Juventino J. García

Solvent Effects and Activation Parameters in the Competitive Cleavage of C−CN and C−H Bonds in 2-Methyl-3-Butenenitrile Using [(dippe)NiH]2

The reaction of [(dippe)NiH]2 with 2-methyl-3-butenenitrile (2M3BN) in solvents spanning a wide range of polarities shows significant differences in the ratio of C-H and C-CN activated products. C-H cleavage is favored in polar solvents, whereas C-C cleavage is favored in nonpolar solvents. This variation is attributed to the differential solvation of the transition states, which was further supported through the use of sterically bulky solvents and weakly coordinating solvents. Variation of the temperature of reaction of [(dippe)NiH]2 with 2M3BN in decane and N,N-dimethylformamide (DMF) allowed for the calculation of Eyring activation parameters for the C-CN activation and C-H activation mechanisms. The activation parameters for the C-H activation pathway were DeltaH(double dagger) = 11.4 +/- 5.3 kcal/mol and DeltaS(double dagger) = -45 +/- 15 e.u., compared with DeltaH(double dagger) = 17.3 +/- 2.6 kcal/mol and DeltaS(double dagger) = -29 +/- 7 e.u. for the C-CN activation pathway. These parameters indicate that C-H activation is favored enthalpically, but not entropically, over C-C activation, implying a more ordered transition state for the former.

Mechanistic Insights on the Hydrodesulfurization of Biphenyl-2-thiol with Nickel Compounds

The reactivity of the nickel(I) dimer [(dippe)Ni(mu-H)](2) (1) with biphenyl-2-thiol was explored with the aim of clarifying the key step of sulfur extrusion during the hydrodesulfurization process using dibenzothiophene (DBT). These reactions were monitored by variable temperature NMR experiments which allowed the complete characterization and isolation of [(dippe)(2)Ni(2)(mu-H)(mu-S-2-biphenyl)] (3). The latter compound evolves to the terminal nickel-hydride [(dippe)Ni (eta(1)-C-2-biphenyl)(H)] (4) and transient [(dippe)NiS] (5), to ultimately yield [(dippe)(2)Ni(2)(mu-S)] (2) and biphenyl as the resulting HDS products. The reactivity of 1 and biphenyl-2-thiol was examined using different ratios of reactants, which allowed preparation of [(dippe)Ni(eta(1)-S-biphenyl-2-thiolate)(2)] (6) when using an excess of this substrate. The reactivity of 6 with 1 was addressed, yielding compound 2 and an equivalent amount of biphenyl.

Perturbation of the Dimer Interface of Triosephosphate Isomerase and its Effect on Trypanosoma cruzi

Background Chagas disease affects around 18 million people in the American continent. Unfortunately, there is no satisfactory treatment for the disease. The drugs currently used are not specific and exert serious toxic effects. Thus, there is an urgent need for drugs that are effective. Looking for molecules to eliminate the parasite, we have targeted a central enzyme of the glycolytic pathway: triosephosphate isomerase (TIM). The homodimeric enzyme is catalytically active only as a dimer. Because there are significant differences in the interface of the enzymes from the parasite and humans, we searched for small molecules that specifically disrupt contact between the two subunits of the enzyme from Trypanosoma cruzi but not those of TIM from Homo sapiens (HTIM), and tested if they kill the parasite. Methodology/Principal Findings Dithiodianiline (DTDA) at nanomolar concentrations completely inactivates recombinant TIM of T. cruzi (TcTIM). It also inactivated HTIM, but at concentrations around 400 times higher. DTDA was also tested on four TcTIM mutants with each of its four cysteines replaced with either valine or alanine. The sensitivity of the mutants to DTDA was markedly similar to that of the wild type. The crystal structure of the TcTIM soaked in DTDA at 2.15 Å resolution, and the data on the mutants showed that inactivation resulted from alterations of the dimer interface. DTDA also prevented the growth of Escherichia coli cells transformed with TcTIM, had no effect on normal E. coli, and also killed T. cruzi epimastigotes in culture. Conclusions/Significance By targeting on the dimer interface of oligomeric enzymes from parasites, it is possible to discover small molecules that selectively thwart the life of the parasite. Also, the conformational changes that DTDA induces in the dimer interface of the trypanosomal enzyme are unique and identify a region of the interface that could be targeted for drug discovery.

On the Catalytic Hydrodefluorination of Fluoroaromatics Using Nickel Complexes: The True Role of the Phosphine

Homogeneous catalytic hydrodefluorination (HDF) of fluoroaromatics under thermal conditions was achieved using nickel(0) compounds of the type [(dippe)Ni(η(2)-C6F6-nHn)] where n = 0-2, as the catalytic precursors. These complexes were prepared in situ by reacting the compound [(dippe)Ni(μ-H)]2 with the respective fluoroaromatic substrate. HDF seems to occur homogeneously, as tested by mercury drop experiments, producing the hydrodefluorinated products. However, despite previous findings by other groups, we found that these HDF reactions were actually the result of direct reaction of the alkylphosphine with the fluoroaromatic substrate. This metal- and silane-free system is the first reported example of a phosphine being able to hydrodefluorinate on its own.

Stereoselective Hydrogenation of Aromatic Alkynes Using Water, Triethylsilane, or Methanol, Mediated and Catalyzed by Ni(0) Complexes

The use of complexes of the type [(P-P)Ni(eta(2)-C,C-alkyne)] (P-P = 1,2-bis(di-isopropyl-phosphinoethane or 1,2-bis(diterbutylphosphino-ethane) in the presence of water, triethylsilane/water, or methanol as hydrogen sources yields the selective production of E- or Z- aromatic alkenes from the corresponding alkynes. For instance, in the case of diphenylacetylene (dpa) and water, a metal-mediated process was found to yield trans-stilbene stoichiometrically, whereas in the case of triethylsilane/water and methanol, a catalytic system (1% mol) was found. The catalytic systems gave >95% conversion to cis- or trans-stilbene, respectively. The use of a variety of substituents on the aromatic ring was also assessed. Deuterium-labeling studies using D(2)O allowed the confirmation of water as the hydrogen source for the alkyne reduction.

Analysis of a hydrodesulfurization process— 2 [1]. The reactions of 2- and 3-methylthiophenes with tris(triethylphosphine)platinum(0)

Abstract The oxidative insertion reactions of 2-methylthiophene (2-MeT) and 3-methylthiopene (3-MeT) with Pt(PEt3)3 (1), were examined as models for the first step in a platinum catalysed hydrodesulfurization. 2-MeT gave a single isomer, 1-bis(triethylphosphine)platina-2-thia-3-methylcyclohexa-3,5-diene (2), characterized spectroscopically. 3-MeT gave two isomers (ratio 1:1.6), 1-bis(triethylphosphine)platina-2-thia-5-methylcyclohexa-3,5-diene (3b), dentified spectroscopically, and 1-bis(triethylphosphine)platina-2-thia-4-methylcyclohexa-3,5-diene (3a), identified spectroscopically and by an X-ray crystal structure determination. The thiophenes in the thiametallacycles can be displaced by free thiophenes and measurements show that the equilibrium constants decrease in the order [Pt(C,S-3-MeT)(PEt3)2]+T[Keqm(3/0) = 2.30 (after 7 h)] ; [Pt(C,S-3-MeT)(PEt3)2]+2-MeT [Keqm(3/2) = 2.20 (after 12 h)]; and [Pt(C,S-2-MeT)(PEt3)3]+T [Keqm(2/0) = 1.45 (after 20 h)]. The order of stability in the complexes is T > 2-MeT > 3-MeT. Equilibrium is attained more rapidly in the 3-MeT complexes than in those of 2-MeT. Details of the X-ray structure of the previously prepared complex 5, [Pt(PEt3)2{C,S-C12H8S}], derived from dibenzothiophene, are also given and these two structures are compared with that for complex 4, [Pt(PEt3)2{C,S-C8H6S}], derived from benzothiophene. Comple 3a, 4 and 5 share the common feature of a six-membered thiaplatinacycle, which is planar in 3a, nearly so in 4, but very severely distorted in 5; however, many of the bond lengths and angles are similar.

Reduction of CO2 and SO2 with low valent nickel compounds under mild conditions

The reaction of [(dippe)Ni(μ-H)](2) (A) (dippe = 1,2-bis(diisopropyl-phosphinoethane) with CO(2) in toluene afforded the carbonyl nickel(0) compounds of the type {(dippe)Ni(CO)](2)(μ-dippe)}(1) and (dippe)Ni(CO)(dippe==O)] (2), which were characterized by standard spectroscopic methods; complex (1) was also characterized by single crystal X-ray diffraction. Reaction of (A) with SO(2) yields the thiosulfate nickel(II) compound [Ni(dippe)(S(2)O(3))] (5), which was fully characterized by standard spectroscopic methods and X-ray crystallography. In both cases, a reduction reaction of CO(2) to CO and SO(2) to S(2)O(3)(2-) with (A) took place under mild conditions.

Facile cyclotrimerization of CF3CCH and CF3CCCF3 with bimetallic rhodium catalysts

Abstract Complexes with the formulation [{Rh(μ-SR F )(C 8 H 12 )} 2 ] R F = C 6 F 5 1 , C 6 F 4 H- p 2 and C 6 H 4 F- p 3 ) have been used as catalyst precursors for the cyclotrimerization of CF 3 CCH and CF 3 CCCF 3 at room temperature and under atmospheric pressure.

Rhodium– and iridium–perfluorobenzenethiolato complexes, [(C5Me5)Ir(SC6F5)2], [(C5Me5)Ir(SC6F4H-p)2] and [(C5Me5)2Rh2(µ-SC6F5)3][(C5Me5)Rh(SC6F5)3]: syntheses, crystal structures and solution behaviour

Reaction of [(C5Me5)2M2(µ-Cl)2Cl2](M = Rh 1a or Ir 1b) with Pb(SRF)2 gave [(C5Me5)Ir(SRF)2]2b(RF= C6F5 or C6F4H-p) containing five-co-ordinate IrIII, or ionic [(C5Me5)2Rh2(µ-SRF)3][(C5Me5)Rh(SRF)3]3a(RF= C6F5 or C6F4H-p) containing six-co-ordinate RhIII in both the anion and cation. Complexes 2b and 3a(RF= C6F5) were characterised by single-crystal X-ray determinations; the structures of 2b(RF= C6F5 or C6F4H-p) are very similar, but in the former the SC6F5 ligands are related by a plane of symmetry. The NMR spectra of 2b in solution are consistent with the mirror-symmetric solid-state structure. However, those of the rhodium complexes 3a, while consistent with the ionic solid-state structures in methanol, show quite different features in less-polar solvents, indicating that they participate in the equilibrium [(C5Me5)2Rh2(µ-SRF)3][(C5Me5)Rh(SRF)3]⇌ 3[(C5Me5)Rh(SRF)2] where [(C5Me5)Rh(SRF)2] has a similar structure to that of 2b(RF= C6F5). Complexes 1a and 1b reacted with Pb(SC6H4F-p)2 to give salts formulated as the triply bridged [(C5Me5)2M2(µ-SC6H4F-p)3]Cl·H2O (M = Rh 4a cr Ir 4b), while 1b reacted with Ag(SCF3) to afford the diiridium complexes [(C5Me5)2Ir2(µ-SCF3)2(SCF3)2]5b and [(C5Me5)2Ir2(µ-SCF3)3]Cl·H2O 6b.

Rhodium– and iridium–perfluorophenylthiolato complexes: the X-ray structures of [(C5Me5)Ir(SC6F4H)2] and [(C5Me5)2Rh2(µ-SC6F5)3][(C5Me5)Rh(SC6F5)3] and evidence for novel equilibria in solution

Reaction of [(C5Me5M)2(µ-Cl)2Cl2](M = Rh, Ir) with [Pb(SRf)2] gave covalent [(C5Me5)Ir(SRf)2](Rf= C6F4H, 2b-F4), and ionic [(C5Me5)2Rh2(µ-SRf)3][(C5Me5)Rh(SRf)3](Rf= C6F5, 2a-F5), characterised by single crystal X-ray determinations; NMR spectra of 2b-F4 and its analogues are compatible with a retention of the solid state structure in solution for iridium, while those of 2a-F5 and its analogues indicate that the rhodium complexes participate in equilibria: 3[(C5Me5)2Rh(SRf)2]⇌[(C5Me5)2Rh2(µ-SRf)3][(C5Me5)Rh(SRf)3].