Anzar Khan

Efficient synthesis of multifunctional polymers via thiol–epoxy “click” chemistry

We demonstrate high efficiency and simplicity of the thiol-epoxy reaction towards preparation of a wide range of main-chain as well as end-chain multifunctional polymers.

Enzyme Sensitive Synthetic Polymer Micelles Based on the Azobenzene Motif

In this study, we investigate the potential of an artificial structural motif, azobenzene, in the preparation of enzyme sensitive polymeric nanostructures. For this purpose, an azobenzene linkage is established at the copolymer junction of an amphiphilic diblock copolymer. This polymer assembles into a micellar structure in water. Treatment with the enzyme azoreductase, in the presence of coenzyme NADPH, results in the cleavage of the azo-based copolymer junction and disruption of the micellar assembly. These results suggest that azobenezene is a useful non-natural structural motif for the preparation of enzyme responsive polymer nanoparticles. Due to the presence of azoreductase in the human intestine, such nanomaterials are anticipated to find applicability in the arena of colon-specific delivery systems.

Multifunctional Trackable Dendritic Scaffolds and Delivery Agents

Dendrimers and other 3-D molecular assemblies are attractive scaffolds for biological delivery agents and diagnostic probes[1,2] due to their globular shape, modular structure, monodispersity and plurality of functional end groups.[3] To address this potential, a number of strategies and related dendritic architectures have been developed for delivery of bioactive molecules to desired cells or tissue,[4] with encapsulation[5] and covalent attachment to the dendritic chain ends being two major approaches.[6] While the encapsulation of drugs or dyes within the inner cavities of the dendrimer is promising,[5] in most cases only a limited number of guest molecules can be encapsulated even with dendrimers of high generations.[4d] Moreover, the non-covalent nature of the encapsulation makes it a challenge to control the stability of the loaded carrier and subsequent release of the payload.[4e] An alternative strategy exploits the large number of dendritic chain ends to carry the cargo molecules.[6] However, loading of large amounts of hydrophobic drugs or dyes can alter the dendrimer surface properties and decrease its solubility and bio-compatibility.[7] Partial functionalization[8] alleviates this issue but results in random chain end modification leading to a dispersity in loading, variable bio-performance and in many cases only low degrees of surface functionalization can be achieved without significantly changing the surface properties.[9]

Thiol–epoxy ‘click’ polymerization: efficient construction of reactive and functional polymers

The thiol–epoxy ‘click’ process is employed as a polymerization reaction to prepare linear polymer chains substituted with free hydroxyl groups. Post-polymerization modification of the hydroxyl units afforded functional polymers exhibiting substituent dependent properties. In this way, functionalized macromolecules are obtained in two simple synthetic steps from commercially available monomer building blocks and reagents.

Facile and General Preparation of Multifunctional Main-Chain Cationic Polymers through Application of Robust, Efficient, and Orthogonal Click Chemistries

Poly(ß-hydroxyl amine)s are prepared from readily available small molecular building blocks at ambient conditions. These macromolecules can be transformed into main-chain cationic polymers upon quaternization of the backbone amine units. The modular and mild nature of the synthesis allows for incorporation of multiple (2-4) chemically distinct reactive sites in the polymer chain. Modifications of the reactive sites afford multifunctional polymers with tunable properties. The orthogonal nature of the involved chemistries sets the synthetic pathway free from any functional group protection/deprotection requirements. This feature also allows for alteration of the modification sequence.

Enzyme-Triggered Cascade Reactions and Assembly of Abiotic Block Copolymers into Micellar Nanostructures

Catalytic action of an enzyme is shown to transform a non-assembling block copolymer, composed of a completely non-natural repeat unit structure, into a self-assembling polymer building block. To achieve this, poly(styrene) is combined with an enzyme-sensitive methacrylate-based polymer segment carrying carefully designed azobenzene side chains. Once exposed to the enzyme azoreductase, in the presence of coenzyme NADPH, the azobenzene linkages undergo a bond scission reaction. This triggers a spontaneous 1,6-self-elimination cascade process and transforms the initially hydrophobic methacrylate polymer segment into a hydrophilic hydroxyethyl methacrylate structure. This change in chemical polarity of one of the polymer blocks confers an amphiphilic character to the diblock copolymer and permits it to self-assemble into a micellar nanostructure in water.

A general synthetic strategy to prepare poly(ethylene glycol)-based multifunctional copolymers

We report polyethylene glycol-based reactive diblock copolymer as well as random copolymer scaffolds that can be transformed into desired bifunctional copolymers in two synthetic steps. Synthesis of the general scaffolds is achieved via a controlled atom transfer radical polymerization process while the functional groups are introduced via thiol–epoxy ‘click’ and esterification reactions.

Protecting-group-free synthesis of chain-end multifunctional polymers by combining ATRP with thiol–epoxy ‘click’ chemistry

By combining ATRP polymerization with thiol–epoxy ‘click’ chemistry, a general, efficient, and protection/deprotection-free route is developed for the preparation of chain-end multifunctional polymers.

Designing functionalizable hydrogels through thiol–epoxy coupling chemistry

A novel and modular strategy has been developed for the preparation of reactive and functionalized hydrogels. In this strategy, thiol-epoxy coupling chemistry was employed for the formation of a hydrophilic network. The hydroxyl groups, generated during the coupling process, were then engaged in anchoring a fluorescent probe to the hydrogel scaffold.

Homopolymer bifunctionalization through sequential thiol–epoxy and esterification reactions: an optimization, quantification, and structural elucidation study

In this study, we probe various aspects of a post-polymerization double-modification strategy involving sequential thiol–epoxy and esterification reactions for the preparation of dual-functional homopolymers. For this, a general reactive scaffold, poly(glycidyl methacrylate), carrying an aromatic end-group was prepared through an atom transfer radical polymerization (ATRP) process. The glycidyl side-chains of this polymer were subjected to a base-catalyzed ring opening reaction with the thiol nucleophiles. A systematic variation in the catalyst type, catalyst loading, reaction medium, reaction temperature, and reaction time suggested that the choice and amount of catalyst had a significant impact on the outcome of the thiol–epoxy reaction. End-group analysis by 1H-NMR spectroscopy was employed to quantify the degree of the epoxy group conversion into the corresponding thio-ether moiety. The secondary hydroxyl groups generated as a result of the first functionalization reaction were then employed in the anchoring of a second functional group to the polymer repeat unit through an esterification reaction. Quantification studies suggested that an excess of the activated acid molecules was necessary to observe quantitative functional group transformation. Elemental analysis confirmed the chemical composition of the functionalized polymers. The obtained bi-functionalized polymers could be converted into a water soluble amphipathic structure in which each polymer repeat unit was substituted with a hydrophilic ammonium cation and a hydrophobic alkyl chain. Besides these, a carefully planned model compound study was also conducted to examine the regio-chemical aspects of the prepared polymers.