Functional-Polymer Library through Post-Polymerization Modification of Copolymers Having Oleate and Pentafluorophenyl Pendants.

Poly[2-(methacryloyloxy)ethyl oleate-co-pentafluorophenyl methacrylate] [P(MAEO-co-PFPMA)] random copolymers with oleate and pentafluorophenyl side-chain pendants were synthesized. These copolymers were utilized as dual-reactive polymeric scaffolds in a range of post-polymerization modification strategies involving thiol-ene and para-fluoro-thiol substitution, amidation, trans-esterification, and epoxidation followed by amidation. The 2-(methacryloyloxy)ethyl oleate (MAEO) functional handle in the copolymer is open to functionalization at its internal double bond through thermally initiated thiol-ene reaction, whereas the pentafluorophenyl moiety of the pentafluorophenyl methacrylate (PFPMA) unit undergoes para-fluoro-thiol substitution under basic conditions at room temperature. By means of these modification approaches, the P(MAEO-co-PFPMA) copolymer was orthogonally ligated with thiol compounds having, for example, alkyl, hydroxyl, and protected amine functional groups. Furthermore, different functional groups such as benzyl, allyl, methacrylate, pyrene, and water-soluble poly(ethylene glycol) were easily introduced into the side chain of the P(MAEO-co-PFPMA) copolymer by amidation, trans-esterification, and epoxidation followed by amidation. Functionalization of both the reactive pendants with the various organic substituents was confirmed by 1 H and 19 F NMR spectroscopy, gel permeation chromatography, and fluorescence spectroscopy.

Monitoring aggregation of a pH-responsive polymer via proton exchange.

Understanding the changes in the macro-structure of amphiphilic pH-responsive polymers remains a relevant issue due to their potential use as drug delivery carriers. Since some of the amphiphilic polymers are known to exchange hydrogen ions with an aqueous solvent, we monitor the effective change of the surface to volume ratio of such polymer aggregates using solution-state nuclear magnetic resonance (NMR) spectroscopy. The surface to volume ratio with the help of UV-visible spectroscopy is shown to yield the average diameter of the polymer aggregates. We show that the proposed method not only satisfactorily corroborates the existing notions of how the aggregation of these polymers takes place as a function of pH, but also provides a quantitative estimate of the size of the aggregates.

Polymer-Chlorambucil Drug Conjugates: A Dynamic Platform of Anticancer Drug Delivery.

Recently, polymer drug conjugates (PDCs) have attracted considerable attention in the treatment of cancer. In this work, a simple strategy has been developed to make PDCs of an antitumor alkylating agent, chlorambucil, using a biocompatible disulphide linker. Chlorambucil-based chain transfer agent was used to prepare various homopolymers and block copolymers in a controlled fashion via reversible addition-fragmentation chain transfer polymerization. Chlorambucil conjugated block copolymer, poly(polyethylene glycol monomethyl ether methacrylate)-b-poly(methyl methacrylate), formed nanoaggregates in aqueous solutions, which are characterized by dynamic light scattering and field emission-scanning electron microscopy. Finally, the simplicity of the design is exemplified by performing a release study of chlorambucil under reducing condition by using D,L-dithiothreitol.

Polyisobutylene-based glycopolymers as potent inhibitors for in vitro insulin aggregation.

A family of amphiphilic diblock copolymers containing a hydrophobic polyisobutylene (PIB, Mn = 1000 g mol-1) segment and a hydrophilic block with sugar pendants has been synthesized by combining living cationic and reversible addition-fragmentation chain transfer (RAFT) polymerization techniques; to explore their potential in insulin fibrillation inhibition. The glucose content in the hydrophilic segment has been tailor-made from 20 to 57 units to prepare block copolymers. The removal of the acetates from the pendent glucose units resulted in amphiphilic block copolymers that generated micellar aggregates in aqueous media. The treatment of insulin with these block copolymers affected the fibril formation process which was demonstrated using an array of biophysical techniques, namely, thioflavin T (ThT) fluorescence, tyrosine (Tyr) fluorescence, Nile red (NR) fluorescence, isothermal titration calorimetry (ITC), etc. The Tyr fluorescence assay and NR fluorescence study revealed the crucial role of hydrophobic interaction in the inhibition process, whereas ITC measurements confirmed the importance of polar interaction. Thus, the block copolymers exhibit potent inhibition of insulin fibrillation owing to hydrophobic (from PIB segment) and glycosidic cluster effect (from sugar pendant block).

Block Copolymer Synthesis by the Combination of Living Cationic Polymerization and Other Polymerization Methods.

The foremost limitation of block copolymer synthesis is to polymerize two or more different types of monomers with different reactivity profiles using a single polymerization technique. Controlled living polymerization techniques play a vital role in the preparation of wide range of block copolymers, thus are revolutionary techniques for polymer industry. Polymers with good control over molecular weight, molecular weight distribution, chain-end functionality and architectures can be prepared by these processes. In order to improve the existing applications and create new opportunities to design a new block copolymer system with improved physical and chemical properties, the combination of two different polymerization techniques have tremendous scope. Such kinds of macromolecules may be attended by combination of homopolymerization of different monomers by post-modification techniques using a macroinitiator or by using a dual initiator which allows the combination of two mechanistically distinct techniques. This review focuses on recent advances in synthesis of block copolymers by combination of living cationic polymerization with other polymerization techniques and click chemistry.

Recyclable macromolecular thermogels for Hg(II) detection and separation via sol-gel transition in complex aqueous environments.

The sensitive detection and quantitative separation of toxic heavy metal ions in aqueous media are of great importance. In this study, a thermogelling poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) triblock copolymer (P1) was synthesized, and difluoroboron dipyrromethene (BODIPY) fluorophore integrated with thiosemicarbazide units was attached to the chain ends of P1 through consecutive post-polymerization modifications, leading to P4. P4 exhibited rapid and selective detection of Hg(II) in 100% aqueous media via turn-on fluorescence emission with a limit of detection (LOD) of as low as 0.461 µM. This turn-on emission behavior is attributed to the suppression of CË­N isomerization caused by the formation of a coordination complex between P4 and Hg(II) ions. The selective and quantitative removal of Hg(II) among various metal ions was achieved by trapping chelated Hg(II) ions inside the dehydrated P4 gel via thermo-controlled sol-gel-dehydrated gel transitions. Treating the Hg(II) ion-trapped dehydrated gels with sodium sulfide (Na2S) in acetone/water at room temperature led to HgS precipitates, and P4 in solution was dried and recycled. This recyclable thermoresponsive macromolecular probe is promising for not only Hg(II) detection but also its separation and removal from complex aqueous environments.

BODIPY-Derived Polymeric Chemosensor Appended with Thiosemicarbazone Units for the Simultaneous Detection and Separation of Hg(II) Ions in Pure Aqueous Media.

Developing a simple and cheap analytical method for the selective detection and quantitative separation of toxic ions present in aqueous media is the biggest challenge faced by the chemosensing research community. Here, a 5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5 H-dipyrrolo-diazaborinine-derived water-soluble polymer integrated with thiosemicarbazone units was rationally designed and synthesized for the simultaneous detection and separation of Hg(II) ions in pure aqueous solution. The water-soluble polymer scaffold poly( N, N'-dimethyl acrylamide- co-5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5 H-dipyrrolo-diazaborinine-2-carbaldehyde) was synthesized by reversible addition-fragmentation chain transfer polymerization, followed by post-polymerization modification with thiosemicarbazide, leading to the formation of the target probe, P1. The nonemitting P1 exhibited bright yellow emission upon exposure to Hg(II) ions, with a limit of detection as low as 0.37 µM. This turn-on emission behavior triggered by Hg(II) ions might originate from the suppression of isomerization around the C═N bond of the thiosemicarbazone moiety caused by the formation of a coordination complex between P1 and Hg(II) ions. In addition, P1 displayed excellent selectivity toward Hg(II) ions over other metal cations. Finally, the selective removal of Hg(II) ions from an aqueous solution containing various metal ions was achieved by precipitation, which is probably caused by the fact that coordination complexes whereby Hg(II) ions acted as bridgeheads between P1 molecules had formed.

Uptake and Release of Species from Carbohydrate Containing Organogels and Hydrogels.

Hydrogels are used for a variety of technical and medical applications capitalizing on their three-dimensional (3D) cross-linked polymeric structures and ability to act as a reservoir for encapsulated species (potentially encapsulating or releasing them in response to environmental stimuli). In this study, carbohydrate-based organogels were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of a ß-D-glucose pentaacetate containing methacrylate monomer (Ac-glu-HEMA) in the presence of a di-vinyl cross-linker; these organogels could be converted to hydrogels by treatment with sodium methoxide (NaOMe). These materials were studied using solid state 13C cross-polarization/magic-angle spinning (CP/MAS) NMR, Fourier transform infrared (FTIR) spectroscopy, and field emission scanning electron microscopy (FE-SEM). The swelling of the gels in both organic solvents and water were studied, as was their ability to absorb model bioactive molecules (the cationic dyes methylene blue (MB) and rhodamine B (RhB)) and absorb/release silver nitrate, demonstrating such gels have potential for environmental and biomedical applications.

Polyisobutylene-Based pH-Responsive Self-Healing Polymeric Gels.

This work demonstrates the successful application of dynamic covalent chemistry for the construction of self-healing gels from side-chain primary amine leucine pendant diblock copolymers of polyisobutylene (PIB) ((P(H2N-Leu-HEMA)-b-PIB)) in the presence of PIB based dialdehyde functionalized cross-linker (HOC-PIB-CHO) through imine (-HC═N-) bond formation without aiding any external stimuli. Gels were synthesized in 1,4-dioxane at room temperature at varied wt % of gelator concentration, [H2N]/[CHO] ratios and molecular weight of the block segments. The mechanical property of gels was examined by rheological measurements. We observed higher value of storage modulus (G') than the loss modulus (G″) within the linearity limits of deformation, indicating the rheological behavior in the gel is dominated by an elastic property rather than a viscous property. The G' values significantly depend upon the extent of cross-linking in the gel network. To establish self-healing property of the gels, rheology analysis through step-strain measurements (strain = 0.1 to 200%) at 25 °C was performed. The polymeric gel network shows reversible sol-gel transition for several cycles by adjusting the pH of the medium with the help of hydrochloric acid (HCl) and triethylamine (Et3N) triggers. FT-IR spectroscopy established formation of imine bonds in the gel network and these gels showed poor swelling behavior in various organic solvents because of the small interstitial porosity, confirmed by field emission-scanning electron microscopy (FE-SEM).

Remarkable swelling capability of amino acid based cross-linked polymer networks in organic and aqueous medium.

This work reports design and synthesis of side chain amino acid based cross-linked polymeric gels, able to switch over from organogel to hydrogel by a simple deprotection reaction and showing superabsorbancy in water. Amino acid based methacrylate monomers, tert-butoxycarbonyl (Boc)-l/d-alanine methacryloyloxyethyl ester (Boc-l/d-Ala-HEMA), have been polymerized in the presence of a cross-linker via conventional free radical polymerization (FRP) and the reversible addition-fragmentation chain transfer (RAFT) technique for the synthesis of cross-linked polymer gels. The swelling behaviors of these organogels are investigated in organic solvents, and they behave as superabsorbent materials for organic solvents such as dichloromethane, acetone, tetrahydrofuran, etc. Swollen cross-linked polymer gels release the absorbed organic solvent rapidly. After Boc group deprotection from the pendant alanine moiety, the organogels transform to the hydrogels due to the formation of side chain ammonium (-NH3(+)) groups, and these hydrogels showed a significantly high swelling ratio (∼560 times than their dry volumes) in water. The morphology of organogels and hydrogels is studied by field emission scanning electron microscopy (FE-SEM). Amino acid based cross-linked gels could find applications as absorbents for oil spilled on water as well as superabsorbent hydrogels.

CdS quantum dots doped tuning of deswelling kinetics of thermoresponsive hydrogels based on poly(2-(2-methoxyethoxy)ethyl methacrylate).

Thermoresponsive poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA) based hybrid nanocomposite hydrogels (NCH) were synthesized by dispersing preformed cadmium sulfide (CdS) quantum dots (QDs) in the reaction mixture followed by polymerization via reversible addition-fragmentation chain transfer (RAFT) technique. High doping capacity and negligible QDs leakage were observed for hydrophilic QDs doped hydrogels (hpl-NCH) due to H-bonding interactions between QDs and pendant groups of hydrogel network. The hpl-NCH networks showed improved structural/orientational order and swelling ratios with increasing doping concentration compared to the organic hydrogel (OH). Opposite trends were observed for bulk-CdS (NCH-bulk) and 1-dodecanethiol capped CdS (NCH-DDT) doped hydrogels. Swelling induced linear retardance and quenching of photoluminescence (PL) intensity for hydrogels were exploited to study the deswelling kinetics respectively by Mueller matrix polarimetry and solid state fluorimetry, which were further corroborated with gravimetric analysis. For all the NCH, deswelling process significantly decreased with increasing temperature, which followed the order: 30 > 45 > 60 °C. Slower deswelling was observed for NCH-bulk and hpl-NCH compared to the OH, and also with increase in doping concentration due to the formation of skin layer. However, NCH-DDT exhibited accelerated deswelling process and the order was reversed with respect to doping concentration due to DDT mediated enhanced hydrophobic aggregation and water leakage channels created by long hydrophobic free-mobile nature of QDs surface tethered DDT molecules. The presented methodology provides tunable deswelling of PMEO2MA based hydrogels by doping with hydrophilically/hydrophobically modified CdS QDs.