Molybdenum Center Research Articles

The mononuclear molybdenum enzymes.

Molybdenum is the only second-row transition metal required by most living organisms, and is nearly universally distributed in biology. Enzymes containing molybdenum in their active sites have long been recognized,1 and at present over 50 molybdenum-containing enzymes have been purified and biochemically characterized; a great many more gene products have been annotated as putative molybdenum-containing proteins on the basis of genomic and bioinformatic analysis.2 In certain cases, our understanding of the relationship between enzyme structure and function is such that we can speak with confidence as to the detailed nature of the reaction mechanism and, with the availability of high-resolution X-ray crystal structures, the specific means by which transition states are stabilized and reaction rate is accelerated within the friendly confines of the active site. At the same time, our understanding of the biosynthesis of the organic cofactor that accompanies molybdenum (variously called molybdopterin or pyranopterin), the manner in which molybdenum is incorporated into it, and then further modified as necessary prior to insertion into apoprotein has also (in at least some cases) become increasingly well understood. It is now well-established that all molybdenum-containing enzymes other than nitrogenase (in which molybdenum is incorporated into a [MoFe7S9] cluster of the active site) fall into three large and mutually exclusive families, as exemplified by the enzymes xanthine oxidase, sulfite oxidase, and DMSO reductase; these enzymes represent the focus of the present account.3 The structures of the three canonical molybdenum centers in their oxidized Mo(VI) states are shown in Figure 1, along with that for the pyranopterin cofactor. The active sites of members of the xanthine oxidase family have an LMoVIOS-(OH) structure with a square-pyramidal coordination geometry. The apical ligand is a Mo=O ligand, and the equatorial plane has two sulfurs from the enedithiolate side chain of the pyranopterin cofactor, a catalytically labile Mo–OH group, and most frequently a Mo=S. Nonfunctional forms of these enzymes exist in which the equatorial Mo=S is replaced with a second Mo=O; in at least one member of the family the Mo=S is replaced by a Mo=Se, and in others it is replaced by a more complex –S–Cu–S–Cys to give a binuclear center. Members of the sulfite oxidase family have a related LMoVIO2(S–Cys) active site, again square-pyramidal with an apical Mo=O and a bidentate enedithiolate Ligand (L) in the equatorial plane but with a second equatorial Mo=O (rather than Mo–OH) and a cysteine ligand contributed by the protein (rather than a Mo=S) completing the molybdenum coordination sphere. The final family is the most diverse structurally, although all members possess two (rather than just one) equiv of the pyranopterin cofactor and have an L2MoVIY(X) trigonal prismatic coordination geometry. DMSO reductase itself has a catalytically labile Mo=O as Y and a serinate ligand as X completing the metal coordination sphere of oxidized enzyme. Other family members have cysteine (the bacterial Nap periplasmic nitrate reductases), selenocysteine (formate dehydrogenase H), –OH (arsenite oxidase), or aspartate (the NarGHI dissimilatory nitrate reductases) in place of the serine. Some enzymes have S or even Se in place of the Mo=O group. Members of the DMSO reductase family exhibit a general structural homology to members of the aldehyde:ferredoxin oxidoreductase family of tungsten-containing enzymes;4 indeed, the first pyranopterin-containing enzyme to be crystallographically characterized was the tungsten-containing aldehyde:ferredoxin oxidoreductase from Pyrococcus furiosus,5 a fact accounting for why many workers in the field prefer “pyranopterin” (or, perhaps waggishly, “tungstopterin”) to “molybdopterin”. The term pyranopterin will generally be used in the present account. Open in a separate window Figure 1 Active site structures for the three families of mononuclear molybdenum enzymes. The structures shown are, from left to right, for xanthine oxidase, sulfite oxidase, and DMSO reductase. The structure of the pyranopterin cofactor common to all of these enzymes (as well as the tungsten-containing enzymes) is given at the bottom.

Synthesis and spectroscopic characterization of monometallic molybdenum (VI) complexes derived from bis(2-hydroxy-1-naphthaldehyde)succinoyldihydrazone

Molybdenum complexes [(μ2-O)2(MoO2)2(H4nsh)2]·2A·2C2H5OH (where A=O (1), py (2), 2-pic (3), 4-pic (4) and 5-pic (5)) have been synthesized in absolute ethanol from bis(2-hydroxy-1-naphthaldehyde)succinoyldihydrazone. The composition of the complexes has been deduced on the basis of the data obtained from elemental analyses and thermo-analytical data. All complexes are non-electrolyte in DMSO solution as evident from low value of molar conductance in the range 2.2–3.3Ω−1cm2mol−1. The complexes are diamagnetic and have molybdenum in +6 oxidation state. The dihydrazone coordinates to the molybdenum centre as a neutral bidentate ligand through two azomethine nitrogen atoms only. This is revealed by the downfield shift of δ(CHN) signals by 0.16–0.44ppm as compared to that in the free dihydrazone. The carbon atoms closer to azomethine nitrogen atoms downfield shift confirming the coordination of azomethine nitrogen atoms. The ν(CN) stretching vibrations also shift to lower frequency in the IR spectra of the complexes. Apart from the intra ligand bands, the complexes show a new absorption band in the region 421–423nm attributed to charge-transfer transition from dihydrazone ligand to molybdenum centre. The dihydrazone is present in anti-cis conformation in all of the complexes. The complexes develop a new kind of intramolecular hydrogen bonding between naphtholic OH groups of coordinated dihydrazone.

Substrate Orientation and Specificity in Xanthine Oxidase: Crystal Structures of the Enzyme in Complex with Indole-3-acetaldehyde and Guanine

Xanthine oxidase is a molybdenum-containing hydroxylase that catalyzes the hydroxylation of sp(2)-hybridized carbon centers in a variety of aromatic heterocycles as well as aldehydes. Crystal structures of the oxidase form of the bovine enzyme in complex with a poor substrate indole-3-acetaldehyde and the nonsubstrate guanine have been determined, both at a resolution of 1.6 Å. In each structure, a specific and unambiguous orientation of the substrate in the active site is observed in which the hydroxylatable site is oriented away from the active site molybdenum center. The orientation seen with indole-3-acetaldehyde has the substrate positioned with the indole ring rather than the exocyclic aldehyde nearest the molybdenum center, indicating that the substrate must rotate some 30° in the enzyme active site to permit hydroxylation of the aldehyde group (as observed experimentally), accounting for the reduced reactivity of the enzyme toward this substrate. The principal product of hydroxylation of indole-3-acetaldehyde by the bovine enzyme is confirmed to be indole-3-carboxylic acid based on its characteristic UV-vis spectrum, and the kinetics of enzyme reduction are reported. With guanine, the dominant orientation seen crystallographically has the C-8 position that might be hydroxylated pointed away from the active site molybdenum center, in a configuration resembling that seen previously with hypoxanthine (a substrate that is effectively hydroxylated at position 2). The ∼180° reorientation required to permit reaction is sterically prohibited, indicating that substrate (mis)orientation in the active site is a major factor precluding formation of the highly mutagenic 8-hydroxyguanine.

New molybdenum (VI) catalyst for the epoxidation of alkenes and oxidation of sulfides: An experimental and theoretical study

The preparation and catalytic activity of molybdenum(VI) dioxido complex [MoO2L(C2H5OH)] (L=N′-[1-(2-hydroxynaphthyl)ethylidene]-2-hydroxy benzohydrazide) are reported. The reaction of the respective benzohydrazide ligand and the Mo(VI) dioxido precursor, [MoO2(acac)] (acac=acetylacetonate), in ethanol afforded the [MoO2L(C2H5OH)] complex. Structure of the complex was unequivocally established by single-crystal X-ray crystallography. The X-ray structure of complex reveals a six coordinate molybdenum center with a distorted octahedral geometry. By using the AIM analysis, topological properties of the electron density were analyzed to define the bond path between atoms. The AIM calculations indicate that the ligand H2L coordinates to the molybdenum ion in the enol-enamine form (not keto-amine). An insight in the electronic structure of the complex was also obtained by using the density functional theory (DFT). The [MoO2L(C2H5OH)] complex was successfully applied as a catalyst in both, the epoxidation of olefins with tert-butyl hydroperoxide (TBHP) and the oxidation of sulfides with urea hydrogen peroxide (UHP), to form the corresponding sulfoxides.

Chloro- and Trifluoromethyl-Substituted Flanking-Ring m-Terphenyl Isocyanides: η6-Arene Binding to Zero-Valent Molybdenum Centers and Comparison to Alkyl-Substituted Derivatives

Presented herein are synthetic and structural studies exploring the propensity of m-terphenyl isocyanide ligands to provide flanking-ring η(6)-arene interactions to zerovalent molybdenum centers. The alkyl-substituted m-terphenyl isocyanides CNAr(Mes2) and CNAr(Dipp2) (Ar(Mes2) = 2,6-(2,4,6-Me3C6H2)2C6H3; Ar(Dipp2) = 2,6-(2,6-(i-Pr)2C6H3)2C6H3) react with Mo(η(6)-napthalene)2 in a 3:1 ratio to form tris-isocyanide η(6)-arene Mo complexes, in which a flanking mesityl or 2,6-diisopropylphenyl group, respectively, of one isocyanide ligand is bound to the zerovalent molybdenum center. Thermal stability and reactivity studies show that these flanking ring η(6)-arene interactions are particularly robust. To weaken or prevent formation of a flanking-ring η(6)-arene interaction, and to potentially provide access to the coordinatively unsaturated [Mo(CNAr(R))3] fragment, the new halo-substituted m-terphenyl isocyanides CNAr(Clips2) and CNAr(DArF2) (Ar(Clips) = 2,6-(2,6-Cl2C6H3)2(4-t-Bu)C6H2; Ar(DArF2) = 2,6-(3,5-(CF3)2C6H3)2C6H3) have been prepared. Relative to their alkyl-substituted counterparts, synthetic and structural studies demonstrate that the flanking aryl rings of CNAr(Clips2) and CNAr(DArF2) display a lower tendency toward η(6)-binding. In the case of CNAr(DArF2), it is shown that an η(6)-bound 3,5-bis(trifluoromethyl)phenyl group can be displaced from a zerovalent molybdenum center by three molecules of acetonitrile. This observation suggests that the CNAr(DArF2) ligand effectively masks low-valent metal centers in a fashion that provides access to low-coordinate isocyano targets such as [Mo(CNAr(R))3]. A series of Mo(CO)3(CNAr(R))3 complexes were also prepared to compare the relative π-acidities of CNAr(Mes2), CNAr(Clips2), and CNAr(DArF2). It is found that CNAr(DArF2) shows increased π-acidity relative to CNAr(Mes2) and CNAr(Clips2), despite the fact that its electron-withdrawing CF3 groups are fairly distal to the terminal isocyano unit.

Tris(3,5-di-tert-butylcatecholato)molybdenum(VI): Lewis Acidity and Nonclassical Oxygen Atom Transfer Reactions

In the solid state, tris(3,5-di-tert-butylcatecholato)molybdenum(VI) forms a dimer with seven-coordinate molybdenum and bridging catecholates. NMR spectroscopy indicates that the dimeric structure is retained in solution. The molybdenum center has a high affinity for Lewis bases such as pyridine or pyridine-N-oxide, forming seven-coordinate monomers with a capped octahedral geometry, as illustrated by the solid-state structure of (3,5-(t)Bu2Cat)3Mo(py). Structural data indicate that the complexes are best considered as Mo(VI) with substantial π donation from the nonbridging catecholates to molybdenum. Both the dimeric and the monomeric tris(catecholates) react rapidly with water to form free catechol and oxomolybdenum bis(catecholate) complexes. Monooxomolybdenum complexes are also obtained, more slowly, on reaction with dioxygen, with organic products consisting mostly of 3,5-di-tert-butyl-1,2-benzoquinone with minor amounts of the extradiol oxidation product 4,6-di-tert-butyl-1-oxacyclohepta-4,6-diene-2,3-dione. The pyridine-N-oxide complex reacts on heating (with excess pyO) to form initially (3,5-(t)Bu2Cat)2MoO(Opy) and ultimately MoO3(Opy), with quinone and free pyridine as the only organic products. The decay of (3,5-(t)Bu2Cat)3Mo(Opy) shows an accelerated, autocatalytic profile because the oxidation of its product, (3,5-(t)Bu2Cat)2MoO(Opy), produces an oxo-rich, catecholate-poor intermediate which rapidly conproportionates with (3,5-(t)Bu2Cat)3Mo(Opy), providing an additional pathway for its conversion to the mono-oxo product. The tris(catecholate) fragment Mo(3,5-(t)Bu2Cat)3 deoxygenates Opy in this nonclassical oxygen atom transfer reaction slightly less rapidly than does its oxidized product, MoO(3,5-(t)Bu2Cat)2.

Synthesis, characterization and the thermal isomerization mechanism of a series of trans-tetracarbonyl-bis(phosphinite)molybdenum(0) complexes and an evaluation of their potential to form heterobimetallic compounds

The reactions of coordinated phosphorus-donor ligands have previously been used to prepare bimetallic trans-[cis-Mo(CO)4(PPh2NHCH2CH2NCH(o-C6H4)O)2]M (M = Ni(II), Cu(II)) complexes. Similar bimetallic complexes containing trans-tetracarbonyl-bis(phosphinite)molybdenum(0) centers could be even more interesting because they could serve as molecular gyroscopes. In an attempt to prepare such complexes, the three intermediate compounds trans-Mo(CO)4(PPh2Cl)2 (1), trans-Mo(CO)4(PPh2NHCH2CH2NH2)2 (2), and trans-Mo(CO)4(PPh2NHCH2CH2NCH(o-C6H4)OH)2 (3) were successfully synthesized and fully characterized by multinuclear NMR spectroscopy, elemental analysis and X-ray crystallography. However, the reaction of 3 with Ni(OAc)2(H2O)4 yielded a mixture of crude products with the previously reported trans-[cis-Mo(CO)4(PPh2NHCH2CH2NCH(o-C6H4)O)2]Ni being the only product successfully isolated. The cis product was formed due to facile trans–cis isomerization during the coordination of the Ni(II) to 3. To gain more insight into such isomerizations, the trans–cis isomerizations of 2 and 3 have been followed by 31P{1H} NMR spectroscopy. The reactions follow reversible first order kinetics and appear to display intramolecular mechanisms due to the lack of carbonyl substitutions of the phosphinamidite ligands when the isomerizations are performed under CO atmospheres. Eyring analyses performed on the two complexes show that they have nearly identical activation energies (2: ΔH = 10 ± 2 kJ mol−1, ΔS = 39 ± 5 J mol−1 K−1; 3: ΔH = 11 ± 2 kJ mol−1, ΔS = 41 ± 7 J mol−1 K−1).

Catalytic conversion of nitrogen to ammonia by an iron model complex

The reduction of N2 to NH3 is a requisite transformation for life.1 While it is widely appreciated that the iron-rich cofactors of nitrogenase enzymes facilitate this transformation,2-5 how they do so remains poorly understood. A central element of debate has been the exact site(s) of nitrogen coordination and reduction.6,7 The synthetic inorganic community placed an early emphasis on Mo8, because Mo was thought to be an essential element of nitrogenases3 and because pioneering work by Chatt and coworkers established that well-defined Mo model complexes could mediate the stoichiometric conversion of N2 to NH3.9 This chemical transformation can be performed in a catalytic fashion by two well-defined molecular systems that feature Mo centres.10,11 However, it is now thought that Fe is the only transition metal essential to all nitrogenases,3 and recent biochemical and spectroscopic data has implicated Fe instead of Mo as the site of N2 binding in the FeMo-cofactor.12 In this work, we describe a tris(phosphine)borane-supported Fe complex that catalyzes the reduction of N2 to NH3 under mild conditions, wherein >40% of the H+/e- equivalents are delivered to N2. Our results indicate that a single Fe site may be capable of stabilizing the various NxHy intermediates generated en route to catalytic NH3 formation. Geometric tunability at Fe imparted by a flexible Fe-B interaction in our model system appears to be important for efficient catalysis.13-15 We propose that the interstitial light C-atom recently assigned in the nitrogenase cofactor may play a similar role,16,17 perhaps by enabling a single Fe site to mediate the enzymatic catalysis via a flexible Fe-C interaction.18

3,4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a potent inhibitor of xanthine oxidase: A potential therapeutic agent for treatment of hyperuricemia and gout

Hyperuricemia, excess of uric acid in the blood, is a clinical problem that causes gout and is also considered a risk factor for cardiovascular disease. The enzyme xanthine oxidase (XO) produces uric acid during the purine metabolism; therefore, discovering novel XO inhibitors is an important strategy to develop an effective therapy for hyperuricemia and gout. We found that 3,4-dihydroxy-5-nitrobenzaldehyde (DHNB), a derivative of the natural substance protocatechuic aldehyde, potently inhibited XO activity with an IC50 value of 3μM. DHNB inhibited XO activity in a time-dependent manner, which was similar to that of allopurinol, a clinical XO inhibitory drug. DHNB displayed potent mixed-type inhibition of the activity of XO, and showed an additive effect with allopurinol at the low concentration. Structure–activity relationship studies of DHNB indicated that the aldehyde moiety, the catechol moiety, and nitration at C-5 were required for XO inhibition. DHNB interacted with the molybdenum center of XO and was slowly converted to its carboxylic acid at a rate of 10−10mol/L/s. In addition, DHNB directly scavenged free radical DPPH and ROS, including ONOO− and HOCl. DHNB effectively reduced serum uric acid levels in allantoxanamide-induced hyperuricemic mice. Furthermore, mice orally given a large dose (500mg/kg) of DHNB did not show any side effects, while 42% of allopurinol (500mg/kg)-treated mice died and their offspring lost their fur. Thus, DHNB could be an outstanding candidate for a novel XO inhibitory drug that has potent activity and low toxicity, as well as antioxidant activity and a distinct chemical structure from allopurinol.

Deoxygenation of Mono-oxo Bis(dithiolene) Mo and W Complexes by Protonation

Protonation-assisted deoxygenation of a mono-oxo molybdenum center has been observed in many oxotransferases when the enzyme removes an oxo group to regenerate a substrate binding site. Such a reaction is reported here with discrete synthetic mono-oxo bis(dithiolene) molybdenum and tungsten complexes, the chemistry of which had been rarely studied because of the instability of the resulting deoxygenated products. An addition of tosylic acid to an acetonitrile solution of [Mo(IV)O(S2C2Ph2)2](2-) (1) and [W(IV)O(S2C2Ph2)2](2-) (2) results in the loss of oxide with a concomitant formation of novel deoxygenated complexes, [M(MeCN)2(S2C2Ph2)2] (M = Mo (3), W (4)), that have been isolated and characterized. Whereas protonation of 1 exclusively produces 3, two different reaction products can be generated from 2; an oxidized product, [WO(S2C2Ph2)2](-), is produced with 1 equiv of acid while a deoxygenated product, [W(MeCN)2(S2C2Ph2)2] (4), is generated with an excess amount of proton. Alternatively, complexes 3 and 4 can be obtained from photolysis of [Mo(CO)2(S2C2Ph2)2] (5) and [W(CO)2(S2C2Ph2)2] (6) in acetonitrile. A di- and a monosubstituted adducts of 3, [Mo(CO)2(S2C2Ph2)2] (5) and [Mo(PPh3)(MeCN)(S2C2Ph2)2] (7) are also reported.

Probing the role of a conserved salt bridge in the intramolecular electron transfer kinetics of human sulfite oxidase

Sulfite oxidase (SO) is a vital metabolic enzyme that catalyzes the oxidation of toxic sulfite to sulfate. The proposed mechanism of this molybdenum cofactor dependent enzyme involves two one-electron intramolecular electron transfer (IET) steps from the molybdenum center to the iron of the b 5-type heme and two one-electron intermolecular electron transfer steps from the heme to cytochrome c. This work focuses on how the electrostatic interaction between two conserved amino acid residues, R472 and D342, in human SO (hSO) affects catalysis. The hSO variants R472M, R472Q, R472K, R472D, and D342K were created to probe the effect of the position of the salt bridge charges, along with the interaction between these two residues. With the exception of R472K, these variants all showed a significant decrease in their IET rate constants, k et, relative to wild-type hSO, indicating that the salt bridge between residues 472 and 342 is important for rapid IET. Surprisingly, however, except for R472K and R472D, all of the variants show k cat values higher than their corresponding k et values. The turnover number for R472D is about the same as k et, which suggests that the change in this variant is rate-limiting in catalysis. Direct spectroelectrochemical determination of the Fe(III/II) reduction potentials of the heme and calculation of the Mo(VI/V) potentials revealed that all of the variants affected the redox potentials of both metal centers, probably due to changes in their environments. Thus, the position of the positive charge of R472 and that of the negative charge of D342 are both important in hSO, and changing either the position or the nature of these charges perturbs IET and catalysis.

Dioxidomolybdenum(VI) Complexes Containing Ligands with the Bipyrrolidine Backbone as Efficient Catalysts for Olefin Epoxidation

AbstractAir‐stable chiral dioxidomolybdenum(VI) complexes of the type [MoO2(L)] (L = L12–; 1, L = L22–, 2) were prepared by the reaction of [MoO2Cl2] with the bis(phenol) ligands 1,4‐bis(2‐hydroxy‐benzyl)‐(S,S)‐2,2′‐bipyrrolidine [(S,S)‐H2L1] and 1,4‐bis(2‐hydroxy‐3,5‐di‐tert‐butylbenzyl)‐(S,S)‐2,2′‐bipyrrolidine [(S,S)‐H2L2). They were characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and single‐crystal X‐ray diffraction analysis, which revealed a distorted octahedral coordination geometry around the molybdenum(VI) center with a cis‐α configuration. The Mo–Ooxo bond lengths are almost equal and vary only between 1.701 and 1.7091 Å. Complexes 1 and 2 were found to be efficient and selective catalysts for various olefin epoxidation reactions. Catalyst loadings of 0.5 mol‐%, the use of 2 equiv. of oxidant (tert‐butyl hydroperoxide), as well as unchanged catalyst performance over three consecutive catalytic runs demonstrate the excellent stability of the catalysts. Various challenging substrates including 1‐octene or limonene were converted selectively to their corresponding epoxides. However, no asymmetric induction was observed.

Synthesis and electrochemical characterisation of Molybdenum(VI) complexes of disalicylaldehyde malonoyl-dihydrazone

Molybdenum(VI) complexes composition [(μ2-O)2(MoO2)2(H4L)2]⋅2A (where H4L=H4slmh; A=H2O (1), pyridine (py, 2), 2-picoline (2-pic, 3), 3-picoline (3-pic, 4), 4-picoline (4-pic, 5)) have been isolated in solid state from the reaction of MoO2(acac)2 and disalicylaldehyde malonoyldihydrazone in 1:1M ratio in ethanol at higher temperature. The complexes have been synthesised and characterised by various physiochemical and spectroscopic studies. The structure of the molybdenum(VI) of all complexes has been established by elemental analyses, electronic, IR, 1H NMR and CV spectral studies. The dihydrazone is coordinated to the metal centres in keto enol form in all the complexes (1)–(5). The electronic spectra of the complexes are dominated by strong charge transfer bands. All of the complexes involve six coordinated molybdenum centre with octahedral arrangement of donor atoms.

Synthesis and Characterization of Hydrido Carbonyl Molybdenum and Tungsten PNP Pincer Complexes.

In the present study the Mo(0) and W(0) complexes [M(PNP)(CO)3] as well as seven-coordinate cationic hydridocarbonyl Mo(II) and W(II) complexes of the type [M(PNP)(CO)3H]+, featuring PNP pincer ligands based on 2,6-diaminopyridine, have been prepared and fully characterized. The synthesis of Mo(0) complexes [Mo(PNP)(CO)3] was accomplished by treatment of [Mo(CO)3(CH3CN)3] with the respective PNP ligands. The analogous W(0) complexes were prepared by reduction of the bromocarbonyl complexes [W(PNP)(CO)3Br]+ with NaHg. These intermediates were obtained from the known dinuclear complex [W(CO)4(μ-Br)Br]2, prepared in situ from W(CO)6 and stoichiometric amounts of Br2. Addition of HBF4 to [M(PNP)(CO)3] resulted in clean protonation at the molybdenum and tungsten centers to generate the Mo(II) and W(II) hydride complexes [M(PNP)(CO)3H]+. The protonation is fully reversible, and upon addition of NEt3 as base the Mo(0) and W(0) complexes [M(PNP)(CO)3] are regenerated quantitatively. All heptacoordinate complexes exhibit fluxional behavior in solution. The mechanism of the dynamic process of the hydrido carbonyl complexes was investigated by means of DFT calculations, revealing that it occurs in a single step. The structures of representative complexes were determined by X-ray single-crystal analyses.

Biochemical Characterization of Molybdenum Cofactor-free Nitrate Reductase from Neurospora crassa

Nitrate reductase (NR) is a complex molybdenum cofactor (Moco)-dependent homodimeric metalloenzyme that is vitally important for autotrophic organism as it catalyzes the first and rate-limiting step of nitrate assimilation. Beside Moco, eukaryotic NR also binds FAD and heme as additional redox active cofactors, and these are involved in electron transfer from NAD(P)H to the enzyme molybdenum center where reduction of nitrate to nitrite takes place. We report the first biochemical characterization of a Moco-free eukaryotic NR from the fungus Neurospora crassa, documenting that Moco is necessary and sufficient to induce dimer formation. The molybdenum center of NR reconstituted in vitro from apo-NR and Moco showed an EPR spectrum identical to holo-NR. Analysis of mutants unable to bind heme or FAD revealed that insertion of Moco into NR occurs independent from the insertion of any other NR redox cofactor. Furthermore, we showed that at least in vitro the active site formation of NR is an autonomous process.

DFT+U Investigation of Propene Oxidation over Bismuth Molybdate: Active Sites, Reaction Intermediates, and the Role of Bismuth

The mechanism by which propene is selectively oxidized to acrolein over bismuth molybdate has been investigated using the DFT+U variant of density functional theory. In agreement with experiment, the kinetically relevant step is found to be the initial abstraction of hydrogen by lattice oxygen. Several candidate lattice oxygen sites have been examined, the most active of which is found to be a bismuth-perturbed molybdenyl Mo═O oxygen. Hydrogen abstraction generates an allyl radical intermediate, which can diffuse freely across the catalyst surface and ultimately binds to a second molybdenyl oxygen to form an allyl alkoxy intermediate. A second hydrogen is abstracted from this intermediate to produce acrolein. Calculations suggest that only molybdenum centers are reduced during the reaction. However, presence of bismuth in the catalyst is essential for providing the requisite structural and electronic environment at the active site.

Oxo–Mo(IV)(dithiolene)thiolato Complexes: Analogue of Reduced Sulfite Oxidase

A series of [Mo(IV)O(mnt)(SR)(N-N)](-) (mnt = maleonitriledithiolate; R = Ph, nap, p-Cl-Ph, p-CO2H-Ph, and p-NO2-Ph; N-N = 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen)) complexes analogous to the reduced active site of enzymes of the sulfite oxidase family has been synthesized and their participation in electron transfer reactions studied. Equatorial thiolate and dithiolene ligations have been used to closely simulate the three sulfur coordinations present in the native molybdenum active site. These synthetic analogues have been shown to participate in electron transfer via a pentavalent EPR-active Mo(V) intermediate with minimal structural change as observed electrochemically by reversible oxidative responses. The role of the redox-active dithiolene ligand as an electron transfer gate between external oxidants and the molybdenum center could be envisaged in one of the analogue systems where the initial transient EPR signal with <g> = 2.008 is replaced by the appearance of a typical Mo(V)-centered EPR (<g> = 1.976) signal. The appearance of such a ligand-based transient radical at the initial stage has been supported by the ligand-centered frontier orbital from DFT calculation. A stepwise rationale has been provided by computational study to show that the coupled effects of the diimine bite angle and the thiolato dihedral angle determine the metal- or ligand-based frontier orbital occupancy. DFT calculation has further supported the similarity between the reduced, semireduced, and oxidized resting state of the molybdenum center in Moco of SO with the synthesized complexes and their corresponding one-electron and fully oxidized species.

Poly[bis{μ2-4-[3,5-bis(pyridin-4-yl)phenyl]pyridine}nona-μ2-oxido-tetraoxidocopper(II)tetramolybdenum(VI)

The title compound, [CuMo(4)O(13)(C(21)H(15)N(3))(2)](n), was synthesized by the reaction of ammonium molybdate, copper acetate and 4-[3,5-bis(pyridin-4-yl)phenyl]pyridine (DPPP) in an aqueous medium under hydrothermal conditions. The two unique molybdenum centers and the copper center adopt MoO(4) tetrahedral, MoO(5)N octahedral and CuO(4)N(2) octahedral geometries, respectively. These polyhedra are connected to each other through corner-sharing to form a two-dimensional Cu-Mo-O layer, which is further linked by the DPPP ligands to form the three-dimensional inorganic-organic hybrid framework.

Interaction between Anions and Molybdenum Allyl Dicarbonyl Complexes of 1,4,7-Trithiacyclononane

The labile complex [MoCl(η(3)-methallyl)(CO)(2)(NCMe)(2)] reacts with the ligand 1,4,7-trithiacyclononane ([9]aneS(3)) and the salt NaBAr'(4) to afford [Mo(η(3)-methallyl)(CO)(2)([9]aneS(3))][BAr'(4)] (1⋅BAr'(4)). An analogous reaction of [MoBr(η(3)-allyl)(CO)(2)(NCMe)(2)] yields [Mo(η(3)-allyl)(CO)(2)([9]aneS(3))][BAr'(4)] (2⋅BAr'(4)). The new compounds 1⋅BAr'(4) and 2⋅BAr'(4) were characterized by IR and NMR spectroscopic analysis and X-ray diffraction studies. Both compounds feature the cyclic thioether [9]aneS(3) coordinated as a tridentate ligand to the molybdenum center. The allyl ligand in 2⋅BAr'(4) is aligned with the middle of the OC-Mo-CO angle, which is acute. Both of these features are typical of most pseudo-octahedral allyl dicarbonyl molybdenum complexes. In contrast, the allyl group is rotated in 1⋅BAr'(4), which is attributed to steric hindrance between the methyl substituent and the ligated thioether, and the OC-Mo-CO angle is obtuse. Compound 1⋅BAr'(4) undergoes rapid substitution of [9]aneS(3) by either chloride and fluoride ions in dichloromethane, and the products include the known species [{Mo(η(3)-methallyl)(CO)(2)}(2)(μ-Cl)(3)](-) and a structurally similar new anionic complex with two fluoro and one hydroxo bridging ligands, respectively. Stable supramolecular adducts were formed in the reactions of 1⋅BAr'(4) and 2⋅BAr(4) with bromide, iodide, hydrogensulfate, and methanesulfonate compounds. The binding constants of these adducts in dichloromethane were calculated from (1)H NMR spectroscopic titration data, and the solid-state structures of the 1⋅Br, 1⋅HSO(4), 1⋅I, and 2⋅I adducts were determined by X-ray diffraction studies. The surprising slightly higher stability of the iodide adduct relative to that of bromide was investigated theoretically, with the results pointing to an effect of the differential solvation of the halide ions.

A Theoretical Investigation on the Oxidation of Carbon Monoxide by an Aqueous Molybdocene

Density functional calculations have been performed to rationalize the oxidation of carbon monoxide by [Cp2Mo(OH)(OH2)]+ (Cp = η5-C5H5) to give carbon dioxide and [Cp2MoH(CO)]+. Our results show that the intramolecular nucleophilic mechanism is the most favored both in the gas phase and in water solution, which is in good agreement with experimental results. The rearrangement that takes place during the nucleophilic hydroxide attack with a simultaneous hydrogen migration to the molybdenum center is the rate-determining step in the gas phase with a Gibbs energy barrier of 48.7 kcal mol–1. In water medium, however, this combined process takes place separately and passes through a new [Cp2Mo(COOH)]+-type intermediate. The inclusion of one explicit water molecule in the continuum solvent model computations plays a crucial role to make the nucleophilic hydroxide attack the rate-determining step in the overall reactive process with a Gibbs energy barrier in solution of 21.2 kcal mol–1. Besides this, our results have allowed us to rationalize the relatively low conversion of [Cp2Mo(OH)(OH2)]+ that was experimentally found.