Substituent effects in cephalosporins as assessed by molecular orbital calculations, nuclear magnetic resonance, and kinetics.

For cephalosporins with different side chains at position 3, the quantum mechanically computed charge distribution in the beta-lactam carbonyl group can be correlated with observables, such as carbon-13 chemical-shift differences at C3 and C4 of the dihydrothiazine ring and alkaline rates of hydrolysis of the beta-lactam. The relationship of these properties and the theoretical transition-state energy (TSE) corroborate the fact that chemical reactivity is one important determinant affecting inhibitory activity of cephalosporins against peptidoglycan-regulating enzymes.