89959-07-9Relevant academic research and scientific papers
Reduction of Nitrate to Nitrite by Molybdenum-Mediated Atom Transfer: A Nitrate Reductase Analogue Reaction System
Craig, Julia A.,Holm, R. H.
, p. 2111 - 2115 (1989)
The kinetics of the oxygen atom transfer reaction MoIVO(L-NS2)(DMF) + NO3-=MoVIO2(L-NS2) + NO2- + DMF was investigated in DMF solution (L-NS2=2,6-bis(2,2-diphenyl-2-mercaptoethyl)pyridine(2-)).The reaction is quantitative and well-behaved when conducted in the presence of an excess of nitrate and ca. 1.5 equiv. of sulfamic acid, which rapidly scavenges nitrite that otherwise bleaches the Mo chromophores.It is characterized by saturation kinetics in which nitrate reversibly forms a substrate-Mo(IV) complex that generates products in a first-order pathway with k1=(1.49+/-0.05)*10-3s-1 at 295.5 K, ΔH=23.7+/-0.6 kcal/mol, and ΔS=8.0+/-2.0 eu.The moderate activation entropy suggests that the ground and transition states are structurally similar.The activation enthalpy is indistinguishable from previously reported values for the reductions of S-oxide and N-oxide substrates, which also follow pseudo-first-order kinetics.Inasmuch as the difference in S-O (Me2SO) and N-O (pyridine N-oxide) bond energies is about 14 kcal/mol, the essentially constant activation enthalpies indicate that the transition state is reached without significant substrate bond weakning.The recently introduced thermodynamic reactivity scale for oxo transfer as applied to substrates with N-O bonds is discussed.This work contributes the only well-documented reduction of nitrate to nitrite mediated at a Mo(IV) atom and demonstrates that reduction of nitrate by atom transfer is plausible (but unproven) pathway in the mechanism of action of nitrate reductases.
Kinetics, Mechanisms, and Catalysts of Oxygen Atom Transfer Reactions of S-Oxide and Pyridine N-Oxide Substrates with Molybdenum(IV,VI) Complexes: Relevance to Molybdoenzymes
Caradonna, John P.,Reddy, P. Rabindra,Holm, R. H.
, p. 2139 - 2144 (2007/10/02)
The kinetics and mechanism of the oxygen atom transfer reactions MoO2(L-NS2) + (RF)3P -> MoO(L-NS2)(DMF) + (RF)3PO (1) and MoO(L-NS2)(DMF + XO -> MoO2(L-NS2) + X, with X = (RF)2SO (2) and 3-fluoropyridine N-oxide (3), heve been investigated in DMF solutions (L-NS2 = 2,6-bis(2,2-diphenyl-2-mercaptoethyl)pyridine(2-), RF = p-C6H4F).The following rate constants (297.5 K) and activation parameters were obtained: reaction 1, k2 = 9.7 (4) X 10-3 M-1 s-1, ΔH(excit.) = 11.7 (6) kcal/mol, ΔS(excit.) = -28.4 (1.6) eu; reaction 2, k1 = 14.0 (7) X 10-4 s-1, ΔH(excit.) = 22.1 (1.3) kcal/mol, ΔS(excit.) = 2.6 (1.6) eu; reaction 3, k1 = 16.0 (8) X 10-4 s-1, ΔH(excit.) = 23.4 (1.4) kcal/mol, ΔS(excit.) = 7.2 (2.0) eu. reactions 2 and 3 exhibit saturation kinetics, under which the rate-determining step is intramolecular atom transfer.Mechanisms and transition states are proposed.The activation parameters are the first measured for oxo transfer from substrate; the small activation entropies suggest a transition state structurally similar to the complex MoO(L-NS2)(XO) formed in a labile equilibrium prior to oxo transfer to Mo.Coupling of reaction 1 with reaction 2 or 3 affords the catalytic reaction 4, (RF)3P + XO -> (RF)3PO + X; no reaction occurs in the absence of the Mo catalyst.The kinetics of catalysis were examined by monitoring the concentrations of reactants and products by 19F NMR spectroscopy.After 15 h, each system showed ca. 100 turnovers.Reaction 4 with XO = (RF)2SO has a catalytic rate constant of 7 X 10-3 M-1 s-1, close to the value for reaction 1.This and other considerations show that the catalytic rate is limited by the rate of oxo transfer from the Mo(VI) complex MoO2(L-NS2). An attempt to establish the catalytic mechanism led to detection of inhibition; the inhibitory species could not be identified.These results provide the most detailed information on the kinetics and mechanisms of Mo-mediated oxygen atom transfer and demonstrate the efficacy of 19F NMR for detecting and monitoring catalysis and determining catalytic velocities and rate constants.The relation of these results to the enzymatic reduction of N-oxides ans S-oxides is briefly discussed.
Thermodynamic Fitness of Molybdenum(IV, VI) Complexes for Oxygen Atom Transfer Reactions, Including Those with Enzymatic Substrates
Harlan, Edgar W.,Berg, Jeremy M.,Holm, R. H.
, p. 6992 - 7000 (2007/10/02)
The oxygen (oxo) atom transfer hypothesis for the enzymatic oxidation/reduction of generalized substrate X/XO by the molybdenum oxotransferases (hydroxylases) has been further pursued by an investigation of the reactions of the Mo(VI) and Mo(IV) complexes MoO2(L-NS2) and MoO(L-NS2)(DMF) (L-NS2=2,6-bis(2,2-diphenyl-2-thioethyl)pyridinate(2-)), respectively, in DMF solution.Because of steric hindrance, these molecules execute oxo transfer without formation of a binuclear μ-oxo Mo(V) species.MoO(L-NS2)(DMF) was previously found to reduce quantitatively a variety of sulfoxides, including at least one enzyme substrate.Here this complex is shown to reduce, with formation of MoO2(L-NS2), a series of N-oxides including those of pyridine, nicotinamide, adenine, and tribenzylamine, which are enzyme substrates or pseudosubstrates.Ph3AsO is also reduced by this complex.A previous demonstration of the catalytic partial transfer of 18O in nicotinamide N-oxide to uric acid by xanthine oxidase is interpreted as supporting the oxo transfer hypothesis.MoO2(L-NS2) is reduced by PhSH to MoO(L-NS2)(DMF), further indicating the feasibility of thiols as physiological electron donors.A thermodynamic criterion for the ability of a MoIVO or MoVIO2 complex to reduce or oxidize substrate has been developed on the basis of ΔH values for the reaction X + 1/2O2 -> XO.MoO(L-NS2)(DMF) (21)/MoO2(L-NS2) (22) and MoO(S2CNEt2)2 (20)/MoO2(S2CNEt2)2 (19) are positioned in the reaction series so as to oxidize or reduce (as appropriate) all enzymatic substrates for which thermodynamic data are available.Intermetal oxo transfer reactions of the type MoOLn + MoO2L'n -> MoO2Ln + MoOL'n were investigated with 19-22 and the Schiff base complexes MoO(ssp)(DMF) (18), MoO2(ssp)(DMF) (15), MoO(sap)(DMF) (17), and MoO2(sap)(DMF) (13).These demonstrate the thermodynamic oxo donor order to be S4 (19) > NS2 (22) > ONS (15) > O2N (13); the oxo acceptor order is the reverse.All MoIVO complexes in the set are able to reduce Me2SO to Me2S.This is a necessary but not sufficient thermodynamic criterion for a functional oxo transferase site model.Under the oxo transfer hypothesis, a sufficient model requires access to both the MoIVO and MoVIO2 states at real or effective potentials that can be reached with physiological reductants such that catalysis can be sustained.Evidence is presented that anionic sulfur ligands significantly modulate potentials to values appropriate for catalysis, and that tungsten, having more negative potentials than molybdenum in analogous complexes, is unsuitable for this purpose.
A Model for the Active Sites of Oxo-Transfer Molybdoenzymes: Synthesis, Structure, and Properties
Berg, Jeremy M.,Holm, R. H.
, p. 917 - 925 (2007/10/02)
Development of models for the active sites of oxo-transfer molybdoenzymes has been initiated.Suitable models should be capable of oxygen atom transfer to or from the substrate, approach the native coordination unit, and be inert to formation of μ-oxo Mo(V
A Model for the Active Sites of Oxo-Transfer Molybdoenzymes: Reactivity, Kinetics, and Catalysis
Berg, Jeremy M.,Holm, R. H.
, p. 925 - 932 (2007/10/02)
Oxidation-reduction reactions of substrates in systems containing the complexes Mo(VI)O2(LNS2) and Mo(IV)O(LNS2)(DMF) (LNS2=2,6-bis(2,2-diphenyl-2-mercaptoethyl)pyridine) in DMF solutions at 23 deg C have been investigated as models for the activities of certain oxo-transfer molybdoenzymes.The MoO1,2S2N coordination units are resonable representations of this class of enzymes.MoO2(LNS2) reacts with Ph3P in a second-order process to yield MoO(LNS2)(DMF) and Ph3O with the rate constant k1=7(1)*10-3 M-1 s-1.MoO(LNS2)(DMF) reduces sulfoxides in a two-stage reaction involving equilibrium formation of the R2SO adduct (K=4.2-16*103) followed by R2S formation (k1=1.36-1.70*10-3 s-1).The small dependence of K and k1 on substrate structure suggests that the adduct is O-ligated to Mo(IV).These reactions exhibit the frequent enzymatic property of substrate saturation kinetics.One substrate is d-biotin d-(S-oxide), the natural substrate of the Mo-dependent enzyme biotin S-oxide reductase from E. coli, indicating the biological significance of the reactions.Evidence concerning this and other physiological sulfoxide reducing activities is summarized.Oxo transfers to and from substrate have been coupled to produce a catalytic system which turns over the reaction Me2SO+Ph3P->Me2S+Ph3PO, in which Me2SO serves as a model substrate.No reaction is observed in the absence of the Mo catalyst.The initial catalytic rate is given by k, with k=6*10-3 M-1 s-1.This rate is limited by the rate of reduction of MoO2(LNS)2 by Ph3P.The sulfoxide reducing system developed here is characterized by substrate saturation kinetics, transformation of a biological substrate, and a well-defined catalytic cycle capable of turnover of hundreds of equivalents of a model substrate without intervention of a physiologically unrealistic μ-oxo-Mo(V) dimer.This system joins others recently devised in a broad development of reactivity models of metalloenzymes.
