporates they tend to crystallize which results in unique morphology. When NDI-connected polymer P9 was examined, it also showed uniform spherical nanoparticles but with much shorter dimensions (height = 15 ± 1, width = 59 ± 2 nm), suggesting distinct role played by the NDI chromophore in controlling the film morphology (Figure 7, bottom image).22 To understand the precise role of NDI in tuning the morphology may require detailed studies, which is out of the scope for this paper but will be addressed shortly. However, this is a demonstration on a key role that could be played by even a single chain-end functionality to tune the properties, may it be photophysical or macroscopic, of a macromolecule.

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CONCLUSIONS

In conclusion, we have shown ROP of lactide using a structurally simple initiator containing a pyridyl disulfide functional group to achieve chain-end-functionalized polylactide. The terminal pyridyl disulfide was utilized in two different 8566

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Figure 6. (a) Functionalization of polylactide by NDI chromophore. (b) UV/vis (solid line) and intensity normalized PL (dotted line) spectra of NDI-SH (black line, concentration = 0.01 mM) and P9 (red line, concentration = 0.5 mg/mL) in THF. Inset: images of the solution under UV light (λex = 365 nm). (c) PL spectra (λex = 340 nm) of NDI-SH (black line, concentration = 0.01 mM) and P9 (emission intensity was normalized with NDI-SH with respect to the absorption of NDI chromophore) in THF. (d) CIE color diagram corresponds to the emission spectrum of P9 (red dotted line in (b)).

ways for various chain-end modifications. First, it was treated with reducing agent DTT to produce free sulfhydryl group which was utilized for chain-end modifications using thiol−ene, thiol−acrylate, and thiol−maleimide reactions with a chromophoric moiety containing suitable complementary functionalities. In all cases quantitative functional group attachment could be established by chain-end analysis using UV/vis studies. This approach was further extended to connect thiolterminated polylactide and acrylate-terminated PEO which resulted in A−B type block copolymer with an acid labile βthiopropionate linker in between which could be disconnected under mild acidic conditions, resulting in the two constituent polymers. In another complementary approach we could demonstrate quantitative attachment of functional moieties containing a free sulfhydryl functionality to the pyridyl disulfide-terminated polylactide by facile thiol−disulfide exchange. Attachment of a photophysically rich NDI chromophore by this approach resulted in a polymer which could emit almost pure white light on its own and also produced uniform nanoscale morphology on surface. Considering enormous interest that lies with this class of biodegradable polymers, we believe the current approach demonstrating versatile chain-end modification and generation of stimuli responsive (pH as well

as redox) linkers will be highly relevant in achieving structurally diverse materials based on polylactide scaffold, and once that happens implications will be galore.

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EXPERIMENTAL SECTION

Materials and Methods. Reagents and polymerization catalyst were purchased from Sigma-Aldrich Chemical Co. and used without further purification unless mentioned. Lactide monomer was recrystallized from ethyl acetate before polymerization. Solvents were obtained from commercial sources and purified by prescribed methods.23 Spectroscopic grade solvents were used for UV−vis and photoluminescence experiments. 1H NMR data were obtained on a Bruker DPX-300 MHz NMR spectrometer, and spectra were calibrated against TMS. UV−vis spectra were recorded in a Perkin-Elmer Lambda 25 spectrometer. Photoluminescence spectra were recorded in a Fluoromax-3 spectrophotometer from HORIBA Jobin Yvon. Atomic force microscopy (AFM) images were obtained by an AUTOPROBE CP base unit, di CP-II instrument, model no. AP-0100. FT-IR spectra were recorded with a PerkinElmer Spectrum 100FT-IR spectrometer. Molecular weight of the polymer was determined by a Waters gel permeation chromatograph (GPC) equipped with a Waters 515 HPLC pump and a Waters 2414 refractive index (RI) detector using THF solvent. Molecular weight and PDI were calculated with respect to PMMA standards. Column temperature and flow rate were maintained at 35 °C and 1 mL/min, respectively. 8567

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Figure 7. AFM height images (3D view is shown in Figure S9) and height profile across a−b of (top) P1 and (bottom) P9. In both cases THF solutions (concentration = 1 mg/mL) were drop-casted on a silicon wafer and air-dried before images were taken. Synthesis of P1. The lactide monomer (600 mg, 4.165 mmol), initiator 1 (15.6 mg, 0.083 mmol), catalyst Sn(Oct)2 (25 mg, 0.0624 mmol), and dry toluene (0.8 mL) were placed in a reaction tube equipped with a rubber septum and was degassed by purging argon gas for 15 min. Then it was placed in a preheated oil bath and stirred at 120 °C in sealed condition for 48 h. Heating was stopped and cooled to rt, and it was precipitated out from cold MeOH (∼100 mL); the solid obtained was repeatedly washed with diethyl ether and dried under vacuum to get the desired polymer as white powder in 70% yield. 1H NMR (CDCl3, 500 MHz, TMS): δ (ppm) = 5.21 (broad peak, 1H), 3.74 (t, 2H), 2.90 (t, 2H) and 1.54 (broad peak, 3H). FTIR (KBr, cm−1): 1752 for ester carbonyl. GPC: Mn = 7200, PDI = 1.20 Synthesis of P2. A solution of P1 (60 mg) in THF (5 mL) was added with DTT (9 mg), and the solution was stirred at rt for 5 h. THF was removed under vacuum and diethyl ether was added to the solid mass and stirred for 20 min, and then it was kept at 4 °C for 30 min. Subsequently, it was centrifuged to get the resulting polymer as white powder in almost quantitative yield. Absence of any peak at 280 nm in the UV/vis spectra confirmed complete removal of the pyridyl disulfide group. Synthesis of P3. To a solution of polymer P2 (30 mg) and compound 2 (3 mg) in THF (1 mL), Me2PPh (6 mg) was added, and the solution was stirred at rt under an inert atmosphere for 20 h. Then the solution was poured in cold diethyl ether while solid precipitate came out. It was centrifuged and dried under vacuum to get the desired polymer (20 mg) as a white powder. 1H NMR, UV/vis, and PL spectra of the resulting polymer clearly demonstrated incorporation of the functional group in the chain end. Synthesis of P4. A solution of P2 (15 mg), compound 3 (2 mg), and AIBN (0.3 mg) in dry THF (2 mL) was degassed by purging argon and stirred at 70 °C under an inert atmosphere for 24 h. Heating was stopped, solution was allowed to cooled to rt, and the polymer was precipitated out from cold diethyl ether and isolated as white powder (10 mg). UV/vis and PL spectra of the resulting polymer confirmed quantitative functionalization.

Synthesis of P5. Polymer P2 (15 mg), compound 4 (1.7 mg), and triethylamine (1 μL) were dissolved in dry THF (1 mL), degassed, and stirred at 50 °C under an inert atmosphere for 24 h. Heating was stopped, solvent was evaporated, and cold MeOH was added to the vessel while white precipitate came out which was centrifuged and washed with cold diethyl ether to produce the resulting polymer as white powder (11 mg). UV/vis and PL spectra of the resulting polymer confirmed quantitative functionalization. Synthesis of P6. A solution of acryloyl chloride (100 μL) in dry dichloromethane (5 mL) was added to an ice-cold solution of commercially available poly(ethylene glycol) monomethyl ether (molecular weight = 2000 g/mol) (500 mg) and triethylamine (174 μL) in DCM (5 mL), and the reaction mixture was stirred under an inert atmosphere for 12 h at rt. After that the solution was washed with H2O (3 × 30 mL), brine (2 × 10 mL), and saturated aqueous NaHCO3 solution (1 × 20 mL), and the organic layer was dried over anhydrous Na2SO4 and solvent was removed to get the resulting polymer as white solid (410 mg). 1H NMR (CDCl3, 500 MHz, TMS): δ (ppm) = 6.43−6.42 (1H, m), 6.16−6.12 (1H, m), 5.84−5.82 (1H, m), 4.32 (2H, t), 3.7−3.3 (4H, m), and 3.37 (3H, s). Synthesis of P7. Polymers P2 (20 mg) and P6 (7 mg) were dissolved in THF (1 mL), and to this Me2PPh (4 mg) was added; the solution was degassed and stirred at rt under an inert atmosphere for 12 h. Then THF was removed, and water was added to the solid and washed several times followed by washing with hexane. Then the polymer was dried under vacuum to produce the resulting polymer as white solid (12 mg). 1H NMR (CDCl3, 500 MHz, TMS): δ (ppm) = 5.21 (broad peak, 1H), 4.32 (2H, t), 3.7−3.6 (4H, m), 3.37 (3H, s), and 1.54 (broad peak, 3H). Synthesis of P8. To a solution of polymer P1 (10 mg) in THF (2 mL), compound 5 (2 mg) was added, and the reaction mixture was stirred at rt for 4 h, THF was removed, and the solid was washed with water several times to get the desired polymer (7 mg) as white solid. Detail characterization data are presented in the main text. 8568

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Synthesis of P9. A solution of P1 (10 mg) in THF (1 mL) was added with NDI-SH (0.6 mg), and the reaction mixture was stirred at rt for 8 h and precipitated out from cold MeOH and washed with cold diethyl ether to get the desired polymer as light yellow solid (9 mg). Detail characterization data are presented in the main text. Acid-Induced Cleavage of P7. A solution of polymer P7 (5 mg) in MeOH (1 mL) was added with TFA (20 μL), and the reaction mixture was stirred at rt for 48 h; then all the volatiles were removed under reduced pressure, and the solid obtained was redissolved in THF and injected in GPC. Ellman’s Test. To a solution of a polymer under investigation in THF (0.5 mg/mL), Ellman’s reagent was added (∼5 mg) followed by addition of Et3N (20 μL), and it was stirred for 30 min. UV/vis spectra of the solution were checked before and after Ellman’s treatment to detect presence of free thiol functionality by monitoring the absorption band at 440 nm. Atomic Force Microscopy (AFM) Studies. In a typical AFM experiment, 50 μL of THF solution of P1/P9 (0.5 mg/mL) was dropcasted on a silicon wafer and allowed to air-dry for 4 h before images were taken.

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ASSOCIATED CONTENT

S Supporting Information *

Synthesis and characterization data of various small molecules containing thiol containing and thiol reactive functional groups and additional spectral data. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS M.R.M. thanks IACS for a research fellowship, and S.G. thanks CSIR, New Delhi, India, for financial support (Project No. 01/ 2366/10/EMR11). We thank Dr. Raja Shunmugam, IISER Kolkata, for GPC analysis and Mr. Rabindranath Banik for AFM measurements.

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