Functional, degradable polyester materials synthesized from poly(epsilon-caprolactone-co-2-oxepane-1,5-dione): An investigation into the derivatization, self assembly, and degradation behavior of poly(epsilon-caprolactone)-based materials
Date of Award
Doctor of Philosophy (PhD)
Biocompatible, degradable polymers possessing a high degree of complexity are an extremely desirable target for many applications. In order to further develop the range and utility of materials made from aliphatic polyesters, poly(epsilon-caprolactone-co-2-oxepane-1,5-dione) (P(CL-co-OPD)) was used as a polymeric precursor for the construction of a series of functional polyester-based materials. By taking advantage of the electrophilic ketone moieties characteristic of the OPD repeat unit, small molecule and polymer grafts were attached to the PCL backbone through the formation of both hydrazone and ketoxime ether linkages. This work has focused on both the synthesis and characterization of functional, degradable polyesters, including amphiphilic block graft copolymers, that possess significant potential for future use in diagnostic and therapeutic applications.
A dansyl-functionalized poly(epsilon-caprolactone) was synthesized by reacting (P(CL-co-OPD) with dansyl hydrazine. The resulting dansylated-PCL displayed interesting fluorescence behavior and showed solvent polarity dependance as the fluorescence emission maxima shifted from 494 nm in toluene to 526 nm in dimethyl sulfoxide (DMSO). Analysis of the emission maximum of the dansyl-grafted polymer and a dansyl-functionalized small molecule analog with respect to three different solvent polarity parameters indicated that the fluorescence emission spectra of the dansylated polymer was influenced by solvent polarity, but that the dansyl fluorophore was overall less sensitive to the surrounding medium when grafted onto the polyester backbone.
Degradable, amphiphilic graft copolymers of poly(epsilon-caprolactone)-graft-poly(ethylene oxide), PCL-g-PEO, were synthesized via a grafting onto strategy taking advantage of the ketones presented along the backbone of the statistical copolymer (PCL-co-OPD). Through the formation of stable ketoxime ether linkages, 3 kDa poly(ethylene oxide) (PEO) grafts and p-methoxybenzyl (pMeOBn) side chains were incorporated onto the polyester backbone with a high degree of fidelity and efficiency, as verified by NMR spectroscopy and GPC analysis (90% grafting efficiency in some cases). The resulting block graft copolymers displayed significant thermal differences, specifically a depression in the observed melting transition temperature, Tm, in comparison to the parent PCL and PEO polymers. These amphiphilic block graft copolymers underwent self assembly in aqueous solution with the P(CL-co-OPD-co-(OPD-g-PEO)) polymer forming globular micelles and a P(CL-co-OPD-co-(OPD-g-PEO)-co-(OPD-g-pMeOBn)) forming cylindrical or rod-like micelles, as observed by transmission electron microscopy (TEM) and atomic force microscopy (AFM).
PCL-g-PEO copolymers synthesized from PCL-co-OPD that still contained free OPD units were found to undergo an early and rapid degradation upon being dispersed in aqueous solution. P(CL92-co-OPD5-co-(OPD-g-PEO)9) showed immediate signs of degradation upon being dispersed in aqueous solution based upon both 1H NMR spectroscopy and gel permeation chromatography (GPC) analysis. The solution state aggregates showed a minimal increase in aggregate size moving from a number-averaged hydrodynamic diameter (Dh) of 13 ± 3 nm at 0 h to 17 ± 3 nm at 24 h based upon analysis by dynamic light scattering (DLS). An increase in diameter upon degradation was corroborated by transmission electron microscopy (TEM) images showing circular particles that had a Dav of 15 ± 4 nm and 22 ± 5 nm at 0 and 24 h respectively. P(CL92-co-(OPD-g-PEO)8-co-(OPD-g-pMeOBn)6), a polyester having no free OPD units, showed no signs of rapid degradation over 24 h by 1H NMR or GPC analysis. Characterization of the solution state aggregates by DLS and TEM indicated that the circular particles formed by the PCL-g-PEO copolymer maintained both their size and morphology while being dispersed in aqueous solution for 24 h. P(CL327-co-OPD22-co-(OPD-g-PEO)15-co-(OPD-g-pMeOBn)8), a significantly larger PCL-PEO ketoxime ether conjugate possessing free OPD units, also showed signs of backbone degradation by 1H NMR and GPC upon being transitioned into aqueous solution. DLS analysis, of the solution state aggregates formed by this amphiphilic block graft copolymer showed no substantial changes in the hydrodynamic diameter over time. However, characterization by TEM showed a transition from circular to rod-like or cylindrical aggregates as hydrolysis occurred.
Chair and Committee
Karen L. Wooley and Joshua A. Maurer
Willam E. Buhro, Garland R. Marshall, Jacob Schaefer, Jay R. Turner
Iha, Rhiannon K., "Functional, degradable polyester materials synthesized from poly(epsilon-caprolactone-co-2-oxepane-1,5-dione): An investigation into the derivatization, self assembly, and degradation behavior of poly(epsilon-caprolactone)-based materials" (2010). Arts & Sciences Electronic Theses and Dissertations. 503.