Charles G. Riordan

Synthetic modeling of zinc thiolates: quantitative assessment of hydrogen bonding in modulating sulfur alkylation rates.

A series of mononuclear zinc thiolate complexes have been prepared and fully characterized. The reactions of the complexes with alkyl halides, leading to zinc halides and the corresponding thioethers, have been examined by kinetic methods. In toluene, the reactions obey a second-order rate law displaying activation parameters consistent with a SN2 attack of the zinc-bound thiolate on the carbon electrophile. Intramolecular hydrogen bonding of an amide N—H to the thiolate sulfur reduces the nucleophilicity and consequently, the rate of alkylation more than 30-fold at 25°C. The H-bonding shows an inverse H/D isotope effect of 0.33 (60°C) ascribed to differential H-bonding for the two isotopomers due to zero point energy differences. These model studies provide quantitative evaluation of H-bonding on reaction rates relevant to zinc thiol-activating proteins.

Monovalent iron in a sulfur-rich environment.

A series of low-coordinate, paramagnetic iron complexes in a tris(thioether) ligand environment have been prepared. Reduction of ferrous {[PhTt(tBu)]FeCl}2 [1; PhTt(tBu) = phenyltris((tert-butylthio)methyl)borate] with KC8 in the presence of PR3(R = Me or Et) yields the high-spin, monovalent iron phosphine complexes [PhTt(tBu)]Fe(PR3) (2). These complexes provide entry into other low-valent derivatives via ligand substitution. Carbonylation led to smooth formation of the low-spin dicarbonyl [PhTt(tBu)]Fe(CO)2 (3). Alternatively, replacement of PR 3 with diphenylacetylene produced the high-spin alkyne complex [PhTt(tBu)]Fe(PhCCPh) (4). Lastly, 2 equiv of adamantyl azide undergoes a 3 + 2 cycloaddition at 2, yielding high-spin dialkyltetraazadiene complex 5.

Binuclear complexes containing a methylnickel moiety: relevance to organonickel intermediates in acetyl coenzyme A synthase catalysis.

A series of binuclear NiNi complexes supported by a single thiolate bridge and containing a methylnickel moiety have been prepared and fully characterized. The complexes represent structural analogues for the proposed organonickel intermediate in the acetyl coenzyme A synthase catalytic cycle. Variable temperature 31P NMR spectroscopy was used to examine dynamic behavior of the thiolate bridging interaction in two of the derivatives. Kinetic analyses, independent exchange and crossover experiments support an intermolecular exchange mechanism. Carbonylation results in thioester formation via a reductive elimination pathway.

Synthetic chemistry and chemical precedents for understanding the structure and function of acetyl coenzyme A synthase

Acetyl coenzyme A synthase (ACS), found in acetogenic and methanogenic organisms, is responsible for the synthesis and breakdown of acetate. The mechanism by which methylcob(III)alamin, CO and coenzyme A are assembled/disassembled at the active-site A-cluster involves a number of biologically unprecedented intermediates. In the past two years, two protein crystal structures have significantly enhanced the understanding of the structure of the active-site A-cluster, responsible for catalysis. The structure reports spawned a number of important questions regarding the metal ion constitution of the active enzyme, the structure(s) of the spectroscopically identified states and the details of the catalytic mechanism. This Commentary addresses these issues in the framework of existing synthetic and chemical precedent studies aimed at developing rational structure–function correlations and presents structural and reactivity targets for future studies.

Thioether-ligated nickel(I) complexes for the activation of dioxygen

The preparation of phenyltris[1-adamantyl(thiomethyl)]borate [PhTtAd], which incorporates the large 1-adamantyl thioether substituent, is described. This derivative was sought to permit the preparation of four-coordinate nickel(I) complexes. Following a synthetic scheme for the related tert-butyl ligand, [PhTtBut], the following complexes were prepared and characterized fully, [PhTtAd]Ni(CO), [PhTtAd]Ni(PMe3) and [κ2-PhTtAd]Ni(η2-CH2SAd). The last species is a degradation product resulting from attempted reduction of the nickel(II) precursor, [PhTtAd]NiCl, in the absence of a ligand suitable for trapping the nickel(I) fragment.

A High-Spin Organometallic Fe−S Compound: Structural and Mössbauer Spectroscopic Studies of [Phenyltris((tert-butylthio)methyl)borate]Fe(Me)

The synthesis and structure of the pseudotetrahedral, sulfur-rich, high-spin organoiron(II) [phenyltris((tert-butylthio)methyl)borate]Fe(Me), [PhTt(tBu)]Fe(Me), 1, are reported. Low-temperature Mössbauer spectroscopic studies reveal an isomer shift of delta = 0.60(3) mm/s and DeltaE(Q) = 0.00(1) mm/s and an S = 2 ground multiplet with a negative zero-field splitting, D = -33(3) cm(-1), E/D approximately = 0.01. The small separation of the ground doublet, Delta approximately = 0.01 cm(-1), allows for observation of X-band EPR signals at g(eff) approximately = 10 (g(z) = 2.6, g(x,y) = 2.00). The relatively large negative zero-field splitting and a highly anisotropic magnetic hyperfine tensor, containing a large orbital z component, {-10(4), -10(4), +33.8(2) MHz}, are concordant with the presence of unquenched orbital angular momentum. Density functional theory (DFT) calculations predict that the lowest-lying orbitals have predominantly d(xy)- and d(x(2)-y(2))-like character, separated by an energy gap small enough to allow mixing through spin-orbit coupling, to generate a negative zero-field splitting, consistent with the experimental observations. The experimental and DFT-calculated isomer shifts are in good agreement (delta(calcd) = 0.5 mm/s). The unusual (for a high-spin ferrous site) null electric field gradients can be qualitatively explained in the frame of the spin-orbit coupling mixing. The very small Fermi contact component of the magnetic hyperfine tensor (A(FC)(exp) = -9 MHz) is not well described by the DFT approach (A(FC)(calcd) = +2 MHz). To our knowledge, this is the first study of a sulfur-coordinated high-spin organoiron(II) complex.

Synthetic Analogs for Evaluating the Influence of N-H---S Hydrogen Bonds on the Formation of Thioester in Acetyl Coenzyme A Synthase

A series of square planar methylnickel(II) complexes, (dppe)Ni(Me)(SAr) (dppe = 1,2-bis(diphenylphosphino)ethane); 2. Ar = phenyl; 3. Ar = pentafluorophenyl; 4. Ar = o-pivaloylaminophenyl; 5. Ar = p-pivaloylaminophenyl; (depe)Ni(Me)(SAr), (depe = 1,2-bis(diethylphosphino)ethane); 7. Ar = phenyl; 8. Ar = pentafluorophenyl; 9. Ar = o-pivaloylaminophenyl; 10. Ar = p-pivaloylaminophenyl), were synthesized via the reaction of (dppe)NiMe(2) (1) and (depe)NiMe(2) (6) with either the corresponding thiol or disulfide. These complexes were characterized by various spectroscopic methods including (31)P NMR, (1)H NMR, (13)C NMR and infrared spectroscopies and in most cases by X-ray diffraction analyses. Solid state and solution measurements establish that 4 and 9 contain intramolecular N-H...S bonds. Carbonylation of the complexes 2-4, 7-10 leads to (dRpe)Ni(CO)(2) and MeC(O)SAr via the intermediacy of the acylnickel adducts, (dRpe)Ni(C(O)Me)(SAr), detected at low temperature by (31)P NMR spectroscopy. Consistent with experimental observations, density functional theory results reveal that the intramolecular hydrogen bond in 9 stabilizes the acylnickel adduct compared with its non-hydrogen-bonded adduct, 10. Oxidative addition of MeC(O)SC(6)F(5) to (dRpe)Ni(COD) followed by spontaneous decarbonylation proceeds in variable yields generating 3 and 8.

Acetyl coenzyme A synthase: new insights into one of Nature’s bioorganometallic catalysts

The Ni-Fe-S proteins carbon monoxide dehydrogenase (COdH) and acetyl coenzyme A synthase (ACS) are enzymes crucial to the global carbon cycle, as they interconvert C1 entities, CO2, CO, and CH3equivalent, via redox reactions that allow certain archae and eubacteria to grow autotrophically, fixing CO2 via the Wood–Ljungdahl pathway for their anabolic metabolism [1]. The ancestry of the organisms may be traced to the time of the origin of life, with these enzymes representing Nature’s earliest catalysts [2]. The redox reactions promoted by COdH and ACS, Eqs. 1 and 2, are reminiscent of the industrial water-gas shift and Monsanto acetic acid synthesis reactions, respectively, that may serve to connect the biological and organometallic communities while expanding the bioorganometallic paradigm beyond B12 chemistry [3]: COþH2O CO2 þ 2Hþ þ 2e ð1Þ

New synthetic routes to a disulfidodinickel(II) complex: characterization and reactivity of a Ni2(mu-eta2:eta2-S2) core.

Activation of elemental sulfur by the monovalent nickel complex [PhTt (tBu)]Ni(CO) [PhTt(tBu)=phenyl{tris[(tert-butylmethyl)thio]methyl}borate] generates the disulfidodinickel(II) complex 2. This species is alternatively accessible via thermal decomposition of [PhTt (tBu)]Ni(SCPh3). Spectroscopic, magnetic, and X-ray diffraction studies establish that 2 contains a mu-eta(2):eta(2)-S2 ligand that fosters antiferromagnetic exchange coupling between the Ni (II) ions. This observation is in contrast to the lighter congener, oxygen, which strongly favors the bis(mu-oxo)dinickel(III) structure. 2 oxidizes PPh 3 to SPPh3 and reacts with O2, generating several products, one of which has been identified as [(PhTt (tBu))Ni]2(mu-S) (3).

C–H Activation by a Diselenido Dinickel(II) Complex

Addition of selenium to the nickel(I) complex, [Ni(Me4[12]aneN4)(CO)]PF6, effects a redox reaction leading to the diselenido dinickel(II) complex, {[(Ni(Me4[12]aneN4)]2(Se2)}(PF6)2, in 70% crystalline yield. The products structure features a μ-η(2):η(2)-Se2 ligand with Se-Se bond length of 2.379(13) Å. Upon mild heating, {[(Ni(Me4[12]aneN4)]2(μ-η(2):η(2)-Se2)}(PF6)2 oxidizes 9,10-dihydroanthracene or 1,4-cyclohexadiene forming the terminal hydroselenide, [Ni(Me4[12]aneN4)(SeH)]PF6, and anthracene or benzene, respectively. [Ni(Me4[12]aneN4)(SeH)]PF6 cleanly converts back to the diselenido dinickel(II) adduct upon addition of a phenoxy radical.