Synthesis and structures of bis(dithiolene)molybdenum complexes related to the active sites of the DMSO reductase enzyme family

Structural analogues of the reduced (Mo(IV)) sites of members of the DMSO reductase family of molybdoenzymes are sought. These sites usually contain two pterin-dithiolene cofactor ligands and one protein-based ligand. Reaction of [Mo(MeCN)3(CO)3] and [Ni(S2C2R2)2] affords the trigonal prismatic complexes [Mo(CO)2(S2C2R2)2] (R = Me (1), Ph (2)), which by carbonyl substitution serve as useful precursors to a variety of bis(dithiolene)molybdenum-(IV,V) complexes. Reaction of 1 with Et4NOH yields [MoO(S2C2Me2)2]2- (3), which is readily oxidized to [MoO(S2C2Me2)2]1- (4). The hindered arene oxide ligands ArO- afford the square pyramidal complexes [Mo(OAr)(S2C2R2)2]1- (5, 6). The ligands PhQ- affordthe trigonal prismatic monocarbonyls [Mo(CO)(QPh)(S2C2Me2)2]1- (Q = S (8), Se (12)) while the bulky ligand ArS- forms square pyramidal [Mo(SAr)(S2C2R2)2]- (9, 10). In contrast, reactions with ArSe- result in [Mo(CO)(SeAr)(S2C2R2)2]1-(14, 15), which have not been successfully decarbonylated. Other compounds prepared by substitution reactions of 1 and 2 include the bridged dimers [Mo2(mu-Q)2(S2C2Me2)4]2- (Q = S (7), Se (11)) and [Mo2(mu-SePh)2(S2C2Ph2)4]2- (13). The complexes 1, 3-5, 7-10, 12-14, [Mo(S2C2Me2)3] (16), and [Mo(S2C2Me2)3]1- (17) were characterized by X-ray structure determinations. Certain complexes approach the binding arrangements in at least one DMSO reductase (5/6) and its Ser/Cys mutant, and in dissimilatory nitrate reductases (9/10). This investigation provides the initial demonstration of the new types of bis(dithiolene)molybdenum(IV) complexes available through [Mo(CO)2(S2C2R2)2] precursors, some of which will be utilized in reactivity studies. (Ar = 2,6-diisopropylphenyl or 2,4,6-triisopropylphenyl.)     

Bis(dithiolene)molybdenum analogues relevant to the DMSO reductase enzyme family: synthesis, structures, and oxygen atom transfer reactions and kinetics.

A series of dithiolene complexes of the general type [Mo(IV)(QR')(S(2)C(2)Me(2))(2)](1)(-) has been prepared and structurally characterized as possible structural and reactivity analogues of reduced sites of the enzymes DMSOR and TMAOR (QR' = PhO(-), 2-AdO(-), Pr(i)()O(-)), dissimilatory nitrate reductase (QR' = 2-AdS(-)), and formate dehydrogenase (QR' = 2-AdSe(-)). The complexes are square pyramidal with the molybdenum atom positioned 0.74-0.80 A above the S(4) mean plane toward axial ligand QR'. In part on the basis of a recent clarification of the active site of oxidized Rhodobacter sphaeroides DMSOR (Li, H.-K.; Temple, C.; Rajagopalan, K. V.; Schindelin, H. J. Am. Chem. Soc. 2000, 122, 7673), we have adopted the minimal reaction paradigm Mo(IV) + XO right arrow over left arrow Mo(VI)O + X involving desoxo Mo(IV), monooxo Mo(VI), and substrate/product XO/X for direct oxygen atom transfer of DMSOR and TMAOR enzymes. The [Mo(OR')(S(2)C(2)Me(2))(2)](1)(-) species carry dithiolene and anionic oxygen ligands intended to simulate cofactor ligand and serinate binding in DMSOR and TMAOR catalytic sites. In systems with N-oxide and S-oxide substrates, the observed overall reaction sequence is [Mo(IV)(OR')(S(2)C(2)Me(2))(2)](1)(-) + XO --> [Mo(VI)O(OR')(S(2)C(2)Me(2))(2)](1)(-) --> [Mo(V)O(S(2)C(2)Me(2))(2)](1)(-). Direct oxo transfer in the first step has been proven by isotope labeling. The reactivity of [Mo(OPh)(S(2)C(2)Me(2))(2)](1)(-) (1) has been the most extensively studied. In second-order reactions, 1 reduces DMSO and (CH(2))(4)SO (k(2) approximately 10(-)(6), 10(-)(4) M(-)(1) s(-)(1); DeltaS(double dagger) = -36, -39 eu) and Me(3)NO (k(2) = 200 M(-)(1) s(-)(1); DeltaS(double dagger) = -21 eu) in acetonitrile at 298 K. Activation entropies indicate an associative transition state, which from relative rates and substrate properties is inferred to be concerted with X-O bond weakening and Mo-O bond making. The Mo(VI)O product in the first step, such as [Mo(VI)O(OR')(S(2)C(2)Me(2))(2)](1)(-), is an intermediate in the overall reaction sequence, inasmuch as it is too unstable to isolate and decays by an internal redox process to a Mo(V)O product, liberating an equimolar quantity of phenol. This research affords the first analogue reaction systems of biological N-oxide and S-oxide substrates that are based on desoxo Mo(IV) complexes with biologically relevant coordination. Oxo-transfer reactions in analogue systems are substantially slower than enzyme systems based on a k(cat)/K(M) criterion. An interpretation of this behavior requires more information on the rate-limiting step(s) in enzyme catalytic cycles. (2-Ad = 2-adamantyl, DMSOR = dimethyl sulfoxide reductase, TMAOR = trimethylamine N-oxide reductase)     

Comparative kinetics and mechanism of oxygen and sulfur atom transfer reactions mediated by bis(dithiolene) complexes of molybdenum and tungsten

Although the kinetics and mechanism of metal-mediated oxygen atom (oxo) transfer reactions have been examined in some detail, sulfur atom (sulfido) transfer reactions have not been similarly scrutinized. The reactions [M(IV)(O-p-C(6)H(4)X')(S(2)C(2)Me(2))(2)](1-) + Ph(3)AsQ --> [M(VI)Q(O-p-C(6)H(4)X')(S(2)C(2)Me(2))(2)](1-) + Ph(3)As (M = Mo, W; Q = O, S) with variable substituent X' have been investigated in acetonitrile in order to determine the relative rates of oxo versus sulfido transfer at constant structure (square pyramidal) of the atom acceptor and of atom transfer at constant structure of the atom donor and metal variability of the atom acceptor. All reactions exhibit second-order kinetics and entropies of activation (-25 to -45 eu) consistent with an associative transition state. At parity of atom acceptor, k(2)(S) (0.25-0.75 M(-1)s(-1)) > k(2)(O) (0.023-0.060 M(-1)s(-1)) with M = Mo and k(2)(S) (4.1-66.7 M(-1)s(-1)) > k(2)(O) (1.8-9.8 M(-1)s(-1)) with M = W. At constant atom donor and X', k(2)(W) > k(2)(Mo) with reactivity ratios k(2)(W)/k(2)(Mo) = 78-184 (Q = O) and 16-89 (Q = S). Rate constants refer to 298 K. At constant M and Q, rates increase in the order X' = Me less, similar OMe < H < Br < COMe < CN; increasing electron-withdrawing propensity accelerates reaction rates. The probable transition state involves significant Ph(3)AsQ...M bond-making (X' rate trend) and concomitant As-Q bond weakening (bond energy order As-O > As-S). Orders of oxo and sulfido donor ability of substrates and complexes are deduced on the basis of qualitative reactivity properties determined here and elsewhere. This work complements previous studies of the reaction systems [M(IV)(O-p-C(6)H(4)X')(S(2)C(2)Me(2))(2)](1-)/XO where the substrates are N-oxides and S-oxides and k(2)(W) > k(2)(Mo) at constant substrate also applies. The reaction order of substrates is Me(3)NO > (CH(2))(4)SO > Ph(3)AsS > Ph(3)AsO. This research provides the first quantitative information of metal-mediated sulfido transfer.     

Functional analogue reaction systems of the DMSO reductase isoenzyme family: probable mechanism of S-oxide reduction in oxo transfer reactions mediated by bis(dithiolene)-tungsten(IV,VI) complexes

The recent development of structural and functional analogues of the DMSO reductase family of isoenzymes allows mechanistic examination of the minimal oxygen atom transfer paradigm M(IV) + QO M(VI) O + Q with the biological metals M = Mo and W. Systematic variation of the electronic environment at the WIV center of desoxo bis(dithiolene) complexes is enabled by introduction of para-substituted phenyl groups in the equatorial (eq) dithiolene ligand and the axial (ax) phenolate ligand. The compounds [W(CO)2(S2C2(C6H4-p-X)2)2] (54-60%) have been prepared by ligand transfer from [Ni(S2C2(C6H4-p-X)2)2] to [W(CO)3(MeCN)3]. A series of 25 complexes [W(IV)(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- ([X4,X'], X = Br, F, H, Me, OMe; X' = CN, Br, H, Me, NH2; 41-53%) has been obtained by ligand substitution of five dicarbonyl complexes with five phenolate ligands. Linear free energy relationships between E1/2 and Hammett constant p for the electron-transfer series [Ni(S2C2(C6H4-p-X)2)2]0,1-,2- and [W(CO)2(S2C2(C6H4-p-X)2)2]0,1-,2- demonstrate a substituent influence on electron density distribution at the metal center. The reactions [WIV(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4SO [W(VI)O(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4S with constant substrate are second order with large negative activation entropies indicative of an associative transition state. Rate constants at 298 K adhere to the Hammett equations log(k([X4,X']/k[X4,H]) = rho(ax)sigma(p) and log(k[X4,X']/k([H4,X']) = 4rho(eq)sigma(p). Electron-withdrawing groups (EWG) and electron-donating groups (EDG) have opposite effects on the rate such that k(EWG) > k(EDG). The effects of X' on reactivity are found to be approximately 5 times greater than that of X (rho(ax) = 2.1, rho(eq) = 0.44) in the Hammett equation. Using these and other findings, a stepwise oxo transfer reaction pathway is proposed in which an early transition state, of primary W(IV)-O(substrate) bond-making character, is rate-limiting. This is followed by a six-coordinate substrate complex and a second transition state proposed to involve atom and electron transfer leading to the development of the W(VI)=O group. This work is the most detailed mechanistic investigation of oxo transfer mediated by a biological metal.     

Reaction systems related to dissimilatory nitrate reductase: nitrate reduction mediated by bis(dithiolene)tungsten complexes

Kinetics of the oxygen atom transfer reactions [M(IV)(QC6H2-2,4,6-Pr(i)3)(S2C2Me2)2]1- + XO --> [M(VI)O(QC6H2-2,4,6-Pr(i)3)(S2C2Me2)2]1- + X in acetonitrile with substrates XO = NO3- and (CH2)4SO have been determined. The reactants are bis(dithiolene) complexes with M = Mo, W and sterically encumbered axial ligands with Q = O, S to stabilize mononuclear square pyramidal structures. The complex [MoIV(SC6H2-2,4,6-Pr(i)3)(S2C2Me2)2]1- is an analogue of the active site of dissimilatory nitrate reductase which in the reduced state contains a molybdenum atom bound by two pyranopterindithiolene ligands and a cysteinate residue. Nitrate reduction was studied with tungsten complexes because of unfavorable stability properties of the molybdenum complexes. Product nitrite was detected by a colorimetric method. All reactions with both substrates are second-order with associative transition states (deltaS approximately -20 eu). Variation of atoms M and Q, together with data from prior work, allows certain kinetics comparisons to be made. Among them, k2W/k2Mo = 25 for (CH2)4SO reduction (Q = S), an expression of the kinetic metal effect. Further, k2S/k2O = 28 and approximately 10(4) for nitrate and (CH2)4SO reduction, respectively, effects attributed to relatively more steric congestion in achieving the transition state with hindered phenolate vs thiolate ligands. The effect is more pronounced with the larger substrate. These results demonstrate the feasibility of tungsten-mediated nitrate reduction by direct atom transfer using molecules with both axial thiolate and phenolate ligands. Complexes of the type [M(IV)(OR)(S2C2Me2)2] are capable of reducing biological N-oxide, S-oxide, and nitrate substrates and thus constitute functional analogue reaction systems of enzymic transformations.     

Synthesis and structures of bis(dithiolene)tungsten(IV,VI) thiolate and selenolate complexes: approaches to the active sites of molybdenum and tungsten formate dehydrogenases

Formate dehydrogenases are molybdenum- or tungsten-containing enzymes that catalyze the oxidation of formate to carbon dioxide. Among the significant characteristics of the mononuclear active sites are coordination of two pyranopterindithiolene ligands and selenocysteinate to the metal in oxidation states IV-VI. The first detailed investigation of the synthesis and structures of bis(dithiolene)tungsten selenolate and analogous thiolate complexes of relevance to formate dehydrogenases has been undertaken. Some 17 complexes of the types [WIV(QR)(S2C2Me2)2]-, [WVIO(QR)(S2C2Me2)2]-, and [WVIS(QR)(S2C2Me2)2]- (Q = S, Se; R = tert-butyl, 1-adamantyl) and the desoxo species [WVI(SR)(OSiR'3)(S2C2Me2)2] (R' = Me, Ph) were prepared. Ten structures of representative members of these types were determined; WIV complexes are square-pyramidal and WVI complexes are six-coordinate, with geometries intermediate between octahedral and trigonal-prismatic. Selenolate complexes are less stable than similar thiolate species; decomposition products were identified as [WV2(mu2-Q)2(S2C2Me2)2]2- and [WIV,V2(mu2-Se)(S2C2Me2)4]-. The several [MoIV(QR)(S2C2Me2)2]- complexes prepared earlier and the tungsten compounds synthesized in this work form a family of molecules whose overall stereochemistry and metric features are those expected in the absence of protein structural constraints.     

Substitution and oxidation reactions of bis(dithiolene)tungsten complexes of potential relevance to enzyme sites

Structurally characterized tungstoenzymes contain mononuclear active sites in which tungsten is coordinated by two pterin-dithiolene ligands and one or two additional ligands that have not been identified. In this and prior investigations (Sung, K.-M.; Holm, R. H. Inorg. Chem. 2000, 39, 1275; J. Am. Chem. Soc. 2001, 123, 1931), stable coordination units of bis(dithiolene)tungsten(IV,V,VI) complexes potentially related to enzyme sites have been sought by exploratory synthesis. In this work, additional members of the sets [WL(S2C2Me2)2](2-,-) and [WLL'(S2C2Me2)2](2-,-) have been prepared and structurally characterized. Tungsten(IV) complexes obtained by substitution are carbonyl displacement products of [W(CO)2(S2C2Me2)2] and include those with the groups W(IV)S (4), W(IV)(O2CPh) (5), and W(IV)(2-AdQ)(CO) (Q = S (6), Se (7); Ad = adamantyl). Those obtained by oxidation reactions contain the groups W(V)O (9), W(V)(QPh)2 (Q = S (10), Se (11)), W(VI)S(OPh) (12), and W(VI)O2 (14). The latter two complexes were obtained from W(IV) precursors using sulfur and oxygen atom transfer reactions, respectively. Complexes 4 and 9 are square pyramidal; 6, 7, 10, and 11 are distorted trigonal prismatic with cis ligands LL'; and 12 and 14 are distorted octahedral. Complexes 4, 10, and 11 support three-membered electron transfer series. Attempts to oxidize 4 to the W(V)S complex results in the formation of binuclear [W2(mu2-S)2(S2C2Me2)4](2-) having distorted octahedral coordination. The 21 known functional groups WL and WLL' in mononuclear bis(dithiolene) complexes prepared in this and prior investigations are tabulated. Of those with physiological-type ligands, it remains to be seen which (if any) of these ligation modes are displayed by enzyme sites.     

Synthesis, structure and redox properties of bis(cyclopentadienyl)dithiolene complexes of molybdenum and tungsten

The compounds [Cp(2)M(S(2)C(2)(H)R)] (M = Mo or W; R = phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl or quinoxalin-2-yl) and [Cp(2)Mo(S(2)C(2)(Me)(pyridin-2-yl)] have been prepared by a facile and general route for the synthesis of dithiolene complexes, viz. the reaction of [Cp(2)MCl(2)] (M = Mo or W) with the dithiolene pro-ligand generated by reacting the corresponding 4-(R)-1,3-dithiol-2-one with CsOH. These Mo compounds were reported previously (Hsu et al., Inorg. Chem. 1996, 35, 4743); however, the preparative method employed herein is more versatile and generates the compounds in good yield and all of the W compounds are new. Electrochemical investigations have shown that each compound undergoes a diffusion controlled one-electron oxidation (OX(I)) and a one-electron reduction (RED(I)) process; each redox change occurs at a more positive potential for a Mo compound than for its W counterpart. The mono-cations generated by chemical or electrochemical oxidation are stable and the structures of both components of the [Cp(2)Mo(S(2)C(2)(H)R)](+)/[Cp(2)Mo(S(2)C(2)(H)R)] (R = Ph or pyridin-3-yl) redox couples have been determined by X-ray crystallography. For each redox related pair, the changes in the Mo-S, S-C and C-C bond lengths of the {MoSCCS} moiety are generally consistent with OX(I) involving the loss of an electron from a π-orbital that is Mo-S and C-S antibonding and C-C bonding in character. These results have been interpreted successfully within the framework provided by DFT calculations accomplished for [Cp(2)M(S(2)C(2)(H)Ph)](n) (M = Mo or W; n = +1, 0 or -1). The HOMO of the neutral compounds is derived mainly from the dithiolene π(3) orbital (65%); therefore, OX(I) is essentially a dithiolene-based process. The similarity of the potentials for OX(I) (ca. 30 mV) for analogous Mo and W compounds is consistent with this interpretation and the EPR spectra of each of the Mo cations show that the unpaired electron is coupled to the dithiolene proton but relatively weakly to (95,97)Mo. The DFT calculations indicate that the unpaired electron is more localised on the metal in the mono-anions than in the mono-cations. In agreement with this, the EPR spectrum of each of the Mo-containing mono-anions manifests a larger (95,97)Mo coupling (A(iso)) than observed for the corresponding mono-cation and RED(I) for a W compound is significantly (ca. 300 mV) more negative than that of its Mo counterpart. [Cp(2)W(S(2)C(2)(H)(quinoxalin-2-yl))] is anomalous; RED(I) occurs at a potential ca. 230 mV more positive than expected from that of its Mo counterpart and the EPR spectrum of the mono-anion is typical of an organic radical. DFT calculations indicate that these properties arise because the electron is added to a quinoxalin-2-yl π-orbital.     

Desoxo molybdenum(IV) and tungsten(IV) bis(dithiolene) complexes: monomer-dimer interconversion involving reversible thiol bridge formation

Two series of thiol-bridged dimeric desoxo molybdenum(IV) and tungsten(IV) bis(dithiolene) complexes, [Et(4)N](2)[M(IV)(2)(SR)(2)(mnt)(4)] [M = Mo, R = (1) -Ph, (2) -CH(2)Ph, (3) -CH(2)CH(3), (4) -CH(2)CH(2)OH; M = W, R = (1a) -Ph, (2a) -CH(2)Ph, (3a) -CH(2)CH(3), (4a) -CH(2)CH(2)OH] and one monomeric desoxo complex, [Et(4)N](2)[WIV(SPh)(2)(mnt)(2)] (5a) are reported. These complexes are diamagnetic, and crystal structures of each of the complex (except 5a) exhibits a dimeric {M(IV)(2)(SR)(2)} core without any metal-metal bond where each metal atom possesses hexa coordination. The M-SR distance ranges from 2.437 to 2.484 Angstrom in molybdenum complexes and from 2.418 to 2.469 Angstrom in tungsten complexes. These complexes display Mo-S(R)-Mo angles ranging from 92.84 degrees to 96.20 degrees in the case of 1-4 and W-S(R)-W angles ranging from 91.20 degrees to 96.25 degrees in the case of 1a-4a. Interestingly, both the series of Mo(IV) and W(IV) dimeric complexes respond to an unprecedented interconversion between the dimer and the corresponding hexacoordinated monomer upon change of pH. This pH-dependent interconversion establishes the fact that even the pentacoordinated Mo(IV) and W(IV) bis(dithiolene) moieties are forced to dimerize; these can easily be reverted back to the corresponding monomeric complex, reflecting the utility of dithiolene ligand in stabilizing the Mo(IV)/W(IV) moiety in synthesized complexes similar to the active sites present in native proteins.     

A density functional study of oxygen atom transfer reactions between biological oxygen atom donors and molybdenum(IV) bis(dithiolene) complexes

Density functional calculations have been used to investigate oxygen atom transfer reactions from the biological oxygen atom donors trimethylamine N-oxide (Me(3)NO) and dimethyl sulfoxide (DMSO) to the molybdenum(IV) complexes [MoO(mnt)(2)](2-) and [Mo(OCH(3))(mnt)(2)](-) (mnt = maleonitrile-1,2-dithiolate), which may serve as models for mononuclear molybdenum enzymes of the DMSO reductase family. The reaction between [MoO(mnt)(2)](2-) and trimethylamine N-oxide was found to have an activation energy of 72 kJ/mol and proceed via a transition state (TS) with distorted octahedral geometry, where the Me(3)NO is bound through the oxygen to the molybdenum atom and the N-O bond is considerably weakened. The computational modeling of the reactions between dimethyl sulfoxide (DMSO) and [MoO(mnt)(2)](2-) or [Mo(OCH(3))(mnt)(2)](-) indicated that the former is energetically unfavorable while the latter was found to be favorable. The addition of a methyl group to [MoO(mnt)(2)](2-) to form the corresponding des-oxo complex not only lowers the relative energy of the products but also lowers the activation energy. In addition, the reaction with [Mo(OCH(3))(mnt)(2)](-) proceeds via a TS with trigonal prismatic geometry instead of the distorted octahedral TS geometry modeled for the reaction between [MoO(mnt)(2)](2-) and Me(3)NO.     

Generation of bis(dithiolene)dioxomolybdenum(VI) complexes from bis(dithiolene)monooxomolybdenum(IV) complexes by proton-coupled electron transfer in aqueous media

Electron transfer oxidation reaction of bis(dithiolene)monooxomolybdenum(iv) (Mo(IV)OL(x)) complexes is studied as a model of oxidative-half reaction of arsenite oxidase molybdenum enzymes. The reactions are revealed to involve proton-coupled electron transfer. Electrochemical oxidation of Mo(IV)OL(x) yields the corresponding bis(dithiolene)dioxomolybdenum(vi) complexes in basic solution, where the conversion of Mo(IV)OL(dmed) supported by a smaller electron donating dithiolene ligand (1,2-dicarbomethoxyethylene-1,2-dithiolate, L(dmed)) to Mo(VI)O(2)L(dmed) is faster than that of Mo(IV)OL(bdt) with a larger electron donating dithiolene ligand (1,2-benzenedithiolate, L(bdt)) under the same conditions. Titration experiments for the electrochemical oxidation reveal that the reaction involves two-electron oxidation and two equivalents of OH(-) consumption per Mo(IV)OL(x). In the conversion process of Mo(IV)OL(x) to Mo(VI)O(2)L(x), the five-coordinate bis(dithiolene)monooxomolybdenum(v) complex (Mo(V)OL(x)) being a one-electron oxidized species of Mo(IV)OL(x) is suggested to react with OH(-). Mo(V)OL(x) reacts with OH(-) in CH(3)CN or C(2)H(5)CN in a 2?:?2 ratio to give one equivalent Mo(IV)OL(x) and one equivalent Mo(VI)O(2)L(x), which is confirmed by the UV-vis and IR spectroscopies. The low temperature stopped-flow analysis allows investigations of the mechanism for the reaction of Mo(V)OL(x) with OH(-). The kinetic study for the reaction of Mo(V)OL(dmed) with OH(-) suggests that Mo(V)OL(dmed) reacts with OH(-) to give a six-coordinate oxo-hydroxo-molybdenum(v) species, Mo(V)O(OH), and, then, the resulting species undergoes successive deprotonation by another OH(-) and oxidation by a remaining Mo(V)OL(dmed) to yield the final products Mo(IV)OL(dmed) and Mo(VI)O(2)L(dmed) complexes in a 1?:?1 ratio. In this case, the Mo(V)O(2) species are involved as an intermediate in the reaction. On the other hand, in the reaction of Mo(V)OL(bdt) with OH(-), coordination of OH(-) to the Mo(V) centre to give a six-coordinate Mo(V)O(OH)L(bdt) species becomes the rate limiting step and other intermediates are not suggested. On the basis of these results, the ligand effects of the dithiolene ligands on the reactivity of the bis(dithiolene)molybdenum complexes are discussed.     

X-ray spectroscopy of enzyme active site analogues and related molecules: bis(dithiolene)molybdenum(IV) and -tungsten(IV,VI) complexes with variant terminal ligands

The X-ray absorption spectra at the molybdenum and selenium K-edges and the tungsten L2,3-edges are acquired for a set of 14 Mo(IV) and W(IV,VI) bis(dithiolene) complexes related to the active sites of molybdo- and tungstoenzymes. The set includes square pyramidal [MoIVL(S2C2Me2)2]- (L = O2-, R3SiO-, RO-, RS-, RSe-) and [WIV(OR)(S2C2Me2)2]-, distorted trigonal prismatic [MoIV(CO)(SeR)(S2C2Me2)2]- and [WIV(CO)L(S2C2Me2)2]- (L = RS-, RSe-), and distorted octahedral [WVIO(OR)(S2C2Me2)2]-. The dithiolene simulates the pterin-dithiolene cofactor ligand, and L represents a protein ligand. Bond lengths are determined by EXAFS analysis using the GNXAS protocol. Normalized edge spectra, non-phase-shift-corrected Fourier transforms, and EXAFS data and fits are presented. Bond lengths determined by EXAFS and X-ray crystallography agree to < or = 0.02 A as do the M-Se distances determined by both metal and selenium EXAFS. The complexes [MoIV(QR)(S2C2Me2)2]- simulate protein ligation by the DMSO reductase family of enzymes, including DMSO reductase itself (Q = O), dissimilatory nitrate reductase (Q = S), and formate dehydrogenase (Q = Se). Edge shifts of these complexes correlate with the ligand electronegativities. Terminal ligand binding is clearly distinguished in the presence of four Mo-S(dithiolene) interactions. Similarly, five-coordinate [ML(S2C2Me2)2]- and six-coordinate [M(CO)L(S2C2Me2)2]- are distinguishable by edge and EXAFS spectra. This study expands a previous XAS investigation of bis(dithiolene)metal(IV,V,VI) complexes (Musgrave, K. B.; Donahue, J. P.; Lorber, C.; Holm, R. H.; Hedman, B.; Hodgson, K. O. J. Am. Chem. Soc. 1999, 121, 10297) by including a larger inventory of molecules with variant physiologically relevant terminal ligation. The previous and present XAS results should prove useful in characterizing and refining metric features and structures of enzyme sites.     

Synthesis and structures of bis(dithiolene)-tungsten(IV) complexes related to the active sites of tungstoenzymes

Recent protein crystallographic results on tungsten enzymes and primary sequence relationships between certain molybdenum and tungsten enzymes provoke interest in the generalized bis(dithiolene) complexes [WIV(QR)(S2C2R'2)2]1- and [WVIO(QR)(S2C2R'2)2]1- (Q = O, S, Se) as minimal representations of enzyme sites. The existence and stability of W(IV) complexes have been explored by synthesis. Reaction of [W(CO)2(S2C2Me2)2] (1) with PhO- results in complete CO substitution to give [W(OPh)(S2C2Me2)2]1- (2). Reaction of 1 with PhQ- affords the monocarbonyls [W(CO)(QPh)(S2C2Me2)2]1- (Q = S (3), Se (5)). The use of sterically demanding 2,4,6-Pri3C6H2Q- also yields monocarbonyls, [W(CO)(QC6H2-2,4,6-Pri3)(S2C2Me2)2]1- (Q = S (4), Se (6)). The X-ray structures of square pyramidal 2 and trigonal prismatic 3-6 (with unidentate ligands cis) are described. The tendency to substitute one or both carbonyl ligands in 1 in the formation of [MIV(QAr)(S2C2Me2)2]1- and [MIV(CO)(QAr)(SeC2Me2)2]1- with M = Mo and W is related to the M-Q bond length and ligand steric demands. The results demonstrate a stronger binding of CO by W(IV) than Mo(IV), a behavior previously demonstrated by thermodynamic and kinetic features of zerovalent carbonyl complexes. Complexes 3-6 can be reversibly reduced to W(III) at approximately -1.5 V versus SCE. On the basis of the potential for 2(-2.07 V), monocarbonyl ligation stabilizes W(III) by approximately 500 mV. This work is part of a parallel investigation of the chemistry of bis(dithiolene)-molybdenum (Lim, B. S.; Donahue, J. P.; Holm, R. H. Inorg. Chem. 2000, 39, 263) and -tungsten complexes related to enzyme active sites.     

A bis(η-cyclopentadienyl)cobalt complex of a bis-dithiolene: a chemical analogue of the metal centres of the DMSO reductase family of molybdenum and tungsten enzymes, in particular ferredoxin aldehyde oxidoreductase

The synthesis is described of a bis-ene-1,2-dithiolate pro-ligand, designed to model the stereochemical situation in the cofactor of the tungsten enzyme ferredoxin aldehyde oxidoreductase from Pyrococcus furiosus. Each masked ene-1,2-dithiolate unit is mounted on a pyrano[2,3-b]tetrahydroquinoxaline tricycle, comparable to the pyrano[2,3-g]tetrahydropteridines found in all molybdoenzymes and tungsten analogues. Hydrolytic release of the bis-ligand was confirmed by its entrapment as a double (η⁵-C₅H₅)Co complex.     

Synthesis and reactivity of molybdenum and tungsten bis(dinitrogen) complexes supported by diphosphine chelates containing pendant amines

Molybdenum and tungsten bis(dinitrogen) complexes of the formula M(N(2))(2)(PNP)(2) (M = Mo and W) and W(N(2))(2)(dppe)(PNP), supported by diphosphine ligands containing a pendant amine of the formula (CH(2)PR(2))(2)NR' = P(R)N(R')P(R) (R = Et, Ph; R' = Me, Bn), have been prepared by Mg reduction of metal halides under an N(2) atmosphere. The complexes have been characterized by NMR and IR spectroscopy, X-ray crystallography, and cyclic voltammetry. Reactivity of the target Mo and W bis(dinitrogen) compounds with CO results in the formation of dicarbonyl complexes.     

An expanded set of functional groups in bis(dithiolene)tungsten(IV,VI) complexes related to the active sites of tungstoenzymes, Including WIV-SR and WVI-O(SR)

The active sites of tungstoenzymes have the formulations W(IV,V)L(S(2)pd)(2) and W(VI)LL'(S(2)pd)(2), in which two pyranopterindithiolene cofactor ligands (S(2)pd) are chelated to a tungsten atom. Ligands L and/or L' are not fully defined in any wild-type enzyme. The feasibility of various coordination fragments (functional groups) in potential bis(dithiolene)tungsten site analogues has been examined in previous work by exploratory synthesis. This investigation expands the range of accessible functional groups. The synthetic scheme originates with [W(CO)(2)(S(2)C(2)Me(2))(2)], whose carbonyl groups are labile to substitution. Complexes [W(IV,VI)LL'(S(2)C(2)Me(2))(2)](1-) are described in terms of their functional groups W(IV,VI)LL'. Reaction of the dicarbonyl with formate in acetonitrile/THF affords W(IV)(CO)(eta(1)-HCO(2)) (4) and in Me(2)SO W(VI)O(eta(1)-HCO(2)) (7) by an oxo transfer reaction. Carboxylates yield six-coordinate W(IV)(eta(2)-O(2)CR) (1-3, R = Ph, Me, Bu(t)) with C(2)(v) symmetry. Reaction of 3 (R = Bu(t)) with Me(3)SiSR (R = C(6)H(2)-2,4,6-Pr(i)(3)) gives W(IV)(SR) (5), which undergoes oxo and sulfido atom transfer to form W(VI)O(SR) (8) and W(VI)S(SR) (9), respectively. Attempts to prepare corresponding selenolate complexes, pertinent to the active site of formate dehydrogenase, were unsuccessful, including reactions of W(VI)OCl (10) with RSe(-). Structure proofs of 2-10 were obtained by X-ray structure determinations. Some 26 functional group types in bis(dithiolene)W(IV,V,VI) molecules have now been achieved by synthesis. It remains to be seen which are incorporated in an enzyme site. A number of them (e.g., 5) are directly analogous to molybdoenzyme sites, and may possess corresponding reactivity with biological substrates, as do W(IV)(OR)/W(VI)O(OR) (prepared earlier) in the reduction of N- and S-oxides by atom transfer.     

In situ generation of oxo-sulfidobis(dithiolene)tungsten(VI) complexes: active-site models for the aldehyde ferredoxin oxidoreductase family of tungsten enzymes

Oxo-sulfidobis(dithiolene)tungsten(VI) complexes were prepared in situ by the reaction of oxobis(dithiolene)tungsten(V) precursors with hydrosulfide (SH-). The complexes, characterized by UV-vis, electrospray ionization mass spectrometry, IR, and resonance Raman spectroscopies, model the proposed coordination environment and observed hydrolytic reactions of members of the aldehyde ferredoxin oxidoreductase family of tungsten enzymes.     

New oxovanadium bis(1,2-dithiolate) compounds that mimic the hydrogen-bonding interactions at the active sites of mononuclear molybdenum enzymes

Reaction of VO(acac)(2) with 1,2-dithiols in the presence of triethylamine gives pentacoordinate oxovanadium complexes [HNEt(3)](2)[VO(bdt)(2)] (1), [HNEt(3)](2)[VO(tdt)(2)] (2), and [HNEt(3)](2)[VO(bdtCl(2))(2)] (3) (where H(2)bdt = 1,2-benzenedithiol, H(2)tdt = 3,4-toluenedithiol, and H(2)bdtCl(2) = 3,6-dichloro-1,2-benzenedithiol). Compounds 1-3 have been characterized by IR, UV/visible, EPR, and mass spectroscopies. The X-ray crystal stuctures of 1 and 2 show hydrogen-bonding interactions between the terminal oxo atom and triethylammonium counterions and between ligand sulfur atoms and the counterions. These interactions are comparable with those found at the active sites of mononuclear molybdenum enzymes.     

Metathesis polymerization of norbornene and terminal acetylenes catalyzed by bis(acetonitrile) complexes of molybdenum and tungsten

The ring-opening metathesis polymerization (ROMP) of norbornene catalyzed by bis(acetonitrile) molybdenum and tungsten complexes, [M(η³-C₃H₅)Cl(CO)₂(NCMe)₂] (1-Mo: M = Mo, 1-W: M = W), which have two labile acetonitrile ligands, has been investigated. These complexes catalyzed the ROMP of norbornene as a single-component initiator. The highly cis-selective polymerization proceeded in a THF solution (95% for 1-Mo and 96% for 1-W), whereas polymerization in CH₂Cl₂ or toluene resulted in lower cis selectivity. The polymerization of terminal acetylenes using these complexes was also examined. The tungsten complex 1-W showed a high catalytic activity for the polymerization of terminal acetylenes, such as phenyl- and tert-butylacetylene. A highly active catalytic system for the ROMP of norbornene was achieved by the activation of the tungsten complex, 1-W, with one equivalent of phenylacetylene, giving poly(norbornene) with a high molecular weight (M_n = 391 × 10⁴) and a high cis selectivity (cis  89%).     

Synthesis of the active sites of molybdoenzymes: MoO2(VI) and MoO(IV)-dithiolene complexes mimicking enzymatic reactions of sulphite oxidase with saturation kinetics

[Mo^VIO₂(S₂C₂(CN)₂)₂]₂₋ (┘1) and [Mo^IVO(S₂C₂(CN)₂)₂]²⁻ (2) mimick oxidoreductase enzymatic activities of sulphite oxidase with biological electron donor, SO ₃ ²⁻ , andin vitro electron acceptor, [Fe(CN)₆]³⁻, demonstrating proton coupled electron transfer reaction in water and inhibition of the oxidation of (2) in the presence of KCN. The sulphite exidizing system is characterized by substrate saturation kinetics indicating the biological significance of the reactions