Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.