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.     

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.     

Oxo/sulfidotungstate(VI) as precursors to W(VI)O2, W(VI)OS, and W(VI)S2 complexes and W(IV)-dithiolene chelate rings

Synthetic models leading to oxosulfidotungsten(VI) groups and dithiolene chelate rings have been investigated. The heterogeneous reaction systems [WO4-nSn]2-/2Ph3SiCl/Me4phen (n = 0-2) in acetonitrile afford the complexes [WQ2(OSiPh3)2(Me4phen)] (1-3) in the indicated yields containing the groups W(VI)O2 (1; 86%), W(VI)O2 (2; 45%), and W(VI)S2 (3; 83%). In the crystalline state these complexes have imposed C2 symmetry, with cis-oxo/sulfido and trans-silyloxide ligands. 1H NMR spectra indicate that this stereochemistry is retained in solution. The colors of 2 (yellow, 367 nm) and 3 (orange, 451 nm) arise from LMCT absorptions at the indicated wavelengths. These results demonstrate that the silylation procedure previously introduced for the preparation of molecules with the Mo(VI)OS group (Thapper, et al. Inorg. Chem. 1999, 38, 4104) extends to tungsten. Methods for the formation of dithiolene chelate rings MS2C2R2 in reactions with sulfide-bound M = Mo or W precursors are summarized. In a known reaction type, 3 and activated acetylenes rapidly form [W(IV)(OSiPh3)2(Me4phen)(S2C2R2)] (R = CO2Me, 4, 83%, and Ph, 5, 98%). In a new reaction type not requiring the isolation of an intermediate, the systems [MO2S2]2-/2Ph3SiCl/Me4phen/PhC=CPh in acetonitrile afford 5 (68%) and [Mo(IV)(OSiPh3)2(Me4phen)(S2C2Ph2)] (6; 61%). Complexes 5 and 6 are isostructural, maintain the trans-silyloxide stereochemistry, and exhibit chelate ring dimensions indicative of ene- 1,2-dithiolate coordination. Reductions in the -1.4 to -1.7 V range are described as metal-centered. It remains to be seen whether the oxo/sulfidotungsten(VI) groups in 1-3 eventuate in the active sites of tungstoenzymes. (Me4phen = 3,4,7,8-tetramethyl-1,10-phenanthroline.)     

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.     

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)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.)     

Analogue reaction systems of selenate reductase

Analogue reaction systems of selenate reductase, which reduces substrate in the overall enzymatic reaction SeO4(2-) + 2H+ + 2e- --> SeO3(2-) + H2O, have been developed using bis(dithiolene) complexes of Mo(IV) and W(IV). On the basis of the results of EXAFS analysis of the oxidized and reduced enzyme, the minimal reaction Mo(IV)OH + SeO4(2-) --> Mo(VI)O(OH) + SeO3(2-) is probable. The square pyramidal complexes [M(OMe)(S2C2Me2)2](1-) (M = Mo, W) were prepared as structural analogues of the reduced enzyme site. The systems, [ML(S2C2Me2)2](1-)/SeO4(2-) (L = OMe, OPh, SC6H2-2,4,6-Pr(i)3) in acetonitrile, cleanly reduce selenate to selenite in second-order reactions whose negative entropies of activation implicate associative transition states. Rate constants at 298 K are in the 10(-2)-10(-4) M(-1) s(-1) range with DeltaS++ = -12 to -34 eu. When rate constants are compared with previous data for the reduction of (CH2)4SO, Ph3AsO, and nitrate by oxygen atom transfer, reactivity trends dependent on the metal, axial ligand L, and substrate are identified. As in all other cases of substrate reduction by oxo transfer, the kinetic metal effect k(2)W > k(2)Mo holds. A proposal from primary sequence alignments suggesting that a conserved Asp residue is a likely ligand in the type II enzymes in the DMSO reductase family has been pursued by synthesis of the [Mo(IV)(O2CR)(S2C2Me2)2](1-) (R = Ph, Bu(t)) complexes. The species display symmetrical eta2-carboxylate binding and distorted trigonal prismatic stereochemistry. They serve as possible structural analogues of the reduced sites of nitrate, selenate, and perchlorate reductases under the proposed aspartate coordination. Carboxylate binding has been crystallographically demonstrated for one nitrate reductase, but not for the other two enzymes.     

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)     

A new class of sulfido/oxo(dithiolene)-molybdenum(IV) complexes derived from sulfido/oxo-bis(tetrasulfido)molybdenum(IV) anions

Mono(dithiolene)sulfidomolybdenum(IV) complexes, [MoS(S4)(bdt)](2-) (2) and [MoS(S4)(bdtCl2)](2-) (3) (1,2-benzenedithiolate = bdt, 3,6-dichloro-1,2-benzenedithiolate = bdtCl2), were prepared by the substitution reaction of a tetrasulfido ligand in known [MoS(S4)2](2-) (1) with the corresponding dithiol. Complexes 2 and 3 were irreversibly oxidized to give bis(mu-sulfido) dimolybdenum(V) species, {[MoS(bdt)]2(mu-S)2}(2-) (4) and {[MoS(bdtCl2)]2(mu-S)2}(2-) (5), in aerobic acetonitrile. Mono(dithiolene)oxomolybdenum(IV) complexes, [MoO(S4)(bdt)](2-) (7) and [MoO(S4)(bdtCl2)](2-) (8), that are oxo derivatives of 2 and 3 were also synthesized from a known [MoO(S4)2](2-) (6) of an oxo derivative of 1 and the corresponding dithiol. Further, the electrophilic addition of dimethyl acetylenedicarboxylate to 7 gave [MoO(bdt)(S2C2(COOMe)2)](2-) (9), and ligand substitution of the tetrasulfido group of 7 with bdt and bdtCl2 yielded [MoO(bdt)2](2-) ( 10) and [MoO(bdt)(bdtCl2)](2-) (11), respectively. New sulfido/oxo molybdenum complexes were characterized by (1)H NMR, IR, ESI-MS, Raman, and UV-vis spectroscopies; cyclic voltammetry; and elemental analysis, and crystal structures of 2, 3, 5, 7, and 8 were determined by X-ray analysis.     

Monodithiolene molybdenum(V, VI) complexes: a structural analogue of the oxidized active site of the sulfite oxidase enzyme family

The active sites of the xanthine oxidase and sulfite oxidase enzyme families contain one pterin-dithiolene cofactor ligand bound to a molybdenum atom. Consequently, monodithiolene molybdenum complexes have been sought by exploratory synthesis for structural and reactivity studies. Reaction of [MoO(S(2)C(2)Me(2))(2)](1-) or [MoO(bdt)(2)](1-) with PhSeCl results in removal of one dithiolate ligand and formation of [MoOCl(2)(S(2)C(2)Me(2))](1-) (1) or [MoOCl(2)(bdt)](1-) (2), which undergoes ligand substitution reactions to form other monodithiolene complexes [MoO(2-AdS)(2)(S(2)C(2)Me(2))](1-) (3), [MoO(SR)(2)(bdt)](1-) (R = 2-Ad (4), 2,4,6-Pr(i)(3)C(6)H(2) (5)), and [MoOCl(SC(6)H(2)-2,4,6-Pr(i)(3))(bdt)](1-) (6) (Ad = 2-adamantyl, bdt = benzene-1,2-dithiolate). These complexes have square pyramidal structures with apical oxo ligands, exhibit rhombic EPR spectra, and 3-5 are electrochemically reducible to Mo(IV)O species. Complexes 1-6 constitute the first examples of five-coordinate monodithiolene Mo(V)O complexes; 6 approaches the proposed structure of the high-pH form of sulfite oxidase. Treatment of [MoO(2)(OSiPh(3))(2)] with Li(2)(bdt) in THF affords [MoO(2)(OSiPh(3))(bdt)](1-) (8). Reaction of 8 with 2,4,6-Pr(i)(3)C(6)H(2)SH in acetonitrile gives [MoO(2)(SC(6)H(2)-2,4,6-Pr(i)(3))(bdt)](1-) (9, 55%). Complexes 8 and 9 are square pyramidal with apical and basal oxo ligands. With one dithiolene and one thiolate ligand of a square pyramidal Mo(VI)O(2)S(3) coordination unit, 9 closely resembles the oxidized sites in sulfite oxidase and assimilatory nitrate reductase as deduced from crystallography (sulfite oxidase) and Mo EXAFS. The complex is the first structural analogue of the active sites in fully oxidized members of the sulfite oxidase family. This work provides a starting point for the development of both structural and reactivity analogues of members of this family.     

Oxo transfer reactions mediated by bis(dithiolene)tungsten analogues of the active sites of molybdoenzymes in the DMSO reductase family: comparative reactivity of tungsten and molybdenum.

The discovery of tungsten enzymes and molybdenum/tungsten isoenzymes, in which the mononuclear catalytic sites contain a metal chelated by one or two pterin-dithiolene cofactor ligands, has lent new significance to tungsten-dithiolene chemistry. Reaction of [W(CO)(2)(S(2)C(2)Me(2))(2)] with RO(-) affords a series of square pyramidal desoxo complexes [W(IV)(OR')(S(2)C(2)Me(2))(2)](1)(-), including R' = Ph (1) and Pr(i)() (3). Reaction of 1 and 3 with Me(3)NO gives the cis-octahedral complexes [W(VI)O(OR')(S(2)C(2)Me(2))(2)](1)(-), including R' = Ph (6) and Pr(i)() (8). These W(IV,VI) complexes are considered unconstrained versions of protein-bound sites of DMSOR and TMAOR (DMSOR = dimethylsulfoxide reductase, TMAOR = trimethylamine N-oxide reductase) members of the title enzyme family. The structure of 6 and the catalytic center of one DMSO reductase isoenzyme have similar overall stereochemistry and comparable bond lengths. The minimal oxo transfer reaction paradigm thought to apply to enzymes, W(IV) + XO --> W(VI)O + X, has been investigated. Direct oxo transfer was demonstrated by isotope transfer from Ph(2)Se(18)O. Complex 1 reacts cleanly and completely with various substrates XO to afford 6 and product X in second-order reactions with associative transition states. The substrate reactivity order with 1 is Me(3)NO > Ph(3)AsO > pyO (pyridine N-oxide) > R(2)SO > Ph(3)PO. For reaction of 3 with Me(3)NO, k(2) = 0.93 M(-)(1) s(-)(1), and for 1 with Me(2)SO, k(2) = 3.9 x 10(-)(5) M(-)(1) s(-)(1); other rate constants and activation parameters are reported. These results demonstrate that bis(dithiolene)W(IV) complexes are competent to reduce both N-oxides and S-oxides; DMSORs reduce both substrate types, but TMAORs are reported to reduce only N-oxides. Comparison of k(cat)/K(M) data for isoenzymes and k(2) values for isostructural analogue complexes reveals that catalytic and stoichiometric oxo transfer, respectively, from substrate to metal is faster with tungsten and from metal to substrate is faster with molybdenum. These results constitute a kinetic metal effect in direct oxo transfer reactions for analogue complexes and for isoenzymes provided the catalytic sites are isostructural. The nature of the transition state in oxo transfer reactions of analogues is tentatively considered. This research presents the first kinetics study of substrate reduction via oxo transfer mediated by bis(dithiolene)tungsten complexes.     

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.     

Synthesis and characterisation of second-generation metallodithiolene complexes of the type [Tp*ME(dithiolene)](M=Mo, W; E=O, S) and a novel 'organoscorpionate' complex of tungsten

Paramagnetic, chalcogenido-M(v) dithiolene complexes, [Tp*ME{S2C2(CO2Me)2}][M=Mo, E=O, S; M=W, E=O, S; Tp*=hydrotris(3,5-dimethylpyrazol-1-yl)borate] are generated in the reactions of dimethyl acetylenedicarboxylate (DMAC) and the sulfur-rich complexes NEt4[Tp*MoS(S4)] and NEt4[Tp*WS3]; the oxo complexes result from hydrolysis of the initial sulfido products. As well, a novel 'organoscorpionate' complex, [W{S2C2(CO2Me)2}{SC2(CO2Me)2-Tp*}], has been isolated from the reactions of NEt4[Tp*WS3] with excess DMAC. Complexes , and have been isolated and characterised by microanalytical, mass spectrometric, spectroscopic and (for and) X-ray crystallographic techniques. Complexes and have been partially characterised by mass spectrometry and IR and EPR spectroscopy. Six-coordinate, distorted-octahedral contains a terminal sulfido ligand (W=S=2.108(3)A), a bidentate dithiolene ligand (S-Cav=1.758 A, C=C=1.332(10)A) and a fac-tridentate Tp* ligand. Seven-coordinate contains a planar, bidentate dithiolene ligand (S-Cav=1.746 A, C=C=1.359(5)A) and a novel pentadentate 'organoscorpionate' ligand formed by the melding of DMAC, sulfido and trispyrazolylborate units. The latter is coordinated through two pyrazolyl N atoms (kappa2-N,N') and a tridentate kappa3-S,C,C' unit appended to N-beta of the third (uncoordinated) pyrazolyl group. The second-generation [Tp*ME(dithiolene)] complexes represent a refinement on first-generation [Tp*ME(arene-1,2-dithiolate)] complexes and their synthesis affords an opportunity to compare and contrast the electronic structures of true vs. pseudo-dithiolene ligands in otherwise analogous complexes.     

Oxygen/sulfur substitution reactions of tetraoxometalates effected by electrophilic carbon and silicon reagents

Reactions of [MO(4)](2)(-) (M = Mo, W) with certain carbon and silicon electrophiles were investigated in acetonitrile in order to produce species of potential utility in the synthesis of analogues of the sites in the xanthine oxidoreductase enzyme family. Silylation of [MoO(4)](2)(-) affords [MoO(3)(OSiPh(3))](1)(-), which with Ph(3)SiSH is converted to [MoO(2)S(OSiPh(3))](1)(-). Reaction with (Ph(3)C)(PF(6))/HS(-) yields the tetrahedral monosulfido species [MO(3)S](2)(-), previously obtained only from the aqueous system [MO(4)](2)(-)/H(2)S. Dithiolene chelate rings are readily introduced upon reaction with 1,2-C(6)H(4)(SSiMe(3))(2), leading to the square pyramidal trioxo complexes [MO(3)(bdt)](2)(-), a previously unknown dithiolene molecular type. Further ring insertion occurs upon reaction of [WO(3)(bdt)](2)(-) with 1,2-C(6)H(4)(SSiMe(3))(2), giving [WO(2)(bdt)(2)](2)(-). Related reactions occur with [ReO(4)](1)(-). Treatment with 1 equiv of (Me(3)Si)(2)S produces [ReO(3)S](1)(-); with 3 equiv of 1,2-C(6)H(4)(SSiMe(3))(2), [ReO(bdt)(2)](1)(-) is obtained with concomitant Re(VII) --> Re(V) reduction. X-ray structures are reported for [MO(3)S](z)(-) (M = Mo, W, z = 2; M = Re, z = 1), [MO(3)(bdt)](2)(-), and [WO(2)(OSiPh(3))(bdt)](1)(-), a silylation product of [WO(3)(bdt)](2)(-). [MoO(3)(bdt)](2)(-) is related to the site of inactive sulfite oxidase, and [WO(2)(OSiPh(3))(bdt)](1)(-) should closely approximate the metric features of the [(dithiolene)MoO(2)(OH)] site in inactive aldehyde/xanthine oxidoreductase. This work provides convenient syntheses of known and new derivatives of tetraoxometalates, among which is entry to a unique class of oxo-monodithiolene complexes.     

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.     

1,1-ethylenedithiolato complexes of palladium(II) and platinum(II) with isocyanide and carbene ligands

The reactions of [Tl(2)[S(2)C=C[C(O)Me](2)]](n) with [MCl(2)(NCPh)(2)] and CNR (1:1:2) give complexes [M[eta(2)-S(2)C=C[C(O)Me](2)](CNR)(2)] [R = (t)Bu, M = Pd (1a), Pt (1b); R = C(6)H(3)Me(2)-2,6 (Xy), M = Pd (2a), Pt (2b)]. Compound 1b reacts with AgClO(4) (1:1) to give [[Pt(CN(t)Bu)(2)](2)Ag(2)[mu(2),eta(2)-(S,S')-[S(2)C=C[C(O)Me](2)](2)]](ClO(4))(2) (3). The reactions of 1 or 2 with diethylamine give mixed isocyanide carbene complexes [M[eta(2)-S(2)C=C[C(O)Me](2)](CNR)[C(NEt(2))(NHR)]] [R = (t)Bu, M = Pd (4a), Pt (4b); R = Xy, M = Pd (5a), Pt (5b)] regardless of the molar ratio of the reagents. The same complexes react with an excess of ammonia to give [M[eta(2)-(S,S')-S(2)C=C[C(O)Me](2)](CN(t)Bu)[C(NH(2))(NH(t)Bu)]] [M = Pd (6a), Pt (6b)] or [M[eta(2)-(S,S')-S(2)C=C[C(O)Me](2)][C(NH(2))(NHXy)](2)] [M = Pd (7a), Pt (7b)] probably depending on steric factors. The crystal structures of 2b, 4a, and 4b have been determined. Compounds 4a and 4b are isostructural. They all display distorted square planar metal environments and chelating planar E,Z-2,2-diacetyl-1,1-ethylenedithiolato ligands that coordinate through the sulfur atoms.     

Monoanionic molybdenum and tungsten tris(dithiolene) complexes: a multifrequency EPR study

Numerous Mo and W tris(dithiolene) complexes in varying redox states have been prepared and representative examples characterized crystallographically: [M(S(2)C(2)R(2))(3)](z) [M = Mo, R = Ph, z = 0 (1) or 1- (2); M = W, R = Ph, z = 0 (4) or 1- (5); R = CN, z = 2-, M = Mo (3) or W (6)]. Changes in dithiolene C-S and C-C bond lengths for 1 versus 2 and 4 versus 5 are indicative of ligand reduction. Trigonal twist angles (Θ) and dithiolene fold angles (α) increase and decrease, respectively, for 2 versus 1, 5 versus 4. Cyclic voltammetry reveals generally two reversible couples corresponding to 0/1- and 1-/2- reductions. The electronic structures of monoanionic molybdenum tris(dithiolene) complexes have been analyzed by multifrequency (S-, X-, Q-band) EPR spectroscopy. Spin-Hamiltonian parameters afforded by spectral simulation for each complex demonstrate the existence of two distinctive electronic structure types. The first is [Mo(IV)((A)L(3)(5-?))](1-) ((A)L = olefinic dithiolene, type A), which has the unpaired electron restricted to the tris(dithiolene) unit and is characterized by isotropic g-values and small molybdenum superhyperfine coupling. The second is formulated as [Mo(V)((B)L(3)(6-))](1-) ((B)L = aromatic dithiolene, type B) with spectra distinguished by a prominent g-anisotropy and hyperfine coupling consistent with the (d(z(2)))(1) paramagnet. The electronic structure disparity is also manifested in their electronic absorption spectra. The compound [W(bdt)(3)](1-) exhibits spin-Hamiltonian parameters similar to those of [Mo(bdt)(3)](1-) and thus is formulated as [W(V)((B)L(3)(6-))](1-). The EPR spectra of [W((A)L(3))](1-) display spin-Hamiltonian parameters that suggest their electronic structure is best represented by two resonance forms {[W(IV)((A)L(3)(5-?))](1-) ? [W(V)((A)L(3)(6-))](1-)}. The contrast with the corresponding [Mo(IV)((A)L(3)(5-?))](1-) complexes highlights tungsten's preference for higher oxidation states.     

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.     

Metal vs ligand reduction in complexes of dipyrido[3,2-a:2',3'-c]phenazine and related ligands with [(C5Me5)ClM]+ (M = Rh or Ir): evidence for potential rather than orbital control in the reductive cleavage of the metal-chloride bond

Complexes between the chlorometal(III) cations [(C5Me5)ClM]+, M = Rh or Ir, and the 1,10-phenanthroline-derived alpha-diimine (N--N) ligands dipyrido[3,2-a:2',3'-c]phenazine (dppz), 1,4,7,10-tetraazaphenanthrene (tap), or 1,10-phenanthroline-5,6-dione (pdo) were investigated by cyclic voltammetry, EPR, and UV-vis-NIR spectroelectrochemistry with respect to either ligand-based or metal-centered (and then chloride-dissociative) reduction. Two low-lying unoccupied molecular orbitals (MOs) are present in each of these three N wedge N ligands; however, their different energies and interface properties are responsible for different results. Metal-centered chloride-releasing reduction was observed for complexes of the DNA-intercalation ligands dppz and tap to yield compounds [(N--N)(C5Me5)M] in a two-electron step. The separation of alpha-diimine centered optical orbitals and phenazine-based redox orbitals is apparent from the EPR and UV-vis-NIR spectroelectrochemistry of [(dppz)(C5Me5)M](0/*-/2-). In contrast, the pdo complexes undergo a reversible one-electron reduction to yield o-semiquinone radical complexes [(pdo)(C5Me5)ClM]* before releasing the chloride after the second electron uptake. The fact that the dppz complexes undergo a Cl(-)-dissociative two-electron reduction despite the presence of a lowest lying pi* MO (b1(phz)) with very little overlap to the metal suggests that an unoccupied metal/chloride-based orbital is lower in energy. This assertion is confirmed both by the half-wave reduction potentials of the ligands (tap, -1.95 V; dppz, -1.60 V; pdo, -0.85 V) and by the typical reduction peak potentials of the complexes [(L)(C5Me5)ClM](PF6) (tap, -1.1 V; dppz, -1.3 V; pdo, -0.6 V; all values against Fc(+/0)).     

Dioxo-molybdenum(VI) and mono-oxo-molybdenum(IV) complexes supported by new aliphatic dithiolene ligands: new models with weakened Mo=O bond characters for the arsenite oxidase active site

The cis-dioxo-molybdenum(VI) complexes, [MoO2(L(H))2]2- (1b), [MoO2(L(S))(2)]2- (2b), and [MoO2(L(O))2]2- (3b) (L(H) = cyclohexene-1,2-dithiolate, L(S) = 2,3-dihydro-2H-thiopyran-4,5-dithiolate, and L(O) = 2,3-dihydro-2H-pyran-4,5-dithiolate), with new aliphatic dithiolene ligands were prepared and investigated by infrared (IR) and UV-vis spectroscopic and electrochemical methods. The mono-oxo-molybdenum(IV) complexes, [MoO(L(H))2]2- (1a), [MoO(L(S))2]2- (2a), and [MoO(L(O))2]2- (3a), were further characterized by X-ray crystal structural determinations. The IR and resonance Raman spectroscopic studies suggested that these cis-dioxo molybdenum(VI) complexes (1b-3b) had weaker Mo=O bonds than the common Mo(VI)O2 complexes. Complexes 1b-3b also exhibited strong absorption bands in the visible regions assigned as charge-transfer bands from the dithiolene ligands to the cis-MoO2 cores. Because the oxygen atoms of the cis-Mo(VI)O2 cores are relatively nucleophilic, these complexes were unstable in protic solvents and protonation might occur to produce Mo(VI)O(OH), as observed with the oxidized state of arsenite oxidase.