Metalloenzyme models for the biotransformation of nitroglycerin to nitric oxide

The complexes {lcub}HB{lcub}Me₂pz)₃{rcub}MoO₂X, where HB{lcub}Me₂pz)₃ = hydrotris(3,5-dimethyl-1-pyrazolyl) borate and X = Cl; MoTPB, SPh; MoTPBSPh, SPh(heptyl); MoTPBSPH(heptyl), have been studied for their ability to act as molybdoenzyme model catalysts in the reduction of organic nitrates to NO. All three complexes were capable of efficient degradation of nitroglycerin (GTN) to products including nitric oxide in the presence of different P(III) reducing cofactors and different solvents/aqueous environments. Organic nitrites, NO₂ and NO₃ were also reduced to give NO by MoTPB P(III) systems. Furthermore, all three models were shown to catalyze the oxidation of Ph₃P to Ph₃PO with GTN as the substrate in anaerobic CH₂Cl₂.; The chemical conversion of GTN to NO requires 3 electrons. The simplest mechanism to account for GTN reduction involves a 2e− reduction to RONO followed by a 1e− reduction of RONO to NO, although NO₂− cannot be ruled out as an intermediate. Reactions of RONO and NO2 with model followed Michaelis-Menten kinetics with rates of NO showing them to be kinetically competent intermediates for GTN reduction. DMSO as a competitive substrate inhibited NO formation from both GTN and isoamyl nitrite.; GTN degradation products were determined to be 1,2 and 1,3-GDN, NO ₂−, NO₃−, and N ₂O based on HPLC, GC, and Greiss experiments. The observed stoichiometry for the reaction of GTN (100mM), Ph₃P (20mM) and MoTPB (1mM) in anaerobic CH₂Cl₂ after 30 minutes is such that for every 1 mol of Ph₃P oxidized, 7 moles of GTN are reduced. The amount of nitrogen products quantified was less than 15% of the theoretical yields.