Virinder S. Parmar

CHEMO-ENZYMATIC SYNTHESIS AND CHARACTERIZATION OF NOVEL FUNCTIONALIZED AMPHIPHILIC POLYMERS

ABSTRACT The condensation copolymerization of Dimethyl 5-hydroxyisophthalate (1) with Polyethylene glycols (PEGs) (2a–2d) of varying molecular weights, catalyzed by Novozyme-435 (immobilized Candida antarctica lipase B) in bulk is reported. The structures of the resulting polymers, Poly[(poly(oxyethylene)-oxy-5-hydroxyisophthaloyl] (3a–3c) were characterized by 1H (1D and 2D) and 13C-NMR spectroscopic experiments. Further, these polymers have been derivatized by attaching decanyl and 12-hydroxydodecanyl chains to the phenolic hydroxyl group. The resulting amphiphilic polymeric systems were characterized by detailed spectroscopic analysis. Light Scattering Photometry as well as Gel Per meation Chromatography were used to evaluate the particle size and molecular weights of the polymers. In principle, the method developed is flexible so that it can be used to generate a wide array of functionalized amphiphilic polymers. In the absence of biocatalytic transformation, such structural control would be extremely difficult or currently impossible to obtain.

Synthesis of novel poly(ethylene glycol) based amphiphilic polymers

Abstract The synthesis of new amphiphilic polyesters based on poly(ethylene glycol) (PEGs) and studies on their solution properties are reported. Two novel monomers, dimethyl 5-n-butoxy isophthalate (2) and dimethyl 5-n-octoxy isophthalate (3) were synthesized. Three series of novel amphiphilic polyesters, i.e. poly(ethyleneoxy isophthalate)s (10–15), poly(ethyleneoxy n-butoxy isophthalate)s (16–21) and poly(ethyleneoxy n-octoxy isophthalate)s (22–27) have been synthesized from PEGs of different sizes and dimethyl isophthalates 1–3 via the transesterification–polycondensation using dibutyltin diacetate as a catalyst. The structures of the polyesters were established from a detailed analysis of their spectra, i.e. FTIR, 1H-NMR (one- and two-dimensional) and 13C-NMR. By adjusting the ratio of hydrophobic (diesters) and hydrophilic (PEGs) segments in polymers, their main chain structures and solution properties could be changed. The viscosity molecular weights (Mv) of polymers, obtained from Mark–Houwink–Sakurada relationship having poly(ethylene terephthalate) as a model, were in the range of 4500–32,000 g/mol. Intrinsic viscosities were studied based on polymer backbone length (PEGs effect) and pendant group (diesters effect) and these were found to be dependent on molecular weights of the PEGs used.

Self-assembly of PEG and diester copolymers : Effect of PEG length, linker, concentration and temperature

The formation of micelles in a solvent that is selective for one of the blocks is one of the most important and useful properties of block copolymers. Recently, we have synthesized copolymers of polyethylene glycol and various dimethyl esters, which self‐assemble into nano micellar aggregates in aqueous media. These nano micelles are very effective in solubilizing otherwise insoluble drugs. The structure, interaction and size of these nano micelles are very important and critical to design an efficient drug delivery system. In the present work, we have studied the effect of hydrophilic block, PEG length, linker, concentration and temperature on these nano micellar structures and interactions by static light scattering techniques.

Design and Synthesis of Novel Pegylated 4‐Methylcoumarins

Coumarins are well known for their antioxidant and anti‐edema activities. Their antioxidant property gets enhanced with a methyl group at the C‐4 position of the pyran ring. To increase the antioxidant potential and their hydrophilicity, a lipase (Novozyme 435) catalyzed copolymerization of 4‐methylcoumarin diesters and polyethylene glycols (PEGs) has been carried out to give novel copolymers.

Novel PEGylated Amphiphilic Copolymers as Nanocarriers for Drug Delivery: Synthesis, Characterization and Curcumin Encapsulation

Amphiphilic polymers can self assemble into micellar nano-particles and can be effectively used as nano carriers for drug delivery. A number of macromolecular delivery systems are under investigation to improve the efficacy of prospective drugs. In this study, seven new co-polymers were synthesized under mild reaction conditions in bulk (without solvent) by chemoenzymatic approach using Candida antarctica lipase (Novozyme 435) and molecular sieves, subsequently these polymers were treated with different long chain bromoalkanes and acid chlorides for attachment of the lipophilic moieties to the backbone polymer via an ether or an ester linkage, respectively in order to make them amphiphilic. These synthesized nano-particles demonstrated high drug loading capacity and have the potential to encapsulate hydrophobic drugs.

Indo-U.S. collaborative studies on biocatalytic generation of novel molecular architectures

Biocatalytic polymerization reactions on a variety of substrates leading to value-added polymers have been summarized. The main focus of this review is on the control of molecular architecture during enzymatic polymerization reactions. Combined with chemical reactions, several extremely flexible chemo-enzymatic synthetic procedures are described to produce families of new polymeric materials with novel properties. The properties of the synthesized polymers and their applications in various fields, such as drug delivery and flame retardant materials, have also been studied and discussed.

Enzymatic synthesis of multi-component copolymers and their structural characterization

The use of enzymes in synthetic applications has increased dramatically in the recent years and the field of polymer science is part of this trend. Synthesis of a variety of polymers using lipase catalyzed (Candida antarctica) polymerization reactions has led to a variety of new materials with interesting properties in our laboratories. This paper describes the synthesis of multi-component polyesters and mixed polymers having polyester and polyamide linkages under solvent-less conditions using Candida antarctica lipase B. The effect of a third component, i.e. a series of 1,ω-alkanediols (1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, 1,10-decanediol, 1,12-dodecanediol, 1,14-tetradecanediol and 1,16-hexadecanediol) on the copolymerization reaction of dimethyl 5-hydroxyisophthalate with poly(ethylene glycol 600) has been studied and the mechanism for the incorporation of the third component is proposed. We have also studied the effect of different functional groups during terpolymerization reaction of dimethyl 5-hydroxyisophthalate with poly(ethylene glycol) by adding a third component having different functionalities (1,6-hexanediol, 1,6-hexanediamine or 1,6-hexanedithiol) and compared the effect of hydroxyl, amine and thiol groups on the polymerization reactions.

Candida antarctica Lipase B Catalyzed Copolymerizations of Non‐proteinogenic Amino Acids and Poly(Ethylene Glycol) to Generate Novel Functionalized Polyesters

Abstract The condensation copolymerization of non‐proteinogenic amino acid derivatives 1–9 with polyethylene glycol (PEG, Mw 600) (10), catalyzed by lipases in bulk is reported. Five different lipases (porcine pancreatic lipase, Candida rugosa lipase, Candida antarctica lipase, Pseuodomonas AY lipase, and Pseudomonas cepacia lipase) were tested to catalyze the copolymerization of diethyl‐α‐acetamido, α‐(3‐trifluromethylbenzyl)‐malonate (7) with poly(ethylene glycol 600) (10) in bulk at 65°C. All other enzymes except C. antarctica lipase B (Novozyme‐435) failed to produce the polymer. Therefore, C. antarctica lipase B was used for the synthesis of copolymers starting with non‐proteinogenic amino acid derivatives 1–9 and PEG (Mw 600) (10) to give to polymers 11–19, which were characterized by 1H (1D and 2D) and 13C NMR spectroscopic data. Light scattering photometry, as well as gel permeation chromatography were used to evaluate the particle size and molecular weights of the polymers. The effects of reaction parameters in chain extension have been systemically investigated. In principle, the method developed is flexible so that it can be used to generate a wide array of functionalized polyesters. In the absence of biocatalytic transformation, such structural control would be extremely difficult or currently impossible to obtain.

Synthesis and Characterization of Novel Amphiphilic Polymers as Drug Delivery Nano Carriers

Polymer nano-particles have been widely investigated in the last decade due to a variety of potential applications. In particular, polymers which can self assemble into micellar nano-particles can be effectively used as vehicles for drug delivery. Considerable efforts are underway to develop better drug delivery nano carriers for high drug loading capacity for a wide variety of bioactive compounds. In this study, several new polymers were synthesized in bulk (solventless condition) by a chemo-enzymatic methodology using Candida antarctica lipase B (Novozyme 435) and molecular sieves (MS). The synthesized polymers demonstrated high drug loading capacity and the potential to encapsulate drugs which are poorly soluble in aqueous solvents.

Biocatalytic Synthesis and Characterization of Copolymers Based on Poly(Ethylene Glycol) and Unsaturated Methyl Esters

Biocatalytic organic synthesis has proved to be a significant breakthrough in the area of polymer synthesis. Environmentally benign methodology and the use of mild reaction conditions are a hallmark of this approach. We have studied the biocatalytic synthesis of unsaturated polyesters under solvent‐less conditions by the condensation copolymerization of dimethyl fumarate and dimethyl maleate with polyethylene glycol (PEG) catalyzed by Novozyme‐435 (immobilized Candida antarctica lipase B). The structures of the resulting polymers, poly(ethylene glycol)‐co‐dimethyl fumarate and poly(ethylene glycol)‐co‐dimethyl maleate were studied from their 1H and 13C‐NMR spectra. The molecular weights of polymers were determined by size exclusion chromatography.