PhD Thesis
Branched Glycopolymers
Sharmila Muthukrishnan (03/2003-11/2005)
Support: Axel H. E. Müller
Summary
Linear and branched glycopolymers of a sugar-carrying acrylate monomer, 3-O-acryloyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (AIGlc), were synthesized via atom transfer radical polymerization (ATRP). Self-condensing vinyl copolymerization (SCVCP) via ATRP was employed for the synthesis of highly branched glycoacrylates. The successful synthesis of linear and branched glycoacrylates were confirmed by ¹H NMR, GPC/viscosity and MALDI-TOF mass spectrometry. Relationships between dilute solution viscosity and molecular weight were determined, and the Mark-Houwink exponent for branched poly(AIGlc)s typically varied between 0.28 and 0.20, depending on the degree of branching. The degree of branching (DB), evaluated by ¹H NMR, are in good agreement with the calculated values, providing the facile and successful synthesis of branched glycopolymers using SCVCP. The linear and branched polymers were converted into water-soluble ones by the deprotection of the isopropylidene groups. The complete deprotection was confirmed by ¹H NMR, FT-IR and GPC, respectively.
The sugar-carrying methacrylate monomer, 3-O-methacryloyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (MAIGlc) was used to synthesize linear and branched glycomethacrylates via ATRP. Homopolymerization resulted in linear poly(MAIGlc) of controlled molecular weight and molecular weight distribution. Randomly branched poly(MAIGlc)s were synthesized using a methacrylic inimer, 2-(2-bromoisobutyryloxy)ethyl methacrylate (BIEM) via SCVCP. The successful synthesis of linear and branched poly(MAIGlc)s were confirmed by GPC, GPC/viscosity analyses, as well as ¹H, 13C, and 2D NMR measurements. Mark-Houwink exponents between 0.20 and 0.34 were obtained within reasonable polymerization time (4 h), which was very much faster than the corresponding glyco-polyacrylates. Linear and branched poly(MAIGlc)s were finally deprotected to yield water-soluble glycomethacrylates.
Then, the facile one-pot self-condensing ATRP was utilized to synthesize surface-grafted branched glycopolymers. The hyperbranched glycomethacrylates were grafted from a silicon wafer consisting of a covalently attached initiator layer of α-bromoester fragments by using SCVCP of a methacrylic inimer, BIEM and sugar-carrying methacrylate monomer, MAIGlc. The thickness and roughness of the resulting surfaces were estimated using ellipsometry and scanning force microscopy (SFM) and found to depend on the catalyst amount and the comonomer ratio, γ. In the case of a linear polymer brush, the surface was relatively smooth and uniform. Deprotection of the isopropylidene groups of the branched and linear polymer brushes resulted in hydrophilic surfaces as investigated by contact angle measurements and DRIFT-IR. A significant difference in Br content between linear and branched polymers brushes was observed by X-ray photoelectron spectroscopy (XPS) which demonstrates the feasibility to control and modify the surface chemical functionality. Due to the presence of the α-bromoester terminal units, such surfaces can be further modified and can be employed in future for several biological applications.
Then, the synthesis of glycocylindrical brushes ("molecular sugar sticks") with poly(3-O-methacryloyl-α,β-D-glucopyranose), (PMAGlc) side chains, was achieved using the 'grafting from' approach via atom transfer radical polymerization (ATRP) of the monomer, MAIGlc. The formation of well-defined brushes with narrow length distribution was confirmed by GPC with a multi-angle light scattering detector (MALS) and ¹H NMR. The worm-like nature of the glycocylindical brushes was visualized using SFM. The initiating efficency of the initiating sites of the polyinitiator, poly(2-(2-bromoisobutyryloxy)ethyl methacrylate) were determined to be in the range of 0.23 < f < 0.38 by cleaving the side chains from the backbone by basic solvolysis. After deprotection of the isopropylidene groups of PMAIGlc side chains, SFM measurements, cryogenic transmission electron microscopy and dynamic light scattering showed a stretched, worm-like structure due to the hydration of the sugar moieties.
Finally, glycomethacrylate hybrid stars were synthesized using a silsesquioxane nanoparticles-based macroinitiator of ca. 58 initiator functions and MAIGlc as monomer via ATRP using the "core first" approach. Well-defined glycostars could be synthesized by restricting the polymerization to low conversion. The molecular weights of the star polymers were determined using GPC with viscosity and multi-angle light scattering (MALS) detectors. Analysis of the arms cleaved by basic solvolysis indicated the initiation site efficiency of the silsesquioxane-based macroinitiator is about 44 % which could be due to bulkiness of the monomer, MAIGlc as well as the influence of the structure of the macroinitiator, some functions possibly being less accessible than others. The morphology of the protected as well as deprotected stars were visualized using SFM and scanning electron microscopy (SEM) and found to be spherical in THF and water solution, respectively.
Such glycopolymers of different branched architectures synthesized via ATRP, have very high density of sugar moieties which can be in future manipulated to understand nature's multivalent processess, their interactions with proteins, in drug delivery etc due to their enhanced biocompatibility and hydrophilicity.