Theoretical Study of Guanidino-Phenol Based Antibacterial Compounds

N. Derbel, I. Clarot, M. Mourer, J.B. Regnouf-de-Vains, M.F. Ruiz-López

Keywords: calixarene, pKa, antibacterial compounds, ab initio calculations


The resistance of pathogenic microorganisms to existing antibiotics is a major public health problem worldwide and has emphasized the urgent need for developing new drugs. Several experimental groups have provided important contributions recently but much work still remains to be done. Some of us have synthesized a novel series of polycationic compounds based on a calix[4]arene architecture and have evidenced promising antibacterial activities of this chemical family.1-6 The most active molecule is the tetra-p-guanidinoethyl-calix[4]arene shown in the Scheme, for which the mechanism of action, thought to be a disorganizing interaction with the bacterial wall, has not been elucidated yet. In this work, we have carried out a theoretical investigation on the structure and properties (pKa’s) of this system and of its parent compound p-guanidinoethyl-phenol in aqueous media. Comparison with experiments will be discussed.