Electrochemistry of β-lapachone and its diazoderivative: Relevance to their compared antimicrobial activities

Abstract

A new diazo derivative ( 2) of β-lapachone ( 1) is synthesized in one step and good yield (72%). New and significant antimicrobial activity data toward several strains of resistant Staphylococcus aureus for β-lapachone are presented. For the new compound, compared with β-lapachone, the modification of the redox center decreased drastically the biological activity, a fact that could be rationalized by the electrochemical results. The redox properties of both compounds are investigated, in aprotic medium (DMF + 0.1 mol L −1 TBAP), using a glassy carbon electrode. For the diazoquinone, an unique irreversible monoelectronic reduction peak is observed. The reduction mechanism corresponds to an ECC process, where the first chemical reaction is the fast unimolecular loss of dinitrogen, leading to a transient carbene anion radical, which captures a hydrogen atom and furnishes a phenolate derivative. Addition of different proton sources (phenol, benzoic acid) does not affect at all the reduction wave, but leads to the disappearance of the corresponding anodic wave, due to the protonation of the phenolate anion. The reduction of 2 occurs at more negative potential and its anion radical is very short-lived, so this may be the main set of reasons, which prevents the generation of reactive oxygen species in situ and might be the reason for its lower antimicrobial activity.