Catalytic activities of Schiff base transition metal complexes

Ruthenium-based anticancer chemotherapies are making significant advances in clinical trials. Until recently, the focus has been on coordination complexes, and mechanisms such as "activation by reduction" and "transferrin-targeted delivery" have been proposed to account for the excellent cytotoxicity and low general toxicity of these complexes. More recently organoruthenium compounds, which to some extent appear not to follow the established rules, have started to be investigated. Despite such differences, similar activities between certain coordination and organometallic compounds suggest similar modes of action are present. DNA, the classic target, is believed to be the dominant mechanism for cytotoxicity with certain ruthenium drugs, while with others, non-classical targets are thought to be more important. In this article we describe these features and show how both ruthenium coordination complexes and organoruthenium compounds represent an ideal scaffold for further drug design and optimisation.

Classical and Non-Classical Ruthenium-Based Anticancer Drugs: Towards Targeted Chemotherapy

Interest in Ru anticancer drugs has been growing rapidly since NAMI-A ((ImH+)[RuIIICl4(Im)(S-dmso)], where Im = imidazole and S-dmso = S-bound dimethylsulfoxide) or KP1019 ((IndH+)[RuIIICl4(Ind)2], where Ind = indazole) have successfully completed phase I clinical trials and an array of other Ru complexes have shown promise for future development. Herein, the recent literature is reviewed critically to ascertain likely mechanisms of action of Ru-based anticancer drugs, with the emphasis on their reactions with biological media. The most likely interactions of Ru complexes are with: (i) albumin and transferrin in blood plasma, the former serving as a Ru depot, and the latter possibly providing active transport of Ru into cells; (ii) collagens of the extracellular matrix and actins on the cell surface, which are likely to be involved in the specific anti-metastatic action of Ru complexes; (iii) regulatory enzymes within the cell membrane and/or in the cytoplasm; and (iv) DNA in the cell nucleus. Some types of Ru complexes can also promote the intracellular formation of free radical species, either through irradiation (photodynamic therapy), or through reactions with cellular reductants. The metabolic pathways involve competition among reduction, aquation, and hydrolysis in the extracellular medium; binding to transport proteins, the extracellular matrix, and cell-surface biomolecules; and diffusion into cells; with the extent to which individual drugs participate in various steps along these pathways being crucial factors in determining whether they are mainly anti-metastatic or cytotoxic. This diversity of modes of action of Ru anticancer drugs is also likely to enhance their anticancer activities and to reduce the potential for them to develop tumour resistance. New approaches to metabolic studies, such as X-ray absorption spectroscopy and X-ray fluorescence microscopy, are required to provide further mechanistic insights, which could lead to the rational design of improved Ru anticancer drugs.

Recent developments in ruthenium anticancer drugs.

Polymer-supported Schiff base complexes in oxidation reactions

Nanoscale microreactor containing (5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane-4,11-diene)nickel(II) were successfully have been prepared by the template condensation of tris(ethylenediamine)nickel(II) complex with acetone within the nanodimensional pores of zeolite Y. This complex were entrapped in the supercage of zeolite Y by a two-step process in the liquid phase (i) inclusion of a nickel(II) precursor complex [Ni(en)3]2+-NaY and (ii) in situ template reaction of the nickel(II) precursor complex with the acetone. The new material [Ni(Me6[14]ane N4]2+-NaY characterized by several techniques: chemical analysis and spectroscopic methods(FT-IR, UV–vis, XPS, XRD, BET, DRS). Analysis of the data indicates that the nickel(II) complex are encapsulated in the nanodimensional pores zeolite and exhibit different from the free this of complex, which can arise from distortions caused steric effects due to the presence of sodium cations, or from interactions with the zeolite matrix. The host–guest nanoscale tetraaza macrocycle was found catalytic activity. Cyclohexene was catalytically oxidized in the presence of molecular oxygen and [Ni(Me6[14]ane N4)]2+-NaY in the absence of solvent at 70 °C, affording 2-cyclohexene-1-ol and 2-cyclohexene-1-one. The effect of temperature, and the amount of [Ni(Me6[14]ane N4)]2+-NaY used on the catalytic activity and product selectivity were discussed.

Nanoscale microreactor-encapsulation 14-membered nickel(II) hexamethyl tetraaza: synthesis, characterization and catalytic activity

M(salen) complexes (M=Mn(III), Ni(II); salen=bis-(salicyldene)ethylenediamine) have been encapsulated in zeolite Y and characterised. Mn(salen)+ complex was also anchored in montmorillonite clay and characterised. Epoxidation of olefins, viz. cyclohexene, cyclooctene and 1-hexene with terminal oxidants (NaOCl, KHSO5) was carried out with the anchored catalyst complexes and found that the epoxidation of linear olefin (1-hexene) is selectively facile than cyclic olefins. Experimental results are compared with those reported for M(salen) complexes catalysed olefin epoxidation in homogeneous and heterogenised-homogeneous catalytic conditions.

Olefin epoxidation catalysed by Schiff-base complexes of Mn and Ni in heterogenised-homogeneous systems

Cationic [Ru III (app)(bipy)(H 2 O)] 2+ ( 1 ) complex (H 2 app= N -(hydroxyphenyl)pyridine-2-carboxaldimine; bipy=2,2'-bipyridyl) has been synthesized and characterized by physico-chemical methods. Complex 1 is found to be an effective catalyst in the oxidation of both saturated and unsaturated hydrocarbons by using tert -butylhydroperoxide ( t -BuOOH). A mechanism involving formation of and transfer from a reactive high valent Ru(V)-oxo species as catalytic intermediate is proposed for the catalytic processes. The results of the product distribution in the present investigation clearly indicate the preference for side-on approach of olefins and the high electrophilic nature of RuO bond in [Ru V (app)(bipy)O] 2+ intermediate complex, which leads to the higher affinity of hydrogen atom/hydride abstraction than oxo-transfer to CC double bond.

Oxidation of organic substrates catalyzed by a novel mixed-ligand ruthenium(III) complex

Oxo-transfer catalysis from t-BuOOH with C–H bond insertion using tridentate Schiff-base-chelate complexes of ruthenium(III)

[RuIII(amp)(bipy)(H2O)]+ complex (1) has been synthesized and characterized by physico-chemical methods. The complex 1 is found to be an effective catalyst in the oxidation of benzene to phenol by using tert-butylhydroperoxide (t-BuOOH). A high valent Ru(V)-oxo species as catalytic intermediate formed in the reaction of 1 with t-BuOOH is proposed to be the source of oxygen atom in the oxidized product. A mechanism involving stacking of benzene followed by the O atom insertion seems to be operative in the formation of phenol from benzene.

Oxidation of benzene with tert-butylhydroperoxide catalyzed by a novel [RuIII(amp)(bipy)(H2O)]+ complex: first report of homogeneously catalyzed oxo-transfer reaction in benzene oxidation

Anannya Mitra

Papers

Olefin epoxidation catalysed by Schiff-base complexes of Mn and Ni in heterogenised-homogeneous systems

Oxidation of organic substrates catalyzed by a novel mixed-ligand ruthenium(III) complex

Oxo-transfer catalysis from t-BuOOH with C–H bond insertion using tridentate Schiff-base-chelate complexes of ruthenium(III)

Oxidation of benzene with tert-butylhydroperoxide catalyzed by a novel [RuIII(amp)(bipy)(H2O)]+ complex: first report of homogeneously catalyzed oxo-transfer reaction in benzene oxidation

Synthesis, characterization and reactivity of a novel ruthenium(II) complex containing polypyridyl ligand