Correlation of Penicillin Structure with Rate Constants for Basic Hydrolysis

The rates of degradation of 16 different penicillins have been determined at 35°C in borate buffer, pH9.2, by use of stability-indicating HPLC assay procedures. The best-fit was sought between pseudo first-order hydrolytic rate constants and different types of structural descriptor. Constitutional, topological, geometric and electrostatic descriptors were calculated using WHIM-3D/QSAR and CODESSA software. Advanced semi-empirical and ab-initio calculations were performed using AMPAC software. CODESSA was used to develop (multi)linear correlation models, perform cluster analysis of the experimental data and molecular descriptors, and interpret the developed models. The best correlations with the rates of hydrolysis of the drugs were found for topological, electrostatic and quantum-chemical descriptors.