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A new Pd(II) complex of formula [Pd(en)(2-pyc)] + (where, en is ethylenediamine and 2-pyc is 2-pyridinecarboxylate anion) and its reported Pt(II) analogue, i.e. [Pt(en)(2-pyc)] + have been made by an improved synthetic procedure, yielding above 80%. They have been characterized by FT-IR, UV-Vis, 1 H NMR, 13 C NMR, conductivity and elemental analysis. Single crystal structural determination of [Pt(en)(2-pyc)] + displayed that the Pt(II) cation in this complex coordinated by 2-pyc and en each as five member chelate resulting in slightly distorted square-planar array. The time-dependent spectroscopic analysis of these compounds in aqueous medium demonstrated their structural stabilities. The cytotoxic activities of Pd(II) and Pt(II) complexes, free 2-pyc and carboplatin (as standard drug) were assayed in-vitro against the HCT-116 and MCF-7 as cancerous and MCF 10 A and CCD-841 as normal cell lines. They showed the IC 50 order of: carboplatin > 2-pyc > Pt(II) > Pd(II) and lower activities against non-cancerous cells. CT-DNA binding of the Pd(II), Pt(II) and 2-pyc free ligand were explored individually. In this relation, UV-Vis and fluorescence titrations disclosed quenching of CT-DNA absorption and emissions by the compounds via dynamic mechanism and formation of H-bonds and van der Waals forces between them. The interaction was further validated and verified by viscosity measurements and gel electrophoresis. Partition coefficient determination showed that all three compounds have more lipophilicity than cisplatin. Furthermore, docking analysis and molecular dynamics simulation were done to evaluate the nature of interaction between aforementioned compounds and CT-DNA. The finding results demonstrated that these agents interact with CT-DNA via groove binding and were in agreement with experimental results.Communicated by Ramaswamy H. Sarma.

To evaluate the biotransformation and the mechanism of binding as well as the biological impact of metal-based- drugs involving Pd(II), known to have high potency and low toxicity for use as anticancer therapeutics, in the present study, a newly synthesized palladium (II) complex, [Pd(CPF)(OH 2 ) 2 ] 2+ (where CPF is ciprofloxacin), has been synthesized and characterized and thoroughly evaluated for its antimicrobial properties. The interaction of the diaqua complex with CT-DNA and BSA was studied through various techniques, including UV-vis spectroscopy, thermal denaturation, viscometry, gel electrophoresis, ethanol precipitation, and molecular docking studies. The results indicate that the complex exhibits a robust binding interaction with CT-DNA, possibly via minor groove binding and (or) electrostatic interactions. Furthermore, the complex displays good binding affinity towards BSA, indicating its potential as a target for DNA and BSA in biological media. The invitro cytotoxicity assay reveals that this complex can be classified as a promising cell growth inhibitor against MCF-7, HT-29, and A549. Thus, this newly synthesized palladium (II) complex is a promising candidate for further exploration as a potential anticancer therapeutic., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The four new ligands, dialkyl esters of ( S , S )-propylenediamine- N , N '-di-(2,2'-di-(4-hydroxy-benzil))acetic acid (R 2 - S , S -pddtyr·2HCl) (R = ethyl (L1), propyl (L2), butyl (L3), and pentyl (L4)) and corresponding palladium(II) complexes have been synthesized and characterized by microanalysis, infrared, 1 H NMR and 13 C NMR spectroscopy. In vitro cytotoxicity was evaluated using the MTT assay on four tumor cell lines, including mouse mammary (4T1) and colon (CT26), and human mammary (MDA-MD-468) and colon (HCT116), as well as non-tumor mouse mesenchymal stem cells. Using fluorescence spectroscopy were investigated the interactions of new palladium(II) complexes [PdCl 2 (R 2 - S , S -pddtyr)]; (R = ethyl (C1), propyl (C2), butyl (C3), and pentyl (C4)) with calf thymus human serum albumin (HSA) and DNA (CT-DNA). The high values of the binding constants, K b , show the good binding of all complexes for HSA and CT-DNA. The mentioned ligands and complexes were also tested on K SV , show the good binding of all complexes for HSA and CT-DNA. The mentioned ligands and complexes were also tested on in vitro antimicrobial activity against 11 microorganisms. Testing was performed by the microdilution method, where the minimum inhibitory concentration (MMC) and the minimum microbicidal concentration (MMC) were determined.

Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where L1 = 2,6-bis(5,6-diphenyl-1,2,4-triazin-3-yl)pyridine and L2 = 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine), were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1 H NMR spectroscopy and MALDI-TOF mass spectrometry. The substitution reactions of 1-4 complexes with L-methionine (L-met), L-cysteine (L-cys) and guanosine-5'-monophosphate (5'-GMP), were studied spectrophotometrically at physiological conditions. Complexes with ligand L1 (1 or 3) were more reactive than those with ligand L2 (2 or 4) by a factor ranging up to 1.57 and 3.71, respectively. The order of reactivity of the nucleophiles was: L-met > L-cys > 5'-GMP. The interactions of complexes with calf thymus-DNA (CT-DNA) and human serum albumin (HSA) were studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. All studied complexes can interact with DNA through the intercalation and minor groove binding, where the latter was preferred. The binding constants (10 3 and 10 4  M -1 ) for the interaction of complexes with HSA indicate the moderate binding affinity of complexes 1-4 to protein. The trends in the experimental results of binding studies between complexes 3 and 4 with DNA and HSA were compared to those obtained from the molecular docking study. Biological evaluation of cytotoxicity of 1 and 2 on HCT-116 and MDA-MB-231 cell lines showed significant cytotoxic and prooxidative character, while 2 also exerted extraordinary selectivity towards colon cancer in comparison to breast cancer cells. The nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity of bis(triazinyl)pyridine complexes of Pt(II) and Pd(II) were studied., (© 2021. Society for Biological Inorganic Chemistry (SBIC).)

Treatments of N-(pyridin-2-ylmethyl)pyrazine-2-carboxamide (L1), N-(quinolin-8-yl)pyrazine-2-carboxamide (L2), N-(quinolin-8-yl)picolinamide (L3) and N-(quinolin-8-yl)quinoline-2-carboxamide (L4) with [PdCl2(NCMe)]2 afforded the corresponding Pd(ii) complexes, [Pd(L1)Cl] (PdL1); [Pd(L2)Cl] (PdL2); [Pd(L3)Cl] (PdL3); and [Pd(L4)Cl] (PdL4) in moderate yields. Structural characterisation of the compounds was achieved by NMR and FT-IR spectroscopies, elemental analyses and single crystal X-ray crystallography. The solid-state structures of complexes PdL2-PdL4 established the presence of one tridentate carboxamide and Cl ligands around the Pd(ii) coordination sphere, to give distorted square planar complexes. Electrochemical investigations of PdL1-PdL4 showed irreversible one-electron oxidation reactions. Kinetics reactivity of the complexes towards bio-molecules, thiourea (Tu), l-methionine (L-Met) and guanosine 5'-diphosphate disodium salt (5'-GMP) decreased in the order: PdL1 > PdL2 > PdL3 > PdL4, in tandem with the density functional theory (DFT) data. The complexes bind favourably to calf thymus (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions agrees with the substitution kinetics trends. The in vitro cytotoxic activities of PdL1-PdL4 were examined in cancer cell lines A549, PC-3, HT-29, Caco-2, and HeLa, and a normal cell line, KMST-6. Overall, PdL1 and PdL3 displayed potent cytotoxic effects on A549, PC-3 HT-29 and Caco-2 comparable to cisplatin. All the investigated complexes exhibited lower toxicity on normal cells than cisplatin.

Four [(N^N^N)Pd (II) Cl] + complexes [chloride-(2,2':6',2''-terpyridine)Pd(II)]Cl (PdL1), [chlorido(2,6-bis(N-pyrazol-2-yl)pyridine)Pd(II)]Cl (PdL2), [chlorido(2,6-bis(3,5-dimethyl-N-pyrazol-2-yl)pyridine)Pd(II)]Cl (PdL3) and [chlorido(2,6-bis(3,5-dimethyl-N-pyrazol-2-ylmethyl)pyridine)Pd(II)]BF 4 (PdL4) were synthesized and characterized. The rates of substitution of these Pd(II) complexes with thiourea nucleophiles viz; thiourea (Tu), N,N'-dimethylthiourea (Dmtu) and N,N,N',N'-tetramethylthiourea (Tmtu) was investigated under pseudo first-order conditions as a function of nucleophile concentration [Nu] and temperature using the stopped-flow technique. The observed rate constants vary linearly with [Nu]; k obs  = k 2 [Nu] and decreased in the order: PdL1 > PdL2 > PdL3 ≫ PdL4. The lower π-acceptability of the cis-coordinated N-pyrazol-2-yl groups (which coordinates via pyrazollic-N π-donor atoms) of the PdL2-4 significantly decelerates the reactivity relative to PdL1. Furthermore, the six-membered chelates having methylene bridge in PdL4 do not allow π-extension in the ligand and introduces steric hindrance further lowering the reactivity. Trends in DFT calculated data supported the observed reactivity trend. Spectrophotometric titration data of complexes with calf thymus DNA (CT-DNA) and viscosity measurements of the resultant mixtures suggested that associative interactions occur between the complexes and CT-DNA, likely through groove binding with high binding constants (K b  = 10 4  M -1 ). In vitro MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxic activity data showed that PdL1 was the most potent complex against MCF7 breast cancer cells; its IC 50 value is lower than that of cisplatin. The results demonstrate how modification of a spectator ligand can be used to slow down the reactivity of Pd(II) complexes. This is of special importance in controlling drug toxicity in both pharmaceutical and biomedical applications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Two new sets of Schiff bases 2-chloroquinolin-3-yl-methylene-pyridin-2-amine (CMPA) and 2-chloroquinolin-3-yl-methylene-pyrazole-5-amine-3-thole (CMPT) and their respective palladium (II) complexes have been synthesised and characterized with the aid of elemental analysis, IR, 1 H & 13 C NMR, UV-Vis., and electrochemical studies. The surface morphology of palladium complexes were examined by Scanning Electron Microscopic image. The binding affinities of complexes with CT-DNA were carried out by absorption spectra and cyclic voltammetric studies. The observed hypochromic (~20%) and bathochromic (~30%) shifts indicates that the complexes bind with Guanine base pair of CT-DNA via intercalation. The increasing cathodic peak potential from +0.968 eV to +1.104 eV in complexes confirm the presence of intercalation. Anti-inflammatory activities of both ligands and complexes have been studied using carrageenan induced hind paw edema in Wistar rats. The change in paw volume revealed that the maximum percentage of inhibition was observed in metal complex at 5th hour with a dose of 200 mg/kg. In order to evaluate the binding affinity of ligand and metal complex, molecular interaction analysis were performed by maestro implemented in Schrodinger., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: In order to discover new agents for chemotherapy with improved properties compared to the existing agents and bearing in mind the fact that some Pd complexes possess better antitumor activity and exhibit less kidney toxicity compared to cisplatin, a series of novel square-planar palladium(II) complexes [Pd (L)2] (3a-f) with O,O bidentate ligands [L = ethyl 2- hydroxy-alkyl(aryl)-4-oxo-2-butenoate] were synthesized., Methods: All complexes were characterized by spectral (UV-Vis, IR, NMR, ESI-MS) and X-ray analysis and examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Fluorescence spectroscopic method was used for investigations of the interactions between CT-DNA or bovine serum albumin (BSA) and complex 3c. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and complex 3c., Results: Complexes that showed the best results, 3c, 3d, and 3e, were placed under further investigations. Selected complexes induced apoptosis and cell cycle arrest in HeLa and MDA-MB 231 cells. Low concentrations of 3c and 3e showed strong to moderate synergism with low concentrations of cisplatin. The interaction of 3d with cisplatin was antagonistic in all used concentrations, but low IC50 value indicates its usefulness as a single cytotoxic agent. It was also noted that the change of viscosity is more pronounced in DNA solution after addition of complex 3c., Conclusion: Obtained results indicate that the novel palladium(II) complexes have the potential to become candidates for treatment in anticancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Thirteen novel palladium(II) complexes of the general formula [Pd(bipy)(O,O'-dkt)](PF 6 ), (where bipy is 2,2'-bipyridine and O,O'-dkt is β-diketonate ligand hispolon or its derivative) have been prepared through a metal-ligand coordination method that involves spontaneous formation of the corresponding diketonate scaffold. The obtained palladium(II) complexes have been characterized by NMR spectroscopy, ESI-mass spectrometry as well as elemental analysis. The cytotoxicity analysis indicates that most of the obtained palladium(II) complexes show promising growth inhibition in three human cancer cell lines. Flow cytometry analysis shows complex 3e could promote intracellular reactive oxygen species (ROS) accumulation and lead cancer cell death. And the suppression of ROS accumulation and the rescue of cell viability in HeLa cells by N-acetyl-L-cysteine (NAC) suggest the possible link between the increase in ROS generation and cytotoxicity of complex 3e. Flow cytometry analysis also reveal that complex 3e cause cell cycle arrest in the G2/M phase and collapse of the mitochondrial membrane potential, promote the generation of ROS and lead to tumor cell apoptosis. The interactions of complex 3e with calf thymus DNA (CT-DNA) have been evaluated by UV-Vis spectroscopy, fluorescence quenching experiments and viscosity measurements, which reveal that the complex interact with CT-DNA through minor groove binding and/or electrostatic interactions. Further, the results of fluorescence titration and site marker competitive experiment on bovine serum albumin (BSA) suggest that complex 3e can quench the fluorescence of BSA via a static quenching process and bind to BSA in Sudlow's site II., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this study, four Co(III)-, Cu(II)-, Zn(II)- and Pd(II)-based potent antibacterial complexes of formula K 3 [Co(ox) 3 ]·3H 2 O ( I ), [Cu(phen) 2 Cl]Cl·6.5H 2 O ( II ), [Zn(phen) 3 ]Cl 2 ( III ) and [Pd(phen) 2 ](NO 3 ) 2 ( IV ) (where ox is oxalato and phen is 1,10-phenanthroline) were synthesized. They were characterized by elemental analysis, molar conductivity measurements, UV-vis, Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance ( 1 H-NMR) techniques. These metal complexes were ordered in three combination series of I + II , I + II + III and I + II + III + IV . Antibacterial screening for each metal complex and their combinations against Gram-positive and Gram-negative bacteria revealed that all compounds were more potent antibacterial agents against the Gram-negative than those of the Gram-positive bacteria. The four metal complexes showed antibacterial activity in the order I > II > III > IV , and the activity of their combinations followed the order of I + II + III + IV > I + II + III > I + II . The DNA-binding properties of complex ( I ) and its three combinations were studied using electronic absorption and fluorescence (ethidium bromide displacement assay) spectroscopy. The results obtained indicated that all series interact effectively with calf thymus DNA (CT-DNA). The binding constant ( K b ), the number of binding sites ( n ) were obtained based on the results of fluorescence measurements. The calculated thermodynamic parameters supported that hydrogen bonding and van der Waals forces play a major role in the association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series. Communicated by Ramaswamy H. Sarma.K sv ) were obtained based on the results of fluorescence measurements. The calculated thermodynamic parameters supported that hydrogen bonding and van der Waals forces play a major role in the association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series. Communicated by Ramaswamy H. Sarma.

The aim of this study was synthesis of two new water-soluble fluorescent palladium and platinum complexes with formulas of [Pt(DACH)(FIP)](NO 3 ) 2 and [Pd(DACH)(FIP)](NO 3 ) 2 , respectively, where FIP is 2-(furan-2-yl)-1H-imidazo[4,5-f][1,10] phenanthroline and DACH is 1R,2R-diaminocyclohexane. Fluorescence spectroscopy, circular dichroism (CD), thermal denaturation measurement, ionic strength, and kinetic study displayed groove binding of Pt complex on DNA, while due to binding of Pd complex, B form of DNA convert to Z form. Due to electrostatic interaction of Pd complex with DNA, the DNA form is converted and it provides enough space for Pd complex to insert between base stacking of DNA. UV-vis study shows two complexes could denature the DNA at low concentrations in exothermic process and Pt complex is more active than Pd complex. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line HCT116 after incubation time of 24 h using MTT assay and higher activity was observed for the platinum complex. Interaction of the two metal derivative complexes was studied by molecular docking and molecular dynamics simulation. The results showed that Pt complexes have higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA.

Four Co(III)-, Cu(II)-, Zn(II)-, and Pd(II)-based potent antibacterial complexes of formula K 3 [Co(ox) 3 ].3H 2 O (I), [Cu(bpy) 2 Cl]Cl.5H 2 O (II), [Zn(bpy) 3 ]Cl 2 (III), and [Pd(bpy) 2 ](NO 3 ) 2 (IV) (where ox is oxalate and bpy is 2,2'-bipyridine) were synthesized. They were characterized by elemental analyses, molar conductance measurements, UV-Vis, FTIR, 1 H NMR, and 13 C NMR spectra. These metal complexes were ordered in three combination series of I + II, I + II + III, and I + II + III + IV. Antibacterial activity was tested for each of these four metal complexes and their combinations against Gram-positive and Gram-negative bacteria. All compounds were more potent antibacterial agents against the Gram-negative than those of the Gram-positive bacteria. The four metal complexes showed antibacterial activity in the order I > II > III > IV and the activity of their combinations followed the order of I + II + III + IV > I + II + III > I + II. CT-DNA binding studies of complex I and its three combinations were carried out using UV-vis spectral titration, displacement of ethidium bromide (EB), and electrophoretic mobility assay. The results obtained from UV-vis studies indicated that all series interact effectively with CT-DNA. Fluorescence titration revealed that the complexes quench DNA-EB strongly through the static quenching procedures. The binding constant (K b ), the Stern-Volmer constant (K sv ), and the number of binding sites (n) were determined at different temperatures of 293, 300, and 310 K, respectively. The calculated thermodynamic parameters supported that hydrogen binding and Van der Waals forces play a major role in association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series.

Six new dinuclear Pd(II) complexes, [{Pd(2,2'-bipy)Cl} 2 (μ-pz)](ClO 4 ) 2 (Pd1), [{Pd(dach)Cl} 2 (μ-pz)](ClO 4 ) 2 (Pd2), [{Pd(en)Cl} 2 (μ-pz)](ClO 4 ) 2 (Pd3), [{Pd(2,2'-bipy)Cl} 2 (μ-4,4'-bipy)](ClO 4 ) 2 (Pd4), [{Pd(dach)Cl} 2 (μ-4,4'-bipy)](ClO 4 ) 2 (Pd5) and [{Pd(en)Cl} 2 (μ-4,4'-bipy)](ClO 4 ) 2 (Pd6) (where 2,2'-bipy=2,2'-bipyridyl, pz=pyrazine, dach=trans-(±)-1,2-diaminocyclohexane, en=ethylenediamine, 4,4'-bipy=4,4'-bipyridyl) have been synthesized and characterized by elemental microanalysis, IR, 1 H NMR and MALDI-TOF mass spectrometry. The pK a values of corresponding diaqua complexes were determined by spectrophotometric pH titration. Substitution reactions with thiourea (Tu), l-methionine (l-Met), l-cysteine (l-Cys), l-histidine (l-His) and guanosine-5'-monophosphate (5'-GMP) were studied under the pseudo-first order conditions at pH7.2. Reactions of Pd1 with Tu, l-Met and l-Cys were followed by decomposition of complexes, while structures of dinuclear complexes were preserved during the substitution with nitrogen donors. Interactions with calf-thymus DNA (CT-DNA) were followed by absorption spectroscopy and fluorescence quenching measurements. All complexes can bind to CT-DNA exhibiting high intrinsic binding constants (K b =10 4 -10 5 M -1 ). Competitive studies with ethidium bromide (EB) have shown that complexes can displace DNA-bound EB. High values of binding constants towards bovine serum albumin protein (BSA) indicate good binding affinity. Finally, all complexes showed moderate to high cytotoxic activity against HeLa (human cervical epithelial carcinoma cell lines) and MDA-MB-231 (human breast epithelial carcinoma cell lines) tumor cell lines inducing apoptotic type cell death, whereas normal fibroblasts were significantly less sensitive. The impact on cell cycle of these cells was distinctive, where Pd4, Pd5 and Pd6 showed the most prominent effect arresting MDA-MB-231 (human lung fibroblast cell lines) cell in G1/S phase of cell cycle., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Palladium(II) complexes of type [Pd(L n )Cl 2 ] and [Pd(bdt)(L n )] have been synthesized using 2-acetyl pyridine derivatives(L n ) and benzene-12-dithiol(bdt). The synthesized complexes have been characterized by various analytical techniques like thermo gravimetric analysis, elemental analysis, conductance measurement, and spectroscopic techniques like elemental analysis, mass spectra, absorption spectra, IR, 1 H NMR, energy-dispersive X-ray spectroscopy. The interaction of the complexes with calf-thymus DNA (CT-DNA) has been explored by absorption titration, viscosity measurement methods. Based on the observations, an intercalative binding mode of DNA has been proposed. In order to provide additional evidence for the intercalation mode of binding between the complex and CT-DNA, fluorescence titration experiment was performed. In addition, molecular modeling study has been carried out with the aim of establishing the complex's binding mode. Antibacterial activity study of the complexes have been screened against pathogenic bacteria such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Serratia marcescens, and Pseudomonas aeruginosa. Gel electrophoresis assay demonstrates that all the complexes can cleave the pUC19 plasmid DNA.

New cytotoxic, mononuclear Pt and Pd coordination complexes featuring the planar, multi-donor ligand (2,3-f)pyrazino(1,10)phenanthroline-2,3-dicarboxylic acid (H 2 PPDA) have been synthesized under hydrothermal conditions (in water, at high temperature and pressure) and fully characterized. The complexes were proven to be isostructural by applying the single-crystal X-ray diffraction technique. UV-Vis and fluorescence spectroscopy investigations on their interaction with fish sperm DNA revealed a considerable binding capacity while gel electrophoresis provided evidence in favor of cleavage of pBR322 plasmid DNA. The newly synthesized complexes manifested significant in vitro cytotoxic activity against two different human cancer cell lines, the KB and JEKO cells, with cell death mainly caused by apoptosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The complexes [Pd(valp)2(imidazole)2] (1), [Pd(valp)2(pyrazine)2] (2) (valp is sodium valproate) have been synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR and UV-Vis spectrometry. The interaction of complexes with CT-DNA has been investigated using spectroscopic tools and viscosity measurement. In each case, the association constant (Kb) was deduced from the absorption spectral study and the number of binding sites (n) and the binding constant (K) were calculated from relevant fluorescence quenching data. As a result, a non-covalent interaction between the metal complex and DNA was suggested, which could be assigned to an intercalative binding. In addition, the interaction of 1 and 2 was ventured with bovine serum albumin (BSA) with the help of absorption and fluorescence spectroscopy measurements. Through these techniques, the apparent association constant (Kapp) and the binding constant (K) could be calculated for each complex. Evaluation of cytotoxic activity of the complexes against four different cancer cell lines proved that the complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate. Moreover, density functional theory (DFT) calculations were employed to provide more evidence about the observed data. The majority of trans isomers were supported not only by energies, but also by the similarity of its calculated IR frequencies, UV adsorptions and NMR chemical shifts to the experimental values., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Metal complexes of the general formula [ML(H2O)Cl]nH2O; n=1 for M=Ni and Pt and n=2 for M=Pd, L=Schiff base (HL) derived from the condensation of 3-amino-1,2,4-triazole and 2-hydroxy-1-naphthaldehyde, were prepared. The synthesized ligand and its metal complexes were characterized on the basis of elemental analyses, spectral and magnetic studies as well as thermal analysis. The IR spectra revealed that the ligand is coordinated to the metal ions in bidentate manner via the N-atom of the azomethine group and the phenolic OH group. Square planar geometry was proposed for Pd(II) and Pt(II) complexes and tetrahedral for Ni(II) complex. The ligand and its metal complexes were screened against the sensitive organisms Escherichia coli as Gram-negative bacteria, Staphylococcus aureus as Gram-positive bacteria, Aspergillus flavus and Candida albicans as fungi. Moreover, the anticancer activity of the ligand and its metal complexes was evaluated in liver carcinoma (HEPG2) cell line. The results obtained indicated that the Schiff base ligand is more effective than its metal complexes towards the tested cell line. Ni(II), Pd(II) and Pt(II) complexes as well as the free Schiff base ligand were tested for their antioxidant activities. The DNA-binding properties of the studied complexes have been investigated by electronic absorption and viscosity measurements., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)]2(μ-X)2 [X=OAc (1), X=Cl (2)] and trans-N,P-[M(C,N)X(PPh3)] [M=Pd, X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1-4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1-4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1-5 was in between the ranges of activity of the commercial antibiotic compounds cefixime and roxithromycin. Complexes 1-2 and 4-5 presented also antioxidant activity. Compounds 1-5 alter the DNA tertiary structure in a similar way to cisplatin, but at higher concentration, and do not present a high efficiency as cathepsin B inhibitors. Compound 5 has not been previously described, and its preparation, characterization, and X-ray crystal structure are reported., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Two triptycene-based ligands with pendant bromophenyl units have been prepared. These triptycene derivatives have been used as synthons for the synthesis of di and tri nuclear palladium complexes. The organic molecules and their corresponding organometallic complexes have been fully characterized using nuclear magnetic resonance (NMR), infrared (IR) spectroscopy and mass spectrometry. The mode of binding and effect of the complexes on pUC19 plasmid, calf thymus DNA and oligomer duplex DNA have been investigated by a host of analytical methods. The complexes brought about unwinding of supercoiled plasmid and the unwinding angle was found to be related to the binding affinity of the complexes with DNA, where both these parameters were guided by the structure of the complexes. Concentration-dependent inhibition of endonuclease activity of SspI and BamHI by the complexes indicates preference for G/C sequence for binding to DNA. However, neither the complexes did not introduce any cleavage at abasic site in oligomer duplex DNA, nor they created linear form of the plasmid upon co-incubation with the DNA samples. The interactions of the complexes with DNA were found to be strongly guided by the structure of the complexes, where intercalation as well as groove binding was observed, without inflicting any damage to the DNA. The mode of interaction of the complexes with DNA was further confirmed by isothermal calorimetry.

A derivative of thiouracil ligand was prepared. Ni(II), Pd(II), Pt(IV), Cu(II) and UO2(2+) complexes were prepared. The elemental and different spectral tools were used for their characterization. A binegative tetradentate mode is the general coordination behavior of the ligand towards all metal ions used. The structural geometries were varied from square-planer (Pt, Pd(II)), square-pyramidal (Cu(II)) and octahedral (UO2(2+)). The geometry optimization implementing the hyperChem reveals that the Cu(II) complex is the most stable one. The thermogravimetric analysis supports the presence of solvent molecules attached with most complexes. The biological investigation was studied on different microorganisms as gram-positive, gram-negative and fungia. The Ni(II) complex shows the most toxic activity towards most organisms used. The degradation effect of DNA was studied by the use of investigated compounds and reveal that the Ni(II) and Pd(II) complexes are the most effective on the DNA degradation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Four metal complexes [Pd(L(1))Cl(2)·2H(2)O] (1), [Pt(L(1))Cl(2)·2H(2)O] (2), [Pd(L(2))Cl(2)·H(2)O] (3) and [Pt(L(2))Cl(2)·H(2)O] (4) (L(1) = 2,2'-bipyridyl-5,5'-dicarboxylic acid, L(2) = 2,2'-bipyridyl-4,4'-dicarboxylic acid) have been synthesized under hydrothermal conditions and fully characterized by IR and (1)H-NMR spectra, elemental analysis, and X-ray single crystal diffraction analysis. Interactions of these complexes with fish sperm DNA (FS-DNA) were investigated using UV-Vis absorption and fluorescence spectroscopic methods. Further insight was brought by quantum chemistry calculations by means of G03 package and taking B3LYP functional Lanl2dz Gen basis set. Agarose gel electrophoresis run on pBR322 plasmid DNA gave proof that all four complexes exhibit efficient DNA cleavage. Complexes 1-4 manifested cytotoxic specificity and a significant cancer cell inhibitory rate. Independent apoptosis tests under the light microscope, performed on hematoxylin-eosin stained HeLa cells, evidenced morphological changes induced by all the complexes.

A new water-soluble palladium(II) complex, [Pd(bpy)(pyr-Ac]NO₃ in which bpy = 2,2'-bipyridine and pyr-Ac is 1-pyrrolacetato, has been synthesized and characterized by spectroscopic methods (¹H NMR, FT-IR, and UV-Vis), molar conductivity measurements, and elemental analysis. The results obtained from elemental analysis and conductivity measurements confirmed the stoichiometry of ligand and its complex while the characteristic peaks in UV-Vis and FT-IR and resonance peaks in (¹H NMR spectra confirmed the formation of ligand frameworks around the palladium ion. The 50% cytotoxic concentration (Ic₅₀) of new synthesized Pd(II) complex was determined by using MTT assay against human breast cancer cell line, T47D. The interaction between the Pd(II) complex with calf thymus DNA was studied at different temperatures by using absorption spectroscopy, fluorescence titration spectra, ethidium bromide displacement, and gel chromatography studies. The results obtained by absorption spectroscopy revealed that the Pd(II) complex can bind to DNA cooperatively at low concentrations. Several binding parameters in the above interaction were calculated by the fluorescence quenching method. The quenching mechanism was suggested to be the static quenching. The thermodynamic parameters: enthalpy change (ΔH °), entropy change (ΔS °), and Gibbs free energy (ΔG °), showed that van der Waals and hydrogen binding are predominant intermolecular forces between Pd(II) complex and DNA. These results were also consistent with the results obtained from Scatchard's plots.

With the purpose of evaluating the ability of Pd(II) complex to interact with DNA molecule as the main biological target, two new complexes [Pd(bpy)(OH(2))(2)] (1) and [Pd(Phenpip)(OH(2))(2)] (2), where (bpy=2,2'-bipyridine; Phenpip=1-phenylpiperazine), have been synthesized and the binding properties of these complexes with CT-DNA were investigated. The intrinsic binding constants (K(b)) calculated from UV-Vis absorption studies were 3.78×10(3) M(-1) and 4.14×10(3)M(-1) for complexes 1 and 2 respectively. Thermal denaturation has been systematically studied by spectrophotometric method and the calculated ΔT(m) was nearly 5 °C for each complex. All the results suggest an electrostatic and/or groove binding mode for the interaction between the complexes and CT-DNA. The redox behavior of the two complexes in the absence and in the presence of calf thymus DNA has been investigated by cyclic voltammetry. The cyclic voltammogram exhibits one quasi-reversible redox wave. The change in E(1/2), ΔE(p) and I(pc)/I(pa) supports that the two complexes exhibit strong binding to calf thymus DNA. Further insight into the binding of complexes with CT-DNA has been made by gel electrophoresis, where the binding of complexes is confirmed through decreasing the intensity of DNA bands. The two complexes have been screened for their antimicrobial activities using the disc diffusion method against some selected Gram-positive and Gram-negative bacteria. The activity data showed that both complexes were more active against Gram-negative than Gram-positive bacteria. It may be concluded that the antimicrobial activity of the compounds is related to cell wall structure of bacteria., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The coordination propensities of 4(N,N')-diethylaminosalicylaldehyde-4(N)-substituted thiosemicarbazones (H(2)L(1-4)) were investigated by reacting with an equimolar amount of [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various spectroscopic techniques. The structure determination of the complexes [Pd(DeaSal-tsc)(PPh(3))] (1), [Pd(DeaSal-mtsc)(PPh(3))] (2) and [Pd(DeaSal-etsc)(PPh(3))] (3) by X-ray crystallography showed that ligands are coordinated in a dibasic tridentate ONS donor fashion forming stable five and six membered chelate rings. The binding ability of complexes (1-4) to calf-thymus DNA (CT DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic and an intercalative binding mode have been proposed. The protein binding studies have been monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using lysozyme as a model protein. As determined by MTT assays, complex 3 exhibited a higher cytotoxic effect towards human lung cancer cell line (A549) and liver cancer cells (HepG2). LDH, NO assay and cellular uptake of the complexes have been studied. Further, antibacterial activity studies of the complexes have been screened against the pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, MIC50 values of the complexes showed that the complexes exhibited significant activity against the pathogens and among the complexes, 3 exhibited higher activity., (This journal is © The Royal Society of Chemistry 2012)

The interaction of new 1, 10-phenanthrolineoctyldithiocarbamatopalladium (II) nitrate with DNA from calf thymus was investigated at 300 and 310 K in a Tris-HCl buffer of pH 7.0 medium containing 20 mM sodium chloride. This water soluble, square planar Pd(II) complex has been synthesized and spectroscopic (electronic, infrared, and nuclear magnetic resonance) and elemental analysis of the complex are discussed. This complex shows greater growth inhibitory activity against human tumor cell line K562 than cisplatin. Results of UV-visible studies show that the complex exhibits cooperative binding with DNA and denatures the DNA at an extremely low concentration (∼11.98 μM). Fluorescence studies reveal that the mode of binding of this complex with DNA seems to be intercalation. The results of sephadex G-25 column show that the binding of metal complex with DNA is so strong that it does not readily break. Several binding and thermodynamic parameters are also described. They may shed light on the mechanisms of interaction of this agent with DNA, which should be quite different from that of cisplatin.

The interaction of calf thymus DNA (CT-DNA) with a novel synthesized and characterized Palladium (II) complex with the formula of [Pd (Et-dtc) (phen)] NO(3) (where phen is 1,10-phenanthroline and Et-dtc is ethyldithiocarbamate) was extensively studied by various spectroscopic techniques. UV-vis studies imply that there is a set of 6 binding sites for the complex on DNA with positive cooperativity in the binding process. This complex unexpectedly denatures the DNA at very low concentration (approximately 9.8 microM). Gel filtration studies indicate that the binding of metal complex with DNA is strong enough not to readily break. Fluorescence studies show that the palladium complex intercalates in DNA through the planar 1,10-phenanthroline ligand presented in its structure. Several binding and thermodynamic parameters are also described. Furthermore, anti-tumor studies of this water soluble complex against human cell tumor lines (K562) have been done. It shows 50% cytotoxic concentration (Ic(50)) value much lower than that of cisplatin., (Copyright 2010 Elsevier B.V. All rights reserved.)

Four complexes [Pd(L)(bipy)Cl].4H(2)O (1), [Pd(L)(phen)Cl].4H(2)O (2), [Pt(L)(bipy)Cl].4H(2)O (3), and [Pt(L)(phen)Cl].4H(2)O (4), where L = quinolinic acid, bipy = 2,2'-bipyridyl, and phen = 1,10-phenanthroline, have been synthesized and characterized using IR, (1)H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes to FS-DNA was investigated by electronic absorption titration and fluorescence spectroscopy. The results indicate that the complexes bind to FS-DNA in an intercalative mode and the intrinsic binding constants K of the title complexes with FS-DNA are about 3.5 x 10(4) M(-1), 3.9 x 10(4) M(-1), 6.1 x 10(4) M(-1), and 1.4 x 10(5) M(-1), respectively. Also, the four complexes bind to DNA with different binding affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave pBR322 plasmid DNA.

A series of Pd(II) complexes with a benzenealkyl dicarboxlate chain, with the formulas [Pd(L(n))(bipy)].mH(2)O (bipy = 2,2'-bipyridine, complex 1: L(1) = phenylmalonate, m = 2.5; complex 2: L(2) = benzylmalonate, m = 1; complex 3: L(3) = phenethylmalonate, m = 2; complex 4: L(4) = phenylpropylmalonate, m = 5), have been prepared in an attempt to correlate factors about the carbon chain of the compounds with DNA binding and cytotoxic activity. The binding of complexes with fish sperm DNA (FS-DNA) was carried out by UV absorption and fluorescence spectra. A gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic effects of these complexes were examined on four cancer cell lines, HeLa, Hep-G2, KB, and AGZY-83a. The four complexes exhibited cytotoxic specificity and a significant cancer cell inhibitory rate. An apparent dependence of DNA-binding properties and cytotoxicity on the carbon chain length was obtained: the longer the carbon chain length, the higher the efficiency of DNA-binding and the greater the cytotoxicity.

The dinuclear complexes [Pd(2)(L)(2)(bipy)(2)] (1), [Pd(2)(L)(2)(phen)(2)] (2), [Pt(2)(L)(2)(bipy)(2)] (3) and [Pt(2)(L)(2)(phen)(2)] (4), where bipy=2,2'-bipyridine, phen=1,10-phenanthroline and L=2,2'-azanediyldibenzoic dianion) dibridged by H(2)L ligands have been synthesized and characterized. The binding of the complexes with fish sperm DNA (FS-DNA) were investigated by fluorescence spectroscopy. The results indicate that the four complexes bound to DNA with different binding affinity, in the order complex 4>complex 3>complex 2>complex 1, and the complex 3 binds to DNA in both coordination and intercalative mode. Gel electrophoresis assay demonstrates the ability of the complexes to cleave the pBR 322 plasmid DNA. The cytotoxic activity of the complexes was tested against four different cancer cell lines. The four complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate.

The enumeration of absolute cell numbers and cell proliferation in clinical samples is important for diagnostic and research purposes. Detection of cellular DNA with fluorescent dyes is the most commonly used approach for cell enumeration in cytometry. Inductively coupled plasma mass spectrometry (ICPMS) has been recently introduced to the field of protein and cell surface antigen identification via ICPMS-linked immunoassays using element-labeled affinity reagents such as gold and lanthanide-conjugated antibodies. In the present work, we describe novel methods for using metallointercalators that irreversibly bind DNA and low concentrations of rare earth metals added to cell growth media for rapid and sensitive measurement of cell numbers by mass spectrometry. We show that Ir- and Rh-containing metallointercalators are useful reagents for labeling cells and normalizing signals when studying antigen expression on different types and numbers of cells. Results are presented for solution analysis performed by conventional ICPMS and compared to measurements obtained on the novel flow cytometer mass spectrometer (FC-MS) instrument, designed to analyze multiple antigens and DNA simultaneously in single cells.

Pd(II) and Pt(II) complexes with the anions of the model nucleobases 1-methylthymine (1-MethyH), 1-methyluracil (1-MeuraH), and 1-methylcytosine (1-MecytH) of the types [Pd(dmba)(mu-L)]2 [dmba = N,C-chelating 2-((dimethylamino)methyl)phenyl; L = 1-Methy, 1-Meura or 1-Mecyt] and [M(dmba)(L)(L')] [L = 1-Methy or 1-Meura; L' = PPh(3) (M = Pd or Pt), DMSO (M = Pt)] have been obtained. Palladium complexes of the types [Pd(C6F5)(N-N)(L)] [L = 1-Methy or 1-Meura; N-N = N,N,N',N'-tetramethylethylenediamine (tmeda), 2,2'-bipyridine (bpy), or 4,4'-dimethyl-2,2'-bipyridine (Me2bpy)] and [NBu4][Pd(C6F5)(1-Methy)2(H2O)] have also been prepared. The crystal structures of [Pd(dmba)(mu-1-Methy)]2, [Pd(dmba)(mu-1-Mecyt)]2.2CHCl3, [Pd(dmba)(1-Methy)(PPh3)].3CHCl3, [Pt(dmba)(1-Methy)(PPh3)], [Pd(tmeda)(C6F5)(1-Methy)], and [NBu4][Pd(C6F5)(1-Methy)2(H2O)].H2O have been established by X-ray diffraction. The DNA adduct formation of the new platinum complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the platinum complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the new platinum complexes against the tumor cell line HL-60. All the new platinum complexes were more active than cisplatin (up to 20-fold in some cases).

The Pd(II) complexes, [PdCl(2)(1,2-pn)] and [PdCl(2)(1,3-pn)] (pn is diaminopropane), were synthesized and characterized by analytical and spectroscopic (FT-IR, (1)H NMR and (13)C NMR) techniques. UV difference spectral study performed on Pd-pn/DNA systems, indicate a pronounced interaction of palladium complexes with DNA in cell-free media; comparison of lambda(max), Abs(max) and %H values observed for the two compounds might be attributed to structural differences of the chelated ligand rings. Results obtained from electrophoretic analysis of Pd complexes in presence of pBR322 plasmid DNA show a clear decreasing of the supercoiled (SC) DNA form mobility, that could be attributed to unwinding of the double helix; a parallel increasing of the open-circular (OC) DNA form mobility is also noted, this fact implying that the binding of complexes either shortens or condenses the DNA helix. Interaction studies of Pd complexes with plasmid DNA in different buffer systems indicate that DNA binding efficiency capable of modifying the tertiary structure of pBR322 decreased from NaClO(4) to Hepes 2, Hepes 1 [Hepes=4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid], and Tris [(hydroxymethyl)aminomethane] buffers, in this order. Moreover, the level of DNA modifications produced by palladium complexes in 10 mM NaClO(4) remains unchanged after transferring the samples into the medium required for subsequent biophysical or biochemical analyses.

Pd(II) and Pt(II) new complexes with simple aromatic diamines were synthesised and characterised with the aim of studying their possible antitumour activity. The aromatic diamines chosen were 2,3-diaminotoluene (2,3 dat), 3,4-diaminotoluene (3,4 dat), 4,5-diaminoxylene (4,5 dax) and 2,3-diaminophenol (2,3 dap). The complexes, of formulae cis-[MCl(2)(diamine)], were characterised by elemental analysis, conductivity measurements, 1H, 13C(1H) and 195Pt NMR spectroscopy. The X-ray crystal structure was also resolved for the palladium complexes with 2,3-diaminotoluene and 4,5-diaminoxylene. The DNA adduct formation of the eight new complexes synthesised was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the four platinum complexes against the cisplatin resistant tumour cell line A2780cisR.

The intraperitoneal administration of PtCl4 or Pd(NO3)2 at levels of 28 or 56 mumole/kg body weight decreased the thymidine incorporation into DNA of spleen, liver, kidney, and testis. Spleen was most sensitive to both the platinum and the palladium salt. In liver, DNA syntheses in parenchymal cells and stromal cells were about equally sensitive to PtCl4. In control rats, only 20-30% of the 3H in the acid-soluble fraction of liver or spleen was in the form of thymidine and its phosphate esters 2 hr after the intraperitoneal injection of 3H-thymidine; prior injection of PtCl4 (56 mumol/kg body weight) did not change the pattern.