Investigation on the interaction of newly designed potential antibacterial Zn(II) complexes with CT-DNA and HSA

Two Zn(II) complexes of formula [Zn(bpy)(Gly)]NO₃ (I) and [Zn(phen)(Gly)]NO₃ (II) (where bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and Gly = glycine) were synthesized and characterized by elemental analysis, molar conductance measurements, UV–vis, FT-IR, and ¹H NMR spectra. The interaction ability of these complexes with calf thymus DNA was monitored using spectroscopic methods, including UV–vis absorption spectroscopy, ethidium bromide displacement, Fourier transform infrared, and electrophoretic mobility assay. Further, the human serum albumin interactions of complexes I and II were investigated using UV–vis absorption spectroscopy, fluorescence quenching, circular dichroism, and Fourier transform infrared. The results obtained from these analyses indicated that both complexes interact effectively with CT-DNA and HSA. The binding constant (K_b), the Stern–Volmer constant (K_sv), and the number of binding sites (n) at different temperatures were determined for CT-DNA and HSA. Also, the negative ΔH° and ΔS° values showed that both hydrogen bonds and van der Waals forces played major roles in the association of CT-DNA-Zn(II) and HSA-Zn(II) complex formation. The displacement experiments suggested that Zn(II)-complexes primarily bound to Sudlow’s site II of HSA. The distance between the donor (HSA) and the acceptor (Zn(II) complexes) was estimated on the basis of the Forster resonance energy transfer (FRET) and the alteration of HSA secondary structure induced by the compounds were confirmed by FT-IR spectroscopy. The complexes follow the binding affinity order of I > II with DNA and II > I with HSA. Finally, Antibacterial activity of complexes I and II have been screened against gram positive and gram negative bacteria.     

The crystal structures and absolute configurations of the anti-tumor complexes Pt(oxalato)(1R,2R-cyclohexanediamine) and Pt(malonato)(1R,2R-cyclohexanediamine)

The absolute configurations of the anti-tumor complexes [Pt(oxalato)(trans-l-dach)] and [Pt(malonato) (trans-l-dach)] (trans-l-dach = 1R,2R-cyclohexanediamine) have been determined by X-ray anomalous scattering techniques. These complexes are particularly interesting because they show higher anti-tumor activity than the corresponding Pt complexes with other 1,2-cyclohexanediamine(dach) ligands, namely those with trans-d-dach (1S,2S-dach) or cis-dach (1R,2S-dach). The oxalato and malonato ligands are found to bind to the Pt atom in a chelating fashion, through one oxygen atom from each of the two carboxylate groups. Crystallographic details: Pt(oxalato)(trans-l-dach): space group P2₁ (monoclinic); a = 11.230(11) Å, b = 9.914(5) Å, c = 4.716(3) Å, β = 90.86(6)°; R = 4.0% for 1256 reflections. Pt(malonato)(trans-l-dach): space group P2₁ (monoclinic); a = 11.568(5) Å, b = 10.007(5) Å, c = 5.187(3) Å, β = 99.16(4)°; R = 4.8% for 1675 reflections.     

Effect of lipophilicity of amylamine and amylglycine ligands on biological activity of new anticancer cisplatin analog

Investigation of side effects and solubility of anticancer drugs is a major challenge in chemotherapy science. Thus, design and synthesis of cisplatin analogs with higher lipophilicity as novel water-soluble anticancer drugs is valuable. In this work, two new Pt(II) complexes were synthesized with formula cis-[Pt(NH₃)₂(amylgly)]NO₃ and cis-[Pt(amylamine)₂(amylgly)]NO₃, where gly is penthyl glycine as an amino acid. The new compounds were synthesized and extensively characterized using analytical techniques; spectroscopic methods, and conductivity measurement. The anticancer activity of synthesized complexes was investigated against colon cancer cell line HCT116 using MTT assay and results showed excellent anticancer activity with Cc₅₀ values of 36 and 270 M after 24-h incubation time for cis-[Pt(NH₃)₂(amylgly)]NO₃ and cis-[Pt(NH₂-amyl)₂(amylgly)]NO₃, respectively; which is lower than that for cisplatin. These complexes were also interacted with highly polymerized calf thymus DNA and the binding mode of the complexes to CT-DNA was evaluated by fluorescence, circular dichroism, and UV spectroscopy. The calculation of binding and thermodynamic of Pt(II) complexes with CT-DNA can provide deeper insight into mechanism of the action of these types of complexes with nucleic acids. So, thermodynamic parameters were also determined according to isothermal titration. In comparison with cis-[Pt(NH₃)₂(amylgly)]NO₃ in DNA interaction, the result show that cis-[Pt(NH₂-amyl)₂(amylgly)]NO₃ has higher affinity with binding constant K_f = 8.72 mM to CT-DNA. The results indicate that cis-[Pt(amylamine)₂(amylgly)]NO₃ with large and bulky aliphatic group bind to CT-DNA by different modes and covalent and groove bindings were preferred mode of interaction with DNA.     

Effect of ancillary ligands on the photophysical properties of Ru(II) complexes bearing a highly conjugated diimine ligand: A density functional theory study

Two bis-heteroleptic Ru(II) complexes [Ru(bpy)₂(pcip)]²⁺ (1, bpy = 2,2′-bipyridine, pcip = 2-[4-phenylcarboxy]-1H-imidazol[4,5-f][1,10]phenanthroline) and [Ru(phen)₂(pcip)]²⁺ (2, phen = 1,10-phenanthroline), bearing highly conjugated diimine ligands, were prepared and isolated as their PF₆ salts. The bpy-derivative 1 showed better photophysical properties (emission quantum yield, lifetime of the emitting state, and the radiative decay rate constant) than the phen-compound 2. These results followed by theoretical calculations at DFT level established a comprehensive understanding between the structural parameters and the photophysical properties, as well as of the influence of π conjugation and the symmetry of the molecules on spectroscopic characteristics. These results provide fundamental photophysical data for selecting ancillary ligands in the design and improvement of Ru-based light-harvesting complexes.     

Molecular Structure and Cytotoxicity of 3D-Transition Metal Complexes Capable to Form a Stable Metal-Nitrogen Bond

Abstract

The cytotoxicity of several Co(II), Ni(II), Cu(II) and Zn(II) complexes with various molecular structures and geometries, has been tested on LoVo and 2008 cells at 1–100 μM concentration for 24 h exposure. On the basis of 24 h results, the exposure time was prolonged to 48 and to 72 hours. The most potent complexes result [Cu(tren)(H₂O)]²⁺ 2Cl^?, E, [CoCl₃(H₂Meppz)], G, and [CoCl₃(HMe₂ppz)], H, (tren=tris(2-aminoethyl)amine, H₂Meppz=1-methylpiperazin-1-ium, HMe₂ppz=1,4-dimethylpiperazin-1-ium cations). Nevertheless, these complexes are able to induce cell growth reduction of about 50% at highest doses tested (1-100 μM) and after 72 h exposure.     

Tuning electronic structure and photophysical properties of [Ir(ppy)2(py)2]+ by substituents binding in pyridyl ligand: a computational study

Iridium (III) 2-phenylpyridine (ppy) complexes with two suitable monodentate L ligands [Ir(ppy)(2)(L)(2)](+) (ppy = 2-phenylpyridine, py = pyridine, L = 4-pyCN 1, 4-pyCHO 2, 4-pyCl 3, py 4, 4-pyNH(2) 5) were studied by density functional theory (DFT) and time-dependent DFT methods. The influences of ligands L on the electronic structure and photophysical properties were investigated in detail. The compositions and energy levels of the lowest unoccupied molecular orbital (LUMO) are changed more significantly than those of the highest occupied molecular (HOMO) by tuning L ligands. With the electronegativity decrease of L ligands 4-pyCN > 4-pyCHO > 4-pyCl > py > 4-pyNH(2), the LUMO distributing changes from py to ppy, and the absorptions have an obvious red shift. The calculated results showed that the transition character of the absorption and emission can be changed by adjusting the electronegativity of the L ligands. In addition, no solvent effect was observed in the absorptions and emissions.     

Adduct formation between ternary Pt(II)-amino acid-aromatic diimine complexes and flavin mononucleotide and its effect on redox properties

Adduct formation of ternary Pt(II) complexes composed of an amino acid and an aromatic diimine, [Pt(A)(DA)] (A = glycinate (Gly), alaninate (Ala), valinate, or arginine (Arg); DA = 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen)), with flavin mononucleotide (FMN) and anthraquinone-2-sulfonate (AQS) were investigated by spectroscopic, X-ray diffraction, and electrochemical methods. The Pt(II) complexes formed 1:1 [Pt(A)(DA)]-FMN adducts by stacking with the aromatic moiety of FMN, and the stability constants, log K, for the systems with [Pt(A)(phen)] (A = Gly, Ala, and Arg) and [Pt(Arg)(bpy)] were determined to be 2.83(8)-3.42(6) from ¹H NMR spectra at 25 °C in D₂O (I = var.). The structure of the adduct [Pt(Ala)(phen)](AQS) (1) was determined by X-ray analysis to involve a π-π stacking interaction between coordinated phen and AQS with the distance of 3.400(7) Å and a hydrogen bond between the sulfonate moiety of AQS and the amino group of coordinated Ala. Cyclic voltammetry of the 1:1 [Pt(A)(DA)]-FMN systems in a phosphate buffer (pH 7.0) showed that the potentials, E_1/2, for the two-electron redox process of FMN shifted to higher values by 18-31 mV as compared with the value for free FMN.     

Synthesis, crystallography, phosphorescence of platinum complexes coordinated with 2-phenylpyridine and a series of β-diketones

Metallocyclic platinum(II) complexes coordinating with 2-phenylpyridine (ppy) and a series of β-diketone ancillary O^∧O ligands, (ppy)Pt(acac), (ppy)Pt(ba), (ppy)Pt(dbm), and (ppy)Pt(tta) (acac = acetylacetone, ba = benzoylacetone, dbm = dibenzoylmethane, tta = thenoyltrifluoroacetone) were synthesized. The crystal structure, absorption, emission, quantum yield and phosphorescence life time were characterized. As the conjugative π system of the O^∧O ligand increases in the order acac < ba < dbm, or there is a group -CF₃to attract the electron density of the tta ligand, the quantum yield decreases in the order (ppy)Pt(acac) > (ppy)Pt(ba) > (ppy)Pt(dbm) > (ppy)Pt(tta) due to an energy back-flow from ppy to the O^∧O ligand, a trend also in contrast to the phosphorescence emission spectra and time decay (biexponentially, ∼0.7-13 μs).     

Platinum(II) complexes with 2-acetyl pyridine thiosemicarbazone. Synthesis, crystal structure, spectral properties, antimicrobial and antitumour activity

An interesting series of new platinum complexes has been synthesized by the reaction of Na(2)PtCl(4) with 2-acetyl pyridine thiosemicarbazone, HAcTsc. The new complexes, [Pt(AcTsc)Cl], [Pt(HAcTsc)(2)]Cl(2) and [Pt(AcTsc)(2)], have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(AcTsc)Cl] has been solved by single-crystal X-ray diffraction. The anion of HAcTsc coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. Double intermolecular hydrogen bonds (NH-Cl), pi-pi and weak Pt-Pt and Pt-pi contacts lead to aggregation and to a two-dimensional supramolecular assembly. The antibacterial and antifungal effect of the novel platinum(II) complexes and the related palladium(II) complexes, [Pd(AcTsc)Cl], [Pd(HAcTsc)(2)]Cl(2) and [Pd(AcTsc)(2)], were studied in vitro. The complexes were found to have a completely lethal effect on Gram+ bacteria, while the same complexes showed no bactericidal effect on Gram- bacteria. Additionally, the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] showed effective antifungal activity towards yeast. Among these compounds [33], the most effective in inducing antitumour and cytogenetic effects are the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] while the rest, display marginal cytogenetic and antitumour effects.     

Novel polynuclear platinum adducts detected during the reactions of [Pt(Met-S,N)Cl2] with gamma-glutathione and L-cysteine

The reactions of platinum(II) complexes with thiol containing molecules are highly relevant to the mechanism of action of platinum-based drugs. This work presents the electrospray mass spectrometry (ESMS) and NMR results on the reactions of [Pt(l-MetH-S,N)Cl(2)] (l-MetH: l-methionine) with gamma-glutathione (GSH) and l-cysteine (l-Cys) at different pH and different molar ratios. Polymeric species such as [Pt(2)(micro-SG-S)(2)(Met-S,N)(2)], [Pt(3)(micro-SG-S)(4)(Met-S,N)(2)], [Pt(4)(micro-SG-S)(6)(Met-S,N)(2)] and [Pt(5)(micro-SG-S)(8)(Met-S,N)(2)] (l-Met: deprotonated l-methionine) were detected and were stable for long hours. For both reactions, the polymerization extent decreased with the increase of pH. For the reaction of l-Cys, only mononuclear complex [Pt(l-Met-S,N)(l-Cys-S,N)] was observed when pH>9. The observation and identification of polymeric (higher than binuclear) adducts of Pt(II)/GSH and Pt(II)/l-Cys appears to be unprecedented.     

Effects of amine ligand bulk and hydrogen bonding on the rate of reaction of platinum(II) diamine complexes with key nucleotide and amino acid residues

NMR spectroscopy has been used to observe the effects of the amine ligand on the rate of reaction of platinum diamine and triamine complexes with DNA and protein residues. Whereas [Pt(dien)Cl]Cl and [Pt(dien)(D(2)O)](2+) have been known to react faster with thioether residues such as N-AcMet than with 5'-GMP, we found that [Pt(Me(4)en)(D(2)O)(2)](2+) appeared to react faster with 5'-GMP. To quantitatively assess the factors influencing the rates of reaction, rate constants at pH 4 were determined for the reactions of [Pt(en)(D(2)O)(2)](2+) [en = ethylenediamine] and [Pt(Me(4)en)(D(2)O)(2)](2+) with N-AcMet, N-AcHis, 5'-GMP, and Guo (guanosine). In each case the less bulky complex ([Pt(en)(D(2)O)(2)](2+)) reacts more quickly than does the bulkier [Pt(Me(4)en)(D(2)O)(2)](2+), as expected. Both complexes reacted faster with 5'-GMP; however, analysis of the rate constants suggests that the [Pt(en)(D(2)O)(2)](2+) complex favors reaction with 5'-GMP due to hydrogen bonding with the 5'-phosphate, whereas [Pt(Me(4)en)(D(2)O)(2)](2+) disfavors reaction with N-AcMet due to steric clashes. Bulk had relatively little effect on the rate constant with N-AcHis, suggesting that peptides or proteins that coordinate via His residues would not have their reactivity affected by bulky diamine ligands.     

Preparation of platinum(II) complexes with L-serine using KI. X-ray crystal structure, HPLC and 195Pt NMR spectra

The preparation of platinum(II) complexes containing L-serine using K(2)[PtCl(4)] and KI as raw materials was undertaken. The cis-trans isomer ratio of the complexes in the reaction mixture differed significantly depending on whether KI was present or absent in the reaction mixture. One of the two [Pt(L-ser-N,O)(2)] complexes (L-ser=L-serinate anion) prepared using KI crystallizes in the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions a=8.710(2) A, b=9.773(3) A, c=11.355(3) A, Z=4. The crystal data revealed that this complex has a cis configuration. The other [Pt(L-ser-N,O)(2)] complex also crystallizes in the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions a=7.0190(9) A, b=7.7445(6) A, c=20.946(2) A, Z=4. The crystal data revealed that this complex has a trans configuration. The 195Pt NMR chemical shifts of trans-[Pt(L-ser-N,O)(2)] and cis-[Pt(L-ser-N,O)(2)] complexes are -1632 and -1832 ppm, respectively. 195Pt NMR and HPLC measurements were conducted to monitor the reactions of the two [Pt(L-ser-N,O)(2)] complexes with HCl. Both 195Pt NMR and HPLC showed that the reactivities of cis- and trans-[Pt(L-ser-N,O)(2)] toward HCl are different: coordinated carboxyl oxygen atoms of trans-[Pt(L-ser-N,O)(2)] were detached faster than those for cis-[Pt(L-ser-N,O)(2)].     

Platinum(II) complexes with spatially encumbered chelates; syntheses, structure and photophysics

Treatment of the spatially congested 5-(6-methylpyridin-2-yl)-3-trifluoromethyl-1,2,4-triazole (fmptzH) chelate with K₂PtCl₄ in basic media gave a pale-yellow complex [Pt(fmptz)₂] (1), for which the single crystal X-ray diffraction study showed a highly distorted square-planar coordination geometry with one N-Pt-N vector significantly deviated from linearity. This complex undergoes slow equilibration in refluxing THF to afford a dinuclear complex [Pt(fmptz)(μ-fmptz)]₂ (2), showing reversible transformation of one fmptz chelate to the distinctive bridging mode. Synthesis of the less spatially congested, heteroleptic complexes [Pt(fppz)(fmptz)] (3) and [Pt(iqbpz)(fmptz)] (4) were successfully achieved by combination of [Pt(fppzH)Cl₂] and [Pt(iqbpzH)Cl₂] with one equiv. of fmptzH ligand under similar condition, fppzH = 5-(2-pyridyl)-3-trifluoromethyl-pyrazole and iqbpzH = 5-(1-isoquinolyl)-3-tert-butyl-pyrazole. Only the derivative 4 was found to be weakly emissive in both fluid and solid states at room temperature.     

5-Fluorouracil-cisplatin adducts with potential antitumor activity

Using 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum(II) (cisplatin, CDDP) as starting compounds, 5-FU-cisplatin adducts cis-[Pt(NH(3))(2)(HFU)Cl] (1) and cis-[Pt(NH(3))(2)(HFU)(2)] (2) were prepared. The obtained complexes were characterized by IR, ES-MS and 1H NMR spectroscopy. Complex 1 reacted with guanosine-5'-monophosphate (5'-GMP) and gave rise to a stable mixed-ligand complex cis-[Pt(NH(3))(2)(HFU)(GMP)] (3), whereas 2 did not undergo a similar reaction. In vitro cell growth inhibition tests of complexes 1 and 2 exhibited moderate antitumor activities against the melanoma B16-BL6 cell line. This work provides the basis for a potential alternative for the combinational use of 5-FU and CDDP in cancer therapy.     

Design,synthesis, MTT assay,DNA interaction studies of platinum(II) complexes

The square planar Pt(II) complexes of the type [Pt(Lⁿ)(Cl₂)] (where Lⁿ = L^1?3 = thiophene-2-carboxamide derivatives and L^4?6 = thiophene-2-carbothioamide derivatives) have been synthesized and characterized by physicochemical and various spectroscopic studies. MIC method was employed to inference the antibacterial potency of complexes in reference to free ligands and metal salt. Characteristic binding constant (K_b) and binding mode of complexes with calf thymus DNA (CT-DNA) were determined using absorption titration (0.76–1.61 × 10⁵ M^?1), hydrodynamic chain length assay and fluorescence quenching analysis, deducing the partial intercalative mode of binding. Molecular docking calculation displayed free energy of binding in the range of –260.06 to –219.63 kJmol^?1. The nuclease profile of complexes towards pUC19 DNA shows that the complexes cleave DNA more efficiently compared to their respective metal salt. Cytotoxicity profile of the complexes on the brine shrimp shows that all the complex exhibit noteworthy cytotoxic activity with LC₅₀ values ranging from 7.87 to 15.94 μg/mL. The complexes have been evaluated for cell proliferation potential in human colon carcinoma cells (HCT 116) and IC₅₀ value of complexes by MTT assay (IC₅₀ = 125–1000 μg/mL).     

Synthesis, spectral study and cytotoxicity of platinum(II) complexes with 2,9-disubstituted-6-benzylaminopurines

A series of platinum(II) complexes with 2,9-disubstituted-6-benzylaminopurines has been prepared. The complexes have the following composition: cis-[Pt(Boh)(2)Cl(2)] (1), cis-[Pt(Oc)(2)Cl(2)] (2), cis-[Pt(Ros)(2)Cl(2)] (3), cis-[Pt(i-PrOc)(2)Cl(2)] (4), cis-[Pt(BohH(+))(2)Cl(2)]Cl(2) (5), cis-[Pt(OcH(+))(2)Cl(2)]Cl(2) (6), cis-[Pt(RosH(+))(2)Cl(2)]Cl(2) (7) and cis-[Pt(i-PrOcH(+))(2)Cl(2)]Cl(2) (8), where Boh=2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine, Oc=2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine, Ros=2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine and i-PrOc=2-(2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine. The complexes have been characterized by elemental analyses, conductivity measurements and their infrared, ES+mass (electrospray mass spectra in the positive ion mode) and NMR ((1)H, (13)C, (15)N and (195)Pt) spectra. The results obtained from the physical studies, particularly from multinuclear NMR spectroscopy, show that in all the investigated complexes (1-8), two molecules of purine derivative are coordinated to platinum via the N(7) atom of the imidazole ring in a cis-configuration. The prepared compounds have been screened for their in vitro cytotoxicity against G-361 (human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) cell lines. All complexes are significantly more active than the initial 2,9-disubstituted-6-benzylaminopurine derivatives. In the case of some tumour cell lines, IC(50) values for the complexes (1, 3, 4, 5, 8) are significantly lower than those obtained for cisplatin and oxaliplatin. The best cytotoxicity was achieved for the complex (3) for which IC(50) values range from 1 to 2 microM.     

Studies of interactions between platinum(II) complexes and some biologically relevant molecules

The reactions of Pt(II) complexes, cis-[Pt(NH3)2Cl2], [Pt(terpy)Cl]+, [Pt(terpy)(S-cys)]2+, and [Pt(terpy)(N7-guo)]2+, where terpy=2,2':6',2'-terpyridine, S-cys=L-cysteine, and N7-guo=guanosine, with some biologically relevant ligands such as guanosine-5'-monophosphate (5'-GMP), L-cysteine, glutathione (GSH) and some strong sulfur-containing nucleophiles such as diethyldithiocarbamate (dedtc), thiosulfate (sts), and thiourea (tu), were studied in aqueous 0.1 M Hepes at pH of 7.4 using UV-vis, stopped-flow spectrophotometry, and 1H NMR spectroscopy.     

Molecular structure and cytotoxicity of 3D-transition metal complexes capable to form a stable metal-nitrogen bond

The cytotoxicity of several Co(II), Ni(II), Cu(II) and Zn(II) complexes with various molecular structures and geometries, has been tested on LoVo and 2008 cells at 1-100 microM concentration for 24 h exposure. On the basis of 24 h results, the exposure time was prolonged to 48 and to 72 hours. The most potent complexes result [Cu(tren)(H2O)]2+ 2Cl-, E, [CoCl3(H2Meppz)], G, and [CoCl3(HMe2ppz)], H, (tren=tris(2-aminoethyl)amine, H2Meppz=1-methylpiperazin-1-ium, HMe2ppz=1,4-dimethylpiperazin-1-ium cations). Nevertheless, these complexes are able to induce cell growth reduction of about 50% at highest doses tested (1-100 microM ) and after 72 h exposure.     

The influence of methionine-containing peptides on the reaction of carboplatin with 5'-guanosine monophosphate: a comparison with cisplatin

The pH- and time-dependent reaction of the anticancer drug carboplatin, [Pt(cbdca-kappa(2)O,O')(NH(3))(2)] (cbdca=cyclobutane-1,1-dicarboxylate), with the tripeptides H-glyglymet-OH (glycylglycyl-L-methionine) and Ac-glyglymet-OH at 313 K was investigated by high-performance liquid chromatography, NMR and mass spectrometry. The relative stability of the initial ring-opened kappaS complex [Pt(cbdca-kappaO)(Ac-glyglymet-OH-kappaS)(NH(3))(2)] leads to increased formation of the kinetically favoured kappaS:kappaS' bis-adduct [Pt(Ac-glyglymet-OH-kappaS)(2)(NH(3))(2)](2+) in comparison with cisplatin. As a result a second 1:2 reaction pathway kappaS-->kappaS:kappaS'-->kappa(2)N(M), S:kappaS'-->kappa(3)N(G2),N(M), S:kappaS', where N(M) and N(G2) represent, respectively, metallated methionine and glycine nitrogen atoms, competes with the 1:1 route kappaS-->kappa(2)N(M), S-->kappa(3)N(G2),N(M), S also observed for cisplatin. Cleavage of N-acetylglycine at the backbone C(O)-N bond to the second gly residue (G2) is observed after 100 h for the respective tridentate complexes [Pt(Ac-glyglyH(-1)metH(-1)-OH-kappa(3)N(G2),N(M), S) (Ac-glyglymet-OH-kappaS)] and [Pt(Ac-glyglyH(-1)metH(-1)-OH-kappa(3)N(G2),N(M), S)(NH(3))] at pH <5.2. The longevity of the initial kappaS complex leads to about an eight-fold increase in the rate of formation of the kappaN7:kappaN7' bis-adduct [Pt(5'-GMP-kappaN7)(2)(NH(3))(2)](2-) for the reaction of carboplatin with 5'-GMP(2-) at pH 7 in the presence of Ac-glyglymet-OH. A mixed-ligand kappaS:kappaN7 species [Pt(5'-GMP-kappaN7)(Ac-glyglymet-OH-kappaS)(NH(3))(2)] provides the major precursor for this 1:2 nucleotide complex and kappaN7 coordination of 5'-GMP(2-) is also observed in the kappa(2)N(M),S:kappaN7 complex [Pt(5'-GMP-kappaN7)(Ac-glyglymetH(-1)-OH-kappa(2)N(M),S)(NH(3))(2)](-) formed by substitution of the ammine ligand trans to the methionine sulphur. As the intermediate kappaS:kappaN7 species is formed rapidly within the first 10 h of reaction, these results suggest that the transfer reaction pathway kappaS-->kappaS:kappaN7-->kappaN7:kappaN7' involving kappaS platinated peptides could play an important role in accelerating the rate of DNA binding for carboplatin.     

Ruthenium(II) carbonyl complexes containing S-methylisothiosemicarbazone based tetradentate ligand: synthesis, characterization and biological applications

A series of hexa-coordinated ruthenium(II) complexes of the type [Ru(CO)(B)L ⁿ ] (n = 1–4; B = PPh₃, AsPh₃ or Py) have been synthesized by reacting dibasic quadridentate Schiff base ligands H₂L ⁿ (n = 1–4) with starting complexes [RuHCl(CO)(EPh₃)₂(B)] (E = P or As; B = PPh₃, AsPh₃ or Py). The synthesized complexes were characterized using elemental and various spectral studies including UV–Vis, FT-IR, NMR (¹H, ¹³C and ³¹P) and mass spectroscopy. An octahedral geometry was tentatively proposed for all the complexes based on the spectral data obtained. The experiments on antioxidant activity showed that the ruthenium(II) S-methylisothiosemicarbazone Schiff base complexes exhibited good scavenging activity against various free radicals (DPPH, OH and NO). The in vitro cytotoxicity of these complexes has been evaluated by MTT assay. The results demonstrate that the complexes have good anticancer activities against selected cancer cell line, human breast cancer cell line (MCF-7) and human skin carcinoma cell line (A431). The DNA cleavage studies showed that the complexes have better cleavage of pBR 322 DNA.