Rahul Tyagi

Biocatalytic “green” synthesis of PEG-based aromatic polyesters: optimization of the substrate and reaction conditions

The condensation copolymerization of a variety of linker molecules with polyethylene glycols (PEGs) of varying molecular weights, catalyzed by lipases under solvent-less conditions is reported. Previously, we reported the lipase-catalyzed condensation polymerization of dimethyl 5-hydroxyisophthalate with polyethylene glycol. Herein we have used a number of linker molecules with hydroxyl, amino, carboxylic acid, alkoxy, amido and alkoxycarbonyl moieties. Also, studies were conducted on the effects of the reaction parameters on the polymerization reactions. The hydrophilic segment was also varied, i.e. polyethylene glycols with molecular weights 300, 600, 900 and 1500 have been used for copolymerization with dimethyl 5-hydroxyisophthalate. The molecular weight of the polyethylene glycol affected the polymer yield and molecular weight. In principle, the method developed is flexible so that it can be used to generate a wide array of functionalized amphiphilic copolymers. In the absence of biocatalytic transformation, such structural control is extremely difficult or currently impossible to obtain.

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.

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.

Introducing Chirality into Nonionic Dendritic Amphiphiles and Studying Their Supramolecular Assembly

Chiral head groups have been introduced into water-soluble hydroxyl-terminated nonionic amphiphiles and the impact of the head group stereochemistry on the supramolecular ultrastructures has been studied. Enantiomeric isomers were compared with the achiral meso form and the racemic mixture by means of cryogenic transmission electron microscopy and circular dichroism spectroscopy. Structurally, all amphiphiles are composed of the first-generation hydrophilic polyglycerol head group coupled to a single hydrophobic hexadecyl chain through an amide linkage and diaromatic spacer. The enantiomers aggregate to form twisted ribbons with uniform handedness, whereas the meso stereoisomer and racemic mixture produce elongated assemblies, namely, tubules and platelets, but without a chiral ultrastructure. Simulations on the molecular packing geometries of the stereoisomers indicate different preferential assembly routes that explain the individual supramolecular aggregation behavior.

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 Modification of Naturally Occurring Iron Porphyrin

Hematin, a hydroxyferriprotoporphyrin, is the stable, oxidized form of heme. Heme has been reported to be the active catalytic center of naturally occurring peroxidases such as horseradish peroxidase (HRP). While there have been reports on the use of hematin as a catalyst for oxidative polymerization reactions, these reactions could be carried out only at high pH conditions due to limited aqueous solubility of hematin at lower pH conditions. We report here the biocatalytic modification of hematin using a lipase, Novozyme-435. Hematin has been modified by tethering monomethoxy polyethylene glycol (mPEG) chains which provide aqueous solubility over a fairly wide range of pH conditions. This pegylated Hematin (PEG-Hematin) is synthesized via a one-step solventless reaction and the products formed can be isolated with minimal purification. The PEG-Hematin synthesized serves as a robust alternative to HRP for the polymerization of aniline and phenol.

Design and Lipase Catalyzed Synthesis of 4-Methylcoumarin-siloxane Hybrid Copolymers

Poly dimethylsiloxanes with amino end groups were copolymerized with diesters of 4-methylcoumarins enzymatically using a lipase (Candida antarctica lipase) as a biocatalyst. In a separate synthesis, 4-methylcoumarin was also incorporated into the poly siloxanes-isophthalate copolymers by functionalization of hydroxyl groups in the isophthalate moiety. The synthesis and characterization of two sets of novel copolymers are presented. The thermal and flammability properties of these polymers have also been studied using TGA and microcalorimetry, respectively.