An inorganic functional group approach to the systematic synthesis and reactivity studies of binuclear Mo/S and Mo/S/O complexes

A number of general reactions, based on molybdenum-coordinated sulphido or polysulphido ligands, can account for the synthesis of many members of the [Mo2V(S)n(S2)6-n]2-, [Mo2V(O)(S)n(S2)5-n]2- and [Mo2V(O)2(S)n(S2)4-n]2- homologous series. These reactions include: (a) sulphur addition and sulphur abstraction reactions; (b) oxidative removal of the Sx2- ligands and their replacement by substitutionally labile ligands; (c) oxidation of coodinated RS- ligands by Sx0 fragments, and in situ generation of Sx2- ligands; (d) oxidative dimerization reactions of molybdenum(IV) complexes; and (e) reductive elimination of Sx0 fragments. The synthesis of the new [(Cp)MoV(O)([mu]-S)2MoV(O)S4]- and [(Cp)MoV(O)([mu]-S)2MoV(O)S2]- anions has alowed the use of 1H NMR spectroscopy to monitor the solution behaviour and reactivity of the MoV(O)S2 group. The existence of the MoV(O)S2+S2aiMoV(O)S4 equilibrium has been unequivocally established. The [(Cp)MoV(O)([mu]-S)2MoV(O)S2]- complex gives a vinyl disulphide derivative by insertion of dicarbomethoxyacetylene, DMA, into the Mo-[eta]2-S2 group. Upon prolonged heating to 70[deg]C the vinyl disulphide ligand is converted quantitatively to a dithiolene ligand. The same conversion takes place swiftly at ambient temperatures when catalytic amounts of S8 are present in the reaction medium. Reaction pathways for both the thermal and catalytic conversions have been suggested by 1H NMR studies. Preliminary studies of the utility of the (Et4N)[Mo2O2S8Cl], [Ni(DMF)6][Mo2O2S8Cl]2, (Et4N)2[Mo4O4S18] and (Ph4P)2[Mo2S6] complexes as catalysts for the hydrodesulphurization of thiophene are reported. The Ni/Mo catalyst obtained from [Ni(DMF)6][Mo2O2S8Cl]2 is at least 10 times more effective than a commercial Co/Mo catalyst.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28247/1/0000700.pd

Unique reactivity characteristics of Mo-coordinated S2-2 and S2-4 ligands

The synthesis of the new dithiolene complexes, [{(MeOOC)2C2S2}2Mo([mu]2-S)]-2 and [OMo(S2C2(COOMe)2)2]-, is reported. These complexes are obtained by the reaction of dicarbomethoxyacetylene (DMA) with either [(S4)Mo(S)([mu]2-S)2Mo(S)(S4)]2- or [(CS4)Mo(S)([mu]2-S)2Mo(S)(CS4)]2- and [OMo(S4)2]2-, respectively. The reaction of [(S4)Mo(O)([mu]2-S)2Mo(O)(S2)]2- with DMA results in the new dithiolene complex [{(MeOOC)2C2S2}Mo(O)([mu]2-S)]-2, which is the isomeric form of the vinyl disulfide complex obtained in the reaction of the [(S2)Mo(O)([mu]2-S)2Mo(O)(S2)]2- complex with DMA. The difference in reactivity between the two complexes that contain the same [Mo2O2S2]2+ core is attributed to the intrinsically different reactivity characteristics of the S2-4 and S2-2 ligands. As a result of Mo-S d[pi]-p[pi] bonding an alternation in the S---S bond lengths is observed in virtually all of the structurally characterized Mo-S4 units. The consequent weakening of the S---S bonds adjacent to the Mo---S bonds allows for the ready dissociation of S02 from the Mo-coordinated S2-4 ligands. This weakening also accounts for the facile formation of dithiolenes in cycloaddition reactions of alkynes with the Mo-S4 units. By comparison, the S---S bond in side-on Mo-coordinated S2-2 ligands is strengthened as a result of depopulation of the ligand [pi]*-orbitals. Reactions of the latter with alkynes do not proceed by cycloaddition. Instead, insertion into the Mo---O bond has been reported for at least one such reaction. The importance of activated polysulfide ligands in the hydrodesulfurization reaction is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26402/1/0000489.pd

UNIQUE REACTIVITY CHARACTERISTICS OF MO-COORDINATED !&-AND S$-LIGANDS

Abstract-Th

Protein Arginine Methyltransferase Product Specificity Is Mediated by Distinct Active-site Architectures*

In the family of protein arginine methyltransferases (PRMTs) that predominantly generate either asymmetric or symmetric dimethylarginine (SDMA), PRMT7 is unique in producing solely monomethylarginine (MMA) products. The type of methylation on histones and other proteins dictates changes in gene expression, and numerous studies have linked altered profiles of methyl marks with disease phenotypes. Given the importance of specific inhibitor development, it is crucial to understand the mechanisms by which PRMT product specificity is conferred. We have focused our attention on active-site residues of PRMT7 from the protozoan Trypanosoma brucei We have designed 26 single and double mutations in the active site, including residues in the Glu-Xaa8-Glu (double E) loop and the Met-Gln-Trp sequence of the canonical Thr-His-Trp (THW) loop known to interact with the methyl-accepting substrate arginine. Analysis of the reaction products by high resolution cation exchange chromatography combined with the knowledge of PRMT crystal structures suggests a model where the size of two distinct subregions in the active site determines PRMT7 product specificity. A dual mutation of Glu-181 to Asp in the double E loop and Gln-329 to Ala in the canonical THW loop enables the enzyme to produce SDMA. Consistent with our model, the mutation of Cys-431 to His in the THW loop of human PRMT9 shifts its product specificity from SDMA toward MMA. Together with previous results, these findings provide a structural basis and a general model for product specificity in PRMTs, which will be useful for the rational design of specific PRMT inhibitors