Tridentate N(2)S ligand from 2,2'-dithiodibenzaldehyde and N,N-dimethylethylenediamine: Synthesis, structure, and characterization of a Ni(II) complex with relevance to Ni Superoxide Dismutase

Nickel Superoxide Dismutase (NiSOD) and the A-cluster of Carbon Monoxide Dehydrogenase/Acetyl Coenzyme A Synthase (CODH/ACS) both feature active sites with Ni coordinated by thiolate and amide donors. It is likely that the particular set of donors is important in tuning the redox potential of the Ni center(s). We report herein an expansion of our efforts involving the use of 2,2′-dithiodibenzaldehyde (DTDB) as a synthon for metal-thiolate complexes to reactions with Ni complexes of N,N-dimethylethylenediamine (dmen). In the presence of coordinating counterions, these reactions result in monomeric square-planar complexes of the tridentate N₂S donor ligand derived from the Schiff-base condensation of dmen and DTDB. In the absence of a coordinating counterion, we have isolated a Ni(II) complex with an asymmetric N₂S₂ donor set involving one amine and one imine N donor in addition to two thiolate donors. This latter complex is discussed with respect to its relevance to the active site of NiSOD.     

Manganese(II) tri-tert-butoxysilanethiolate complexes with imidazole-based coligands: a neutral complex with four independent ligands and MNOS2 core (M=Mn) related to the liver alcohol dehydrogenase catalytic center (M=Zn)

The reaction of [Mn{SSi(OBu(t))3}2(MeOH)4] with imidazole and its two methyl substituted derivatives leads to different types of heteroleptic manganese(II) thiolate complexes. Reaction with 1-methylimidazole gives the silanethiolate devoid of methanol but with two nitrogen ligands and thus central MnN(2)S(2) core. The reaction with imidazole leads to the methanol solvated complex with only one nitrogen ligand but manganese coordination sphere enlarged to MnO(2)NS(2) due to an O,S-chelation by tri-tert-butoxysilanethiolate ligand. Molecules of this compound interact through a set of N-H...(Me)O-H...S hydrogen bonds with methanol hydroxyl group being simultaneously acceptor and donor. With 2-methylimidazole the product is an assembly of two different neutral complexes joined again by hydrogen bonds, however, this time of N-H...S type. One of these complexes has the previously mentioned MnO(2)NS(2) core. The second neutral complex exhibits four donor atoms (MnNOS(2)core) derived from four independent ligands, i.e., two silanethiolate rests, one N-heterocyclic base and one alcohol. This structure presents similarities with a zinc-based alcohol dehydrogenase active site that have never been obtained before, including with other metals (Zn, Co). It may, therefore, be considered the first neutral structural model of liver alcohol dehydrogenase (LADH).     

Synthetic routes to mixed-ligand cobalt(III) dithiocarbamato complexes containing imidazole, amine and pyridine donors and the X-ray crystal structure of a cobalt(III) bis(dithiocarbamato) histamine complex

The binuclear cobalt complex [Co(2)(Me(2)dtc)(5)](+) reacts with a range of nitrogen donor ligands L' or L' to form an equimolar mixture of Co(Me(2)dtc)(3) and the mixed-ligand complexes [Co(Me(2)dtc)(2)(L')(2)](+) or [Co(Me(2)dtc)(2)(L')](+), where (L')(2) is two monodentate ligands and (L') is one bidentate ligand. The complexes prepared by this route contain the monodentate ligands L'=1-methyl-imidazole, 1-methyl-5-nitro-imidazole and benzimidazole, all of which coordinate to cobalt through an imidazole nitrogen atom. Symmetrical bidentate ligand complexes contain the bisimidazole L'=2,2'-bis(4,5-dimethylimidazole), the diamine L'=1,2-diaminobenzene and the pyridine donors L'=2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine and 1,10-phenanthroline. Two examples of complexes with unsymmetrical bidentate imidazole-amine donors were prepared in which L'=4-(2-aminoethyl)imidazole (histamine) and 2-aminomethylbenzimidazole. All new complexes were fully characterised, and the X-ray crystal structure of the histamine complex [Co(Me(2)dtc)(2)(hist)]ClO(4) is also reported.     

Synthesis,characterization, and biological evaluation of technetium(III) complexes with tridentate/bidentate S,E,S/P,S coordination (E = O,N(CH(3)), S): a novel approach to robust technetium chelates suitable for linking the metal to biomolecules

A novel type of mixed-ligand Tc(III) complexes, [Tc(SCH(2)CH(2)-E-CH(2)CH(2)S)(PR(2)S)] (E = S, N(CH(3)); PR(2)S = phosphinothiolate with R = aryl, alkyl) is described. These "3+2"-coordinated complexes can be prepared in a two-step reduction/substitution procedure via the appropriate chloro-containing oxotechnetium(V) complex [TcO(SES)Cl] [E=S, N(CH(3)]. Tc(III) compounds have been fully characterized both in solid and solution states and found to adopt the trigonal-bipyramidal coordination geometry. The equatorial trigonal plane is formed by three thiolate sulfur atoms, whereas the phosphorus of the bidentate P,S ligand and the neutral donor of the tridentate chelator occupy the apical positions. The (99)Tc(III) complexes have been proven to be identical with the (99m)Tc agents prepared at the no-carrier-added level by comparison of the corresponding UV/vis and radiometric HPLC profiles. Challenge experiments with glutathione clearly indicate that this tripeptide has no effect on the stability of the (99m)Tc complexes in solutions. Biodistribution studies have been carried out in rats at 5 and 120 min postinjection. The substituents at the bidentate P,S ligand significantly influence the biodistribution pattern. Remarkable differences are observed especially in brain, blood, lungs, and liver. All the complexes are able to penetrate the blood-brain barrier of rats and showed a relatively fast washout from the brain.     

Characterization of dioxygenated cobalt(II)-carnosine complexes by Raman and IR spectroscopy

Raman and IR studies are carried out on carnosine (beta-alanyl-L-histidine, Carnos) and its complexes with cobalt(II) at different metal/ligand ratios and basic pH. Binuclear complexes that bind molecular oxygen are formed and information regarding the O-O bridge is obtained from the Raman spectra. When the Co(II)/Carnos ratio is 相似文献   

Zinc-thiolate intermediate in catalysis of methyl group transfer in Methanosarcina barkeri.

Methyl group transfer reactions are essential in methane-forming pathways in all methanogens. The involvement of zinc in catalysis of methyl group transfer was studied for the methyltransferase enzyme MT2-A important for methanogenesis in Methanosarcina barkeri growing on methylamines. Zinc was shown to be required for MT2-A activity and was tightly bound by the enzyme with an apparent stability constant of 10(13.7) at pH 7.2. Oxidation was a factor influencing activity and metal stoichiometry of purified MT2-A preparations. Methods were developed to produce inactive apo MT2-A and to restore full activity with stoichiometric reincorporation of Zn(2+). Reconstitution with Co(2+) yielded an enzyme with 16-fold higher specific activity. Cysteine thiolate coordination in Co(2+)-MT2-A was indicated by high absorptivity in the 300-400 nm charge transfer region, consistent with more than one thiolate ligand at the metal center. Approximate tetrahedral geometry was indicated by strong d-d transition absorbance centered at 622 nm. EXAFS analyses of Zn(2+)-MT2-A revealed 2S + 2N/O coordination with evidence for involvement of histidine. Interaction with the substrate CoM (2-mercaptoethanesulfonic acid) resulted in replacement of the second N/O group with S, indicating direct coordination of the CoM thiolate. UV-visible spectroscopy of Co(2+)-MT2-A in the presence of CoM also showed formation of an additional metal-thiolate bond. Binding of CoM over the range of pH 6.2-7.7 obeyed a model in which metal-thiolate formation occurs separately from H(+) release from the enzyme-substrate complex. Proton release to the solvent takes place from a group with apparent pK(a) of 6.4, and no evidence for metal-thiolate protonation was found. It was determined that substrate metal-thiolate bond formation occurs with a Delta G degrees ' of -6.7 kcal/mol and is a major thermodynamic driving force in the overall process of methyl group transfer.     

1H NMR spectroscopic characterization of binary and ternary complexes of cobalt(II) carboxypeptidase A with inhibitors

The binding of L- and D-phenylalanine and carboxylate inhibitors to cobalt(II)-substituted carboxypeptidase A, Co(II)CPD (E), in the presence and absence of pseudohalogens (X = N3-, NCO-, and NCS-) has been studied by 1H NMR spectroscopy. This technique monitors the proton signals of histidine residues bound to cobalt(II) and is therefore sensitive to the interactions of inhibitors that perturb the coordination sphere of the metal. Enzyme-inhibitor complexes, E.I, E.I2, and E.I.X, each with characteristic NMR features, have been identified. Thus, for example, L-Phe binds close to the metal ion to form a 1:1 complex, whereas D-Phe binds stepwise, first to a nonmetal site and then to the metal ion to form a 2:1 complex. Both acetate and phenylacetate also form 2:1 adducts stepwise with the enzyme, but beta-phenylpropionate gives a 2:1 complex without any detectable 1:1 intermediate. N3-, NCO-, and NCS- generate E.I.X ternary complexes directly with Co(II)CPD.L-Phe and indirectly with the D-Phe and carboxylate inhibitor 2:1 complexes by displacing the second moiety from its metal binding site. The NMR data suggest that when the carboxylate group of a substrate or inhibitor binds at the active site, a conformational change occurs that allows a second ligand molecule to bind to the metal ion, altering its coordination sphere and thereby attenuating the bidentate behavior of Glu-72. The 1H NMR signals also reflect alterations in the histidine interactions with the metal upon inhibitor binding. Isotropic shifts in the signals for the C-4 (c) and N protons (a) of one of the histidine ligands are readily observed in all of these complexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

4′-(4-Pyridyl)-2,2′:6′,2″-terpyridine as ligand in the lead(II) complexes, [Pb(pyterpy)(MeOH)I2] · MeOH and [Pb(pyterpy)(μ-AcO)]2(ClO4)2

Two new lead(II) complexes with the ligand 4′-(4-pyridyl)-2,2′:6′,2″-terpyridine (pyterpy), [Pb(pyterpy)(MeOH)I₂] · MeOH and [Pb(pyterpy)(μ-AcO)]₂(ClO₄)₂, have been synthesized and characterized by CHN elemental analysis, ¹H NMR-, ¹³C NMR-, IR spectroscopy and structurally analyzed by X-ray single-crystal diffraction. The thermal stabilities of these compounds were studied by thermal gravimetric (TG) and differential thermal analyses (DTA). The single crystal X-ray analyses show that the coordination number in these complexes is six with three “pyterpy” N-donor atoms and two or three of the anionic ligands. The arrangement of donor atoms in these complexes suggest a gap or hole in the coordination geometry of the lead atoms, possibly occupied by a stereoactive lone pair of electrons on lead(II) and the coordination sphere is hemidirected. The potentially tetradentate ligand 4′-(4-pyridyl)-2,2′:6′,2″-terpyridine (pyterpy) acts as a tridentate donor to Pb(II). The noncoordinated pyridyl group interacts with hydrogen atoms of adjacent molecules and forms normal hydrogen bonds in [Pb(pyterpy)(MeOH)I₂] · MeOH and weak C-H?N interactions for [Pb(pyterpy)(μ-AcO)]₂(ClO₄)₂, thus extending the monomeric structures into one-dimensional networks.     

Electron spin echo modulation and nuclear relaxation studies of staphylococcal nuclease and its metal-coordinating mutants

Electron spin echo envelope modulation (ESEEM) spectroscopy has been applied to the determination of the number of water molecules coordinated to the metal in the binary complex of staphylococcal nuclease with Mn2+, to the ternary enzyme-Mn2+-3',5'-pdTp complex, and to ternary complexes of a number of mutant enzymes in which metal-binding ligands have been individually altered. Quantitation of coordinated water is based on ESEEM spectral comparisons of Mn2+-EDTA and Mn2+-DTPA, which differ by a single inner sphere water, and with Mn2+-(H2O)6. It was found that Mn2+ in the ternary complex of the wild-type enzyme has a single additional coordinated water, as compared to Mn2+ in the binary complex, confirming earlier findings based on T1 measurements of bound water [Serpersu, E. H., Shortle, D. L., & Mildvan, A. S. (1987) Biochemistry 26, 1289-1300]. Ternary complexes of the mutant proteins D40E, D40G, and D21Y have the same number of water ligands as the ternary complex of the wild-type enzyme, while the D21E mutant has one less water ligand. In order to maintain octahedral coordination geometry, these findings require two additional ligands to Mn2+ from the protein in the binary complex of the wild-type enzyme, probably Glu 43 and Asp 19, and one additional ligand from the protein in the ternary D40G and D21E complexes. Other ESEEM studies of ternary Mn2+ complexes of wild-type, D21E, and D21Y mutants indicate the coordination by Mn2+ of a phosphate of 3',5'-pdTp, as demonstrated by a 31P contact interaction of 3.9 +/- 0.3 MHz. Magnetic interaction of Mn2+ with 31P could not be demonstrated with the D40G and D40E mutants, suggesting that metal-phosphate distances are greater in these mutants than in the wild-type protein. In a parallel NMR study of the paramagnetic effects of enzyme-bound Co2+ (which occupies the Mn2+ site on the enzyme) on the T1 of 31P from enzyme-bound 3',5'-pdTp and 5'-TMP, it was found that metal to 5'-phosphate distances are 0.9-1.6 A shorter in ternary complexes of the wild-type enzyme and of the D21E mutant than in ternary complexes of the D40G mutant. In all cases, the 5'-phosphate of pdTp is in the inner coordination sphere of Co2+ and the 3'-phosphate is predominantly in the second coordination sphere.     

Synthesis and X-ray crystal structures of two transition metal complexes based on functionalised 1,5-anhydro-2-deoxy-D-galactitol and methyl 2-deoxy-alpha-D-galactopyranoside

Two new ligands of transition metal cations based on galactose-derived scaffolds were synthesised: 1,5-anhydro-2-deoxy-3,4,6-tri-O-(2-picolyl)-D-galactitol and methyl 2-deoxy-3,4,6-tri-O-(2-picolyl)-alpha-D-galactopyranoside. These ligands permitted the isolation as single crystals of a Co(II) and a Ni(II) complex, respectively. The structures of both complexes were determined by X-ray crystallography showing a coordination sphere including sugar-bound oxygen atoms. The sugar-derived ligands were found to be in both cases in high energy conformations in the crystal structures of the complexes. These conformations contain an arrangement of sugar-bound oxygen atoms similar to those observed in polyol-metal and carbohydrate-metal complexes.     

Electron paramagnetic resonance investigations of exogenous ligand complexes of low-spin ferric chloroperoxidase: further support for endogenous thiolate ligation to the heme iron.

Previous spectroscopic studies of chloroperoxidase have provided evidence for endogenous thiolate sulfur donor ligation to the central heme iron of the enzyme. This conclusion is further supported by recent DNA sequence data which revealed the existence of a third cysteine residue (in addition to a disulfide pair detected earlier) in the protein available for coordination to the heme iron. Thus, chloroperoxidase shares many spectroscopic properties with cytochrome P-450, the only other known thiolate-ligated heme protein. Surprisingly, a previous electron paramagnetic resonance (EPR) study of low-spin ferric chloroperoxidase-ligand complexes (Hollenberg, P.F., Hager, L.P., Blumberg, W.E. and Peisach, J. (1980) J. Biol. Chem. 255, 4801-4807) was unable to provide clear support for the presence of a thiolate ligand, although sulfur coordination was implicated. This was, in part, because an insufficient number of complexes was examined. In this work, we have significantly expanded upon the previous EPR study by using an extensive variety of over twenty exogenous ligands including carbon, nitrogen, oxygen, phosphorus and sulfur donors. Crystal field analysis, using the procedure of Blumberg and Peisach, of the present data in comparison with data for analogous complexes of cytochrome P-450-CAM, thiolate-ligated heme model systems, and myoglobin, is clearly indicative of endogenous thiolate ligation for chloroperoxidase. In addition, the UV-visible absorption and EPR spectral data suggest that a carboxylate ligand is a possible candidate for the endogenous sixth ligand to the heme iron that is responsible for the reversible conversion of ferric chloroperoxidase from high-spin to low-spin at low temperatures (less than 200 K).     

Syntheses and crystal structures of mono-, di- and trinuclear cobalt complexes of a salen type ligand

Three cobalt complexes containing the salen type ligand, bis(salicylidene)-meso-1,2-diphenylethylenediaminato (mdpSal²⁻), are reported. The complexes differ in nuclearity and include the mononuclear, Co(mdpSal) (1), which contains a Co(II) metal center bound to one mdpSal⁻² ligand frame in a square planar geometry. The second complex is the dinuclear [Co(mdpSal)Cl]₂ (2) in which both cobalt ions have been oxidized to the +3 oxidation state. The overall geometry of complex 2 is an edge-sharing bioctahedron with the coordination sphere around each cobalt metal center consisting of one mdpSal⁻² ligand and one Cl⁻ ion. The shared edge between the Co(III) ions contains two bridging phenolate groups, one from each ligand frame. Complex 3 is a linear, mixed valence, trinuclear species, [Co(mdpSal)(OAc)(μ-OAc)]₂Co, with the oxidation states of the metal centers assigned as Co(III)-Co(II)-Co(III). The terminal Co(III) centers are equivalent with the central Co(II) lying on the inversion center of the molecule. Each cobalt ion in 3 adopts an octahedral geometry with the terminal Co(III) ions being bound to one mdpSal²⁻ ligand each. All phenolate groups bridge to the central Co(II). The coordination sphere about each metal center in the trinuclear complex is completed by four acetate groups, two of which bind in a μ-fashion bridging from the terminal Co(III) metal centers to the central Co(II). The complexes have been characterized by X-ray crystallography as well as UV-Vis and IR spectroscopy.     

Structural preferences and thermal stability of complexes with the exo-bidentate ligand 1,2-bis(2-methylimidazol-1-ylmethyl)benzene

We describe a series of new coordination polymers of Cd(II), Co(II) and Ag(I) with 1,2-bis(2-methylimidazol-1-ylmethyl)benzene. All complexes were characterized by single crystal X-ray diffraction which reveals polymeric bridging of metal centers by the ligand in all cases. The cadmium center in complex 1 has a slightly irregular octahedral geometry involving two Cl⁻ ions and four N atoms from individual ligands, resulting in the formation of undulated (4,4) layers. In complex 2 the cobalt(II) ion is coordinated by two Cl⁻ ions and two N atoms from separate ligands. This yields a slightly irregular tetrahedral coordination environment around the metal center and the formation of a 1D zigzag-chain structure. Each of the three Ag(I) complexes (3-5) forms an infinite 1D chain. These three complexes are similar both in conformation and packing mode despite modification of the counterions. The size of the counterion appears to affect the thermal stabilities of the resulting networks.     

Metal coordination core of bleomycin : comparison of metal complexes between bleomycin and its biosynthetic intermediate.

On the basis of electron spin resonance results, the 1:1 Cu(II), Co(II), Co(II)-O₂, and Ni(III) complexes of bleomycin(BLM) have been compared with the corresponding metal complexes of its biosynthetic intermediate(P-3A). The present study suggests that (1) P-3A is an useful ligand for the clarification of metal-binding sites of BLM; (2) the secondary amine, pyrimidine ring nitrogen, deprotonated peptide nitrogen of histidine residue, and histidine imidazole groups as planar ligand donors, and the α-amino group as axial donor, are substantially important for metal-coordination of BLM; and (3) the sugar and bithiazole portions of BLM probably contribute to stabilization of Co(II)-O₂ adduct complex and axial sixth coordination of Cu(II) and Ni(III) complexes.     

Electron paramagnetic resonance studies of MN(II) complexes with myosin subfragment 1 and oxygen 17-labeled ligands

Ligands in the first coordination sphere of Mn(II) in the complex of MnADP with myosin subfragment 1 from rabbit skeletal muscle have been investigated. EPR spectroscopy was used to detect superhyperfine coupling between unpaired electrons of the metal ion and the nuclei of oxygen atoms specifically labeled with oxygen 17. The results show that ADP is a beta-monodentate ligand for Mn(II) and that there are probably two water oxygens directly bound to Mn(II). The inhibitory complex of vanadate with subfragment 1 . MnADP was also investigated. Vanadate-dependent changes in the EPR spectra for enzyme-bound Mn(II) indicate that the coordination sphere of MN(II) changes upon binding of vanadate. ADP remains a beta-monodenate ligand in the complex and experiments with 17O-labeled water indicate that two oxygen atoms originally in water are ligands in the complex. However, the oxygens of vanadate equilibrate with those of water during sample preparation so that one of these ligands may be a vanadate oxygen. Three additional ligands, probably from the protein, are required to complete the sextet of ligands to Mn(II) in both complexes studied.     

Copper(II) and nickel(II) ternary complexes of L-dopa and related compounds

The stability constants of the mixed ligand complexes of L-dopa, L-tyrosine, L-phenylalanine, and dopamine with copper(II) and nickel(II) ions and with 2,2'-bipyridyl and 1,10-phenanthroline were determined pH-metrically at 25 degrees C and an ionic strength of 0.2 mol/dm3 (KCl). Spectral studies were made to establish the binding mode of the ambidentate L-dopa in the ternary complexes. In contrast with the aromatic (N,N) donor atoms, the (O,O) binding mode of L-dopa is particularly favored in its ternary systems with copper(II) and nickel(II); thus, even at physiological pH there is a very considerable formation of (O,O)-bound mixed ligand complexes containing a free amino acid side-chain. Numerous binary transition metal-L-dopa complexes and the ternary complexes formed with various B ligands have been evaluated from a coordination chemistry aspect, with regard to the possibility of their therapeutic application in the treatment of Parkinson disease.     

Spectral studies of cobalt (II)- and Nickel (II)-metallothionein

The zinc and cadmium of native rabbit metallothionein-1 were replaced stoichiometrically with either cobalt (II) or nickel (II). The electronic, magnetic circular dichroic (MCD), and electron spin resonance spectra of Co (II)-metallothionein reflect distorted tetrahedral coordination of the cobalt atoms. Both the d-d and charge-transfer spectral regions closely resemble those of simple cobalt-tetrathiolate complexes, implying that their coordination chemistry is analogous. Ni (II) complex ions and Ni (II)-metallothionein similarly exhibit analogous MCD bands in the d-d region. The circular dichroic bands associated with ligand-metal charge-transfer transitions in the non-d-d region of Co (II)- and Ni (II)-metallothionein afford additional evidence for the similarity in tetrahedral microsymmetry of the two metal derivatives. The known ratio of 20 thiolate ligands to 7 metal ions, in conjunction with the spectral evidence for tetrathiolate coordination in metallothionein, represents good evidence that these metal thiolates are organized in clusters.     

Nuclear magnetic resonance studies of the solution chemistry of metal complexes. 26. Mixed ligand complexes of cadmium, nitrilotriacetic acid, glutathione, and related ligands

The complexation of glutathione and related ligands by the nitrilotriacetic acid complex of Cd2+ (Cd(NTA)-) has been investigated by 1H NMR as a model for the coordination chemistry of Cd2+ and GSH in biological systems. Related ligands included glycine, glutamic acid, cysteine, N-acetylcysteine, penicillamine, N-acetylpenicillamine, mercaptosuccinic acid, and the S-methyl derivative of glutathione. The nature of the complexes formed was deduced from 1H NMR spectra of Cd(NTA)- and the ligands. Mixed ligand complexes (Cd(NTA)L) and single ligand complexes (CdLx) are formed with the thiol ligands, whereas only mixed ligand complexes form with glycine, glutamic acid and S-methylglutathione. Formation constants of the mixed and the single ligand complexes were determined from NMR data. The results indicate that formation constants for binding of a thiolate donor group by Cd2+, either as the free ion or in a coordinately unsaturated complex, are in the range 10(5)-10(6).     

Interaction of metallothionein-2 with platinum-modified 5'-guanosine monophosphate and DNA

Human metallothioneins (MTs), a family of cysteine- and metal-rich metalloproteins, play an important role in the acquired resistance to platinum drugs. MTs occur in the cytosol and the nucleus of the cells and sequester platinum drugs through interaction with their zinc-thiolate clusters. Herein, we investigate the ability of human Zn 7MT-2 to form DNA-Pt-MT cross-links using the cisplatin- and transplatin-modified plasmid DNA pSP73. Immunochemical analysis of MT-2 showed that the monofunctional platinum-DNA adducts formed DNA- cis/ trans-Pt-MT cross-links and that platinated MT-2 was released from the DNA- trans-Pt-MT cross-links with time. The DNA- cis/ trans-Pt-MT cross-links were also formed in the presence of 2 mM glutathione, a strong S-donor ligand. Independently, we used 5'-guanosine monophosphate (5'-GMP) platinated at the N7 position as a model of monofunctional platinum-DNA adducts. Comparison of reaction kinetics revealed that the formation of ternary complexes between Zn 7MT-2 and cis-Pt-GMP was faster than that of the trans isomer. The analysis of the reaction products with time showed that while the formation of ternary GMP- trans-Pt-MT complex(es) is accompanied by 5'-GMP release, a stable ternary GMP- cis-Pt-MT complex is formed. In the latter complex, a fast initial formation of two Pt-S bonds was followed by a slow formation of an additional Pt-S bond yielding an unusual Pt(II)S 3N coordination with N7-GMP as the only N-donor ligand. The ejection of negligible zinc from the zinc-thiolate clusters implies the initial formation of Zn-(mu-SCys)-Pt bridges involving the terminal thiolate ligands. The biological implications of these studies are discussed.     

Synthesis, characterization, X-ray structure and DNA photocleavage by cis-dichloro bis(diimine) Co(III) complexes

Complexes of the type [Co(LL)2Cl2]Cl, where LL = N,N'-ethylenediamine (en), 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendione) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been synthesized and characterized by elemental analyses, IR, UV-visible and NMR spectroscopy. Crystal structure of [Co(phendione)2Cl2]Cl x 0.5 HCl x 3.5 H2O has been solved and refined to R = 0.0552. The crystal is monoclinic with space group C2/c; a = 25.730(2) A, b = 12.375(1) A, c = 18.979(2) A, beta = 119.925(1) degrees and Z = 8. The DNA binding characteristics of the complexes, investigated by covalent binding assay, viscosity measurements and competitive binding fluorescence measurements show that the complexes interact with DNA covalently except the complex containing the planar dppz ligand which intercalates within the base pairs of DNA. The complexes containing en, phen and phendione cleave plasmid pBR 322 DNA upon irradiation under aerobic conditions while the complex containing the dppz ligand cleaves DNA upon irradiation under inert atmosphere. Molecular modeling studies show that the minimized structure of [Co(phendione)2Cl2]+, maintained the octahedral structure while binding to the N7 of guanines and the ligand fits into the major groove without disrupting the helical structure of the B-DNA.