para-substituted N-nitroso-n-oxybenzenamine ammonium salts: A new class ofredox-sensitive nitric oxide releasing compounds

N-Nitroso-N-oxybenzenamine ammonium salts with -OMe, -Me, -H, -F, -Cl, -CF3 , and -SO2Me substituents at the para position of the phenyl ring constitut e a new class of-redox sensitive nitric oxide (NO) releasing compounds. The se compounds yield nitric oxide and the corresponding nitrosobenzene deriva tives by a spontaneous dissociation mechanism after undergoing a one electr on oxidation. Oxidation of these compounds can be achieved through chemical , electrochemical and enzymatic methods. It was observed electrochemically that the amount of NO generated was dependent on the substituent effect and the applied oxidation potential. Electron-withdrawing substituents increas e the oxidation potential of the compound. A linear correlation was observe d when the peak potentials for the oxidation were graphed Versus the Hammet t substituent constant. Density functional theory calculations were also pe rformed on this series of compounds. The theoretical oxidation energies of the corresponding anions show a strong linear correlation with the experime ntal potentials. Furthermore, enzymatic oxidation using horseradish peroxid ase showed a similar substituent effect. These results indicate that substi tution at the par a position of the phenyl ring has a profound effect on th e stability, oxidation potential and enzymatic kinetic properties of the co mpounds. Thus pala-substituted N-nitroso-N'-oxybenzenamine salts comprise a new class of redox-sensitive nitric oxide releasing agents. (C) 2000 Elsev ier Science Ltd. All rights reserved.