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

Abstract

For cephalosporins [antibacterial agents] 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.