Iron(III) Complexes with Non-Steroidal Anti-Inflammatory Drugs: Structure, Antioxidant and Anticholinergic Activity, and Interaction with Biomolecules.

One the main research goals of bioinorganic chemists is the synthesis of novel coordination compounds possessing biological potency. Within this context, three novel iron(III) complexes with the non-steroidal anti-inflammatory drugs diflunisal and diclofenac in the presence or absence of the nitrogen donors 1,10-phenanthroline or pyridine were isolated and characterized by diverse techniques. The complexes were evaluated for their ability to scavenge in vitro free radicals such as hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals, revealing their selective potency towards hydroxyl radicals. The in vitro inhibitory activity of the complexes towards the enzymes acetylcholinesterase and butyrylcholinesterase was evaluated, and their potential to achieve neuroprotection appeared promising. The interaction of the complexes with calf-thymus DNA was examined in vitro, revealing their ability to intercalate in-between DNA nucleobases. The affinity of the complexes for serum albumins was evaluated in vitro and revealed their tight and reversible binding.

Effect of Arylazo Sulfones on DNA: Binding, Cleavage, Photocleavage, Molecular Docking Studies and Interaction with A375 Melanoma and Non-Cancer Cells.

A set of arylazo sulfones, known to undergo N-S bond cleavage upon light exposure, has been synthesized, and their activity in the dark and upon irradiation towards DNA has been investigated. Their interaction with calf-thymus DNA has been examined, and the significant affinity observed (most probably due to DNA intercalation) was analyzed by means of molecular docking "in silico" calculations that pointed out polar contacts, mainly via the sulfonyl moiety. Incubation with plasmid pBluescript KS II revealed DNA cleavage that has been studied over time and concentration. UV-A irradiation considerably improved DNA damage for most of the compounds, whereas under visible light the effect was slightly lower. Moving to in vitro experiments, irradiation was found to slightly enhance the death of the cells in the majority of the compounds. Naphthylazosulfone 1 showed photo-disruptive effect under UV-A irradiation (IC50 ~13 µΜ) followed by derivatives 14 and 17 (IC50 ~100 µΜ). Those compounds were irradiated in the presence of two non-cancer cell lines and were found equally toxic only upon irradiation and not in the dark. The temporal and spatial control of light, therefore, might provide a chance for these novel scaffolds to be useful for the development of phototoxic pharmaceuticals.

Metal Complexes with Naphthalene-Based Acetic Acids as Ligands: Structure and Biological Activity.

Naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid), 1-naphthylacetic acid, 2-naphthylacetic acid and 1-pyreneacetic acid are derivatives of acetic acid bearing a naphthalene-based ring. In the present review, the coordination compounds of naproxen, 1- or 2-naphthylacetato and 1-pyreneacetato ligands are discussed in regard to their structural features (nature and nuclearity of metal ions and coordination mode of ligands), their spectroscopic and physicochemical properties and their biological activities.

pH-Sensitive Gold Nanorods for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Delivery and DNA-Binding Studies.

A facile experimental protocol for the synthesis of poly(ethylene glycol)-modified (PEGylated) gold nanorods (AuNRs@PEG) is presented as well as an effective drug loading procedure using the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP). The interaction of AuNRs@PEG and drug-loaded AuNRs (AuNRs@PEG@NAP) with calf-thymus DNA was studied at a diverse temperature revealing different interaction modes; AuNRs@PEG may interact via groove-binding and AuNRs@PEG@NAP may intercalate to DNA-bases. The cleavage activity of the gold nanoparticles for supercoiled circular pBR322 plasmid DNA was studied by gel electrophoresis while their affinity for human and bovine serum albumins was also evaluated. Drug-release studies revealed a pH-sensitive behavior with a release up to a maximum of 24% and 33% NAP within the first 180 min at pH = 4.2 and 6.8, respectively. The cytotoxicity of AuNRs@PEG and AuNRs@PEG@NAP was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. The development of AuNRs as an efficient non-steroidal anti-inflammatory drugs (NSAIDs) delivery system for chemotherapy is still in its infancy. The present work can shed light and inspire other research groups to work in this direction.

Inhibition of Cancer Cell Proliferation and Bacterial Growth by Silver(I) Complexes Bearing a CH3-Substituted Thiadiazole-Based Thioamide.

Ag(I) coordination compounds have recently attracted much attention as antiproliferative and antibacterial agents against a wide range of cancer cell lines and pathogens. The bioactivity potential of these complexes depends on their structural characteristics and the nature of their ligands. Herein, we present a series of four Ag(I) coordination compounds bearing as ligands the CH3-substituted thiadiazole-based thioamide 5-methyl-1,3,4-thiadiazole-2-thiol (mtdztH) and phosphines, i.e., [AgCl(mtdztH)(PPh3)2] (1), [Ag(mtdzt)(PPh3)3] (2), [AgCl(mtdztH)(xantphos)] (3), and [AgmtdztH)(dppe)(NO3)]n (4), where xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and dppe = 1,2-bis(diphenylphosphino)ethane, and the assessment of their in vitro antibacterial and anti-cancer efficiency. Among them, diphosphine-containing compounds 3 and 4 were found to exhibit broad-spectrum antibacterial activity characteristics against both Gram-(+) and Gram-(-) bacterial strains, showing high in vitro bioactivity with IC50 values as low as 4.6 µΜ. In vitro cytotoxicity studies against human ovarian, pancreatic, lung, and prostate cancer cell lines revealed the strong cytotoxic potential of 2 and 4, with IC50 values in the range of 3.1-24.0 µΜ, while 3 and 4 maintained the normal fibroblast cells' viability at relatively higher levels. Assessment of these results, in combination with those obtained for analogous Ag(I) complexes bearing similar heterocyclic thioamides, suggest the pivotal role of the substituent groups of the thioamide heterocyclic ring in the antibacterial and anti-cancer efficacy of the respective Ag(I) complexes. Compounds 1-4 exhibited moderate in vitro antioxidant capacity for free radicals scavenging, as well as reasonably strong ability to interact with calf-thymus DNA, suggesting the likely implication of these properties in their bioactivity mechanisms. Complementary insights into the possible mechanism of their anti-cancer activity were provided by molecular docking calculations, exploring their ability to bind to the overexpressed fibroblast growth factor receptor 1 (FGFR1), affecting cancer cells' functionalities.

Copper(II) Complexes of 5-Fluoro-Salicylaldehyde: Synthesis, Characterization, Antioxidant Properties, Interaction with DNA and Serum Albumins.

The synthesis, characterization and biological profile (antioxidant capacity, interaction with calf-thymus DNA and serum albumins) of five neutral copper(II) complexes of 5-fluoro-salicylaldehyde in the absence or presence of the N,N'-donor co-ligands 2,2'-bipyridylamine, 2,9-dimethyl-1,10-phenanthroline, 1,10-phenanthroline and 2,2'-bipyridine are presented herein. The compounds were characterized by physicochemical and spectroscopic techniques. The crystal structures of four complexes were determined by single-crystal X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H2O2 was investigated in order to evaluate their antioxidant activity. The interaction of the compounds with calf-thymus DNA possibly takes place via intercalation as suggested by UV-vis spectroscopy and DNA-viscosity titration studies and via competitive studies with ethidium bromide. The affinity of the complexes with bovine and human serum albumins was examined by fluorescence emission spectroscopy revealing the tight and reversible binding of the complexes with the albumins.

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies.

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure-activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as "synthetic nucleases", independently of oxygen and pH. Calf thymus-DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for "on demand" biotechnological applications in drug discovery and medicine.

Organometallic rhenium tricarbonyl-enrofloxacin and -levofloxacin complexes: synthesis, albumin-binding, DNA-interaction and cell viability studies.

Organometallic rhenium complexes have recently been considered in the development of novel antitumor agents due to their suitable properties. A series of rhenium(I) tricarbonyl complexes was synthesized with the quinolone antimicrobial agents enrofloxacin (Herx) and levofloxacin (Hlfx) and solvent (e.g., methanol), imidazole (im) or pyridine (py) as co-ligands. The complexes were characterized by spectroscopic methods. The interaction of the rhenium complexes with bovine serum albumin was investigated by fluorescence emission spectroscopy and the corresponding binding constants were determined. The binding of the rhenium complexes to calf-thymus DNA was monitored by UV-Vis spectroscopy, viscosity measurements and competitive studies with ethidium bromide. These studies indicated that intercalation is the most possible mode of action and the corresponding DNA-binding constants of the complexes were calculated. The cytotoxicity of the Re-complexes against human K-562 erythroleukemia cells was found to be moderate to high. These preliminary results are promising and warrant the design of new Re-complexes with improved properties in future studies.

Toward Multifunctional Materials Incorporating Stepladder Manganese(III) Inverse-[9-MC-3]-Metallacrowns and Anti-Inflammatory Drugs.

The interaction of Mn(ClO4)2·6H2O with salicylaldoxime (H2sao) in the presence of nonsteroidal anti-inflammatory drug (NSAID) sodium diclofenac (Nadicl) or indomethacin (Hindo) leads to the formation of the hexanuclear Mn(III) clusters [Mn6(O)2(dicl)2(sao)6(CH3OH)6] (1) and [Mn6(O)2(indo)2(sao)6(H2O)4] (2) both characterized as stepladder inverse-9-metallacrown-3 accommodating dicl- or indo- ligands, respectively. When the interaction of MnCl2·4H2O with Nadicl or Hindo is in the absence of H2sao, the mononuclear Mn(II) complexes [Mn(dicl)2(CH3OH)4] (3) and [Mn(indo)2(CH3OH)4] (4) were isolated. The complexes were characterized by physicochemical and spectroscopic techniques, and the structure of complexes 1 and 2 was characterized by X-ray crystallography. Magnetic measurements (dc and ac) were carried out in order to investigate the nature of magnetic interactions between the magnetic ions and the overall magnetic behavior of the complexes.

Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies.

Compared to standard treatments for various diseases, photochemotherapy and photo-dynamic therapy are less invasive approaches, in which DNA photocleavers represent promising tools for novel "on demand" chemotherapeutics. A series of p-nitrobenzoyl and p-pyridoyl ester conjugated aldoximes, amidoximes and ethanone oximes were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA. The compounds which possessed appropriate properties were additionally subjected to UVA irradiation at 365 nm. The ability of most of the compounds to photocleave DNA was high at 312 nm, whereas higher concentrations were required at 365 nm as a result of their lower UV absorption. The affinity of selected compounds to calf-thymus (CT) DNA was studied by UV spectroscopy, viscosity experiments and competitive studies with ethidium bromide (EB) revealing that all compounds interacted with CT DNA. The fluorescence emission spectra of the pre-treated EB-DNA exhibited a moderate to significant quenching in the presence of the compounds indicating the binding of the compounds to CT DNA via intercalation as concluded also by DNA-viscosity experiments. For the oxime esters the DNA photocleavage and affinity studies aimed to clarify the role of the oxime nature (aldoxime, ketoxime, amidoxime) and the role of the pyridine and p-nitrophenyl moieties both as oxime substituents and ester conjugates.

Manganese(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid: structure and biological perspectives.

Manganese(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the nitrogen-donor heterocyclic ligands 1,10-phenanthroline (phen), pyridine (py), or 2,2'-bipyridylamine (bipyam) and/or the oxygen-donor ligands H2O or N,N-dimethylformamide (DMF) have been synthesized and characterized. The crystal structures of complexes [Mn(tolf-O)(tolf-O,O')(phen)(H2O)], [Mn2(µ2-tolf-O,O')2(tolf-O,O')2(bipyam)2], [Mn2(µ2-H2O)(µ2-tolf-O,O')2(tolf-O)2(py)4]·1.5MeOH·py, and [Mn(µ2-tolf-O,O')2(DMF)2]n have been determined by X-ray crystallography. The interaction of the complexes with serum albumin proteins was investigated, and relative high binding constant values were calculated. The ability of the compounds to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), and hydroxyl radicals was evaluated, and [Mn(tolf)2(phen)(H2O)] was the most active scavenger among the compounds. The compounds have also exhibited noteworthy in vitro inhibitory activity against soybean lipoxygenase. UV titration studies of the interaction of the complexes with calf-thymus (CT) DNA have proved the binding to CT DNA with [Mn(µ2-tolf)2(DMF)2]n exhibiting the highest DNA-binding constant (Kb = 5.21 (±0.35) × 10(5) M(-1)). The complexes bind to CT DNA probably via intercalation as suggested by DNA-viscosity measurements and competitive studies with ethidium bromide (EB), which revealed the ability of the complexes to displace the DNA-bound EB.

Erbium(III) complexes with fluoroquinolones: Structure and biological properties.

Four erbium(III) complexes with the fluoroquinolones enrofloxacin, levofloxacin, flumequine and sparfloxacin as ligands were synthesized and characterized by a wide range of physicochemical and spectroscopic techniques as well as single-crystal X-ray crystallography. The compounds were evaluated for their activity against the bacterial strains Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Xanthomonas campestris, which was higher than that of the corresponding free quinolones. The interaction mode of the complexes with calf-thymus DNA is via intercalation, as suggested by diverse studies such as UV-vis spectroscopy, DNA-viscosity measurements and competitive studies with ethidium bromide. Fluorescence emission spectroscopy revealed the high affinity of the complexes for bovine and human serum albumin and the determined binding constants suggested a tight and reversible binding of the compounds with both albumins.

Cu(II) complexes with a salicylaldehyde derivative and α-diimines as co-ligands: synthesis, characterization, biological activity. Experimental and theoretical approach.

Copper(II) complexes with an α-diimine show a wide variety of biological activities, such as antibacterial, antifungal, antioxidant and anticancer. In this work, we synthesized and structurally characterized two novel Cu(II) complexes with methyl 3-formyl-4-hydroxybenzoate (HL) and α-diimines: 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen). Crystal structure analysis shows that the formulas of the compounds are [Cu(bipy)(L)(BF4)] (1) and [Cu(phen)(L)(H2O)](BF4)·H2O (2), with BF4- as a ligand in complex 1, which is rarely coordinated to metals. Both complexes have a square pyramidal geometry, while DFT calculations showed that the most stable structures of complexes 1 and 2 in a water/DMSO mixture are square-planar derivatives [Cu(bipy)(L)]+ and [Cu(phen)(L)]+. The antibacterial activity of compounds was evaluated in vitro on four Gram-negative and four Gram-positive bacterial strains. Complex 2 showed greater antibacterial activity towards all bacterial strains comparable to the control compound Amikacin. Complex 2 exerted a strong cytotoxic effect against the tested cancer cell lines (IC50 values ranging from 0.32 to 0.44 µM). Both complexes caused apoptotic cell death in HeLa cells and a noticeable in vitro antiangiogenic effect. In the concentration range of 5 to 100 µM, the complexes showed the absence of a genotoxic effect and displayed a protective effect against oxidative DNA damage induced by H2O2 in human peripheral blood cells. The interaction between the compounds and calf-thymus DNA was evaluated by diverse techniques suggesting a tight binding, which was also confirmed by molecular docking. In addition, it was found that the complexes bind tightly and reversibly to bovine and human serum albumin.

New uses for old drugs: attempts to convert quinolone antibacterials into potential anticancer agents containing ruthenium.

Continuing the study of the physicochemical and biological properties of ruthenium-quinolone adducts, four novel complexes with the general formula [Ru([9]aneS3)(dmso-κS)(quinolonato-κ(2)O,O)](PF6), containing the quinolones levofloxacin (1), nalidixic acid (2), oxolinic acid (3), and cinoxacin (4), were prepared and characterized in solid state as well as in solution. Contrary to their organoruthenium analogues, these complexes are generally relatively stable in aqueous solution as substitution of the dimethylsulfoxide (dmso) ligand is slow and not quantitative, and a minor release of the quinolonato ligand is observed only in the case of 4. The complexes bind to serum proteins displaying relatively high binding constants. DNA binding was studied using UV-vis spectroscopy, cyclic voltammetry, and performing viscosity measurements of CT DNA solutions in the presence of complexes 1-4. These experiments show that the ruthenium complexes interact with DNA via intercalation. Possible electrostatic interactions occur in the case of compound 4, which also shows the most pronounced rate of hydrolysis. Compounds 2 and 4 also exhibit a weak inhibition of cathepsins B and S, which are involved in the progression of a number of diseases, including cancer. Furthermore, complex 2 displayed moderate cytotoxicity when tested on the HeLa cell line.

Erbium(III) coordination compounds with substituted salicylaldehydes: Characterization and biological profile.

Five erbium(III) complexes with salicylaldehyde (saloH for 1), and mono- (5-X-saloH; X = NO2 and Me for 2 and 3, respectively) or di-substituted salicylaldehydes (3,5-diX-saloH; X = Cl and Br for 4 and 5, respectively) were synthesized and characterized by physicochemical and spectroscopic techniques and single-crystal X-ray crystallography. All five complexes have the general formula [Er(deprotonated salicylaldehyde)3(MeOH)(H2O)]. The structure of complexes [Er(3,5-diCl-salo)3(MeOH)(H2O)]·1.5MeOH (complex 4) and [Er(3,5-diBr-salo)3(MeOH)(H2O)]·1.75MeOH (complex 5) were verified by single-crystal X-ray crystallography. The evaluation of antioxidant activity of the complexes was focused on their ability to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) free radicals and to reduce H2O2. The interaction of the complexes with calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and via competitive studies with ethidium bromide in order to evaluate the possible DNA-binding mode and to determine the corresponding DNA-binding constants. The affinity of the complexes for bovine and human serum albumins was explored by fluorescence emission spectroscopy and the corresponding binding constants were determined.

Copper(II) complexes with 3,5-dihalogeno-salicylaldehydes: Synthesis, structure and interaction with DNA and albumins.

Eight copper(II) complexes of 3,5-dichloro-salicyladehyde or 3,5-dibromo-salicyladehyde (3,5-diX-saloH, X = Br or Cl) were synthesized in the absence or presence of a N,N'-donor co-ligand such as 2,2'-bipyridylamine, 1,10-phenanthroline, or 2,2'-bipyridine. The resultant compounds were formulated as [Cu(3,5-diX-salo)2(MeOH)2] (1-2) and [Cu(3,5-diX-salo)(N,N'-donor)Cl] (3-8) and were characterized by diverse techniques. The crystal structures of three complexes were determined by single-crystal X-ray crystallography. Diverse techniques were employed in order to investigate the interaction of the complexes with calf-thymus DNA which showed intercalation as the most possible mode of their interaction. The affinity of the complexes for bovine serum albumin and human serum albumin was evaluated by fluorescence emission spectroscopy in order to calculate the binding constants which suggested a tight and reversible binding. SYNOPSIS: A series of copper(II) complexes with 3,5-dihalogen-substituted salicylaldehydes as ligands were isolated and characterized. In vitro biological studies showed the intercalation of the compounds with calf-thymus DNA and their tight and reversible binding with serum albumins.

Neutral and cationic nickel(II) complexes with substituted salicylaldehydes: Characterization, antibacterial activity, and interaction with biomacromolecules.

Four neutral and six cationic nickel(II) complexes of the substituted salicylaldehydes (X-diCl-saloH), namely 3,5-dichloro-salicylaldehyde (3,5-diCl-saloH) and 5-fluoro-salicylaldehyde (5-F-saloH), were synthesized in the absence or presence of the N,N'-donors 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc), or 2,2'-bipyridylamine (bipyam) as co-ligands and were characterized by various techniques. The obtained complexes bear the general formulas [Ni(X-salo)2(H2O)2], [Ni(3,5-diCl-salo)2(neoc/phen)] and [Ni(X-salo)(N,N'-donor)2](PF6). The crystal structures of three complexes were determined by single-crystal X-ray crystallography revealing a bidentate coordination of the salicylaldehydes. The interaction of the compounds with calf-thymus DNA was studied by diverse techniques which revealed an intercalative interaction for the neutral complexes [Ni(X-salo)2(H2O)2] and [Ni(3,5-diCl-salo)2(neoc/phen)]and the co-existence of electrostatic interactions for the cationic complexes [Ni(X-salo)(N,N'-donor)2](PF6). The compounds bind tightly and reversibly to serum albumins. The antibacterial activity of the compounds was investigated against Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli NCTC 29,212 and Xanthomonas campestris ATCC 1395 and the complexes bearing neoc as co-ligand proved the most potent.

Transition metal(II) complexes with the non-steroidal anti-inflammatory drug oxaprozin: Characterization and biological profile.

A series of copper(II), nickel(II) and cobalt(II) complexes with the non-steroidal anti-inflammatory drug oxaprozin (Hoxa) have been synthesized and characterized by diverse techniques. The crystal structures of two copper(II) complexes, namely the dinuclear complex [Cu2(oxa)4(DMF)2] (1) and the polymeric complex {[Cu2(oxa)4]·2MeOH·0.5MeOH}2 (12) were determined by single-crystal X-ray diffraction studies. In order to evaluate in vitro the antioxidant activity of the resultant complexes, their scavenging ability towards 1,1-diphenyl-picrylhydrazyl (DPPH), hydroxyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals was investigated revealing their high effectiveness against these radicals. The binding of the complexes to bovine serum albumin and human serum albumin was examined and the corresponding determined albumin-binding constants showed a tight and reversible interaction. The interaction of the complexes with calf-thymus DNA was monitored by diverse techniques including UV-vis spectroscopy, cyclic voltammetry, DNA-viscosity measurements and competitive studies with ethidium bromide. Intercalation may be proposed as the most possible DNA-interaction mode of the complexes.

A [24-MC-6] zinc metallacoronate with a nonsteroidal antiinflammatory drug as the constructing ligand.

The interaction of ZnCl(2) with 2-dipyridylketonoxime (=Hpko) and flufenamic acid (=Hfluf) in a basic methanolic solution leads to the formation of a hexanuclear 24-membered metallacoronate, [Zn(6)(OH)(2)(pko)(4)(fluf)(6)] (1), with a [Zn-O-C-O] repeat unit and a nonsteroidal antiinflammatory drug as the constructing ligand. Compound 1 retains its structure in a dimethyl sulfoxide solution, as shown by (1)H NMR spectroscopy and molar conductance.

First palladium(II) and platinum(II) complexes from employment of 2,6-diacetylpyridine dioxime: synthesis, structural and spectroscopic characterization, and biological evaluation.

Employment of the monoanion of 2,6-diacetylpyridine dioxime (dapdoH(2)) as a tridentate chelate in palladium(II) and platinum(II) chemistry is reported. The syntheses, crystal structures, spectroscopic and physicochemical characterization, and biological evaluation are described of [PdCl(dapdoH)] (1) and [PtCl(dapdoH)] (2). Reaction of PdCl(2) with 2 equivs of dapdoH(2) in MeOH under reflux gave 1, whereas the same reaction with PtCl(2) in place of PdCl(2) gave 2 in comparable yields (70-80%). The divalent metal center in both compounds is coordinated by a terminal chloro group and a N,N',N"-tridentate chelating (η(3)) dapdoH(-) ligand. Thus, each metal ion is four coordinate with a distorted square planar geometry. Characterization of both complexes with (1)H and (13)C NMR and UV-vis and electrospray ionization mass spectroscopies confirmed their integrity in DMSO solutions. Interaction of the complexes with human and bovine serum albumin has been studied with fluorescence spectroscopy, revealing their affinity for these proteins with relatively high values of binding constants. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA, and the corresponding DNA binding constants have been evaluated. Cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through intercalation, which has been also shown by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have revealed the ability of the complexes to displace the DNA-bound EB, suggesting competition with EB. The combined work demonstrates the ability of pyridyl-dioxime chelates not only to lead to polynuclear 3d-metal complexes with impressive structural motifs and interesting magnetic properties but also to yield new, mononuclear 4d- and 5d-metal complexes with biological implications.