Comparative molecular field analysis (CoMFA) of herbicidal protoporphyrinogen oxidase inhibitors using standard steric and electrostatic fields and an alternative LUMO field

A set of diphenyl ether herbicides [1] was examined with Comparative Molecular Field Analysis (CoMFA) using standard steric and electrostatic fields and alternative frontier orbitals as 3-D fields to explain observed Protoporphyrinogen oxidase (PPO) enzyme inhibition. Significant CoMFA models were obtained utilizing standard CoMFA and the LUMO field both together and separately. These findings support previous QSAR work that identified several electronic properties as important for PPO inhibition. The resulting CoMFA models identify specific 3-D steric and electronic interactions affecting PPO enzyme binding most significantly.