Cobalt complexes bearing scorpionate ligands: synthesis, characterization, cytotoxicity and DNA cleavage.

A number of novel, water-stable redox-active cobalt complexes of the C-functionalized tripodal ligands tris(pyrazolyl)methane XC(pz)(3) (X = HOCH(2), CH(2)OCH(2)Py or CH(2)OSO(2)Me) are reported along with their effects on DNA. The compounds were isolated as air-stable solids and fully characterized by IR and FIR spectroscopies, ESI-MS(+/-), cyclic voltammetry, controlled potential electrolysis, elemental analysis and, in a number of cases, also by single-crystal X-ray diffraction. They showed moderate cytotoxicity in vitro towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma human cancer cell lines. This viability loss is correlated with an increase of tumour cell lines apoptosis. Reactivity studies with biomolecules, such as reducing agents, H(2)O(2), plasmid DNA and UV-visible titrations were also performed to provide tentative insights into the mode of action of the complexes. Incubation of Co(II) complexes with pDNA induced double strand breaks, without requiring the presence of any activator. This pDNA cleavage appears to be mediated by O-centred radical species.

[1]  S. Lippard,et al.  Redox activation of metal-based prodrugs as a strategy for drug delivery. , 2012, Advanced drug delivery reviews.

[2]  Anna Trakoli.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 99: Some Aromatic Amines, Organic Dyes, and Related Exposures. International Agency for Research on Cancer , 2012 .

[3]  W. Berger,et al.  Anticancer activity of metal complexes: involvement of redox processes. , 2011, Antioxidants & redox signaling.

[4]  A. Kirillov,et al.  Mild, single-pot hydrocarboxylation of linear C5–C9 alkanes into branched monocarboxylic C6–C10 acids in copper-catalyzed aqueous systems , 2011 .

[5]  A. Riyasdeen,et al.  Interaction of rac-[M(diimine)3]2+ (M=Co, Ni) complexes with CT DNA: role of 5,6-dmp ligand on DNA binding and cleavage and cytotoxicity. , 2011, Dalton transactions.

[6]  L. Martins,et al.  Synthesis and structural characterization of iron complexes with 2,2,2-tris(1-pyrazolyl)ethanol ligands: Application in the peroxidative oxidation of cyclohexane under mild conditions , 2011 .

[7]  C. Näther,et al.  Mixed ligand cobalt(II) picolinate complexes: synthesis, characterization, DNA binding and photocleavage. , 2011, Dalton transactions.

[8]  C. Philouze,et al.  Co(II), Ni(II), Cu(II) and Zn(II) complexes of a bipyridine bis-phenol conjugate: generation and properties of coordinated radical species. , 2010, Dalton transactions.

[9]  L. Martins,et al.  Synthesis and coordination chemistry of a new N4-polydentate class of pyridyl-functionalized scorpionate ligands: complexes of Fe(II), Zn(II), Ni(II), V(IV), Pd(II) and use for heterobimetallic systems. , 2010, Inorganic chemistry.

[10]  A. Kirillov,et al.  Mild, single-pot hydrocarboxylation of gaseous alkanes to carboxylic acids in metal-free and copper-promoted aqueous systems. , 2010, Chemistry.

[11]  A. Kirillov,et al.  Bringing an "old" biological buffer to coordination chemistry: new 1D and 3D coordination polymers with [Cu(4)(Hbes)(4)] cores for mild hydrocarboxylation of alkanes. , 2010, Inorganic chemistry.

[12]  L. Martins,et al.  Novel Scorpionate and Pyrazole Dioxovanadium Complexes, Catalysts for Carboxylation and Peroxidative Oxidation of Alkanes , 2010 .

[13]  A. Kirillov,et al.  Metal‐Free and Copper‐Promoted Single‐Pot Hydrocarboxylation of Cycloalkanes to Carboxylic Acids in Aqueous Medium , 2009 .

[14]  L. Martins,et al.  Cu(II) complexes bearing the 2,2,2-tris(1-pyrazolyl)ethanol or 2,2,2-tris(1-pyrazolyl)ethyl methanesulfonate scorpionates. X-Ray structural characterization and application in the mild catalytic peroxidative oxidation of cyclohexane. , 2009, Dalton transactions.

[15]  J. Collins,et al.  Metal complexes as structure-selective binding agents for nucleic acids , 2009 .

[16]  L. Martins,et al.  Scorpionate complexes of vanadium(III or IV) as catalyst precursors for solvent-free cyclohexane oxidation with dioxygen , 2009 .

[17]  A. Kirillov,et al.  Alkanes to carboxylic acids in aqueous medium: metal-free and metal-promoted highly efficient and mild conversions. , 2009, Chemical communications.

[18]  A. Pombeiro,et al.  Oxidations of cycloalkanes and benzene by hydrogen peroxide catalyzed by an {FeIIIN2S2} centre , 2009 .

[19]  E Sabbioni,et al.  Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro. , 2008, Mutagenesis.

[20]  A. Hartwig,et al.  Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms , 2008, Archives of Toxicology.

[21]  L. Martins,et al.  Half‐sandwich scorpionate vanadium, iron and copper complexes: synthesis and application in the catalytic peroxidative oxidation of cyclohexane under mild conditions , 2008 .

[22]  A. Pombeiro,et al.  Amavadin and other vanadium complexes as remarkably efficient catalysts for one-pot conversion of ethane to propionic and acetic acids. , 2008, Chemistry.

[23]  A. Kirillov,et al.  An Infinite Two-Dimensional Hybrid Water−Chloride Network, Self-Assembled in a Hydrophobic Terpyridine Iron(II) Matrix , 2008 .

[24]  P. M. Reis,et al.  Direct and remarkably efficient conversion of methane into acetic acid catalyzed by amavadine and related vanadium complexes. A synthetic and a theoretical DFT mechanistic study. , 2007, Journal of the American Chemical Society.

[25]  L. Martins,et al.  Bis[tris(1-pyrazolyl)methane-κ3N,N′,N′′]copper(II) dichloride methanol disolvate , 2007 .

[26]  A. Kirillov,et al.  3D hydrogen bonded heteronuclear CoII, NiII, CuII and ZnII aqua complexes derived from dipicolinic acid , 2007 .

[27]  I. Garcı́a-Orozco,et al.  Tris(pyrazolyl)methane–chromium(III) complexes as highly active catalysts for ethylene polymerization , 2006 .

[28]  R. Chitta,et al.  Binding, electrochemical activation, and cleavage of DNA by cobalt(II) tetrakis-N-methylpyridyl porphyrin and its beta-pyrrole brominated derivative. , 2006, Bioconjugate chemistry.

[29]  A. Kirillov,et al.  An Aqua-Soluble Copper(II)−Sodium Two-Dimensional Coordination Polymer with Intercalated Infinite Chains of Decameric Water Clusters , 2006 .

[30]  Samar K. Das,et al.  Water¿chloride interactions: Left- and right-handed aqua-chloro supramolecular helices anchored by a chiral Schiff-base nickel complex , 2006 .

[31]  Ji Zhang,et al.  The Oxidative Damage of Plasmid DNA by Ascorbic Acid Derivatives in vitro: The First Research on the Relationship between the Structure of Ascorbic Acid and the Oxidative Damage of Plasmid DNA , 2006, Chemistry & biodiversity.

[32]  E. Suresh,et al.  A hybrid water-chloride structure with discrete undecameric water moieties self-assembled in a heptaprotonated octaamino cryptand. , 2006, Angewandte Chemie.

[33]  F. Luna-Giles,et al.  Structural Impact of Infinite Water Chains on the Self-Assembly of an Inorganic−Metal−Organic Architecture , 2006 .

[34]  S. Pang,et al.  Anticancer activity of a series of platinum complexes integrating demethylcantharidin with isomers of 1,2-diaminocyclohexane. , 2006, Bioorganic & medicinal chemistry letters.

[35]  V. Puranik,et al.  Supramolecular Self-Assembled Ruthenium−Polypyridyl Framework Encapsulating Discrete Water Cluster , 2006 .

[36]  Edward R. T. Tiekink,et al.  Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine , 2005 .

[37]  I. Bernal,et al.  Environment-controlled switching between cyclic hexamer and helical conformations of a water chloride cluster: An old compound viewed in a new perspective , 2005 .

[38]  J. Zaleski,et al.  Metal complex-DNA interactions: from transcription inhibition to photoactivated cleavage. , 2005, Current opinion in chemical biology.

[39]  C. Pettinari,et al.  Metal derivatives of poly(pyrazolyl)alkanes II. Bis(pyrazolyl)alkanes and related systems , 2005 .

[40]  P. Mountford,et al.  Coordination, organometallic and related chemistry of tris(pyrazolyl)methane ligands. , 2005, Dalton transactions.

[41]  Tanja Schwerdtle,et al.  Co(II) and Cd(II) substitute for Zn(II) in the zinc finger derived from the DNA repair protein XPA, demonstrating a variety of potential mechanisms of toxicity. , 2004, Chemical research in toxicology.

[42]  P. Wardman,et al.  Selectivity of effects of redox-active cobalt(III) complexes on tumor tissue. , 2004, Experimental oncology.

[43]  N. Metzler‐Nolte,et al.  Synthesis, structure and comparison of the DNA cleavage ability of metal complexes M(II)L with the N-(2-ethoxyethanol)-bis(2-picolyl)amine ligand L (M = Co, Ni, Cu and Zn). , 2004, Dalton transactions.

[44]  L. Vassilev,et al.  In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2 , 2004, Science.

[45]  N. Osheroff,et al.  Cobalt enhances DNA cleavage mediated by human topoisomerase II alpha in vitro and in cultured cells. , 2004, Biochemistry.

[46]  J. Chisholm,et al.  Extended motifs from water and chemical functional groups in organic molecular crystals , 2003 .

[47]  Samar K. Das,et al.  Small Water Clusters in Crystalline Hydrates , 2003 .

[48]  D. Reger,et al.  Synthesis of Modified Tris(pyrazolyl)methane Ligands: Backbone Functionalization , 2003 .

[49]  Sam Motherwell,et al.  Water clusters in organic molecular crystals , 2002 .

[50]  T. Hambley,et al.  Iron(II) complexes containing poly(1-pyrazolyl)methane ligands , 2002 .

[51]  A. Pombeiro.  Electron-transfer induced isomerizations of coordination compounds , 2001 .

[52]  S. Sakaguchi,et al.  Innovation of Hydrocarbon Oxidation with Molecular Oxygen and Related Reactions , 2001 .

[53]  Ralf Ludwig,et al.  Water: From Clusters to the Bulk. , 2001, Angewandte Chemie.

[54]  K. J. Brown,et al.  Syntheses of tris(pyrazolyl)methane ligands and {[tris(pyrazolyl)methane]Mn(CO)3}SO3CF3 complexes: comparison of ligand donor properties , 2000 .

[55]  H. Lang,et al.  Tris(pyrazolyl)methanesulfonates: A Novel Class of Water-Soluble Ligands. , 2000, Angewandte Chemie.

[56]  F. Kiechle,et al.  Hoechst 33342 induces apoptosis in HL-60 cells and inhibits topoisomerase I in vivo. , 1999, Archives of pathology & laboratory medicine.

[57]  Louis J. Farrugia,et al.  WinGX suite for small-molecule single-crystal crystallography , 1999 .

[58]  G. Zuber,et al.  Sequence Selective Cleavage of a DNA Octanucleotide by Chlorinated Bithiazoles and Bleomycins , 1998 .

[59]  Y. Rojanasakul,et al.  Cobalt-mediated generation of reactive oxygen species and its possible mechanism. , 1998, Journal of inorganic biochemistry.

[60]  B. Ness,et al.  Site-specific cleavage of supercoiled DNA by ascorbate/Cu(II). , 1989, Nucleic acids research.

[61]  R. Fiel.  Porphyrin-nucleic acid interactions: a review. , 1989, Journal of biomolecular structure & dynamics.

[62]  D. R. Eaton,et al.  Oxidation of cobalt(II) amine complexes to mononuclear cobalt(III) complexes by dioxygen , 1987 .

[63]  J. Dabrowiak,et al.  DNA cleavage specificity of a group of cationic metalloporphyrins. , 1986, Biochemistry.

[64]  A. R. Morgan,et al.  The mechanism of DNA strand breakage by vitamin C and superoxide and the protective roles of catalase and superoxide dismutase. , 1976, Nucleic acids research.

[65]  F. Sitas.  IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (incl Sitas F.) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. A Review of Human Carcinogens , 2011 .

[66]  S. Ferrari,et al.  Vitamin B12 as a carrier for targeted platinum delivery: in vitro cytotoxicity and mechanistic studies , 2010, JBIC Journal of Biological Inorganic Chemistry.

[67]  Sanjay K. Jain,et al.  Vitamin B12-mediated transport: a potential tool for tumor targeting of antineoplastic drugs and imaging agents. , 2008, Critical reviews in therapeutic drug carrier systems.

[68]  G. Sheldrick.  A short history of SHELX. , 2008, Acta crystallographica. Section A, Foundations of crystallography.

[69]  G. Mostafa,et al.  Hydrogen-bonded assembly of water and chloride in a 3D supramolecular host , 2006 .

[70]  M. Mascal,et al.  Water oligomers in crystal hydrates--what's news and what isn't? , 2005, Angewandte Chemie.

[71]  C. Pettinari,et al.  1.10 – Polypyrazolylborate and Scorpionate Ligands , 2003 .

[72]  P. M. Reis,et al.  Amavadine as a catalyst for the peroxidative halogenation, hydroxylation and oxygenation of alkanes and benzene , 2000 .

[73]  Osinsky Sp,et al.  pH-dependent organocobalt sources for active radical species: a new type of anticancer agents. , 1999 .

[74]  S. Trofimenko.  Scorpionates: The Coordination Chemistry of Polypyrazolylborate Ligands , 1999 .