Quantitative structure-activity relationships in two-electron reduction of nitroaromatic compounds by Enterobacter cloacae NAD(P)H: Nitroreductase

Henrikas Nivinskas, Ronald L. Koder, Žilvinas Anusevičius, Jonas Šarlauskas, Anne Francesc Miller, Narimantas Čenas

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61 Scopus citations

Abstract

Enterobacter cloacae NAD(P)H:nitroreductase (NR; EC 1.6.99.7) catalyzes the reduction of a series of nitroaromatic compounds with steady-state bimolecular rate constants (kcat/Km) ranging from 104to 107M-1s-1In agreement with a previously proposed scheme of two-step four-electron reduction of nitroaromatics by NR (Koder, R. L., and Miller, A.-F. (1998) Biochim. Biophys. Acta 1387, 395-405), 2 mol NADH per mole mononitrocompound were oxidized. An oxidation of excess NADH by polinitrobenzenes, including explosives 2, 4, 6-trinitrotoluene (TNT) and 2, 4, 6-trinitrophenyl-N-methylnitramine (tetryl), has been observed as a slower secondary process, accompanied by O2consumption. This type of "redox cycling" was not related to reactions of nitroaromatic anion-radicals, but was caused by the autoxidation of relatively stable reaction products. The initial reduction of tetryl and other polinitrophenyl-N-nitramines by E. cloacae NR was analogous to a two-step four-electron reduction mechanism of TNT and other nitroaromatics. The logs kcat/Kmof all the compounds examined exhibited parabolic dependence on their enthalpies of single-electron or two-electron (hydride) reduction, obtained by quantum mechanical calculations. This type of quantitative structure-activity relationship shows that the reactivity of nitroaromatics towards E. cloacae nitroreductase depends mainly on their hydride accepting properties, but not on their particular structure, and does not exclude the possibility of multistep hydride transfer.

Original languageEnglish
Pages (from-to)170-178
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume385
Issue number1
DOIs
StatePublished - Jan 1 2001

Bibliographical note

Funding Information:
This work was supported in part by Lithuanian State Science and Studies Foundation Grant No. T-442 and by PRF Grant ACS-PRF 28379. We thank the staff of Department of Organic Chemistry of Vilnius University for their assistance in quantum chemical calculations.

Keywords

  • Electron transfer
  • Explosive
  • Nitroreductase
  • Pentryl
  • TNT
  • Tetryl

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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