Structure-Activity Relationship Study on Cephalosporins with Mechanism-based Descriptors
Junho Choi, Hojing Kim · Bulletin of the Korean Chemical Society · 1993
The polarizability and the transition state energy of a cephalosporin are assumed to be theoretical indices of the permeability through the outer membrane and of reactivity of -lactam ring with penicillin binding proteins, respectively, in Gram-negative bacteria. They are computed by AM1 method and used as variables of quantitative structure-activity relationship study. The results justify quadratic dependence of the activity on the variables. The intersection of difference volumes between stable cephalosporins and unstable ones manifests that the steric hindrance of 7-side chain is responsible for the -lactamase stability.