Synthesis, Characterization, And Catalytic And Biological Activities of A Mixed-ligand Cobalt(ii) Bipyridyl/diphenylazodioxide Complex

Transition metal complexes have immense importance in the pharmaceutical industry. These types of complexes can be useful catalysts in the synthesis of medicinal compounds and can act as anticancer drugs. In these pharmaceutical applications, 1st-row transition metal-containing complexes offer certain advantages compared to their 2nd and 3rd-row transition metal counterparts. Our motivation was to investigate pharmaceutical applications of transition metal complexes containing both a 1st-row transition metal and unusual ligands to expand the knowledge of a class of complexes that could potentially be beneficial in the pharmaceutical industry. A class of rare ligands that piqued our interest was that of the diaryl azodioxides, cis-Ar(O)NN(O)Ar, which belong to the wider class of organic derivatives of nitric oxide (NO). Our synthesis and pharmaceutical applications of the azodioxide complex salt [Co(bpy){Ph(O)NN(O)Ph}2](PF6)2 have been able to significantly expand the knowledge of azodioxide complexes by displaying an unusual trigonal prismatic coordination geometry for cobalt(II) with only bidentate ligands, showing evidence of ligand-based redox activity, acting as an active catalyst in allylic amination/C-C double-bond transposition reactions, and selectively inducing apoptosis in SK-HEP-1 human liver adenocarcinoma cells. Importantly, catalytic and biological studies of [Co(bpy){Ph(O)NN(O)Ph}2](PF6)2 are ongoing, and focused on its potential for use in the pharmaceutical industry as a drug or catalyst for drug synthesis. Future work will vi involve comparing the catalytic and biological activities of [Co(bpy){Ph(O)NN(O)Ph}2](PF6)2 with other azodioxide complexes prepared by our group to identify structure-activity relationships and inform the design of more efficient catalysts and anti-cancer, pro-apoptotic agents

Allylic Amination and Carbon–carbon Double Bond Transposition Catalyzed by Cobalt(II) azodioxide Complexes

The unusual cobalt(II) diphenylazodioxide complex salts [Co(az)4](PF6)2 and [Co(bpy)(az)2](PF6)2 have been shown to catalyze the allylic amination/C–C double bond transposition reaction of 2-methyl-2-pentene with PhNHOH, with a turnover number of about 4. The mechanism is proposed to involve a nitroso-ene-like transfer of a PhNO moiety from the azodioxide ligand to the alkene, followed by reduction of the organic product to yield a cobalt(III) intermediate, which is itself reduced back to cobalt(II) by PhNHOH, regenerating PhNO. Hetero-Diels-Alder trapping experiments suggest that an “off-metal” mechanism, in which PhNO is released from the cobalt complexes and reacts with the alkenes, is operative, in contrast to an “on-metal” mechanism observed by Nicholas and coworkers for [Fe(az)3](FeCl4)2

Cobalt(II) Diphenylazodioxide Complexes Induce Apoptosis in SK-HEP-1 Cells

The cobalt(II) complex salts [Co(bpy)(az)2](PF6)2 and [Co(az)4](PF6), each bearing the unusual cis-N,N\u27-diphenylazodioxide ligand, were both screened as possible anticancer agents against SK-HEP-1 liver cancer cells. Both compounds were found to induce substantial apoptosis as an increasing function of concentration and time. Measurement of apoptosis-related proteins indicated that both the extrinsic and intrinsic pathways of apoptosis were activated. The apoptotic activity induced by these salts is not displayed either by simple cobalt(II) salts or complexes or by the free nitrosobenzene ligand. Additionally, these compounds did not induce apoptosis, as assessed by poly(adenosine diphosphate-ribose) polymerase cleavage, in several other cell lines

Cobalt(II) Diphenylazodioxide Complexes Induce Apoptosis in SK-HEP-1 Cells

The cobalt(II) complex salts [Co(bpy)(az)2](PF6)2 and [Co(az)4](PF6), each bearing the unusual cis-N,N\u27-diphenylazodioxide ligand, were both screened as possible anticancer agents against SK-HEP-1 liver cancer cells. Both compounds were found to induce substantial apoptosis as an increasing function of concentration and time. Measurement of apoptosis-related proteins indicated that both the extrinsic and intrinsic pathways of apoptosis were activated. The apoptotic activity induced by these salts is not displayed either by simple cobalt(II) salts or complexes or by the free nitrosobenzene ligand. Additionally, these compounds did not induce apoptosis, as assessed by poly(adenosine diphosphate-ribose) polymerase cleavage, in several other cell lines

Electrochemical Studies of Cobalt(II) diphenylazodioxide Complexes

The electrochemical behavior of the unusual cobalt(II) diphenylazodioxide complex salts [Co(az)4](PF6)2 1 and [Co(bpy)(az)2](PF6)2 2 has been studied by cyclic voltammetry. Each complex displays two quasireversible redox couples, which are proposed to correspond to a reduction of Co(II) to Co(I), followed by a ligand-based reduction. Irreversible reductions of 1 are observed at more negative potentials, and are proposed to arise from deposition of elemental Co and the decomposition of transiently formed Co(-I) species. Spectroelectrochemical experiments on both 1 and 2, involving electrolytic reduction followed by reoxidation, are consistent with the quasireversibility observed in the CV measurements

Synthesis and Characterization of Cobalt(II) N,N′‑Diphenylazodioxide Complexes

Removal of chloride from CoCl2 with TlPF6 in acetonitrile, followed by addition of excess nitrosobenzene, yielded the eight-coordinate cobalt(II) complex salt [Co{Ph(O)NN(O)- Ph}4](PF6)2, shown by single-crystal X-ray analysis to have a distorted tetragonal geometry. The analogous treatment of the bipyridyl complex Co(bpy)Cl2 yielded the mixed-ligand cobalt(II) complex salt [Co(bpy){Ph(O)NN(O)Ph}2](PF6)2, whose singlecrystal X-ray structure displays a trigonal prismatic geometry, similar to that of the iron(II) cation in the previously known complex salt [Fe{Ph(O)NN(O)Ph}3](FeCl4)2. The use of TlPF6 to generate solvated metal complex cations from chloride salts or chlorido complexes, followed by the addition of nitrosobenzene, is shown to be a useful synthetic strategy for the preparation of azodioxide complex cations with the noncoordinating, diamagnetic PF6 − counteranion. Coordination number appears to be more important than d electron count in determining the geometry and metal−ligand bond distances of diphenylazodioxide complexes

Coordination Chemistry of Organic Nitric Oxide Derivatives

Organic derivatives of nitric oxide can serve as ligands for transition metals in a variety of fashions. This review surveys recent developments in the coordination chemistry of four main classes of organic NO derivatives: nitrosoalkanes and nitrosoarenes, azodioxides, and nitrosamines. Highlighted work includes evidence that nitrosoarenes can behave as redox-active (“non-innocent”) ligands, an expansion in the number of crystallographically characterized azodioxide complexes, and the synthesis of N-bound primary nitrosamines. Relevance to the bioinorganic chemistry of metalloenzymes is noted

Coordination Chemistry of Organic Nitric Oxide Derivatives

Organic derivatives of nitric oxide can serve as ligands for transition metals in a variety of fashions. This review surveys recent developments in the coordination chemistry of four main classes of organic NO derivatives: nitrosoalkanes and nitrosoarenes, azodioxides, and nitrosamines. Highlighted work includes evidence that nitrosoarenes can behave as redox-active (“non-innocent”) ligands, an expansion in the number of crystallographically characterized azodioxide complexes, and the synthesis of N-bound primary nitrosamines. Relevance to the bioinorganic chemistry of metalloenzymes is noted

Allylic Amination and Carbon–carbon Double Bond Transposition Catalyzed by Cobalt(II) azodioxide Complexes

The unusual cobalt(II) diphenylazodioxide complex salts [Co(az)4](PF6)2 and [Co(bpy)(az)2](PF6)2 have been shown to catalyze the allylic amination/C–C double bond transposition reaction of 2-methyl-2-pentene with PhNHOH, with a turnover number of about 4. The mechanism is proposed to involve a nitroso-ene-like transfer of a PhNO moiety from the azodioxide ligand to the alkene, followed by reduction of the organic product to yield a cobalt(III) intermediate, which is itself reduced back to cobalt(II) by PhNHOH, regenerating PhNO. Hetero-Diels-Alder trapping experiments suggest that an “off-metal” mechanism, in which PhNO is released from the cobalt complexes and reacts with the alkenes, is operative, in contrast to an “on-metal” mechanism observed by Nicholas and coworkers for [Fe(az)3](FeCl4)2

Electrochemical Studies of Cobalt(II) diphenylazodioxide Complexes

The electrochemical behavior of the unusual cobalt(II) diphenylazodioxide complex salts [Co(az)4](PF6)2 1 and [Co(bpy)(az)2](PF6)2 2 has been studied by cyclic voltammetry. Each complex displays two quasireversible redox couples, which are proposed to correspond to a reduction of Co(II) to Co(I), followed by a ligand-based reduction. Irreversible reductions of 1 are observed at more negative potentials, and are proposed to arise from deposition of elemental Co and the decomposition of transiently formed Co(-I) species. Spectroelectrochemical experiments on both 1 and 2, involving electrolytic reduction followed by reoxidation, are consistent with the quasireversibility observed in the CV measurements