COMPARATIVE MOLECULAR-FIELD ANALYSIS OF ARTEMISININ DERIVATIVES - AB-INITIO VERSUS SEMIEMPIRICAL OPTIMIZED STRUCTURES

Based on the belief that structural optimization methods, producing st ructures more closely to the experimental ones, should give better, i. e. more relevant, steric fields and hence more predictive CoMFA models , comparative molecular field analyses of artemisinin derivatives were performed based on semiempirical AM1 and HF/3-21G optimized geometrie s. Using these optimized geometries, the CoMFA results derived from th e HF/3-21G method are found to be usually but not drastically better t han those from AM1. Additional calculations were performed to investig ate the electrostatic field difference using the Gasteiger and Marsili charges, the electrostatic potential fit charges at the AM1 level, an d the natural population analysis charges at the HF/3-21G level of the ory. For the HF/3-21G optimized structures no difference in predictabi lity was observed, whereas for AM1 optimized structures such differenc es were found. Interestingly, if ionic compounds are omitted, differen ces between the various HF/3-21G optimized structure models using thes e electrostatic fields were found.