QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS FOR THE CONVERSION OF NITROBENZIMIDAZOLONES AND NITROBENZIMIDAZOLES BY DT-DIAPHORASE - IMPLICATIONS FOR THE KINETIC MECHANISM

Quantitative structure activity relationships (QSARs) for the conversi on of nitrobenzimidazolones and nitrobenzimidazoles by rat liver DT-di aphorase (EC 1.6.99.2) are described. The parameter used for descripti on of the QSARs is the energy of the lowest unoccupied molecular orbit al (E(LUMO)) of the nitroaromatic compounds. Interestingly, correlatio ns with E(LUMO) were observed for both the natural logarithm of k(cat) , but also for the natural logarithm of k(cat)/K-m. The minimal kineti c model in line with these QSARs is a ping-pong mechanism that include s a substrate binding equilibrium in the second half reaction. (C) 199 8 Federation of European Biochemical Societies.