Selective oxygenation of C-H and CC bonds with H2O2 by high-spin cobalt(II)-carboxylate complexes.

Four cobalt(II)-carboxylate complexes [(6-Me3-TPA)CoII(benzoate)](BPh4) (1), [(6-Me3-TPA)CoII(benzilate)](ClO4) (2), [(6-Me3-TPA)CoII(mandelate)](BPh4) (3), and [(6-Me3-TPA)CoII(MPA)](BPh4) (4) (HMPA = 2-methoxy-2-phenylacetic acid) of the 6-Me3-TPA (tris((6-methylpyridin-2-yl)methyl)amine) ligand were isolated to investigate their ability in H2O2-dependent selective oxygenation of C-H and CC bonds. All six-coordinate complexes contain a high-spin cobalt(II) center. While the cobalt(II) complexes are inert toward dioxygen, each of these complexes reacts readily with hydrogen peroxide to form a diamagnetic cobalt(III) species, which decays with time leading to the oxidation of the methyl groups on the pyridine rings of the supporting ligand. Intramolecular ligand oxidation by the cobalt-based oxidant is partially inhibited in the presence of external substrates, and the substrates are converted to their corresponding oxidized products. Kinetic studies and labelling experiments indicate the involvement of a metal-based oxidant in affecting the chemo- and stereo-selective catalytic oxygenation of aliphatic C-H bonds and epoxidation of alkenes. An electrophilic cobalt-oxygen species that exhibits a kinetic isotope effect (KIE) value of 5.3 in toluene oxidation by 1 is proposed as the active oxidant. Among the complexes, the cobalt(II)-benzoate (1) and cobalt(II)-MPA (4) complexes display better catalytic activity compared to their α-hydroxy analogues (2 and 3). Catalytic studies with the cobalt(II)-acetonitrile complex [(6-Me3-TPA)CoII(CH3CN)2](ClO4)2 (5) in the presence and absence of externally added benzoate support the role of the carboxylate co-ligand in oxidation reactions. The proposed catalytic reaction involves a carboxylate-bridged dicobalt complex in the activation of H2O2 followed by the oxidation of substrates by a metal-based oxidant.

Mechanistic studies of in vitro anti-proliferative and anti-inflammatory activities of the Zn(ii)-NSAID complexes of 1,10-phenanthroline-5,6-dione in MDA-MB-231 cells.

Two zinc(ii)-NSAID complexes [(phendione)ZnII(NPR)2(H2O)2] (1) and [(phendione)ZnII(MFN)2] (2) (HNPR = naproxen and HMFN = mefenamic acid) of 1,10-phenanthroline-5,6-dione (phendione) were isolated and characterized to evaluate their potential as anti-cancer agents. Each of the complexes contains two equivalents of NSAID per zinc(ii)-phendione unit. The complexes are stable in solution under cell culture conditions. Cytotoxic assay on the human breast cancer cell line (MDA-MB-231) reveals that the anti-proliferative activity of phendione is retained in both the complexes. The anti-inflammatory properties of NSAIDs are also preserved in the metal complexes as evident from the PGE2 assay. Both 1 and 2 exhibit selective COX-1 inhibition at a low concentration. Furthermore, the zinc(ii)-naproxen complex (1) disrupts the intercellular bridges displaying in vitro delay in cellular migration and down-regulation of EMT-related genes. The mechanistic studies indicate that the ternary complexes are more active compared to cisplatin and have the potential to overcome cisplatin resistance in MDA MB 231 cells. These findings demonstrate that the zinc(ii)-NSAID complexes are worthy of further in vivo studies for their promising anti-tumor potential.

Oxidative C-N bond cleavage of (2-pyridylmethyl)amine-based tetradentate supporting ligands in ternary cobalt(ii)-carboxylate complexes.

Three mononuclear cobalt(ii)-carboxylate complexes, [(TPA)CoII(benzilate)]+ (1), [(TPA)CoII(benzoate)]+ (2) and [(iso-BPMEN)CoII(benzoate)]+ (3), of N4 ligands (TPA = tris(2-pyridylmethyl)amine and iso-BPMEN = N1,N1-dimethyl-N2,N2-bis((pyridin-2-yl)methyl)ethane-1,2-diamine) were isolated to investigate their reactivity toward dioxygen. Monodentate (η1) binding of the carboxylates to the metal centre favours the five-coordinate cobalt(ii) complexes (1-3) for dioxygen activation. Complex 1 slowly reacts with dioxygen to enable the oxidative decarboxylation of the coordinated α-hydroxy acid (benzilate). Prolonged exposure of the reaction solution of 2 to dioxygen results in the formation of [(DPA)CoIII(picolinate)(benzoate)]+ (4) and [CoIII(BPCA)2]+ (5) (DPA = di(2-picolyl)amine and HBPCA = bis(2-pyridylcarbonyl)amide), whereas only [(DPEA)CoIII(picolinate)(benzoate)]+ (6) (DPEA = N1,N1-dimethyl-N2-(pyridine-2-ylmethyl)-ethane-1,2-diamine) is isolated from the final oxidised solution of 3. The modified ligand DPA (or DPEA) is formed via the oxidative C-N bond cleavage of the supporting ligands. Further oxidation of the -CH2- moiety to -C([double bond, length as m-dash]O)- takes place in the transformation of DPA to HBPCA on the cobalt(ii) centre. Labelling experiments with 18O2 confirm the incorporation of oxygen atoms from molecular oxygen into the oxidised products. Mixed labelling studies with 16O2 and H2O18 strongly support the involvement of water in the C-N bond cleavage pathway. A comparison of the dioxygen reactivity of the cobalt complexes (1-3) with those of several other five-coordinate mononuclear complexes [(TPA)CoII(X)]+/2+ (X = Cl, CH3CN, acetate, benzoylformate, salicylate and phenylpyruvate) establishes the role of the carboxylate co-ligands in the activation of dioxygen and subsequent oxidative cleavage of the supporting ligands by a metal-oxygen oxidant.

Highly Selective and Catalytic Oxygenations of C-H and C=C Bonds by a Mononuclear Nonheme High-Spin Iron(III)-Alkylperoxo Species.

The reactivity of a mononuclear high-spin iron(III)-alkylperoxo intermediate [FeIII (t-BuLUrea )(OOCm)(OH2 )]2+ (2), generated from [FeII (t-BuLUrea )(H2 O)(OTf)](OTf) (1) [t-BuLUrea =1,1'-(((pyridin-2-ylmethyl)azanediyl)bis(ethane-2,1-diyl))bis(3-(tert-butyl)urea), OTf=trifluoromethanesulfonate] with cumyl hydroperoxide (CmOOH), toward the C-H and C=C bonds of hydrocarbons is reported. 2 oxygenates the strong C-H bonds of aliphatic substrates with high chemo- and stereoselectivity in the presence of 2,6-lutidine. While 2 itself is a sluggish oxidant, 2,6-lutidine assists the heterolytic O-O bond cleavage of the metal-bound alkylperoxo, giving rise to a reactive metal-based oxidant. The roles of the urea groups on the supporting ligand, and of the base, in directing the selective and catalytic oxygenation of hydrocarbon substrates by 2 are discussed.