Synthesis, characterization, and DNA binding and cleavage properties of copper(II)-tryptophanphenyl-alanine-1,10-phenanthroline/2,2'-bipyridine complexes

The mononuclear dipeptide‐based Cu^II complexes [Cu^II(trp‐phe)(phen)(H₂O)] ⋅ ClO₄ ( 1 ) and [Cu^II(trp‐phe)(bpy)(H₂O)] ⋅ ClO₄ ( 2 ) (trp‐phe=tryptophanphenylalanine, phen=1,10‐phenanthroline, bpy=2,2′‐bipyridine) were isolated, and their interaction with DNA was studied. They exhibit intercalative mode of interaction with DNA. The intercalative interaction was quantified by Stern Volmer quenching constant (K_sq=0.14 for 1 and 0.08 for 2 ). The Cu^II complexes convert supercoiled plasmid DNA into its nicked circular form hydrolytically at physiological conditions at a concentration as low as 5 μM (for 1 ) and 10 μM (for 2 ). The DNA hydrolysis rates at a complex concentration of 50 μM were determined as 1.74 h⁻¹ (R=0.985) for 1 and 0.65 h⁻¹ (R=0.965) for 2 . The rate enhancement in the range of 2.40–4.10×10⁷‐fold compared to non‐catalyzed double‐stranded DNA is significant. This was attributed to the presence of a H₂O molecule in the axial position of the Cu complexes.     

DNA binding and nuclease activity of copper(II) complexes of tridentate ligands

Two copper(II) complexes, 1 and 2 with L₁ and L₂ [L₁ = 2-hydroxybenzyl(2-(pyridin-2-yl)ethylamine); L₂ = 2-hydroxybenzyl(2-(pyridin-2-yl)methylamine)] ligands, respectively, have been synthesized and characterized. The interaction of both the complexes with DNA has been studied to explore their potential biological activity. The DNA binding properties of the complexes with calf thymus (CT) DNA were studied by spectroscopic titration. The complexes show binding affinity to CT DNA with binding constant (K_b) values in the order of 10⁵ M⁻¹. Thermal denaturation and circular dichroism studies suggest groove binding of the complexes to CT DNA. Complexes also exhibit strong DNA cleavage activity in presence of reducing agents like 3-mercaptopropionic acid and β-mercaptoethanol. Mechanistic studies reveal the involvement of reactive hydroxyl radicals for their DNA cleavage activity.     

Synthesis, DNA binding, and cleavage studies of novel PNA binding cyclen complexes

A novel coumarin‐appended PNA binding cyclen derivative ligand, C1 , and its copper(II) complex, C2 , have been synthesized and characterized. The interaction of these compounds with DNA was systematically investigated by absorption, fluorescence, and viscometric titration, and DNA‐melting and gel‐electrophoresis experiments. DNA Melting and viscometric titration experiments indicate that the binding mode of C1 is a groove binding, and C2 is a multiple binding mode that involves groove binding and electrostatic binding. From the absorption‐titration data, we can state that the primary interaction between CT DNA and the two compounds may be H‐bonds between nucleobases. Fluorescence studies indicate that the binding ability of C1 to d(A)₉ is as twice or thrice as that of other oligodeoxynucleotides. Agarose gel‐electrophoresis experiments demonstrate that C2 is an excellent chemical nuclease, which can cleave plasmid DNA completely within 24 h.     

Synthesis, structure, DNA binding and DNA cleavage activity of oxovanadium(IV) N-salicylidene-S-methyldithiocarbazate complexes of phenanthroline bases

Ternary oxovanadium(IV) complexes [VO(salmdtc)(B)] (1-3), where salmdtc is dianionic N-salicylidene-S-methyldithiocarbazate and B is N,N-donor phenanthroline bases like 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 3), are prepared, characterized and their DNA binding and DNA cleavage activity studied. Complex 3 is structurally characterized by single-crystal X-ray crystallography. The molecular structure shows the presence of a vanadyl group in six-coordinate VN₃O₂S coordination geometry. The S-methyldithiocarbazate Schiff base acts as a tridentate NSO-donor ligand in a meridional binding mode. The N,N-donor heterocyclic base displays a chelating mode of binding with an N-donor site trans to the vanadyl oxo-group. The complexes show a d-d band in the range of 675-707 nm in DMF. They exhibit an irreversible oxidative cyclic voltammetric response near 0.9 V due to the V(V)/V(IV) couple and a quasi-reversible reductive V(IV)/V(III) redox couple near −1.0 V vs. SCE in DMF-0.1 M TBAP. The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range of 7.4 × 10⁴-2.3 × 10⁵ M⁻¹. The thermal denaturation and viscosity binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor chemical nuclease activity in dark in the presence of 3-mercaptopropionic acid (MPA) or hydrogen peroxide. The dpq and dppz complexes show efficient DNA cleavage activity in UV-A light of 365 nm via a type-II mechanistic pathway involving formation of singlet oxygen (¹O₂) as the reactive species.     

Chiral and achiral macrocyclic copper(II) complexes: Synthesis, characterization, and comparative binding studies with calf-thymus DNA

The new chiral macrocyclic complexes [1,2-bis(1H-benzimidazol-2-yl)-1-(1,8-dihydro-1,3,5,8,10,12-hexaazacyclotetradecane)-2-hydroxyethanolate] copper(II) and -nickel(II) perchlorate, 3 and 4, respectively, were synthesized by the reaction of 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol (L) and (1,8-dihydro-1,3,5,8,10,12-hexaazacyclotetradecane)copper(II) and -nickel(II) diperchlorate complexes, 1 and 2, respectively. All complexes were characterized by various spectroscopic techniques. Molar-conductance measurements showed that all of the complexes are ionic in nature. In complexes 3 and 4, the metal center is encapsulated by the ligand L in a pentacoordinated environment. The optical-rotation values ([alpha](D)) of 3 and 4 at 25 degrees indicate that the complexes are chiral. Absorption- and fluorescence-spectral studies, cyclic voltammetry, and viscosity measurements have been carried out to assess the comparative binding of complexes 1 and 3 with calf thymus (CT)-DNA. Analysis of the results suggests that the new chiral complex 3 binds to CT-DNA through a partial intercalation mode that is different from the binding mode of parent achiral complex 1. The complexes 1 and 3 bind to CT-DNA with binding constants K(b) of 2.7 x 10(4) and 6.6 x 10(4) M(-1), respectively. Circular-dichroism (CD) studies have been further employed to ascertain the binding mode of complex 3, which is consistent with the other spectral studies.     

Synthesis, DNA binding, photo-induced DNA cleavage, cytotoxicity and apoptosis studies of copper(II) complexes

Two new Cu(II) complexes, [Cu(acac)(dpq)Cl] () and [Cu(acac)(dppz)Cl] () (acac = acetylacetonate, dpq = dipyrido[3,2-d:20,30-f]quinoxaline, dppz = dipyrido[3,2-a:20,30-c] phenazine), have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes show good binding propensity to calf thymus DNA in the order: 2(dppz) > 1(dpq). Furthermore, two complexes exhibit efficient DNA cleavage activity on natural light or UV-A (365 nm) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The photo-induced DNA cleavage activity of the dppz complex 2 is found to be more efficient than its dpq analogue. In vitro study of the photocytotoxicity of two complexes on HeLa cells indicate that both of them have the potential to act as effective anticancer drugs, with IC₅₀ values of 5.25 ± 0.83 μM (1) and 4.40 ± 0.52 μM (2) in the natural light, and 2.57 ± 0.92 μM (1) and 2.18 ± 0.52 μM (2) in UV-A light. In addition, to detect an apoptotic HeLa body, cells were stained with Hoechst 33342 dye.     

Double-strand DNA cleavage induced by oxindole-Schiff base copper(II) complexes with potential antitumor activity

Some oxindole-Schiff base copper(II) complexes have already shown potential antitumor activity towards different cells, inducing apoptosis in a process modulated by the ligand, and having nuclei and mitochondria as main targets. Here, three novel copper(II) complexes with analogous ligands were isolated and characterized by spectroscopic techniques, having their reactivity compared to the so far most active complex in this class. Cytotoxicity experiments carried out toward human neuroblastoma SH-SY5Y cells confirmed its pro-apoptosis property. DNA cleavage studies were then performed in the presence of these complexes, in order to verify the influence of ligand structural features in its nuclease activity. All of them were able to cause double-strand DNA scissions, giving rise to nicked circular Form II and linear Form III species, in the presence of hydrogen peroxide. Additionally, DNA Form II was also detected in the absence of peroxide when the most active complex, [Cu(isaepy)₂]²⁺ 1, was used. In an effort to better elucidate their interactions with DNA, solutions of the different complexes titrated with DNA had their absorption spectra monitored. An absorbance hyperchromism observed at 260 nm pointed to the intercalation of these complexes into the DNA structure. Further, investigations of 2-deoxy-d-ribose (DR) oxidation catalyzed by each of those complexes, using 2-thiobarbituric acid reactive species (TBARS) method, and detection of reactive oxygen species (ROS) formation by spin-trapping EPR, suggested that their mechanism of action in performing efficiently DNA cleavage occurs preferentially, but not only by oxidative pathways.     

Synthesis, crystal structure, DNA binding and photo-induced DNA cleavage activity of (S-methyl-L-cysteine)copper(II) complexes of heterocyclic bases

Ternary S-methyl-L-cysteine (SMe-l-cys) copper(II) complexes [Cu(SMe-L-cys)(B)(H(2)O)](X) (1-4), where the heterocyclic base B is 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyridoquinoxaline (dpq, 3) and dipyridophenazine (dppz, 4), and X is ClO(4)(-) (1-3) or NO(3)(-) (4), are prepared and their DNA binding and cleavage properties studied. Complexes 2 and 4 are structurally characterized by X-ray crystallography. Both the crystal structures show distorted square-pyramidal (4+1) CuN(3)O(2) coordination geometry of the complexes in which the N,O-donor S-methyl-L-cysteine and N,N-donor heterocyclic base bind at the basal plane with a water molecule as the axial ligand. In addition, the dppz structure shows the presence of a 1D-chain formed due to covalent linkage of the carboxylate oxygen atom belonging to another molecule at the elongated axial site. The crystal structures show chemically significant non-covalent interactions like hydrogen bonding involving the axial aqua ligand and pi-pi interactions between dppz ligands. The complexes display a d-d band in the range of 605-654 nm in aqueous dimethylformamide (DMF) solution (9:1 v/v). The redox active complexes show quasireversible cyclic voltammetric response near 0.1 V in DMF assignable to the Cu(II)/Cu(I) couple. The complexes show good binding affinity to calf thymus (CT) DNA giving the order: 4 (dppz)>3 (dpq)>2 (phen)>1 (bpy). The intrinsic binding constants, obtained from UV-visible spectroscopic studies, are 1.3x10(4) and 2.15 x 10(4) M(-1) for 3 and 4, respectively. Control DNA cleavage experiments using pUC19 supercoiled (SC) DNA and minor groove binder distamycin suggest major groove binding propensity for the dppz complex, while the phen and dpq complexes bind at the minor groove of DNA. Complexes 2-4 show DNA cleavage activity in dark in the presence of a reducing agent 3-mercaptopropionic acid (MPA) via a mechanistic pathway involving formation of hydroxyl radical as the reactive species. The complexes also show efficient photo-induced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency follows the order: 3>4>2. The complexes exhibit significant DNA cleavage activity on irradiation with visible light of 633 nm. Control experiments show inhibition of cleavage in presence of singlet oxygen quenchers like sodium azide, histidine and enhancement of cleavage in D(2)O, suggesting formation of singlet oxygen as a reactive species in a type-II process. The photosensitizing effect of the thiomethyl group of the amino acid is evidenced from the observation of significant DNA photocleavage activity of the phen complex 2 as the phen ligand itself is not a photosensitizer.     

DNA interaction of new copper(II) complexes with sulfonamides as ligands

New copper(II) complexes with sulfonamide ligands have been prepared and characterized. Sulfonamide ligands were prepared through a reaction between 8-aminoquinoline and either 2-mesitylene (Hqmesa), 4-tert-butylbenzene (Hqtbsa), or alpha-toluene (Halphaqtsa) sulfonyl chlorides. The structural analysis carried out for complex [Cu(alphaqtsa)(2)] indicated that the local environment of the Cu(II) cation is between a square planar and a tetrahedral geometry, with stacking of the benzene rings of the sulfonyl ligands between neighbor molecules. Powder EPR spectra at room temperature gave rhombic spectra for the [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] complexes and an axial spectrum for the [Cu(qtbsa)(2)] complex, probably due to the steric hindrance of the methyl groups. Complexes [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] are artificial chemical nucleases that degrade DNA in the presence of sodium ascorbate. A study of the radical scavengers revealed that the ROS (reactive oxygen species) involved in the DNA damage were hydroxyl, singlet oxygen-like species, and superoxide anion.     

Human telomeric G-quadruplex DNA interactions of N-phenanthroline glycosylamine copper(II) complexes

We report in this article the interactions of five N-(1,10-phenanthrolin-5-yl)-β-glycopyranosylamine copper(II) complexes with G-quadruplex DNA. Specifically, the interactions of these compounds with a human telomeric oligonucleotide have been assessed by fluorescence-based assays (FRET melting and G4-FID), circular dichroism and competitive equilibrium dialysis experiments. The metal complexes bind and stabilize G-quadruplex DNA structures with apparent association constants in the order of 10⁴–10⁵ M⁻¹ and the affinity observed is dependent on the ionic conditions utilized and the specific nature of the carbohydrate moiety tethered to the 1,10-phenanthroline system. The compounds showed only a slight preference to bind G-quadruplex DNA over duplex DNA when the quadruplex DNA was folded in sodium ionic conditions. However, the binding affinity and selectivity, although modest, were notably increased when the G-quadruplex DNA was folded in the presence of potassium metal ions. Moreover, the study points towards a significant contribution of groove and/or loop binding in the recognition mode of quadruplex structures by these non-classical quadruplex ligands. The results reported herein highlight the potential and the versatility of carbohydrate bis-phenanthroline metal-complex conjugates to recognize G-quadruplex DNA structures.     

Aminoalcohols incorporating a piperazine ring: Synthesis, complexation of a hexadentate ligand and DNA cleavage capability of copper(II) complexes

The facility of aminoalcohol ligand synthesis via ring opening of cyclohexene oxide with polyamines including a piperazine ring is illustrated here with the syntheses and characterization of (2′-hydroxycyclohexyl)piperazine (1), bis(2′-hydroxycyclohexyl)-piperazine (2), 4-{(2″-hydroxycyclohexyl)-2′-aminoethyl)}piperazine (3), 1-(2″-hydroxycyclohexyl)-4-{(2″-hydroxycyclohexyl)-2′-aminoethyl)}piperazine (4), and 1,4-bis[(2″-hydroxycyclohexyl)-3′-aminopropyl]piperazine (5) described, along with an analogue of 4 in which a single -CH₂-CH₂- alkyl chain replaces the piperazine ring, 1,5-bis[(2′-hydroxycyclohexyl)amine]-3-azapentane (6). The viability of 5 as a hexadentate ligand was established by preparation of its copper(II) complex and subsequent X-ray crystal structure analysis. The complex [Cu(5)](ClO₄)₂ cation lies in a distorted octahedral environment with the four nitrogen donors in an approximate plane also incorporating the copper (Cu-N_tert 2.058(4) A; Cu-N_sec 2.072(4) A) and the two alcohol groups occupying axial sites with elongated bonds (Cu-O 2.415(3) A). The piperazine ring adopts a ‘butterfly wing’ geometry, whereas the two cyclohexane rings are in chair conformations. Significant bond angle distortions occur around the copper, exacerbated by the axial Jahn-Teller bond length distortion. The ability of the copper(II) complexes of the aminoalcohols to promote DNA cleavage was examined. Complexes of 2, 3 and 5 are effectively inactive whereas 4 is an efficient single strand cleavage promoter; however, the more flexible close analogue of 4, 6, also proved ineffective. Such observations for a closely related series indicate the subtle influences of spectator ligand rigidity and steric congestion on DNA cleavage promotion.     

Tris-chelated complexes of nickel(II) with bipyridine derivatives: DNA binding and cleavage,BSA binding,molecular docking,and cytotoxicity

Abstract

Two nickel(II) complexes with substituted bipyridine ligand of the type [Ni(NN)₃](ClO₄)₂, where NN is 4,4′-dimethyl-2,2′-bipyridine (dimethylbpy) (1) and 4,4′-dimethoxy-2,2′-bipyridine (dimethoxybpy) (2), have been synthesized, characterized, and their interaction with DNA and bovine serum albumin (BSA) studied by different physical methods. X-ray crystal structure of 1 shows a six-coordinate complex in a distorted octahedral geometry. DNA-binding studies of 1 and 2 reveal that both complexes sit in DNA groove and then interact with neighboring nucleotides differently; 2 undergoes a partial intercalation. This is supported by molecular-docking studies, where hydrophobic interactions are apparent between 1 and DNA as compared to hydrogen bonding, hydrophobic, and π–π interactions between 2 and DNA minor groove. Moreover, the two complexes exhibit oxidative cleavage of supercoiled plasmid DNA in the presence of hydrogen peroxide as an activator in the order of 1?>?2. In terms of interaction with BSA, the results of spectroscopic methods and molecular docking show that 1 binds with BSA only via hydrophobic contacts while 2 interacts through hydrophobic and hydrogen bonding. It has been extensively demonstrated that the nature of the methyl- and methoxy-groups in ligands is a strong determinant of the bioactivity of nickel(II) complexes. This may justify the above differences in biomolecular interactions. In addition, the in vitro cytotoxicity of the complexes on human carcinoma cells lines (MCF-7, HT-29, and U-87) has been examined by MTT assay. According to our observations, 1 and 2 display cytotoxicity activity against selected cell lines.

Communicated by Ramaswamy H. Sarma     

Synthesis, crystal structure, and DNA-cleaving behavior of 5-substituted benzene-1,3-bis(methylene)-spaced dinuclear copper(II) complexes

Three meta-dicopper complexes, 1-3, based on 5-substituted 1,3-xylylene spacer have been synthesized. These complexes are capable of inducing the transformation of supercoiled DNA (pUC19) to its nicked and linear DNA form in the presence of ascorbate, and their DNA nicking efficiency can be correlated to their DNA-binding ability. The cleavage mechanism is similar to that of the non-substituted meta-dicopper complex A. Amongst the three complexes, 5-(aminomethyl)-substituted complex 3 displayed a higher DNA-binding ability and nicking efficiency than unsubstituted complex A. The CD-spectroscopic study and structural analysis imply that the different CuCu distances and DNA binding modes induced by different 5-substituents on benzene-1,3-bis(methylene) spacer may be responsible for the different DNA cleaving behavior of meta-dicopper complexes.     

Dinuclear and mononuclear copper(II) carboxylate complexes with cis-chelating diacids

The synthesis and crystal structures of two new copper complexes with chelating dicarboxylic acids are described. Reaction of copper(II) acetate with diacid H₂L2 (HO₂CC(Me)₂OArOC(Me)₂CO₂H, Ar=1,3-substituted phenyl) gave a bischelate complex (L2)₂Cu₂ · 2MeOH with the normal paddlewheel structure and tilted, trans-oriented chelate rings with skewed conformations. The overall structure was reasonably well reproduced by density functional calculations on (L2)₂Cu₂. Treatment of the product from reaction of Cu₂(OAc)₄ and diacid H₂L3 (Ar=1,3-substituted 2,4-dibromophenyl) with pyridine gave a six-coordinate mononuclear chelate (L3)Py₂Cu · H₂O in which one chelate carboxylate is monodentate, the other is unsymmetrically bidentate, and the pyridines are cis-coordinated.     

Synthesis, structure, DNA binding and cleavage properties of ternary amino acid Schiff base-phen/bipy Cu(II) complexes

Ternary Cu(II) complexes [Cu(II)(saltrp)(B)] (1,2), (saltrp = salicylidene tryptophan, B = 1,10 phenathroline (1) or 2,2′ bipyridine (2)) were synthesized and characterized. Complex 2 was structurally characterized by single crystal X-ray crystallography. The molecular structure shows a distorted square pyramidal coordination geometry (CuN₃O₂) in which the ONO donor Schiff base is bonded to the Cu(II) in the basal plane. The N,N donor heterocyclic base displays an axial-equatorial binding mode. CT-DNA binding studies revealed that the complexes show good binding propensity (Intrinsic binding constant, K_b = 3.32 × 10⁵ M⁻¹ for 1 and K_b = 3.10 × 10⁵ M⁻¹ for 2). The catalytic role of these complexes in the oxidative and hydrolytic cleavage of DNA was studied in detail. Complex 1 binds and cleaves DNA more efficiently as compared to 2. From the kinetic experiments, rate constants for the hydrolysis of phosphodiester bond of DNA backbone were determined as 1.94 h⁻¹ and 1.05 h⁻¹ for 1 and 2 respectively. It amounts to (2.93-5.41) × 10⁷ fold rate enhancement compared to uncatalyzed double stranded DNA, which is impressive as compared to related Cu(II) Schiff base complexes.     

Synthesis and characterisation of copper(II), zinc(II) and cobalt(II) complexes of salicylglycine, a metabolite of aspirin

Copper(II), nickel(II) and cobalt(II) complexes of the aspirin metabolite salicylglycine (H₂L), of stoichiometry M(HL)₂·solvate, have been prepared and characterised. In these complexes salicylglycinate is coordinated to the metal via its carboxylato group and possibly also its amide oxygen in the copper(II) complex. Under basic conditions copper(II) forms the complex Cu(LH₋₁)·2H₂O·MeOH, in which the ligand is coordinated to the metal via its carboxylate and phenolate oxygen atoms and the deprotonated peptide nitrogen atom.     

Synthesis,X-ray crystal structure,DNA/BSA binding,DNA cleavage and cytotoxicity studies of phenanthroline based copper(II)/zinc(II) complexes

Research on copper^II 1,10-phenanththroline (phen) derivatives continues to attract interest in the context of structure and biological properties. In this paper, two metal complexes [Cu₂(phen)₂(μ-Cl)₂]Cl₂ (1), [Zn(phen)₂(H₂O)Cl]Cl·4H₂O (2) were synthesized and characterized. The crystal structures of 1 and 2 were determined by X-ray diffraction. In order to investigate the biological properties of the prepared complexes, spectroscopic and biological studies were performed. Results of X-ray diffraction showed that 1 and 2 form two types of crystal structures in a given system: dinuclear and mono-nuclear complex. The preliminary study on the DNA cleavage activity has shown that 1 under study behaved as the chemical nucleases. The DNA binding interaction of 1 & 2 with CT-DNA has been investigated by UV–Visible and fluorescence emission spectrometry and the apparent binding constant (K _app) values are 5.1 × 10⁴ and 1.2 × 10⁴ M^?1, respectively. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with 1 & 2 showed that the quenching mechanism might be a static quenching procedure with one binding sites for BSA. In addition, the cytotoxicity of 1 in vitro on tumor cells lines (MCF-7, HepG2 and HT29) was examined by MTT and showed better antitumor effect on the tested cells.     

DNA conformational changes and cleavage by ruthenium(II) nitrofurylsemicarbazone complexes

Metal complexes that establish interactions with DNA are being studied not only because of their potential use as therapeutic agents but also as tools for biochemistry and molecular biology. Searching for drugs with anti-trypanosome activity, we previously synthesized a series of ruthenium mixed ligand dimethyl sulfoxide complexes of the type [Ru(II)Cl(2)(DMSO)(2)L], where L is 5-nitrofurylsemicarbazone derivatives and DMSO is dimethyl sulfoxide. Though they present the ability to bind DNA, no activity against parasites in cell culture was observed. Considering their potential application as molecular tools we further analyzed the interactions with DNA through an electrophoretic approach. Non covalent withdrawal of superhelicity and a rapid nicking activity upon covalent interaction was observed. Inhibition of both effects was observed in the presence of distamycin suggesting the involvement of the DNA minor groove in the interaction with the nitrofurylsemicarbazone ruthenium complexes. In addition cleavage inhibition by dimethyl sulfoxide suggests an oxidative mechanism of action.     

Synthesis and structural analysis of copper(II) cysteine complexes

This report describes the synthesis and structural analysis of stable copper(II) cysteine complexes. Pale pink copper(II) cysteine complexes were synthesized in mole ratios of 1:2, 1:4, and 1:6 of copper(II):cysteine in ethanol. Infrared spectroscopy and X-ray absorption spectroscopy confirmed that copper(II) binding occurred via the thiol ligand of cysteine. XANES analysis showed that the oxidation state of copper remained as copper(II) and the local atomic geometry was similar in all of the cysteine complexes. The EXAFS data indicate that the copper(II) cysteine complexes are forming ring type structures with sulfur ligands from the cysteines acting as bridging ligands. X-ray diffraction revealed that the copper(II) cysteine complexes formed monoclinic cells with maximum crystallinity found in the 1:4 copper(II):cysteine complex.