Synthesis and anticancer activity of certain mononuclear Ru (II) Complexes

Bis(1,10-phenanthroline/2,2′-bipyridine) ruthenium(II)complexes containing TCP, TTZ OPBI, and BTSC ligands (where, TCP = 1-thiocarbamoyl-3,5-diphenyl-2-pyrazoline,TTZ = 2-(3,5-diphenyl-4,5-dihydropyrazol-1-yl)-4-phenylthiazole, OPBI = 2-hydroxyphenyl benzimidazole and BTSC = benzoin thiosemicarbazone) have been prepared and characterized. The spectral data suggested that the ligands were coordinated with the metal through nitrogen, sulfur and oxygen atoms. The target complexes were tested in vivo for anticancer activity against transplantable murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC). All these complexes increased the life span of the EAC-bearing mice, decreased their tumor volume and viable ascitic cell count as well as improved Hb, RBC and WBC counts. These results suggest that the Ru(II) complexes exhibit significant antitumor activity in EAC-bearing mice. It was also observed that the ruthenium complexes protected red blood cells from 2,2′-azo-bis(2-methylpropionamidine) dihydrochloride (AAPH)- induced hemolysis. The inhibitory effect was dose-dependent at a concentration of 20–120 μg/ml.     

Antineoplastic and antibacterial activity of some mononuclear Ru(II) complexes

These ligands (L) show a bidentate behavior, forming octahedral ruthenium complexes. The title complexes were subjected to in-vivo anticancer activity tests against a transplantable murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC) and in-vitro antibacterial activity against several Gram positive and Gram negative bacterial strains. [Ru(bpy)2(ihqs)]Cl2 and [Ru(bpy)2 (hc)]Cl2 (where bpy = 2,2'-bipyridine, ihqs = 7-iodo-8hydroxy quinoline-5-sulphonic acid and hc = 3-hydroxy coumarin) showed promising antitumor activity. Treatment with these complexes prolonged the life span of EAC bearing mice as well as decreased their tumor volume and viable ascitic cell count. All the tested complexes exhibited mild to moderate antibacterial activity.     

Synthesis,antineoplastic and cytotoxic activities of some mononuclear Ru(II) complexes

A series of mononuclear Ru(II) complexes of the type [Ru(S)₂(K)]²⁺, where S = 1,10-phenanthroline/2,2′-bipyridine and K = 4-OH-btsz, 4-CH₃-btsz, 3,4-di-OCH₃-btsz, 4-OH-binh, 4-CH₃-binh, 3,4-di-OCH₃-binh, were prepared and characterized by elemental analysis, FTIR, ¹H-NMR, and mass spectroscopy. The complexes displayed metal–ligand charge transfer (MLCT) transitions in the visible region. These ligands formed bidentate octahedral ruthenium complexes. The title complexes were evaluated for their in vivo anticancer activity against a transplantable murine tumor cell line, Ehrlisch’s ascites carcinoma (EAC), and in vitro cytotoxic activity against human cancer cell lines Molt 4/C₈ and CEM and murine tumor cell line L1210. The ruthenium complexes showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these complexes prolonged the life span of mice bearing EAC tumors by 10–52%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.21 to 24 μM against Molt 4/C₈, 0.16 to 19 μM aginst CEM, and 0.75 to 32 μM against L1210.     

Synthesis, anticancer, and cytotoxic activities of some mononuclear Ru(II) compounds

The synthesis and characterization of ruthenium compounds (Ru1-Ru12) of the type [Ru(S)(2)(K)], (where S=1,10-phenanthroline/2,2'-bipyridine and K=itsz, MeO-btsz, 4-Cl-btsz, 2-Cl-btsz, 2-F-btsz, hfc and itsz=isatin-3-thiosemicarbazone, MeO-btsz=1-(4'-methoxy-benzyl)-thiosemicarbazone, hfc=2-{[3-chloro-4-fluoro-phenylimino]methyl}phenol, 4-Cl-btsz=1-(4'-chlorobenzyl)-thiosemicarbazone, 2-Cl-btsz=1-(2'-chloro benzyl)-thiosemicarbazone, 2-F-btsz=1-(2'-fluorobenzyl)-thiosemicarbazone) are described. These ligands form bidentate octahedral ruthenium compounds. The title compounds were subjected to in vivo anticancer activity against a transplantable murine tumor cell line Ehrlich's Ascites Carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C8, CEM and murine tumor cell line L1210. Ruthenium compounds (Ru1-Ru12) showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these compounds prolonged the life span of mice bearing EAC tumor by 10-43%. In vitro evaluation of these ruthenium compounds revealed cytotoxic activity from 0.24 to 27 microM against Molt 4/C8, 0.27 to 48 microM against CEM, and 0.94 to 248 microM against L1210. Their ligands alone failed to show cytotoxic activity at the concentrations tested (68-405 microM).     

Synthesis and pharmacological activities of some mononuclear Ru(II) complexes

A series of mononuclear Ru(II) complexes of the type [Ru(M)2(U)]2+, where M = 2,2'-bipyridine/1,10-phenanthroline and U = tpl (Ru1), 4-Cl-tpl (Ru2), 4-CH3-tpl (Ru3), 4-CH3O-tpl (Ru4), and 4-NO2-tpl (Ru5), -pai (Ru6), where tpl = thiopicolinanilide and pai = 2-phenyl-azo-imidazole, have been prepared and characterized by IR, UV-Vis, 1H NMR, 13C-NMR, FAB-Mass spectrophotometer, and elemental analysis. The complexes display metal-ligand charge transfer (MLCT) transitions in the visible region. The title complexes were subjected to in vivo anticancer activity tests against a transplantable murine tumor cell line, Ehrlich's ascitic carcinoma (EAC) and in vitro antibacterial activity against Gram positive and Gram negative microorganisms. Ru1-Ru6 were found to increase the life span of the tumor hosts by 19-52%, and decreased tumor volume and viable ascitic cell count. The results of the present study clearly demonstrated the tumor inhibitory activity of the ruthenium chelates against transplantable murine tumor cell line. The treatment with ruthenium complexes could be secondary to tumor regression or due to the action of the compounds itself. The significant antibacterial activity was observed for Ru1-Ru4 against microorganisms like Vibrio cholera 865, Staphylococcus aureus 6571, and Shigella flexneri as compared to that of standard drug chloramphenical. Ru5 showed moderate activity against S. aureus 8530. However, all the complexes fail to show significant antibacterial activity against V. cholera 14033 and Shigella sonnai.     

Modulation of creatine kinase activity by ruthenium complexes

Creatine kinase is a crucial enzyme for brain, heart and skeletal muscle energy homeostasis, and a decrease of its activity has been associated with cell death. Many biological properties have been attributed to ruthenium complexes. In this context, this work was performed in order to evaluate creatine kinase activity from rat brain, heart and skeletal muscle (quadriceps) after administration of ruthenium complexes, trans-[RuCl(2)(nic)(4)] (nic=3-pyridinecarboxylic acid) 180.7 micromol/kg (complex I), trans-[RuCl(2)(i-nic)(4)] (i-nic=4-pyridinecarboxylic acid) 13.6 micromol/kg (complex II), trans-[RuCl(2)(dinic)(4)] (dinic=3,5-pyridinedicarboxylic acid) 180.7 micromol/kg (complex III) and trans-[RuCl(2)(i-dinic)(4)] (i-dinic=3,4-pyridinedicarboxylic acid) 180.7 micromol/kg (complex IV). Our results showed that complex I caused inhibition of creatine kinase activity in hippocampus, striatum, cerebral cortex, heart and skeletal muscle. Besides, complex II did not affect the enzyme activity. complexes III and IV increased creatine kinase activity in hippocampus, striatum, cerebral cortex and heart, but not in skeletal muscle. Besides, none of the complexes in vitro altered creatine kinase activity, suggesting that enzymatic activity is indirectly affected by complexes I, III and IV. It is believed that diminution of creatine kinase in brain of rats caused by complex I may be related to results from other study reporting memory impairment caused by the same complex. Further research is necessary in order to elucidate the effects of ruthenium complexes in other important metabolic enzymes.     

Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: synthesis, characterization and in vitro antitumoral activity

Four dipeptide complexes of the type [PtX(2)(dipeptide)] x H(2)O (X=Cl, I, dipeptide=l-methionylglycine, l-methionyl-l-leucine) were prepared. The complexes were characterized by (1)H, (13)C, (195)Pt NMR and infrared spectroscopy, DTG and elemental analysis. From the infrared, (1)H and (13)C NMR spectroscopy it was concluded that dipeptides coordinate bidentately via sulfur and amine nitrogen donor atoms. Confirmed with (13)C and (195)Pt NMR spectroscopy, each of the complexes exists in two diastereoisomeric forms, which are related by inversion of configuration at the sulfur atom. The (1)H NMR spectrum for the platinum(II) complex with l-methionylglycine and chloro ligands exhibited reversible, intramolecular inversion of configuration at the S atom; DeltaG( not equal)=72 kJ mol(-1) at coalescence temperature 349 K was calculated. In vitro cytotoxicity studies using the human tumor cell lines liposarcoma, lung carcinoma A549 and melanoma 518A2 revealed considerable activity of the platinum(II) complex with l-methionylglycine and chloro ligands. Further in vitro cytotoxic evaluation using human testicular germ cell tumor cell lines 1411HP and H12.1 and colon carcinoma cell line DLD-1 showed moderate cytotoxic activity for all platinum(II) complexes only in the cisplatin-sensitive cell line H12.1. Platinum uptake studies using atomic absorption spectroscopy indicated no relationship between uptake and activity. Potential antitumoral activity of this class of platinum(II) complexes is dependent on the kind of ligands as well as on tumor cell type.     

Spectroscopic and cytotoxic studies of the novel designed palladium(II) complexes: beta-lactoglobulin and K562 as the targets

Since palladium complexes have been reported to show fewer side effects relative to other heavy metal anticancer compounds, in this study a new class of four structurally related anticancer Pd(II) complexes including 2,2'-bipyridin-n-butyl dithiocarbamato Pd(II) nitrate (Com-1), 2,2'-bipyridin-n-hexyl dithiocarbamato Pd(II) nitrate (Com-2), 2,2'-bipyridin glycinato Pd(II) nitrate (Com-3) and 2,2'-bipyridin octylglycinato Pd(II) nitrate (Com-4) was designed. The effect of four synthesized ligands on the protein structure and cell proliferation were investigated. Whey carrier proteins beta-lactoglobulin-A and-B (BLG-A and-B) and chronic myelogenous leukemia cell line K562 were the targets. Fluorescence and CD instruments were used to assess effect of the ligands on the protein structure. Growth inhibitory effect of the Pd(II) complexes towards the cancer cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results of fluorescence studies revealed that the complexes had no dithiocarbamate moiety (compounds 3 and 4) could quench the intrinsic fluorescence emission of the proteins at lower concentrations than those had such moiety (compounds 1 and 2). The far-UV-CD studies revealed that the regular secondary structure of BLG-A and -B did not show any noticeable alteration upon interaction with different of Pd(II)-complexes. The results of cell proliferation assay also displayed that Com-1 and Com-2 had more growth inhibitory activity against K562, than Com-3 and Com-4. Our results suggested that addition of dithiocarbamate moiety to structure of Pd(II) complexes probably has important role to improve the antiproliferative properties of the anticancer ligands and fewer effects on the carrier protein structure.     

Synthesis and structure of cycloruthenated carbonyl complexes and their emission, redox and biological properties

An interesting series of mononuclear organoruthenium complexes of formulation [Ru(CO)(PPh3)2(ap-R)] (where ap-R = -H, -Cl, -Me, -OMe, -OEt) have been synthesized from the reaction of five 2-(arylazo)phenol ligands with ruthenium(II) precursor [RuH(Cl)(CO)(PPh3)3] in benzene under reflux. The 2-(arylazo)phenolate ligands behave as dianionic tridentate ligand and are coordinated to ruthenium through C, N and O by dissociation of the phenolic and phenyl proton at the ortho position of the phenyl ring forming two five-membered chelate rings. These complexes have been characterized by elemental analysis, FT-IR, 1H NMR and UV-visible spectroscopy. In dichloromethane solution all the metal complexes exhibit characteristic metal-to-ligand charge transfer (MLCT) absorption and emission bands in the visible region. The structures of [Ru(CO)(PPh3)2(ap-H)] and [Ru(CO)(PPh3)2(ap-Cl)] have been determined by X-ray crystallography. Cyclic voltammetric data of all the complexes show a Ru(III)/Ru(II) oxidation and reduction Ru(II)/Ru(I) within the range 0.74-0.84 V and -0.38 to -0.50 V vs saturated calomel electrode (SCE) respectively. The potentials are observed with respect to the electronic nature of substituents (R) in the 2-(arylazo)phenolate ligands. Further, the free ligands and their ruthenium complexes have also been screened for their antibacterial and antifungal activities, which have shown great promise in inhibiting the growth of both gram +ve and gram -ve bacteria Staphylococcus aureus and Escherichia coli and fungus Candida albicans and Aspergillus niger. These results made it desirable to delineate a comparison between free ligands and their complexes.     

In vivo inhibition of E. coli growth by a Ru(II)/Pt(II) supramolecule [(tpy)RuCl(dpp)PtCl2](PF6)

Supramolecular complexes consisting of ruthenium chromophores and a cisplatin unit represent an emerging class of bioactive molecules of interest as anti-cancer agents. Although the ability of Ru(II)/Pt(II) heteronuclear complexes to bind to DNA has been demonstrated, the in vivo activity of these complexes has not yet been reported. In the present work, we report the anti-bacterial activity of the complex [(tpy)RuCl(dpp)PtCl(2)](PF(6)) (where dpp=2,3-bis(2-pyridyl)pyrazine, tpy=2,2':6',2'-terpyridine). The impact on bacterial cell growth of exposure to different concentrations of [(tpy)RuCl(dpp)PtCl(2)](PF(6)) and cisplatin was studied. The bioactivity of this complex was found to be due to the presence of the cis-PtCl(2) moiety, as the monometallic synthon [(tpy)RuCl(dpp)](PF(6)) did not inhibit bacterial cell growth.     

Syntheses, characterization and DNA-binding study of chiral complexes DeltaDelta- and LambdaLambda-[Ru(bpy)2(bdptb)Ru(bpy)2]4+

A novel bridging ligand bdptb(2,2'-bis(5,6-diphenyl-1,2,4-triazin-3-yl)-4,4'-bipyridine) and it's chiral diruthenium(II) complex DeltaDelta- and LambdaLambda-[Ru(bpy)2(bdptb)Ru(bpy)2]4+ (Ru2) have been synthesized and characterized by electrospray mass spectra, 1H NMR, UV/visible and circular dichroism spectra. Binding behavior of these dimeric complexes with calf thymus DNA have been investigated by absorption spectra, viscosity measurements, equilibrium dialysis experiments. The electronic absorption spectra hypochromism at the metal-ligand charge transfer of the DeltaDelta- and LambdaLambda-enantiomer are 26.4%, and 40%, and bathochromism of 13.5, and 14 nm in sequence. Equilibrium dialysis experiments results show also the binding-DNA of LambdaLambda-enantiomer is stronger than DeltaDelta-enantiomer. The increasing amounts of the novel dimeric ruthenium(II) complexes on the relative viscosities of calf thymus DNA is smaller than that of the classic intercalators such as [Ru(bpy)2(dppz)]2+ and larger than that of the non-classic intercalators such as Delta-[Ru(phen)3]2+. The experiments suggest the dimeric ruthenium(II) complex may be bound to DNA by groove binder.     

Inhibitory activity of palladium(II) and platinum(II) complexes with isoxazole and its derivatives

The investigation of the inhibitory activity on the membrane bonded ATP-ase of the M(L)₂X₂ complexes [where M = Pd(II), Pt(II); L = isoxazole(isox), 3,5-dimethylisoxazole(3,5-diMeisox), 3-methyl,5-phenylisoxazole(3-Me,5-Phisox), 3,5-diphenylisoxazole-(3,5-diPhisox), and 4-amino-3,5-dimethylisoxazole(4-ADI); X = Cl, Br] is reported. These results show that the complexes with isox and its methyl and phenyl derivatives have a much stronger inhibitory effect than the corresponding free ligands; in the 4-ADI compounds this activity drops. The Pd(II) complexes have a greater effect than the Pt(II) derivatives. The interaction occurs with SH groups and probably also with other active centers of the enzyme. These conclusions have been correlated with the E.S.C.A. spectra. These measurements show that the electron density of the complexes on the central metal ion and N_ring atom or N_ring and N-hexocyclic atoms on passing from chloride to bromide derivatives changes slightly.     

Neutron activation increases activity of ruthenium-based complexes and induces cell death in glioma cells independent of p53 tumor suppressor gene

Novel metal complexes have received great attention in the last decades due to their potential anticancer activity. Notably, ruthenium-based complexes have emerged as good alternative to the currently used platinum-based drugs for cancer therapy, providing less toxicity and side effects to patients. Glioblastoma is an aggressive and invasive type of brain tumor and despite of advances is the field of neurooncology there is no effective treatment until now. Therefore, we sought to investigate the potential antiproliferative activity of phosphine-ruthenium-based complexes on human glioblastoma cell lines. Due to its octahedral structure as opposed to the square-planar geometry of platinum(II) compounds, ruthenium(II) complexes exhibit different structure–function relationship probably acting through a different mechanism from that of cisplatin beyond their ability to bind DNA. To better improve the pharmacological activity of metal complexes we hypothesized that neutron activation of ruthenium in the complexes would allow to decrease the effective concentration of the compound needed to kill tumor cells. Herein we report on the effect of unmodified and neutron activated phosphine ruthenium II complexes on glioblastoma cell lines carrying wild-type and mutated p53 tumor suppressor gene. Induction of apoptosis/authophagy as well as generation of reactive oxygen species were determined. The phosphine ruthenium II complexes tested were highly active against glioblastoma cell lines inducing cell death both through apoptosis and autophagy in a p53 independent fashion. Neutron activation of ruthenium compounds rendered them more active than their original counterparts suggesting a new strategy to improve the antitumor activity of these compounds.     

Synthesis,Characterization, Cellular Uptake,Apoptosis, Cytotoxicity,Dna-Binding,and Antioxidant Activity Studies of Ruthenium(II) Complexes

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)₂(HECIP)](ClO₄)₂ (1) (HECIP = N-ethyl-4-[(1,10)-phenanthroline(5,6-f)imidazol-2-yl]carbazole, dmb = 4,4’-dimethyl-2,2’-bipyridine) and [Ru(dmp)₂(HECIP)](ClO₄)₂ (2) (dmp = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The DNA-binding behaviors of the two complexes were investigated by absorption spectra, viscosity measurements, and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 were determined to be 8.03 (± 0.12) × 10⁴ M^?1 (s = 1.62) and 2.97 (± 0.15) × 10⁴ M^?1 (s = 1.82), respectively. The results suggest that these complexes interact with DNA through intercalative mode. The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 has been evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)] method. Complex 1 shows higher anticancer potency than 2 against the four tumor cell lines. Apoptosis and cellular uptake were investigated. The antioxidant activities of the ligand and these complexes were also performed.     

Structural correlation of catecholase-like activities of oxy-bridged dinuclear copper(II) complexes

Eight oxy-bridged dinuclear copper(II) complexes with catecholase-like sites, [Cu(L1)X]2 (HL1 = 1-diethylaminopropan-2-ol, X=N3- 1, NCO- 2, and NO2- 3), [Cu(L2)X]2 (HL2=N-ethylsalicylaldimine, X=NO3- 4, Cl- 5, N3- 6, NCS- 7), and [Cu(L3)]2(ClO4)2, 8 (HL3=N-(salicylidene)-N'-(2-pyridylaldene)propanediamine) have been prepared and characterized. The single crystal X-ray analysis show that the structures of complexes 6 and 8 are dimeric with two adjacent copper(II) atoms bridged by pairs of micro-oxy atoms from the L2 and L3 ligands. Magnetic susceptibility measurements in the temperature range 4-300 K indicate significant antiferromagnetic coupling for 4, 5 and 7 and ferromagnetic coupling for 6 between the copper(II) atoms. The catecholase activity of complexes for the oxidation of 3,5-di-tert-butylcatechol by O2 was studied and it was found that the complexes with the bond distance of Cu(II)...Cu(II) located at 2.9-3.0 A show higher catecholase activity.     

Chiral ruthenium(II) anthraquinone complexes as dual inhibitors of topoisomerases I and II

Abstract  

DNA topoisomerases (I and II) have been one of the excellent targets in anticancer drug development. Here two chiral ruthenium(II) anthraquinone complexes, Δ- and Λ-[Ru(bpy)₂(ipad)]²⁺, where bpy is 2,2′-bipyridine and ipad is 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline, were synthesized and characterized. As expected, both of the Ru(II) complexes intercalate into DNA base pairs and possess an obviously greater affinity with DNA. Topoisomerase inhibition and DNA strand passage assay confirmed that the two complexes are efficient dual inhibitors of topoisomerases I and II by interference with the DNA religation. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against HeLa, MCF-7, HepG2 and BEL-7402 tumor cell lines. Flow cytometry analysis shows an increase in the percentage of cells with apoptotic morphological features in the sub-G1 phase for Ru(II) complexes. Nuclear chromatin cleavage has also been observed from AO/EB staining assay and alkaline single-cell gel electrophoresis (comet assay). The results demonstrated that Δ- and Λ-[Ru(bpy)₂(ipad)]²⁺ act as dual inhibitors of topoisomerases I and II, and cause DNA damage that can lead to cell cycle arrest and/or cell death by apoptosis.     

Syntheses and DNA-binding studies of two ruthenium(II) complexes containing one ancillary ligand of bpy or phen: [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)2

Two new ruthenium(II) complexes of [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)(2) (bpy=2,2'-bipyridine, phen=1,10-phenanthroline, pp[2,3]p=pyrido[2',3':5,6]pyrazino[2,3-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis and 1H NMR spectra. The calf thymus DNA-binding properties of the two complexes were investigated by UV-visible and emission spectroscopy, competitive binding experiments with ethidium bromide and viscosity measurements. The results indicate that the two complexes intercalate between the base pairs of the DNA tightly with intrinsic DNA-binding constants of 3.08 x 10(6) and 6.53 x 10(6) M(-1) in buffered 50 mM NaCl, respectively, which are much larger than 6.9 x 10(5) M(-1) for [Ru(bpy)2(pp[2,3]p)](ClO4)2 containing two ancillary ligands of bpy.     

Synthesis, complete characterization, and enantioselective electrokinetic separation of functionalized ruthenium complex enantiomers

Electrokinetic chromatography was employed to separate the enantiomers of two novel functionalized ruthenium(II) complexes with different polypyridyl coordination spheres. The use of anionic carboxymethyl-beta-cyclodextrin as chiral mobile phase additive resulted in maximum efficiency and resolution for the enantiomer separation of both transition metal complexes. The syntheses of the [4-(3-hydroxypropyl)-4'-methyl-2,2'-bipyridine]-bis(2,2'-bipyridine)rethenium(II)-bis(tetrafluoroborate) and [4-(3-hydroxypropyl)-4'-methyl-2,2'-bipyridine]-bis(4,4'-dimethyl-2,2'-bypyridine)ruthenium(II)-bis(tetrafluoroborate) complexes and their complete characterization by means of two-dimensional (1)H and (13)C[(1)H] NMR techniques ((1)H-(1)H COSY and (1)H-(13)C HMQC) as well as elemental analyses and MALDI-TOFMS are described in detail. The functionalized complexes can be used as building blocks for further reactions with polymers, biopolymers, surfaces and nanoparticles.     

Preparation and photophysical studies of copper(I) and ruthenium(II) complexes of 4,4′-bis(3,5-dimethoxyphenyl)-6,6′-dimethyl-2,2′-bipyridine

We report the synthesis of a new ligand, 4,4′-bis(3,5-dimethoxyphenyl)-6,6′-dimethyl-2,2′-bipyridine, optimised for binding to copper(I) and with pendant functionality that can eventually be developed into metallodendritic structures. The synthesis and photophysical properties of complexes with copper(I) and ruthenium(II) are reported. The solid state structure of the complex [Cu(1)₂][PF₆] · MeCN (1 = 4,4′-bis(3,5-dimethoxyphenyl)-6,6′-dimethyl-2,2′-bipyridine) is also described.     

Synthesis, crystal structures, and anti-convulsant activities of ternary [Zn(II)(3,5-diisopropylsalicylate)(2)], [Zn(II)(salicylate)(2)] and [Zn(II)(aspirinate)(2)] complexes

Following observations that bis(3,5-diisopropylsalicylato)diaquazinc(II), [Zn(II)(3,5-DIPS)(2)(H(2)O)(2)], had anti-convulsant activity, bis(acetylsalicylate)diaquazinc(II), [Zn(II)(aspirinate)(2)(H(2)O)(2)], and the Zn(II) ternary 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neocuproine, NC) or dimethyl sulfoxide (DMSO) complexes of Zn(II)3,5-diisopropylsalicylate, salicylate, and acetylsalicylate were synthesized and spectroscopically characterized. Anti-convulsant and Rotorod toxicity activities of these complexes were determined to examine their anti-convulsant and undesirable central nervous stimulant or depressant activities of these Zn(II) non-steroidal anti-inflammatory agent complexes. Bis(3,5-diisopropylsalicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(phen)], (1) has one bidentate phen ligand and two mono-deprotonated 3,5-DIPS ligands. One of the carboxylates bonds in an asymmetric chelating mode. The Zn(II) atom exhibits a distorted bicapped rectangular pyramidal environment N(2)O(2)OO (4+1+1 *). In the neocuproine complex, bis(3,5-diisopropylsalicylato)-2,9-dimethyl-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(NC)] (2), the Zn(II) atom has a much more distorted bicapped rectangular pyramidal environment, N(2)O(2)O(2) (4+2 *), compared to 1. The two carboxylate ligands exhibit the same asymmetric coordinating mode with longer metalloelement-oxygen bond distances compared to 1. The space group of [Zn(II)(aspirinate)(2)(H(2)O)(2)] (3), which has been reported as Cc is corrected to C2/c. The zinc atom exhibits a (4+2 *) bicapped square pyramidal environment. While the two ternary phenanthroline-containing complexes, 1 and 2, evidenced weak protection against maximal electroshock (MES)- and subcutaneous Metrazol (scMET) induced seizures, [Zn(II)(3,5-DIPS)(2)(DMSO)(2)], [Zn(II)(aspirinate)(2)(H(2)O)(2)], and bis(salicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(salicylate)(2)(phen)], were found to be particularly useful in protecting against MES and scMET seizures and [Zn(II)(aspirinate)(2)(H(2)O)(2)] and [Zn(II)(salicylate)(2)(phen)] were found to have activity in protecting against Psychomotor seizures, without causing Rotorod toxicity. Activities of these and other Zn(II) complexes of non-steroidal anti-inflammatory agents are consistent with the well-known anti-inflammatory responses of Zn(II)-dependent enzymes. There was also some evidence of Rotorod toxicity consistent with a mechanism of action involving sedative-hypnotic activity of recognized anti-epilepticdrugs.