Coordination of methyl coenzyme M and coenzyme M at divalent and trivalent nickel cyclams: model studies of methyl coenzyme M reductase active site

Divalent and trivalent nickel complexes of 1,4,8,11-tetraazacyclotetradecane, denoted as cyclam hereafter, coordinated by methyl coenzyme M (MeSCoM(-)) and coenzyme M (HSCoM(-)) have been synthesized in the course our model studies of methyl coenzyme M reductase (MCR). The divalent nickel complexes Ni(cyclam)(RSCoM)(2) (R = Me, H) have two trans-disposed RSCoM(-) ligands at the nickel(II) center as sulfonates, and thus, the nickels have an octahedral coordination. The SCoM(2-) adduct Ni(cyclam)(SCoM) was also synthesized, in which the SCoM(2-) ligand chelates the nickel via the thiolate sulfur and a sulfonate oxygen. The trivalent MeSCoM adduct [Ni(cyclam)(MeSCoM)(2)](OTf) was synthesized by treatment of [Ni(cyclam)(NCCH(3))(2)](OTf)(3) with ((n)Bu(4)N)[MeSCoM]. A similar reaction with ((n)Bu(4)N)[HSCoM] did not afford the corresponding trivalent HSCoM(-) adduct, but rather the divalent nickel complex polymer [-Ni(II)(cyclam)(CoMSSCoM)-](n) was obtained, in which the terminal thiol of HSCoM(-) was oxidized to the disulfide (CoMSSCoM)(2-) by the Ni(III) center.     

Carboxylate coordination chemistry of a mononuclear Ni(II) center in a hydrophobic or hydrogen bond donor secondary environment: relevance to acireductone dioxygenase

A series of Ni(II) carboxylate complexes, supported by a chelate ligand having either secondary hydrophobic phenyl groups (6-Ph2TPA, N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine) or hydrogen bond donors (bnpapa, N,N-bis((6-neopentylamino-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine), have been prepared and characterized. X-ray crystallographic studies of [(6-Ph2TPA)Ni(O2C(CH2)2SCH3)]ClO4.CH2Cl2 (4.CH2Cl2) and [(6-Ph2TPA)Ni(O2CCH2SCH3)]ClO(4).1.5CH2Cl2 (5.1.5CH2Cl2) revealed that each complex contains a distorted octahedral Ni(II) center and a bidentate carboxylate ligand. A previously described benzoate complex ([(6-Ph2TPA)Ni(O2CPh)]ClO4 (3)) has similar structural characteristics. Recrystallization of dry powdered samples of 3, 4.0.5CH2Cl2, and 5 from wet organic solvents yielded a second series of crystalline Ni(II) carboxylate complexes having a coordinated monodentate carboxylate ligand ([(6-Ph2TPA)Ni(H2O)(O2CPh)]ClO4 (6), [(6-Ph2TPA)Ni(H2O)(O2C(CH2)2SCH3)]ClO4.0.2CH2Cl2 (7.0.2CH2Cl2), [(6-Ph2TPA)Ni(H2O)(O2CCH2SCH3)]ClO4 (8)) which is stabilized by a hydrogen-bonding interaction with a Ni(II)-bound water molecule. In the cationic portions of 7.0.2CH2Cl2 and 8, weak CH/pi interactions are also present between the methylene units of the carboxylate ligands and the phenyl appendages of the 6-Ph2TPA ligands. A formate complex of the formulation [(6-Ph2TPA)Ni(H2O)(O2CH)]ClO4 (9) was isolated and characterized. The mononuclear Ni(II) carboxylate complexes [(bnpapa)Ni(O2CPh)]ClO4 (10), [(bnpapa)Ni(O2C(CH2)2SCH3)]ClO4 (11), [(bnpapa)Ni(O2CCH2SCH3)]ClO4 (12), and [(bnpapa)Ni(O2CH)]ClO4 (13) were isolated and characterized. Two crystalline solvate forms of 10 (10.CH3CN and 10.CH2Cl2) were examined by X-ray crystallography. In both, the distorted octahedral Ni(II) center is ligated by a bidentate benzoate ligand, one Ni(II)-bound oxygen atom of which accepts two hydrogen bonds from the supporting bnpapa chelate ligand. Spectroscopic studies of 10(-13) suggest that all contain a bidentate carboxylate ligand, even after exposure to water. The combined results of this work enable the formulation of a proposed pathway for carboxylate product release from the active site Ni(II) center in acireductone dioxygenase.     

On the mechanism of methyl-coenzyme M reductase

Methyl-coenzyme M reductase (MCR) catalyzes the reaction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterodisulfide CoM-S-S-CoB. This unique reaction proceeds under strictly anaerobic conditions in the presence of coenzyme F430, a Ni-porphinoid. MCR is a large (alphabetagamma)2 heterohexameric protein complex containing two 50 A long active sites channels. Coenzyme F430 is embedded at the channel bottom and the substrates CH3-SCoM and HS-CoB bind in front of F430 into a solvent free and hydrophobic channel segment. Two principally different catalytic mechanisms are currently discussed. Mechanism I is based on a nucleophilic attack of Ni(I) onto the methyl group of CH3-SCoM yielding methyl-Ni(III) and mechanism II on an attack of Ni(I) onto the thioether sulfur of CH3-SCoM generating a Ni(II)-SCoM intermediate. Both mechanisms are discussed in the light of a large number of data collected about MCR over the last twenty years.     

A nickel hydride complex in the active site of methyl-coenzyme m reductase: implications for the catalytic cycle

Methanogenic archaea utilize a specific pathway in their metabolism, converting C1 substrates (i.e., CO2) or acetate to methane and thereby providing energy for the cell. Methyl-coenzyme M reductase (MCR) catalyzes the key step in the process, namely methyl-coenzyme M (CH3-S-CoM) plus coenzyme B (HS-CoB) to methane and CoM-S-S-CoB. The active site of MCR contains the nickel porphinoid F430. We report here on the coordinated ligands of the two paramagnetic MCR red2 states, induced when HS-CoM (a reversible competitive inhibitor) and the second substrate HS-CoB or its analogue CH3-S-CoB are added to the enzyme in the active MCR red1 state (Ni(I)F430). Continuous wave and pulse EPR spectroscopy are used to show that the MCR red2a state exhibits a very large proton hyperfine interaction with principal values A((1)H) = [-43,-42,-5] MHz and thus represents formally a Ni(III)F430 hydride complex formed by oxidative addition to Ni(I). In view of the known ability of nickel hydrides to activate methane, and the growing body of evidence for the involvement of MCR in "reverse" methanogenesis (anaerobic oxidation of methane), we believe that the nickel hydride complex reported here could play a key role in helping to understand both the mechanism of "reverse" and "forward" methanogenesis.     

Synthesis of an unprecedented bicapped adamantoid [Cu6(mu2-I)(mu3-I)4(mu4-I)(m-tolyl3P)4(CH3CN)2] cluster

The reaction of copper(I) iodide with tri-m-tolylphosphine (m-tolyl(3)P) in acetonitrile yielded the cluster [Cu(6)(mu2-I)(mu3-I)4(mu4-I)(m-tolyl(3)P)4(CH(3)CN)2] (1), with a bicapped adamantoid geometry. In this compound, four Cu atoms are coordinated to four terminally bonded m-tolyl(3)P ligands, two Cu atoms are bonded to two CH(3)CN ligands, and iodide ligands have mu2-I, mu3-I, and mu4-I bonding modes. This compound has four CuI(3)P and two CuI(3)N cores, and geometry around each Cu center is distorted tetrahedral.The polarizable iodide ligand and the position of the methyl group in the phenyl ring attached to the P atom appear to have played the pivotal role in the formation of monomeric bicapped adamantoid geometry, which is unique in copper chemistry.     

X-ray absorption and resonance Raman studies of methyl-coenzyme M reductase indicating that ligand exchange and macrocycle reduction accompany reductive activation

Methyl-coenzyme M reductase (MCR) catalyzes methane formation from methyl-coenzyme M (methyl-SCoM) and N-7-mercaptoheptanoylthreonine phosphate (CoBSH). MCR contains a nickel hydrocorphin cofactor at its active site, called cofactor F(430). Here we present evidence that the macrocyclic ligand participates in the redox chemistry involved in catalysis. The active form of MCR, the red1 state, is generated by reducing another spectroscopically distinct form called ox1 with titanium(III) citrate. Previous electron paramagnetic resonance (EPR) and (14)N electron nuclear double resonance (ENDOR) studies indicate that both the ox1 and red1 states are best described as formally Ni(I) species on the basis of the character of the orbital containing the spin in the two EPR-active species. Herein, X-ray absorption spectroscopic (XAS) and resonance Raman (RR) studies are reported for the inactive (EPR-silent) forms and the red1 and ox1 states of MCR. RR spectra are also reported for isolated cofactor F(430) in the reduced, resting, and oxidized states; selected RR data are reported for the (15)N and (64)Ni isotopomers of the cofactor, both in the intact enzyme and in solution. Small Ni K-edge energy shifts indicate that minimal electron density changes occur at the Ni center during redox cycling of the enzyme. Titrations with Ti(III) indicate a 3-electron reduction of free cofactor F(430) to generate a stable Ni(I) state and a 2-electron reduction of Ni(I)-ox1 to Ni(I)-red1. Analyses of the XANES and EXAFS data reveal that both the ox1 and red1 forms are best described as hexacoordinate and that the main difference between ox1 and red1 is the absence of an axial thiolate ligand in the red1 state. The RR data indicate that cofactor F(430) undergoes a significant conformational change when it binds to MCR. Furthermore, the vibrational characteristics of the ox1 state and red1 states are significantly different, especially in hydrocorphin ring modes with appreciable C=N stretching character. It is proposed that these differences arise from a 2-electron reduction of the hydrocorphin ring upon conversion to the red1 form. Presumably, the ring-reduction and ligand-exchange reactions reported herein underlie the enhanced activity of MCR(red1), the only form of MCR that can react productively with the methyl group of methyl-SCoM.     

New flexible synthesis of pyrazoles with different,functionalized substituents at C3 and C5

Syntheses of pyrazoles featuring a functionalized side chain attached to carbon 3 and varying alkyl and aryl substituents attached to carbon 5 are presented. Installation of R = methyl, isopropyl, tert-butyl, adamantyl, or phenyl groups at C5 is reported here, starting by coupling protected alkynols with acid chlorides RCOCl, forming alkynyl ketones, which are reacted with hydrazine to form the pyrazole nucleus. Alcohol deprotection and conversion to a chloride gave 5-substituted 3-(chloromethyl)- or 3-(2-chloroethyl)pyrazoles. This sequence can be done within 2 d on a 30 g scale in excellent overall yield. Through nucleophilic substitution reactions, the chlorides are useful precursors to other polyfunctional pyrazoles. In the work here, derivatives with side chains LCH(2)- and LCH(2)CH(2)- at C3 (L = thioether or phosphine) were made as ligands. The significance of the ligands made here is that by placing a ligating side chain on a ring carbon (C3), rather than on a ring nitrogen, the ring nitrogen not bound to the metal and its attached proton will be available for hydrogen bonding, depending on the steric environment created by R at C5.     

Model studies of methyl CoM reductase: methane formation via CH3-S bond cleavage of Ni(I) tetraazacyclic complexes having intramolecular methyl sulfide pendants

The Ni(I) tetraazacycles [Ni(dmmtc)](+) and [Ni(mtc)](+), which have methylthioethyl pendants, were synthesized as models of the reduced state of the active site of methyl coenzyme M reductase (MCR), and their structures and redox properties were elucidated (dmmtc, 1,8-dimethyl-4,11-bis{(2-methylthio)ethyl}-1,4,8,11-tetraaza-1,4,8,11-cyclotetradecane; mtc, 1,8-{bis(2-methylthio)ethyl}-1,4,8,11-tetraaza-1,4,8,11-cyclotetradecane). The intramolecular CH(3)-S bond of the thioether pendant of [Ni(I)(dmmtc)](OTf) was cleaved in THF at 75 °C in the presence of the bulky thiol DmpSH, which acts as a proton source, and methane was formed in 31% yield and a Ni(II) thiolate complex was concomitantly obtained (Dmp = 2,6-dimesityphenyl). The CH(3)-S bond cleavage of [Ni(I)(mtc)](+) also proceeded similarly, but under milder conditions probably due to the lower potential of the [Ni(I)(mtc)](+) complex. These results indicate that the robust CH(3)-S bond can be homolytically cleaved by the Ni(I) center when they are properly arranged, which highlights the significance of the F430 Ni environment in the active site of the MCR protein.     

First row divalent transition metal complexes of aryl-appended tris((pyridyl)methyl)amine ligands: syntheses, structures, electrochemistry, and hydroxamate binding properties

Divalent manganese, cobalt, nickel, and zinc complexes of 6-Ph(2)TPA (N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; [(6-Ph(2)TPA)Mn(CH(3)OH)(3)](ClO(4))(2) (1), [(6-Ph(2)TPA)Co(CH(3)CN)](ClO(4))(2) (2), [(6-Ph(2)TPA)Ni(CH(3)CN)(CH(3)OH)](ClO(4))(2) (3), [(6-Ph(2)TPA)Zn(CH(3)CN)](ClO(4))(2) (4)) and 6-(Me(2)Ph)(2)TPA (N,N-bis((6-(3,5-dimethyl)phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; [(6-(Me(2)Ph)(2)TPA)Ni(CH(3)CN)(2)](ClO(4))(2) (5) and [(6-(Me(2)Ph)(2)TPA)Zn(CH(3)CN)](ClO(4))(2) (6)) have been prepared and characterized. X-ray crystallographic characterization of 1A.CH(3)()OH and 1B.2CH(3)()OH (differing solvates of 1), 2.2CH(3)()CN, 3.CH(3)()OH, 4.2CH(3)()CN, and 6.2.5CH(3)()CN revealed mononuclear cations with one to three coordinated solvent molecules. In 1A.CH(3)()OH and 1B.2CH(3)()OH, one phenyl-substituted pyridyl arm is not coordinated and forms a secondary hydrogen-bonding interaction with a manganese bound methanol molecule. In 2.2CH(3)()CN, 3.CH(3)()OH, 4.2CH(3)()CN, and 6.2.5CH(3)()CN, all pyridyl donors of the 6-Ph(2)TPA and 6-(Me(2)Ph)(2)TPA ligands are coordinated to the divalent metal center. In the cobalt, nickel, and zinc derivatives, CH/pi interactions are found between a bound acetonitrile molecule and the aryl appendages of the 6-Ph(2)TPA and 6-(Me(2)Ph)(2)TPA ligands. (1)H NMR spectra of 4 and 6 in CD(3)NO(2) solution indicate the presence of CH/pi interactions, as an upfield-shifted methyl resonance for a bound acetonitrile molecule is present. Examination of the cyclic voltammetry of 1-3 and 5 revealed no oxidative (M(II)/M(III)) couples. Admixture of equimolar amounts of 6-Ph(2)TPA, M(ClO(4))(2).6H(2)O, and Me(4)NOH.5H(2)O, followed by the addition of an equimolar amount of acetohydroxamic acid, yielded the acetohydroxamate complexes [((6-Ph(2)TPA)Mn)(2)(micro-ONHC(O)CH(3))(2)](ClO(4))(2) (8), [(6-Ph(2)TPA)Co(ONHC(O)CH(3))](ClO(4))(2) (9), [(6-Ph(2)TPA)Ni(ONHC(O)CH(3))](ClO(4))(2) (10), and [(6-Ph(2)TPA)Zn(ONHC(O)CH(3))](ClO(4))(2) (11), all of which were characterized by X-ray crystallography. The Mn(II) complex 8.0.75CH(3)()CN.0.75Et(2)()O exhibits a dinuclear structure with bridging hydroxamate ligands, whereas the Co(II), Ni(II), and Zn(II) derivatives all exhibit mononuclear six-coordinate structures with a chelating hydroxamate ligand.     

Nickel(II)-phenoxyl radical complexes: structure-radical stability relationship

Nickel(II) complexes of N3O-donor tripodal ligands, 2,4-di-tert-butyl-6-[([bis(2-pyridyl)methyl]amino)methyl]phenol (HtbuL), 2,4-di-tert-butyl-6-[([(6-methyl-2-pyridyl)methyl](2-pyridylmethyl)amino)methyl]phenol (HtbuLMepy), and 2,4-di-tert-butyl-6-[([bis(6-methyl-2-pyridyl)methyl]amino)methyl]phenol (HtbuL(Mepy)2), were prepared, and [Ni(tbuL)Cl(H2O)] (1), [Ni(tbuLMepy)Cl] (2), and [Ni(tbuL(Mepy)2)Cl] (3) were structurally characterized by the X-ray diffraction method. Complexes 1 and 3 have a mononuclear structure with a coordinated phenolate moiety, while 2 has a dinuclear structure bridged by two chloride ions. The geometry of the Ni(II) center was found to be octahedral for 1 and 2 and 5-coordinate trigonal bipyramidal for 3. Complexes 1-3 exhibited similar absorption spectra in CH3CN, indicating that they all have a mononuclear structure in solution. They were converted to the phenoxyl radicals upon oxidation with Ce(IV), giving a phenoxyl radical pi-pi transition band at 394-407 nm. ESR spectra at low temperature and resonance Raman spectra established that the radical species has a Ni(II)-phenoxyl radical bond. The cyclic voltammograms showed a quasi-reversible redox wave at E1/2=0.46-0.56 V (vs Ag/AgCl) corresponding to the formation of the phenoxyl radical, which displayed a first-order decay with a half-life of 45 min at room temperature for 1 and 26 and 5.9 min at -20 degrees C for 2 and 3, respectively. The radical stability increased with the donor ability of the N ligands.     

A mechanism from quantum chemical studies for methane formation in methanogenesis

The mechanism for methane formation in methyl-coenzyme M reductase (MCR) has been investigated using the B3LYP hybrid density functional method and chemical models consisting of 107 atoms. The experimental X-ray crystal structure of the enzyme in the inactive MCR(ox1)(-)(silent) state was used to set up the initial model structure. The calculations suggest a mechanism not previously proposed, in which the most remarkable feature is the formation of an essentially free methyl radical at the transition state. The reaction cycle suggested starts from a Michaelis complex with CoB and methyl-CoM coenzymes bound and with a squareplanar coordination of the Ni(I) center in the tetrapyrrole F(430) prosthetic group. In the rate-limiting step the methyl radical is released from methyl-CoM, induced by the attack of Ni(I) on the methyl-CoM thioether sulfur. In this step, the metal center is oxidized from Ni(I) to Ni(II). The resulting methyl radical is rapidly quenched by hydrogen-atom transfer from the CoB thiol group, yielding the methane molecule and the CoB radical. The estimated activation energy is around 20 kcal/mol, which includes a significant contribution from entropy due to the formation of the free methyl. The mechanism implies an inversion of configuration at the reactive carbon. The size of the inversion barrier is used to explain the fact that CF(3)-S-CoM is an inactive substrate. Heterodisulfide CoB-S-S-CoM formation is proposed in the final step in which nickel is reduced back to Ni(I). The suggested mechanism agrees well with experimental observations.     

Novel Ring Contraction Reaction for the Synthesis of Functionalized Tetrathiamacrocyclic Ligand Molecules

Chlorination of [14]aneS(4)-ol (1,4,8,11-tetrathiatetradecan-6-ol) and cis/trans-[14]aneS(4)-diol (cis/trans-1,4,8,11-tetrathiatetradecane-6,13-diol) yields the corresponding dichloro-substituted macrocycles [14]aneS(4)-Cl (1,4,8,11-tetrathiatetradecane 6-chloride) and cis/trans-[14]aneS(4)-Cl(2) (cis/trans-1,4,8,11-tetrathiatetradecane 6,13-dichloride) in good yield. Thiomethylation of the chlorides produces the ring-contracted pendent thioether macrocycles [13]aneS(4)-CH(2)SCH(3) (1,4,7,10-tetrathiatridecane-5-(methylthio)methane) and cis/trans-anti-[12]aneS(4)-(CH(2)SCH(3))(2) (1,4,7,10-tetrathiadodecane-5,11-bis((methylthio)methane)). The mechanism of the ring contraction reaction is discussed in terms of the reactivity of the monochlorinated macrocycle toward ring contraction and the stereochemistry of the chlorinated intermediates and the thiomethylated products, which are based on the X-ray crystal structure analyses of trans-[14]aneS(4)-Cl(2) and trans-anti-[12]aneS(4)-(CH(2)SCH(3))(2).     

Nickel complexes of bidentate [S2] and [SN] borato ligands

Nickel(II) complexes of the monoanionic borato ligands [Ph2B(CH2SCH3)2] (abbreviated Ph2Bt), [Ph2B(CH2S(t)Bu)2] (Ph2Bt(tBu)), [Ph2B(1-pyrazolyl)(CH2SCH3)], and [Ph2B(1-pyrazolyl)(CH2S(t)Bu)] have been prepared and characterized. While [Ph2Bt] formed the square planar homoleptic complex, [Ph2Bt]2Ni, the larger [S2] ligand with tert-butyl substituents, [Ph2BttBu], yielded an unexpected organometallic derivative, [Ph2Bt(tBu)]Ni(eta2-CH2SBut), resulting from B-C bond rupture. The analogous thiametallacycle derived from the [S3] ligand, [PhB(CH2S(t)Bu)3] (PhTt(tBu)), has been structurally authenticated (Schebler, P. J.; Mandimutsira, B. S.; Riordan, C. G.; Liable-Sands, L.; Incarvito, C. D.; Rheingold, A. L. J. Am. Chem. Soc. 2001, 123, 331). The [SN] borato ligands formed exclusively the cis stereoisomers upon reaction with Ni(II) sources, [Ph2B(1-pyrazolyl)(CH2SR)]2Ni. Analysis of the Ni(II/I) reduction potentials by cyclic voltammetry revealed a approximately 600 mV anodic shift upon replacement of two thioether donors ([Ph2Bt]2Ni) with two pyrazolyl donors ([Ph2B(1-pyrazolyl)(CH2SCH3)]2Ni) consistent with the all thioether environment stabilizing the lower oxidation state of nickel.     

Binuclear iron-sulfur complexes with bidentate phosphine ligands as active site models of Fe-hydrogenase and their catalytic proton reduction

The displacement of CO in a few simple Fe(I)-Fe(I) hydrogenase model complexes by bisphosphine ligands Ph2P-(CH2)n-PPh2 [with n = 1 (dppm) or n = 2 (dppe)] is described. The reaction of [{mu-(SCH2)2CH2}Fe2(CO)6] (1) and [{mu-(SCH2)2N(CH2CH2CH3)}Fe2(CO)6] (2) with dppe gave double butterfly complexes [{mu-(SCH2)2CH2}Fe2(CO)5(Ph2PCH2)]2 (3) and [{mu-(SCH2)2N(CH2CH2CH3)}Fe2(CO)5(Ph2PCH2)]2 (4), where two Fe2S2 units are linked by the bisphosphine. In addition, an unexpected byproduct, [{mu-(SCH2)2N(CH2CH2CH3)}Fe2(CO)5{Ph2PCH2CH2(Ph2PS)}] (5), was isolated when 2 was used as a substrate, where only one phosphorus atom of dppe is coordinated, while the other has been converted to P=S, presumably by nucleophilic attack on bridging sulfur. By contrast, the reaction of 1 and 2 with dppm under mild conditions gave only complexes [{mu-(SCH2)2CH2}Fe2(CO)5(Ph2PCH2PPh2)] (6) and [{mu-(SCH2)2N(CH2CH2CH3)}Fe2(CO)5(Ph2PCH2PPh2)] (8), where one ligand coordinated in a monodentate fashion to one Fe2S2 unit. Furthermore, under forcing conditions, the complexes [{mu-(SCH2)2CH2}Fe2(CO)4{mu-(Ph2P)2CH2}] (7) and [{mu-(SCH2)2N(CH2CH2CH3)}Fe2(CO)4{mu-(Ph2P)2CH2}] (9) were formed, where the phosphine acts as a bidentate ligand, binding to both the iron atoms in the same molecular unit. Electrochemical studies show that the complexes 3, 4, and 9 catalyze the reduction of protons to molecular hydrogen, with 4 electrolyzed already at -1.40 V versus Ag/AgNO3 (-1.0 V vs NHE).     

Formation of mono-, bi-, tri-, and tetranuclear Ag(I) complexes of C3-symmetric tripodal benzimidazole ligands

The C3-symmetric tripodal ligand tris(2-benzimidazolylmethyl)amine (ntb) and its alkyl-substituted derivatives tris(N-R-benzimidazol-2-ylmethyl)amine (R = methyl, Mentb; R = ethyl, Etntb; R = propyl, Prntb) react with various silver(I) salts to afford mononuclear [Ag(Prntb)(CF3SO3)].0.25H2O, 1, binuclear [Ag2(Mentb)2](CF3SO3)2.H2O, 2, trinuclear [Ag3(Etntb)2](ClO4)3.CH3OH, 3, and tetranuclear [Ag4(ntb)2(CH3CN)2(CF3CO2)2](CF3CO2)2.2H2O, 4. All four complexes have been characterized by elemental analyses, IR spectroscopy, and X-ray crystallography. The Ag(I) ion in 1 is coordinated to the three imine nitrogen atoms of the Prntb ligand and one oxygen atom of the trifluoromethanesulfonate anion in a distorted tetrahedral environment. Dinuclear 2 has C2 symmetry with each Ag(I) atom trigonally coordinated by two arms of one Mentb and one arm of another. Trinuclear 3 has C3 symmetry with a Ag3 regular triangle sandwiched between a pair of Etntb ligands such that one arm of each ligand is involved in linear coordination about an Ag(I) atom. In the tetranuclear complex 4, two linearly coordinated Ag(I) atoms lying on the molecular C2 axis are bridged by a pair of ntb ligands and the remaining pendant arm of each ntb ligand is attached to another Ag(I) atom whose tetrahedral coordination sphere is completed by an acetonitrile molecule and a chelating trifluoroacetate anion. Complexes 2 and 3 may be regarded as an aggregation of two tridentate ligands by a silver dimer and a trinuclear cluster with weak Ag...Ag interactions, respectively, while in 4 the aggregation of two tripodal ligands by four Ag(I) ions affords a multicomponent internal cavity. The packing modes of complexes 1-3 are dominated by weak supramolecular pi...pi and CH...pi interactions. Hexagonal or square channels are generated in 1 and 2, and a honeycomb layer structure is formed in 3 with solvate molecules and counteranions occupying the voids. The crystal structure of 4 consists of a three-dimensional network consolidated by NH...O and OH...O hydrogen bonds.     

Derivatives of Coenzyme F430 with a Covalently Attached α‐Axial Ligand. Part I

X‐Ray structures of the enzyme methyl‐coenzyme M reductase show that the Ni‐center in the prosthetic group coenzyme F430 is penta‐ or hexacoordinated with the carboxamide group of a glutamine residue occupying the axial coordination site on the α‐side of the macrocycle. To obtain diastereoselectively coordinated complexes for mechanistic and spectroscopic studies of the free coenzyme in solution, we aimed to prepare partial‐synthetic derivatives of coenzyme F430 that have a coordinating group attached via a linker to one of the propanoic acid side chains. By using molecular‐mechanics calculations and two different conformational search methods, a set of 50 structures containing imidazole or pyridine units as potential ligands were computationally tested according to geometric criteria defining coordinating conformations. The best candidates proved to be proline‐containing tri‐ and tetrapeptides with a methyl‐histidine as the C‐terminal residue. These linkers were synthesized, and their conformation was determined by NMR. Refinement of the molecular modeling by using the experimentally determined geometric restraints allowed us to decide that the tripeptide Pro‐Pro‐His(π‐Me)‐OMe ( 10 ) was the most promising of all tested structures for attachment to the side chain at C(3) or C(13) of F430.     

Cryoreduction of methyl-coenzyme M reductase: EPR characterization of forms, MCR(ox1) and MCR (red1).

Methyl-coenzyme M reductase (MCR) catalyzes the formation of methyl-coenzyme M (CH(3)S-CH(2)CH(2)SO(3)) from methane. The active site is a nickel tetrahydrocorphinoid cofactor, factor 430, which in inactive form contains EPR-silent Ni(II). Two such forms, denoted MCR(silent) and MCR(ox1)(-)(silent), were previously structurally characterized by X-ray crystallography. We describe here the cryoreduction of both of these MCR forms by gamma-irradiation at 77 K, which yields reduced protein maintaining the structure of the oxidized starting material. Cryoreduction of MCR(silent) yields an EPR signal that strongly resembles that of MCR(red1), the active form of MCR; and stepwise annealing to 260-270 K leads to formation of MCR(red1). Cryoreduction of MCR(ox1)(-)(silent) solutions shows that our preparative method for this state yields enzyme that contains two major forms. One behaves similarly to MCR(silent), as shown by the observation that both of these forms give essentially the same redlike EPR signals upon cryoreduction, both of which give MCR(red1) upon annealing. The other form is assigned to the crystallographically characterized MCR(ox1)(-)(silent) and directly gives MCR(ox1) upon cryoreduction. X-band spectra of these cryoreduced samples, and of conventionally prepared MCR(red1) and MCR(ox1), all show resolved hyperfine splitting from four equivalent nitrogen ligands with coupling constants in agreement with those determined in previous EPR studies and from (14)N ENDOR of MCR(red1) and MCR(ox1). These experiments have confirmed that all EPR-visible forms of MCR contain Ni(I) and for the first time generated in vitro the EPR-visible, enzymatically active MCR(red1) and the activate-able "ready" MCR(ox1) from "silent" precursors. Because the solution Ni(II) species we assign as MCR(ox1)(-)(silent) gives as its primary cryoreduction product the Ni(I) state MCR(ox1), previous crystallographic data on MCR(ox1)(-)(silent) allow us to identify the exogenous axial ligand in MCR(ox1) as the thiolate from CoM; the cryoreduction experiments further allow us to propose possible axial ligands in MCR(red1). The availability of model compounds for MCR(red1) and MCR(ox1) also is discussed.     

Nucleophilic de-coordination and electrophilic regeneration of "hemilabile" pincer-type complexes: formation of anionic dialkyl, diaryl, and dihydride Pt(II) complexes bearing no stabilizing pi-acceptors

Novel anionic dialkyl, diaryl, and dihydride platinum(II) complexes based on the new "long-arm" hemilabile PCN-type ligand C6H4[CH2P(tBu)2](CH2)2N(CH3)2 with the general formula Li+[Pt(PCN)(R)2]- (R=Me (4), Ph (6) and H (9)) were prepared by reaction of [Pt(PCN)(R)] complexes (obtained from the corresponding chlorides) with an equivalent of RLi, as a result of the opening of the chelate ring. Alkylating agents based on other metals produce less stable products. These anionic d8 complexes are thermally stable although they bear no stabilizing pi acceptors. They were characterized by 1H, 31P[1H], 13C, and 7Li NMR spectroscopy; complex 9 was also characterized by single crystal X-ray crystallography, showing that the Li+ ion is coordinated to the nitrogen atom of the open amine arm and to the hydride ligand (trans to the P atom) of a neighboring molecule (H--Li=2.15 A), resulting in a dimeric structure. Complexes 4 and 9 exhibit high nucleophilic reactivity, upon which the pincer complex is regenerated. Reaction of 4 with water, methyl iodide, and iodobenzene resulted in the neutral complex [Pt(PCN)(CH3)] (3) and methane, ethane, or toluene, respectively. Labeling studies indicate that the reaction proceeds by direct electrophilic attack on the metal center, rather than attack on the alkyl ligand. The anionic dihydride complex 9 reacted with water and methyl iodide to yield [Pt(PCN)(H)] (8) and H2 or methane, respectively.     

Activation of alkenes and H2 by [Fe]-H2ase model complexes

The established ability of the Fe(II) bridging hydride species (micro-H)(micro-pdt)[Fe(CO)2(PMe3)]2+, 1-H+, to take-up and heterolytically activate dihydrogen, resulting in H/D scrambling of H2/D2 and H2/D2O mixtures (Zhao et al. Inorg. Chem. 2002, 41, 3917) has prompted a study of simultaneous alkene/H2 activation by such [Fe]H2ase model complexes. That the required photolysis produced an open site was substantiated by substitution of CO in 1-H+ by CH3CN with formation of structurally characterized [(micro-H)(micro-pdt)[Fe(CO)2(PMe3)][Fe(CO)(CH3CN)(PMe3)]]+[PF6]-. Under similar photolytic conditions, H/D exchange reactions between D2 and terminal alkenes (ethylene, propene and 1-butene), but not bulkier alkenes such as 2-butene or cyclohexene, were catalyzed by 1-H+ and the edt (SCH2CH2S) analogue, 2-H+. Substantial regioselectivity for H/D exchange at the internal vinylic hydrogen was observed. The extent to which the olefins were deuterium enriched vs deuterated was catalyst dependent. The stabilizing effect of the binuclear chelating ligands, SCH2CH2CH2S, pdt, and SCH2CH2S, edt, is required for the activity of binuclear catalysts, as the mono-dentate micro-SEt analogue decomposed to inactive products under the photolytic conditions of the catalysis. Reactions of 1 and 2 with EtOSO2CF3 yielded the S-alkylated products, [(micro-SCH2CH2CH2SEt)[Fe(CO)2(PMe3)]2]+[SO3CF3]- (1-Et+), and 2-Et+, rather than micro-C2H5 analogues to the micro-H of 1-H+. The stability and lack of reactivity toward H2 of 1-Et+ and 2-Et+, indicates they are not on the reaction path of the olefin/D2 H/D exchange process. A mechanism with olefin binding to an open site created by CO loss and formation of an Fe-(CH2CHDR) intermediate is indicated. A likely role of a binuclear chelate effect is implicated for the unique S-XXX-S cofactor in the active site of [Fe]H2ase.     

Ligand heterogeneity on monolayer-protected gold clusters

This paper describes the effects of oxidative electronic charging of the Au cores of the monolayer-protected clusters (MPCs), Au140(S(CH2)5CH3)53 and Au38(SCH2CH2Ph)24, on nuclear magnetic resonance (NMR) spectra of their monolayer ligand shells. Previously unresolved fine structure in the 13C NMR hexanethiolate methyl and C5 methylene resonances is seen in spectra of solutions of monodisperse Au140(S(CH2)5CH3)53 MPCs, reflecting magnetically inequivalent ligand sites. Incremented increases in positive cluster core charge, effected by electrochemical charging, cause the spectral fine structure of the methyl resonance to coalesce, becoming a single peak at the Au140(3+) charge state. The spectral changes are reversible; charging back to the original core charge state regenerates the methyl 13C resonance fine structure. Adding an equimolar quantity of a Au(I) thiolate complex, Au(I)[SCH2(C6H4)C(CH3)3], to an uncharged Au140(S(CH2)5CH3)53 MPC solution in d2-methylene chloride causes partial spectral coalescence. 13C NMR spectra of Au38(SCH2CH2Ph)24 MPCs exhibit roughly comparable spectral changes upon positive core charging to the '0', '+1', and '+2' states. The NMR results indicate that exchange between magnetically inequivalent sites occurs at rates of 100 to 400 s(-1), a rate believed to be too fast to be accountable by actual exchanges of ligands between different sites on the Au core. We also describe changes in core electronic spectra of Au140(S(CH2)5CH3)53 induced by positive charging, measured using spectroelectrochemistry.