Regioselective Design of Polysaccharide Ester Graft Copolymers

Abstract

Polysaccharide graft (co)polymers, where a polysaccharide comprises the backbone and a separate (co)polymer comprises grafted side chains, are growing in popularity as blend compatibilizers, sustainable elastomers, self-assembling materials, and drug delivery components. This popularity is attributed to the inherent renewability, abundance, and general low toxicity of the polysaccharide backbone, coupled with the extensive functionality and range of physicochemical properties that can be imparted through attachment of a second polymeric side chain. However, polysaccharide graft (co)polymers can be exceedingly complex due to polymeric attributes of both the backbone and grafted side chains (namely, molecular weight (MW) and molar mass dispersity (Ð)). Further structural complications arise from complexities inherent to the polysaccharide backbone, as the presence of pendant functional groups on each monosaccharide result in polymer grafts (and any other substituents present) originating from up to three positions. In order to properly elucidate relationships between the structure (i.e., topology) of polysaccharide graft (co)polymers and exhibited physicochemical properties, the position of polymer grafts on each repeating unit, degree of substitution (DS) of grafted chains, and MW of grafted chains must be controlled and properly characterized. Regioselective functionalization of polysaccharides is an appealing route to produce well-defined polysaccharide graft (co)polymers. By selectively derivatizing a single functional group per monosaccharide with a moiety capable of polymer conjugation (i.e., grafting-to) or polymer initiation (i.e., grafting-from), the graft density of the ensuing graft (co)polymer can be controlled by limiting the DS at the reactive site. However, regioselective modification of polysaccharides, especially polyglucopyranoses such as amylose and cellulose, is difficult due to the similar reactivities of pendant hydroxy groups. One distinct structural feature of amylose and cellulose is the sole primary hydroxy group located at the C6 position of each monosaccharide. The increased steric accessibility and wider approach angles of the primary C6-OH compared to the more hindered secondary C2/C3-OH is a valuable structural feature that can lend itself to selective functionalization. In this work, two distinct chemistries regioselective for the C6-OH of amylose and cellulose were leveraged to produce well-defined polysaccharide derivatives and graft (co)polymers. The primary C6-OH of amylose was selectively converted to a primary alkyl bromide through treatment with N-bromosuccinimide (NBS) and triphenylphosphine (PPh3), which could subsequently be displaced by the azide anion to prepare a well-defined amylose derivative with functionality reactive for the highly efficient copper-catalyzed azide-alkyne cycloaddition (CuAAC). A series of 2,3-di-O-acetyl-6-azido-6-deoxy (2,3Ac-6N3) amyloses were prepared through efficient transformations with control over DS of acetyl (Ac) and N3 moieties. Prepared 2,3Ac-6N3 amyloses served as the backbone for a series of well-defined amylose acetate-graft-polylactide (AmAc-g-PLA) graft polymers, which show promise as compatibilizers for immiscible blends of highly renewable starch acetate (StAc) and PLA, both of which are sourced from starch feedstocks. Polysaccharide graft polymer compatibilizers (where the backbone comprises a polymer that is miscible with one blend component, and the grafted side chain comprises a polymer that is miscible with the other blend component) have shown promise in stabilizing the morphology of immiscible polymer blends, but are seldom produced with topological control allowing for determination of an ideal graft length or density for compatibilization. To address this, a series of AmAc-g-PLA graft polymers prepared by grafting-to CuAAC of alkyne-terminated PLA with 2,3Ac-6N3 amylose, permitting precise control over graft length and graft density by varying the MW of alkyne-terminated PLA (i.e., graft length) and DS(N3) of 2,3Ac-6N3 amylose (i.e., graft density). Preliminary investigations reveal that effective compatibilization is observed for AmAc-g-PLA graft polymers with low graft density, permitting favorable enthalpic interactions between the AmAc backbone and the StAc phase, and high graft length, allowing for entanglements between PLA side chains and the PLA phase. Selective protection of the C6-OH with the bulky 4-monomethoxytriphenylmethyl (MeOTr) ether is another effective regioselective modification. However, regioselective generation of polysaccharide derivatives employing MeOTr protection chemistry can be time-consuming due to the plethora of protection, functionalization, and deprotection steps. To address this, an efficient, regioselective pathway was developed to produce 2,3-di-O-acyl-6-O-MeOTr (2,3A-6MeOTr) cellulose esters through C6-OH tritylation and C2/C3-OH acylation in a sequential, one-pot manner. Subsequent treatment of 2,3A-6MeOTr cellulose esters with an acyl donor under acidic (yet mild) conditions generated a series of 2,3-di-O-A-6-O-B (2,3A-6B) mixed cellulose esters with up to 100% selectivity for C6-OH protection. Mixed cellulose esters with regioselective incorporation of initiating sites for atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization were prepared, providing an efficient route to well-defined macroinitiators for controlled radical polymerizations. Development of such functional cellulose esters is expected to be invaluable when conducting grafting-from polymerization, as regioselective incorporation of initiating sites will ensure controllable graft density. In comparison to previous routes to polysaccharide graft (co)polymers, the methods described herein offer distinct improvements in control over graft length and graft density. By developing efficient routes to regioselectively substituted polysaccharide derivatives capable of grafting-to and grafting-from polymerization chemistries, topological features most important to optimizing the physicochemical properties of such biobased materials can be identified. The expansion of synthetic strategies described herein will be invaluable to both polymer and polysaccharide chemists aiming to develop a sustainable future by leveraging the fascinating and complex family of polysaccharide graft (co)polymers.