Bis[S-octyl 3-(2-methyl-propyl-idene)di-thio-carb-az-ato-κ2N3,S]nickel(II).

The central NiII atom in the title complex, [Ni(C13H25N2S2)2], is located on an inversion center and adopts a roughly square-planar coordination environment defined by two chelating N,S donor sets of two symmetry-related ligands in a trans configuration. The Ni-N and Ni-S bond lenghts are 1.9193 (14) and 2.1788 (5) Å, respectively, with a chelating N-Ni-S bond angle of 86.05 (4)°. These data are compared with those measured for similar di-thio-carbazato ligands that bear n-octyl or n-hexyl alkyl chains. Slight differences are observed with respect to the phenyl-ethyl-idene derivative where the ligands are bound cis relative to one another.

Interaction with CT-DNA and in vitro cytotoxicity of two new copper(II)-based potential drugs derived from octanoic hydrazide ligands.

Two copper(II) complexes [Cu(Hpmoh)(NO3)(NCS)] (1) and [Cu(peoh)(N3)]2 (2) were designed and synthesized by reaction of Cu(NO3)2·3H2O with hydrazone Schiff base ligands,abbreviated with Hpmoh and Hpeoh. Hpmoh and Hpeoh were prepared by condensation reaction of octanoic hydrazide with pyridine-2-carboxyaldehyde and 2-acetylpyridine, respectively. Complexes 1 and 2 were characterized using different analytical techniques such as FT-IR, UV-Vis, IR, EPR and single X-ray diffraction (XRD) analyses as well as computational methods (DFT). The XRD of 1 and 2 shows a mononuclear or a dinuclear structure with the copper(II) centre adopting a slightly distorted square pyramidal geometry. In water-containing solution and in DMSO, 1 and 2 undergo a partial transformation with formation of [Cu(Hpmoh)(NO3)(NCS)] (1) and [Cu(Hpmoh)(NO3)(H2O/DMSO)] (1a) in one system and [Cu(peoh)(N3)] (2a) in the other one, as supported by DFT calculations. Docking simulations confirmed that the intercalation is the preferred binding mode with DNA for 1, 1a and 2a, but suggested that the minor groove binding is also possible. A significant fluorescence quenching of the DNA-ethidium bromide conjugate was observed upon the addition of complexes 1 and 2 with a quenching constant around 104 M-1 s-1. Finally, both 1 and 2 were examined for anti-cancer activity using MDA-MB-231 (human breast adenocarcinoma) and A375 (malignant melanoma) cell lines through in vitro MTT assay which suggest comparable cancer cell killing efficacy, with the higher effectiveness of 2 due to the dissociation into two [Cu(peoh)(N3)] units.

A novel nickel(II) complex with N,S donor Schiff base: Structural characterisation, DFT, TD-DFT study and catalytic investigation.

One new mononuclear nickel(II) thiosemicarbazone complex (1), has been synthesised from the Schiff base ligand derived from p-anisaldehyde and thiosemicarbazide. Complex 1 is characterized by using different spectroscopic techniques and single crystal X-ray structure analysis. Time dependent density functional theory (TD-DFT) was performed to simulate the electronic spectra of the complex 1 with the help of Polarizable Continuum Model (PCM) model. Complex 1 acts as functional models. The catalytic property has been evaluated from Lineweaver-Burk plot using the Michaelis-Menten approach of enzyme catalysis with a kcat value of the order of 708 h-1.

Crystal structure of bis-{S-octyl-3-[(thio-phen-2-yl)methyl-idene]di-thio-carbazato-κ2N3,S}nickel(II).

In the title complex, [Ni(C14H21N2S3)2], the nickel(II) atom is located on a crystallographic inversion center and exhibits a square-planar coordination environment, being coordinated by two negatively charged N,S-chelating ligands in a trans configuration. In the crystal, the non-H atoms of the complex are practically coplanar (r.m.s. deviation of fitted atoms = 0.135 Å), and the angle between the thienyl and the chelating rings is 6.7 (1)°. The mol-ecules stack at a distance of 3.623 (2) Šalong the b-axis direction.

Crystal structure of bis-[4-(all-yloxy)-N'-(but-2-en-1-yl-idene)benzohydrazidato]nickel(II).

In the title complex, [Ni(C14H15N2O2)2], the nickel(II) atom exhibits a square-planar coordination geometry, being coordinated by two negatively charged N,O chelating ligands in a trans configuration, with the metal located on a crystallographic center of symmetry. The X-ray structural characterization showed the complex to be disordered over two orientations with refined occupancies of 0.898 (2) and 0.102 (2). The whole mol-ecule is close to planar, the five- and six-membered rings subtending a dihedral angle of 7.5 (2)°. The crystal packing is supported by C-H⋯π and C-H⋯O inter-actions that form a di-periodic layered network.

Crystal structure of S-n-octyl 3-(1-phenyl-ethyl-idene)di-thio-carbazate and of its bis-chelated nickel(II) complex.

The nitro-gen-sulfur Schiff base proligand S-n-octyl 3-(1-phenyl-ethyl-idene)di-thio-carbazate, C17H26N2S2 (HL), was prepared by reaction of S-octyl di-thio-carbamate with aceto-phenone. Treatment of HL with nickel acetate yielded the complex bis-[S-n-octyl 3-(1-phenyl-ethyl-idene)di-thio-carbazato]nickel(II), [Ni(C17H25N2S2)2] (NiL 2), which was shown to adopt a tetra-hedrally distorted cis-square-planar coordination geometry, with the NiSN planes of the two ligands forming a dihedral angle of 21.66 (6)°. Changes in the geometry of the L ligand upon chelation of Ni2+ are described, involving a ca 180° rotation around the N(azomethine)-C(thiol-ate) bond.

Crystal structure of bis-{4-[(4-methyl-benz-yl)-oxy]-N'-(4-methyl-benzyl-idene)benzohydrazidato}nickel(II).

In the title complex, [Ni(C23H21N2O2)2], the central NiII atom is located on an inversion centre and exhibits a slightly distorted square-planar N2O2 coordination environment. A trans-configuration of the N,O chelating ligands results from the imposed site symmetry of the central NiII atom. In the crystal, individual mol-ecules stack along the a axis through weak π-π stacking inter-actions between the phenyl rings.

Interaction with bioligands and in vitro cytotoxicity of a new dinuclear dioxido vanadium(V) complex.

One centrosymmetric bis(µ-oxido)-bridged vanadium(V) dimer with molecular formula [(VVO2)2(pedf)2] (1) has been synthesized from the reaction of VOSO4·5H2O with a Schiff base ligand (abbreviated with pedf-) obtained from 2-acetylpyridine and 2-furoic hydrazide in methanol. Complex 1 was characterized by elemental analysis, UV-visible (UV-Vis), Fourier-transform infrared spectra (FT-IR), cyclic voltammetry (CV), electron paramagnetic resonance spectroscopy (EPR) and electrospray ionization-mass spectrometry (ESI-MS) techniques along with single crystal X-ray diffraction (SCXRD). The FT-IR spectral data of 1 indicated the involvement of oxygen and azomethine nitrogen in coordination to the central metal ion. The crystallographic studies revealed a dinuclear oxovanadium(V) complex with the Schiff base coordinated via the ONN donor set with formation of two five-membered chelate rings resulting in a distorted octahedral geometry. The interaction of 1 with calf thymus DNA (CT-DNA) was investigated by spectroscopic measurements and results suggested that the complex binds to CT-DNA via moderate intercalative mode with a binding constant (Kb) around 103 M-1. In addition, the in vitro protein binding behavior was studied by fluorescence spectrophotometric method using both bovine serum albumin (BSA) and human serum albumin (HSA) and a static quenching mechanism was observed for the interaction of the complex with both albumins that occurs with a Kb in the range (5-6) × 103 M-1. In vitro cytotoxicity of complex 1 on lung cancer cells (A549) and human skin carcinoma cell line (A431) demonstrated that the complex had a broad-spectrum of anti-proliferative activity with IC50 value of 64.2 µM and 56.2 µM.

Evaluation of the antitumor activity of a series of the pincer-type metallocomplexes produced from isonicotinohydrazide derivative.

In this work we report on the antitumor properties of a series of pincer-type metallocomplexes [Hg2(HL-keto)Cl4]n (1), [Hg(HL-keto)I2] (2) and [Mn(HL-zwitterion)Cl2]∙MeOH (3∙MeOH), derived from N'-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide (HL) and corresponding metal salts. The Hg(II) and Mn(II) salts are chelated by the keto (HL-keto) or zwitterionic (HL-zwitterion) form of HL, respectively. The cytotoxic effects of these compounds have been accessed against lung adenocarcinoma (A549) and hepatocellular carcinoma (HepG2 and Huh7) cell lines. Complexes 1 and 2 were found to be most efficient against the cell line Huh7 with IC50 value of 2.56 and 9.90 µM, respectively, while they exhibit moderate activity towards cell lines A549 and HepG2, as evidenced from IC50 values in the range 27.98-56.99 µM. Complex 3∙MeOH is less efficient towards all the three cell lines with relatively high IC50 values. The mechanisms of the metallocomplexes killing the aforementioned cells were elucidated by flow cytometry, colony formation and polymerase chain reaction (PCR) analysis of apoptosis related expression of the genes. The results of the cytotoxic effects and antitumor activity on different cell lines are affected by the metal nature and the presence of the coordinated halide.

Catecholase-Like Activity and Theoretical Study in Solid State of a New Ru(III)-Schiff Base Complex.

A new ruthenium(III) complex of molecular formula [Ru(PPh3)Cl2(L)] (1) has been synthesized using the Schiff base ligand obtained from 5-chlorosalicylaldehyde and N,N-dimethylethylenediamine, and characterized by FT-IR, UV-Vis, cyclic voltammetry and single crystal X-ray structural analysis. The metal ion exhibits a slightly distorted octahedral environment where the chelating Schiff base ligand contributes with its NNO donor set. The coordination geometry around the Ru(III) ion is completed by a PPh3 ligand and two chloride anions, and the charge balance is assured by the phenoxo oxygen of the Schiff base. With the aim to analyse the energy related to the halogen bonding interactions in solid state, a theoretical study has been performed on complex 1, by using the MEP and NCI plot computational tools, was also performed with the aim to analyse the energy related to the halogen bonding interaction. Furthermore, complex 1 shows catecholase-like activity in conversion of the model substrate 3,5-di-tert-butylcatechol (3,5-DTBC) to the corresponding 3,5-di-tert-butylquinone (3,5-DTBQ) under aerobic condition. The parameters regarding the enzymatic kinetics have been evaluated from the Lineweaver-Burk plot using the Michaelis-Menten approach of enzyme catalysis. A significant high T.O.N value (2.346×103 h-1) indicates that complex 1 has a very good catalytic efficiency towards 3,5-DTBC.

124 I Radiolabeling of a AuIII -NHC Complex for In Vivo Biodistribution Studies.

AuIII complexes with N-heterocyclic carbene (NHC) ligands have shown remarkable potential as anticancer agents, yet their fate in vivo has not been thoroughly examined and understood. Reported herein is the synthesis of new AuIII -NHC complexes by direct oxidation with radioactive [124 I]I2 as a valuable strategy to monitor the in vivo biodistribution of this class of compounds using positron emission tomography (PET). While in vitro analyses provide direct evidence for the importance of AuIII -to-AuI reduction to achieve full anticancer activity, in vivo studies reveal that a fraction of the AuIII -NHC prodrug is not immediately reduced after administration but able to reach the major organs before metabolic activation.

X-Ray Crystal Structures and Organogelator Properties of (R)-9-Hydroxystearic Acid.

(R)-9-hydroxystearic acid, (R)-9-HSA, is a chiral nonracemic hydroxyacid of natural origin possessing interesting properties as an antiproliferative agent against different cancer types. Considering its potential application for medical and pharmaceutical purposes, the structures and rheological properties of (R)-9-HSA were investigated. Oscillatory rheology measurements reveal that (R)-9-HSA gels only paraffin oil, with less efficiency and thermal stability than its positional isomer (R)-12-HSA. Conversely, (R)-9-HSA affords crystals from methanol, acetonitrile, and carbon tetrachloride. The single crystal structures obtained both at 293 K and 100 K show non-centrosymmetric twisted carboxylic acid dimers linked at the midchain OHs into long, unidirectional chains of hydrogen bonds, owing to head-tail ordering of the molecules. Synchrotron X-ray powder diffraction experiments, performed on the solids obtained from different solvents, show the occurrence of polymorphism in paraffin oil and through thermal treatment of the solid from methanol.

Bioactive Heterometallic CuII-ZnII Complexes with Potential Biomedical Applications.

A series of multinuclear heterometallic Cu-Zn complexes of molecular formula [(CuL)2Zn(dca)2] (1), [(CuL)2Zn(NO3)2] (2), [(CuL)2Zn2(Cl)4] (3), and [(CuL)2Zn2(NO2)4] (4) have been synthesized by reacting [CuL] as a "metalloligand (ML)" (where HL = N,N'-bis(5-chloro-2-hydroxybenzylidene)-2,2-dimethylpropane-1,3-diamine) and by varying the anions or coligands using the same molar ratios of the reactants. All of the four products including the ML have been characterized by infrared and UV-vis spectroscopies and elemental and single-crystal X-ray diffraction analyses. By varying the anions, different structures and topologies are obtained which we have tried to rationalize by means of thorough density functional theory calculations. All of the complexes (1-4) have now been applied for several biological investigations to verify their therapeutic worth. First, their cytotoxicity properties were assessed against HeLa human cervical carcinoma along with the determination of IC50 values. The study was extended with extensive DNA and protein binding experiments followed by detailed fluorescence quenching study with suitable reagents to comprehend the mechanistic pathway. From all of these biological studies, it has been found that all of these heterometallic complexes show more than a few fold improvement of their therapeutic values as compared to the similar homometallic ones probably because of the simultaneous synergic effect of copper and zinc. Among all of the four heterometallic complexes, complex 3 exhibits highest binding constants and IC50 values suggest for their better interaction toward the biological targets and hence have better clinical importance.

Mn(II) complexes of different nuclearity: synthesis, characterization and catecholase-like activity.

Two "end-off" compartmental ligands, 2-formyl-4-chloro-6-N-ethylmorpholine-iminomethyl-phenol (HL1) and 2-formyl-4-methyl-6-N-ethylpyrrolidine-iminomethyl-phenol (HL2) have been designed and three complexes of Mn(ii), one mono-, one di- and a polynuclear, namely Mn(L1)(SCN)2(H2O)] (), [Mn2(L1)(OAc)2](BPh4)] (), and [Mn2(L2)(OAc)2(dca)]n () have been synthesized and structurally characterized. Variable temperature magnetic studies of and have been performed and data analyses reveal that Mn centers are antiferromagnetic coupled with J = -9.15 cm(-1) and J = -46.89, respectively. Catecholase activity of all the complexes has been investigated using 3,5-di-tert-butyl catechol (3,5-DTBC). All are highly active and the activity order on the basis of the kcat value is > > . In order to unveil whether the metal centered redox participation or the radical pathway is responsible for the catecholase-like activity of the complexes, detailed EPR and cyclic voltammetric (CV) studies have been performed. In addition to the six-line EPR spectrum characteristic to Mn(ii), an additional peak at g ∼ 2 is observed when the EPR study is done with the mixture of 3,5-DTBC and the catalyst, suggesting the formation of an organic radical, most likely ligand centered. The CV experiment with the mixture of 3,5-DTBC and the catalyst reveals ligand centered reduction rather than reduction of Mn(ii) to Mn(i). It is thus inferred that complexes show catecholase-like activity due to radical generation.

Relation between the catalytic efficiency of the synthetic analogues of catechol oxidase with their electrochemical property in the free state and substrate-bound state.

A library of 15 dicopper complexes as synthetic analogues of catechol oxidase has been synthesized with the aim to determine the relationship between the electrochemical behavior of the dicopper(II) species in the absence as well as in the presence of 3,5-di-tert-butylcatechol (3,5-DTBC) as model substrate and the catalytic activity, kcat, in DMSO medium. The complexes have been characterized by routine physicochemical techniques as well as by X-ray single-crystal structure analysis in some cases. Fifteen "end-off" compartmental ligands have been designed as 1 + 2 Schiff-base condensation product of 2,6-diformyl-4-R-phenol (R = Me, (t)Bu, and Cl) and five different amines, N-(2-aminoethyl)piperazine, N-(2-aminoethyl)pyrrolidine, N-(2-aminoethyl)morpholine, N-(3-aminopropyl)morpholine, and N-(2-aminoethyl)piperidine. Interestingly, in case of the combination of 2,6-diformyl-4-methylphenol and N-(2-aminoethyl)morpholine/N-(3-aminopropyl)morpholine/N-(2-aminoethyl)piperidine 1 + 1 condensation becomes the reality and the ligands are denoted as L2(1-3). On reaction of copper(II) nitrate with L2(1-3) in situ complexes 3, 12, and 13 are formed having general formula Cu2(L2(1-3))2(NO3)2. The remaining 12 ligands obtained as 1 + 2 condensation products are denoted as L1(1-12), which produce complexes having general formula Cu2(L1(1-12))(NO3)2. Catecholase activity of all 15 complexes has been investigated in DMSO medium using 3,5-DTBC as model substrate. Treatment on the basis of Michaelis-Menten model has been applied for kinetic study, and thereby turnover number, kcat, values have been evaluated. Cyclic voltametric (CV) and differential pulse voltametric (DPV) studies of the complexes in the presence as well as in the absence of 3,5-DTBC have been thoroughly investigated in DMSO medium. From those studies it is evident that oxidation of 3,5-DTBC catalyzed by dicopper(II) complexes proceed via two steps: first, semibenzoquinone followed by benzoquinone with concomitant reduction of Cu(II) to Cu(I). Our study reveals that apparently there is nearly no linear relationship between kcat and E° values of the complexes. However, a detailed density functional theory (DFT) calculation sheds light on this subject. A very good correlation prevails in terms of the energetics associated with the Cu(II) to Cu(I) reduction process and kcat values, as revealed from the combined theoretical and experimental approach.

New water-soluble ruthenium(II) terpyridine complexes for anticancer activity: synthesis, characterization, activation kinetics, and interaction with guanine derivatives.

With the aim of assessing whether ruthenium(II) compounds with meridional geometry might be utilized as potential antitumor agents, a series of new, water-soluble, monofunctional ruthenium(II) complexes of the general formula mer-[Ru(L3)(N-N)X][Y]n (where L3 = 2,2':6',2″-terpyridine (tpy) or 4'-chloro-2,2':6',2″-terpyridine (Cl-tpy), N-N = 1,2-diaminoethane (en), 1,2-diaminocyclohexane (dach), or 2,2'-bipyridine (bpy); X = Cl or dmso-S; Y = Cl, PF6, or CF3SO3; n = 1 or 2, depending on the nature of X) were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and for three of them, i.e., [Ru(Cl-tpy)(bpy)Cl][Cl] (3Cl), [Ru(Cl-tpy)(en)(dmso-S)][Y]2 [Y = PF6 (6PF6), CF3SO3 (6OTf)] and [Ru(Cl-tpy)(bpy)(dmso-S)][CF3SO3]2 (8OTf), the X-ray structure was also determined. The new terpyridine complexes, with the exception of 8, are well soluble in water (>25 mg/mL). (1)H and (31)P NMR spectroscopy studies performed on the three selected complexes [Ru(Cl-tpy)(N-N)Cl](+) [N-N = en (1), dach (2), and bpy (3)] demonstrated that, after hydrolysis of the Cl ligand, they are capable of interacting with guanine derivatives [i.e., 9-methylguanine (9MeG) or guanosine-5'-monophosphate (5'-GMP)] through N7, forming monofunctional adducts with rates and extents that depend strongly on the nature of N-N: 1 ≈ 2 ≫ 3. In addition, compound 1 shows high selectivity toward 5'-GMP compared to adenosine-5'-monophosphate (5'-AMP), in a competition experiment. Quantitative kinetic investigations on 1 and 2 were performed by means of UV/visible spectroscopy. Overall, the complexes with bidentate aliphatic diamines proved to be superior to those with bpy in terms of solubility and reactivity (i.e., release of Cl(-) and capability to bind guanine derivatives). Contrary to the chlorido compounds, the corresponding dmso derivatives proved to be inert (viz., they do not release the monodentate ligand) in aqueous media.

A radical pathway in catecholase activity with nickel(II) complexes of phenol based "end-off" compartmental ligands.

Seven dinuclear and one dinuclear based dicyanamide bridged polymeric Ni(II) complexes of phenol based compartmental ligands (HL(1)-HL(4)) have been synthesized with the aim to investigate their catecholase-like activity and to evaluate the most probable mechanistic pathway involved in this process. The complexes have been characterized by routine physicochemical studies as well as by X-ray single crystal structure analyses namely [Ni2(L(2))(SCN)3(H2O)(CH3OH)] (), [Ni2(L(4))(SCN)3(CH3OH)2] (), [Ni2(L(2))(SCN)2(AcO)(H2O)] (), [Ni2(L(4))(SCN)(AcO)2] (), [Ni2(L(2))(N3)3(H2O)2] (), [Ni2(L(4))(N3)3(H2O)2] (), [Ni2(L(1))(AcO)2(N(CN)2)]n () and [Ni2(L(3))(AcO)2(N(CN)2)] (), [SCN = isothiocyanate, AcO = acetate, N3 = azide, and N(CN)2 = dicyanamide anion; L(1-4) = 2,6-bis(R2-iminomethyl)-4-R1-phenolato, where R1 = methyl and tert-butyl, R2 = N,N-dimethyl ethylene for L(1-2) and R1 = methyl and tert-butyl, R2 = 2-(N-ethyl) pyridine for L(3-4)]. A UV-vis spectrophotometric study using 3,5-di-tert butylcatechol (3,5-DTBC) reveals that all the complexes are highly active in catalyzing the aerobic oxidation of (3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ) in methanol medium with the formation of hydrogen peroxide. An EPR study confirms the generation of radicals during the catalysis. Cyclic voltammetric studies of the complexes in the presence and absence of 3,5-DTBC have been performed. Reduction of Ni(II) to Ni(I) and that of the imine bond of the ligand system have been detected at ∼-1.0 V and ∼-1.5 V, respectively. Coulometric separation of the species at -1.5 V followed by the EPR study at 77 K confirms the species as an organic radical and thus most probably reduced imine species. Spectroelectrochemical analysis at -1.5 V clearly indicates the oxidation of 3,5-DTBC and thus suggests that the radical pathway is supposed to be responsible for the catecholase-like activity exhibited by the nickel complexes. The ligand centred radical generation has further been verified by density functional theory calculation.

Radical pathway in catecholase activity with zinc-based model complexes of compartmental ligands.

Four dinuclear and three mononuclear Zn(II) complexes of phenol-based compartmental ligands (HL(1)-HL(7)) have been synthesized with the aim to investigate the viability of a radical pathway in catecholase activity. The complexes have been characterized by routine physicochemical studies as well as X-ray single-crystal structure analysis: [Zn(2)(H(2)L(1))(OH)(H(2)O)(NO(3))](NO(3))(3) (1), [Zn(2)L(2)Cl(3)] (2), [Zn(2)L(3)Cl(3)] (3), [Zn(2)(L(4))(2)(CH(3)COO)(2)] (4), [Zn(HL(5))Cl(2)] (5), [Zn(HL(6))Cl(2)] (6), and [Zn(HL(7))Cl(2)] (7) [L(1)-L(3) and L(5)-L(7) = 2,6-bis(R-iminomethyl)-4-methylphenolato, where R= N-ethylpiperazine for L(1), R = 2-(N-ethyl)pyridine for L(2), R = N-ethylpyrrolidine for L(3), R = N-methylbenzene for L(5), R = 2-(N-methyl)thiophene for L(6), R = 2-(N-ethyl)thiophene for L(7), and L(4) = 2-formyl-4-methyl-6-N-methylbenzene-iminomethyl-phenolato]. Catecholase-like activity of the complexes has been investigated in methanol medium by UV-vis spectrophotometric study using 3,5-di-tert-butylcatechol as model substrate. All complexes are highly active in catalyzing the aerobic oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ). Conversion of 3,5-DTBC to 3,5-DTBQ catalyzed by mononuclear complexes (5-7) is observed to proceed via formation of two enzyme-substrate adducts, ES1 and ES2, detected spectroscopically, a finding reported for the first time in any Zn(II) complex catalyzed oxidation of catechol. On the other hand, no such enzyme-substrate adduct has been identified, and 3,5-DTBC to 3,5-DTBQ conversion is observed to be catalyzed by the dinuclear complexes (1-4) very smoothly. EPR experiment suggests generation of radicals in the presence of 3,5-DTBC, and that finding has been strengthened by cyclic voltammetric study. Thus, it may be proposed that the radical pathway is probably responsible for conversion of 3,5-DTBC to 3,5-DTBQ promoted by complexes of redox-innocent Zn(II) ion. The ligand-centered radical generation has further been verified by density functional theory calculation.

Factors that influence the antiproliferative activity of half sandwich Ru(II)-[9]aneS3 coordination compounds: activation kinetics and interaction with guanine derivatives.

Half sandwich Ru(II)-[9]aneS3 complexes ([9]aneS3 = 1,4,7-trithiacyclononane) are being studied for their antiproliferative activity. We investigated here the activation kinetics of three such complexes, namely [Ru([9]aneS3)(en)Cl](PF(6)) (1), [Ru([9]aneS3)(bpy)Cl](PF(6)) (2) and [Ru([9]aneS3)(pic)Cl] (3) (en = 1,2-diaminoethane, pic = picolinate), and their interaction with DNA model bases. The aim of the study was to assess how they are affected by the nature and charge of the chelating ligand. The model reactions of 1-3 with the guanine derivatives 9-methylguanine (9MeG), guanosine (Guo), and guanosine 5'-monophosphate (5'-GMP) were studied by NMR spectroscopy. All reactions lead, although with different rates and to different extents, to the formation of monofunctional adducts with the guanine derivatives N7-bonded to the Ru center. Two products, the complexes [Ru([9]aneS3)(en)(9MeG-N7)](PF(6))(2) (4) and [Ru([9]aneS3)(pic)(9MeG-N7)](PF(6)) (10), were structurally characterized also by X-ray crystallography. The structure of 4 is stabilized by strong intramolecular H-bonding between an NH of en and the carbonyl O6 of 9MeG. The kinetics of aquation and anation of complexes 2 and 3, as well as the kinetics and the mechanism of the reaction of complexes 1-3 with the biologically more relevant 5'-GMP ligand were studied by UV-Vis spectroscopy. The rate of the reaction of 1-3 with 5'-GMP depends on the nature of the chelating ligand rather than on the charge of the complex, decreasing in the order 3≈2 > 1. The measured enthalpies and entropies of activation (ΔH(≠) > 0, ΔS(≠) < 0) support an associative mechanism for the substitution process.

New half sandwich Ru(II) coordination compounds for anticancer activity.

With the aim of expanding the structure-activity relationship investigation, the series of Ru(II) half sandwich coordination compounds of the type [Ru([9]aneS3)(chel)(L)](n+) previously described by us (where [9]aneS3 is the neutral face-capping ligand 1,4,7-trithiacyclononane, chel is a neutral or anonic chelating ligand, L = Cl(-) or dmso-S, n = 0-2) was extended to 1,4,7-triazacyclononane ([9]aneN3). In addition, new neutral N-N, and anionic N-O and O-O chelating ligands, i.e. dach (trans-1,2-diaminocyclohexane), pic(-) (picolinate), and acac(-) (acetylacetonate), were investigated in combination with both [9]aneS3 and [9]aneN3. Overall, ten new half-sandwich complexes were prepared and fully characterized and their chemical behaviour in aqueous solution was established. The single-crystal X-ray structures of eight of them, including the versatile precursor [Ru([9]aneN3)(dmso-S)(2)Cl]Cl (9), were also determined. The results of in vitro antiproliferative tests performed on selected compounds against MDA-MB-231 human mammary carcinoma cells confirmed that, in this series, only compounds that hydrolyse the monodentate ligand at a reasonable rate show moderate activity, provided that the chelate ligand is a hydrogen bond donor.