Kinetic-Dependent Bactericidal Efficacy of Nitric Oxide Donors
The antimicrobial efficacy of nitric oxide (*NO) as a function of its release kinetic from *NO donors was examined. *NO donating molecules were synthesized by the formation of Ndiazeniumdiolate, 1-amino-substituted diazen-1-ium-1,2-diolate, on secondary amines by reaction with *NO under basic conditions. The resulting *NO donors (i.e . PROLI/NO, SPER/NO, and DETA/NO) were capable of releasing *NO upon solution immersion under physiological conditions (pH 6.5, 37 °C). Total *NO release and half-life ranged from 3.00-7.07 μmol mg-1 and 0.016-7.14 h, respectively. The distinct *NO-release kinetics of the Ndiazeniumdiolate *NO donors promoted further studies on the effect of kinetics on bactericidal activity against Pseudomonas aeruginosa, a gram-negative pathogen. Comparison of the bactericidal efficacy of the three *NO donors demonstrated enhanced bactericidal efficacy of Ndiazeniumdiolates with intermediate *NO-release kinetics (i.e. SPER/NO). While DETA/NO control exhibited toxicity toward P. aeruginosa, neither PROLI/NO control nor SPER/NO control showed toxicity at the respective minimum bactericidal concentrations. The results of this study highlighted the influence of the chemical property (i.e. *NO-release kinetics) on bactericidal activity of small molecule *NO donors.