Series of Fluorinated Benzimidazole-Substituted Nitronyl Nitroxides: Synthesis, Structure, Acidity, Redox Properties, and Magnetostructural Correlations.

A special series of nitronyl nitroxides was synthesized: 2-(benzimidazol-2'-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyls mono-, di-, tri-, or tetrafluorinated on the benzene ring. The structure of all paramagnets was unambiguously confirmed by single-crystal X-ray diffraction. It was found that in crystals, the radicals are assembled into chains due to intermolecular H-bonds between the benzimidazole moiety (H-bond donor) and the nitronyl nitroxide group or benzimidazole ring (H-bond acceptor). The magnetic properties of nitronyl nitroxides depend on the type of binding of radicals by H-bonds. The magnetic motif of 4-fluoro-, 5-fluoro-, 4,6-difluoro-, 4,5,6-trifluoro-, 4,5,7-trifluoro-, and 4,5,6,7-tetrafluoro-derivatives, as well as the nonfluorinated compound, consists of ferromagnetic chains (J/kB ≈ 20-40 K) formed by the McConnell type I mechanism. In the 5,6-difluoro- and 4,5-difluoro-derivatives, the distances between the paramagnetic centers are large, as a result of which the exchange interactions are weak. According to cyclic voltammetry, paramagnets are oxidized reversibly, while their reduction is a quasi-reversible electron transfer (EC mechanism); experimental redox potentials of radicals correlate well with the calculated values. Quantum chemical assessment of the acidity of benzimidazolyl-substituted nitronyl nitroxides revealed that the introduction of fluorine atoms into the benzene ring enhances the acidity of the paramagnets by more than 5 orders of magnitude.

Synthesis, Crystal Structure and Magnetic Properties of a Trinuclear Copper(II) Complex Based on P-Cresol-Substituted Bis(α-Nitronyl Nitroxide) Biradical.

Trinuclear copper(II) complex [CuII3(NIT2PhO)2Cl4] was synthesized with p-cresol-substituted bis(α-nitronyl nitroxide) biradical: 4-methyl-2,6-bis(1-oxyl-3-oxido-4,4,5,5-tetramethyl-2-imidazolin-2-yl)phenol (NIT2PhOH). The crystal structure of this heterospin complex was determined using single-crystal X-ray diffraction analysis and exhibits four unusual seven-membered metallocycles formed from the coordination of oxygen atoms of the N-O groups and of bridging phenoxo (µ-PhO-) moieties with copper(II) ions. The crystal structure analysis reveals an incipient agostic interaction between a square planar copper center and a hydrogen-carbon bond from one methyl group carried on the coordinated nitronyl-nitroxide radical. The intramolecular Cu∙∙∙H-C interaction involves a six-membered metallocycle and may stabilize the copper center in square planar coordination mode. From the magnetic susceptibility measurements, the complex, which totals seven S = 1/2 spin carriers, has almost a ground state spin S = 1/2 at room temperature ascribed to strong antiferromagnetic interaction between the nitronyl nitroxide moieties and the copper(II) centers and in between the copper(II) centers through the bridging phenoxo oxygen atom.

Revisiting the Ullman's Radical Chemistry for Phthalocyanine Derivatives.

Phthalocyanine derivatives do not cease to gain attention due to their numerous properties and applications (e.g., sensor, PDT). This makes them a unique scaffold for the design of new material. In this context, we were interested to develop the synthesis of an imino nitroxide-substituted phthalocyanine by Ullman's procedure; a challenge due to the intrinsic low solubility of most phthalocyanine derivative in much solvents. To overcome this solubility problem, we designed a phthalocyanine with bulky neopentyl substituents in peripheral positions as counterpart to the imino nitroxide moieties. The imino nitroxide-substituted phthalocyanine was obtained by condensation of a monoformyl-substituted phthalocyanine with 2,3-bis(hydroxylamino)-2,3-dimethylbutane in refluxing THF-MeOH (2:1) mixture in the presence of p-toluenesulfonic acid monohydrate, follow by oxidation with PbO2 . Characterization was performed by electrochemistry, UV/Vis and EPR spectroscopy in solution as well as SQUID in solid state.

NO Releasing and Anticancer Properties of Octahedral Ruthenium-Nitrosyl Complexes with Equatorial 1 H-Indazole Ligands.

With the aim of enhancing the biological activity of ruthenium-nitrosyl complexes, new compounds with four equatorially bound indazole ligands, namely, trans-[RuCl(Hind)4(NO)]Cl2·H2O ([3]Cl2·H2O) and trans-[RuOH(Hind)4(NO)]Cl2·H2O ([4]Cl2·H2O), have been prepared from trans-[Ru(NO2)2(Hind)4] ([2]). When the pH-dependent solution behavior of [3]Cl2·H2O and [4]Cl2·H2O was studied, two new complexes with two deprotonated indazole ligands were isolated, namely [RuCl(ind)2(Hind)2(NO)] ([5]) and [RuOH(ind)2(Hind)2(NO)] ([6]). All prepared compounds were comprehensively characterized by spectroscopic (IR, UV-vis, 1H NMR) techniques. Compound [2], as well as [3]Cl2·2(CH3)2CO, [4]Cl2·2(CH3)2CO, and [5]·0.8CH2Cl2, the latter three obtained by recrystallization of the first isolated compounds (hydrates or anhydrous species) from acetone and dichloromethane, respectively, were studied by X-ray diffraction methods. The photoinduced release of NO in [3]Cl2 and [4]Cl2 was investigated by cyclic voltammetry and resulting paramagnetic NO species were detected by EPR spectroscopy. The quantum yields of NO release were calculated and found to be low (3-6%), which could be explained by NO dissociation and recombination dynamics, assessed by femtosecond pump-probe spectroscopy. The geometry and electronic parameters of Ru species formed upon NO release were identified by DFT calculations. The complexes [3]Cl2 and [4]Cl2 showed considerable antiproliferative activity in human cancer cell lines with IC50 values in low micromolar or submicromolar concentration range and are suitable for further development as potential anticancer drugs. p53-dependence of Ru-NO complexes [3]Cl2 and [4]Cl2 was studied and p53-independent mode of action was confirmed. The effects of NO release on the cytotoxicity of the complexes with or without light irradiation were investigated using NO scavenger carboxy-PTIO.

Room Temperature Magnetic Switchability Assisted by Hysteretic Valence Tautomerism in a Layered Two-Dimensional Manganese-Radical Coordination Framework.

The manganese-nitronyl-nitroxide two-dimensional coordination polymer {[Mn2(NITIm)3]ClO4}n (1) (NITImH = 2-(2-imidazolyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-3-oxide-1-oxyl) undergoes an unusual hysteretic thermo-induced valence tautomeric transition near room temperature, during which the manganese(II) ions are oxidized to manganese(III) and two of the three deprotonated radicals (NITIm-) are reduced to their diamagnetic aminoxyl form (denoted NITRed2-). Upon cooling, the high-temperature species {[MnII2(NITIm)3]ClO4}n (1HT) turns into the low-temperature species {[MnIII2(NITRed)2(NITIm)]ClO4}n (1LT) around 274 K, while on heating the process is reversed at about 287 K. This valence tautomeric phenomenon is supported by temperature-dependent magnetic susceptibility measurements, differential scanning calorimetry (DSC), crystal structure determination, UV-vis absorption, X-ray absorption (XAS), and emission (XES) and electron paramagnetic resonance (EPR) spectroscopies in the solid state.

Polarized Neutron Diffraction as a Tool for Mapping Molecular Magnetic Anisotropy: Local Susceptibility Tensors in Co(II) Complexes.

Polarized neutron diffraction (PND) experiments were carried out at low temperature to characterize with high precision the local magnetic anisotropy in two paramagnetic high-spin cobalt(II) complexes, namely [Co(II) (dmf)6 ](BPh4 )2 (1) and [Co(II) 2 (sym-hmp)2 ](BPh4 )2 (2), in which dmf=N,N-dimethylformamide; sym-hmp=2,6-bis[(2-hydroxyethyl)methylaminomethyl]-4-methylphenolate, and BPh4 (-) =tetraphenylborate. This allowed a unique and direct determination of the local magnetic susceptibility tensor on each individual Co(II) site. In compound 1, this approach reveals the correlation between the single-ion easy magnetization direction and a trigonal elongation axis of the Co(II) coordination octahedron. In exchange-coupled dimer 2, the determination of the individual Co(II) magnetic susceptibility tensors provides a clear outlook of how the local magnetic properties on both Co(II) sites deviate from the single-ion behavior because of antiferromagnetic exchange coupling.

Geometric and Electronic Structures of Nickel(II) Complexes of Redox Noninnocent Tetradentate Phenylenediamine Ligands.

Five tetradentate ligands based on the N,N'-bis(2-amino-3,5-di-tert-butylphenyl)-o-phenylenediamine backbone were prepared, with different substituents at positions 4 and 5 (CH3 (3a), p-CH3O-C6H4 (3b), H (3c), Cl (3d), F (3e)). Their reaction with a nickel(II) salt in air affords the neutral species 4(a-e), which were isolated as single crystals. 4(a-e) feature two antiferromagnetically exchange-coupled diiminosemiquinonate moieties, both located on peripheral rings, and a diamidobenzene bridging unit. Oxidation of 4(a-e) with 1 equiv of AgSbF6 yields the cations 4(a-e)(+), which harbor a single diiminosemiquinonate radical. Significant structural differences were observed within the series. 4b(+) is mononuclear and contains a localized diiminosemiquinonate moiety. In contrast, 4c(+) is a dimer wherein the diiminosemiquinonate radical is rather delocalized over both peripheral rings. 4d(+) represents an intermediate case where the complex is mononuclear, but the radical is fully delocalized. Oxidation of 4(a-e) with 2 equiv of AgSbF6 produces the corresponding mononuclear dications. X-ray diffraction data on 4(b-d)(2+) reveals that the bridging ring retains its diamidobenzene character, whereas both peripheral rings have been oxidized into diiminobenzoquinone moieties. All the complexes were characterized by electrochemistry, EPR, and UV-vis-NIR spectroscopy. Remarkably, the electronic structures of the complexes differ from those reported by Wieghardt et al. for copper and zinc complexes of a related ligand involving a mixed N2O2 donor set (J. Am. Chem. Soc. 1999, 121, 9599). The easier oxidation of phenylenediamine moieties in comparison to aminophenols is proposed to account for the difference.

Synthesis and Straightforward Quantification Methods of Imino Nitroxide-Based Hexaradical Architecture on a Cyclotriphosphazene Scaffold.

The synthesis of a homogeneous neutral hexaradical architecture consisting of six imino nitroxide radical moieties covalently bonded on a cyclotriphosphazene scaffold was reported. The synthesis of hexaradical imino nitroxide compounds follows the Ullman procedure involving the condensation of 2,3-bis(hydroxylamino)-2,3-dimethylbutane with hexa-(4-formylphenoxy)cyclotriphosphazene (3) followed by oxidation of the condensation product hexa-[4-(1-hydroxy-4,4,5,5-tetramethyl-2-imidazoline-2-yl)phenoxy]cyclotriphosphazene (2) by NaIO4. Characterization of hexaradical was performed by X-ray and SQUID in solid state and by EPR, absorption spectroscopy, and electrochemistry in solution. CV of 1 shows an oxidation peak at 1.184 V (vs SCE) and a reduction peak at -0.883 V, both characteristics of the presence of phenyl imino nitroxide (7) moieties, suggesting that the contribution of the cyclotriphosphazene core is negligible. Attention was particularly focused on developing methods, UV-vis spectroscopy and square-wave voltammetry, to quantify the number of radicals in a way to confirm easily and rapidly the polyradicals' structure.

Towards the first theoretical scale of the trans effect in octahedral complexes.

In this paper, we show that trans effects in octahedral complexes can primarily be related to differences in the ability, for a given ligand, to cede electron density to the metal cation under the influence of the ligand at the trans position. Using tools from conceptual DFT or from related paradigms, we highlight these effects on a set of representative examples and further provide the basis for a computational trans effect scale. This quantification notably retrieves the experimental trans orienting series.

Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity.

A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(µ-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (13)C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y(III) and Dy(III), respectively, with formation of [Ln{RuCl3(µ-ox)(NO)}4](5-) (Ln=Y, Dy). While Y(III) is eight-coordinate in 2, Dy(III) is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 µM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells.

New Family of Lanthanide-Based Complexes with Different Scorpionate-Type Ligands: A Rare Case Where Dysprosium and Ytterbium Analogues Display Single-Ion-Magnet Behavior.

A new family of lanthanide complexes [Ln(Tpz)2Bpz]·xCH2Cl2 (Ln = Gd, Tb, Dy, Ho, x = 0.5; Ln = Yb, x = 1; Tpz = hydrotris(pyrazolyl)borate; Bpz = dihydrobis(pyrazolyl)borate) has been synthesized. Those complexes have been characterized by single-crystal X-ray diffraction, and the magnetic properties have been investigated. Both dysprosium and ytterbium analogues display single-ion-magnet behavior, despite the difference in their spatial distribution of 4f electronic charges. Theoretical calculations with crystal field parameters have been carried out to gain better insight of the relaxation pathways that may be involved in those two complexes.

Polynuclear complex family of cobalt(II)/sulfonylcalixarene: one-pot synthesis of cluster salt [Co14(II)]+[Co4(II)]- and field-induced slow magnetic relaxation in a six-coordinate dinuclear cobalt(II)/sulfonylcalixarene complex.

In this paper, we report the synthesis and description of a new family of polynuclear cobalt(II) complexes. Starting from the same initial compounds but varying the reaction time results in the formation of several new clusters, an original structure based on [Co14][Co4] clusters was obtained, representing the first one-pot synthesis of a cobalt aggregate salt reported in the literature. The synthesis and magnetic properties of these cobalt compounds are discussed. Three of them display a binuclear molecular structure (1-3) with two encapsulated Co(II) ions and show slow relaxation of magnetization at small applied magnetic field (Ueff = 10.7 K for 2 and Ueff = 20.3 K for 3), a characteristic of single-molecule-magnet materials.

Terbium(III) and yttrium(III) complexes with pyridine-substituted nitronyl nitroxide radical and different ß-diketonate ligands. Crystal structures and magnetic and luminescence properties.

A terbium(III) complex of nitronyl nitroxide free radical 2-(2-pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro1H-imidazolyl-1-oxy-3-oxide (NIT2Py), [Tb(acac)3NIT2Py]·0.5H2O (3) (acac = acetylacetonate), was synthesized for comparison with the previously reported [Tb(hfac)3NIT2Py]·0.5C7H16 (1) (hfac = hexafluoroacetylacetonate), together with their yttrium analogues [Y(hfac)3NIT2Py]·0.5C7H16 (2) and [Y(acac)3NIT2Py]·0.5H2O (4). The crystal structures show that in all complexes the nitronyl nitroxide radical acts as a chelating ligand. Magnetic studies show that 3 like 1 exhibits slow relaxation of magnetization at low temperature, suggesting single-molecule magnet behavior. The luminescence spectra show resolved vibronic structure with the main interval decreasing from 1600 cm(-1) to 1400 cm(-1) between 80 and 300 K. This effect is analyzed quantitatively using experimental Raman frequencies.

Ruthenium-nitrosyl complexes with glycine, L-alanine, L-valine, L-proline, D-proline, L-serine, L-threonine, and L-tyrosine: synthesis, X-ray diffraction structures, spectroscopic and electrochemical properties, and antiproliferative activity.

The reactions of [Ru(NO)Cl5](2-) with glycine (Gly), L-alanine (L-Ala), L-valine (L-Val), L-proline (L-Pro), D-proline (D-Pro), L-serine (L-Ser), L-threonine (L-Thr), and L-tyrosine (L-Tyr) in n-butanol or n-propanol afforded eight new complexes (1-8) of the general formula [RuCl3(AA-H)(NO)](-), where AA = Gly, L-Ala, L-Val, L-Pro, D-Pro, L-Ser, L-Thr, and L-Tyr, respectively. The compounds were characterized by elemental analysis, electrospray ionization mass spectrometry (ESI-MS), (1)H NMR, UV-visible and ATR IR spectroscopy, cyclic voltammetry, and X-ray crystallography. X-ray crystallography studies have revealed that in all cases the same isomer type (from three theoretically possible) was isolated, namely mer(Cl),trans(NO,O)-[RuCl3(AA-H)(NO)], as was also recently reported for osmium analogues with Gly, L-Pro, and D-Pro (see Z. Anorg. Allg. Chem. 2013, 639, 1590-1597). Compounds 1, 4, 5, and 8 were investigated by ESI-MS with regard to their stability in aqueous solution and reactivity toward sodium ascorbate. In addition, cell culture experiments in three human cancer cell lines, namely, A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma), were performed, and the results are discussed in conjunction with the lipophilicity of compounds.

Unsymmetrical binding modes of the HOPNO inhibitor of tyrosinase: from model complexes to the enzyme.

The deciphering of the binding mode of tyrosinase (Ty) inhibitors is essential to understand how to regulate the tyrosinase activity. In this paper, by combining experimental and theoretical methods, we studied an unsymmetrical tyrosinase functional model and its interaction with 2-hydroxypyridine-N-oxide (HOPNO), a new and efficient competitive inhibitor for bacterial Ty. The tyrosinase model was a dinuclear copper complex bridged by a chelated ring with two different complexing arms (namely (bis(2-ethylpyridyl)amino)methyl and (bis(2-methylpyridyl)amino)methyl). The geometrical asymmetry of the complex induces an unsymmetrical binding of HOPNO. Comparisons have been made with the binding modes obtained on similar symmetrical complexes. Finally, by using quantum mechanics/molecular mechanics (QM/MM) calculations, we studied the binding mode in tyrosinase from a bacterial source. A new unsymmetrical binding mode was obtained, which was linked to the second coordination sphere of the enzyme.

A top-down synthesis route to ultrasmall multifunctional Gd-based silica nanoparticles for theranostic applications.

New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid)-Gd(3+) chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd(3+) by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID) and electron paramagnetic resonance (EPR) to demonstrate the dissolution of the oxide core and by inductively coupled plasma mass spectrometry (ICP-MS), mass spectrometry, fluorescence spectroscopy, (29)Si solid-state NMR, (1)H NMR and diffusion ordered spectroscopy (DOSY) to determine the nanoparticle composition. Relaxivity measurements gave a longitudinal relaxivity r1 of 11.9 s(-1) mM(-1) per Gd at 60 MHz. Finally, potentiometric titrations showed that Gd(3+) is strongly chelated to DOTAGA (complexation constant logß110 =24.78) and cellular tests confirmed the that nanoconstructs had a very low toxicity. Moreover, SRPs are excreted from the body by renal clearance. Their efficiency as contrast agents for MRI has been proved and they are promising candidates as sensitising agents for image-guided radiotherapy.

Lanthanide triangles sandwiched by tetranuclear copper complexes afford a family of hendecanuclear heterometallic complexes [Ln(III)3Cu(II)8] (Ln = La-Lu): synthesis and magnetostructural studies.

Reaction in ethanol of 3-hydroxymethylen-5-methylsalicylaldoxime (H3L) with CuCl2·2H2O and LnCl3·xH2O [Ln = La (1), Ce (2), Pr (3), Nd (4), Eu (5), Gd (6), Tb (7), Dy (8), Er (9), Yb (10), Lu (11), Ho (12)] allowed the synthesis of a family of hendecanuclear heterometallic copper(II)-lanthanide(III) clusters with general formula [Ln(III)3Cu(II)8(HL)6(µ4-O)2Cl6(H2O)8]Cl3 (1-12). According to the single-crystal X-ray diffraction investigation, the complexes are isomorphous and crystallize in the trigonal R32 group. The hendecanuclear cluster is formed by two tetrahedral µ4-oxo {Cu4} clusters assembled by three lanthanide ions sandwiched in between. Along the family, the separation between the {Cu4} moieties increases linearly from Lu to La in good correlation with ionic radius of the lanthanide ions. A comparative analysis of the magnetic data for the lanthanum (1) and lutetium (11) compounds shows the presence of ferromagnetic and antiferromagnetic interactions within the µ4-oxo {Cu4} moieties. For the gadolinium (6) and terbium (7) compounds, the magnetic interactions between the lanthanide and the copper ions are found to be ferromagnetic. The dysprosium (8) compound exhibits single-molecule magnet behavior.

Mechanism elucidation of the cis-trans isomerization of an azole ruthenium-nitrosyl complex and its osmium counterpart.

Synthesis and X-ray diffraction structures of cis and trans isomers of ruthenium and osmium metal complexes of general formulas (nBu4N)[cis-MCl4(NO)(Hind)], where M = Ru (1) and Os (3), and (nBu4N)[trans-MCl4(NO)(Hind)], where M = Ru (2) and Os (4) and Hind = 1H-indazole are reported. Interconversion between cis and trans isomers at high temperatures (80-130 °C) has been observed and studied by NMR spectroscopy. Kinetic data indicate that isomerizations correspond to reversible first order reactions. The rates of isomerization reactions even at 110 °C are very low with rate constants of 10(-5) s(-1) and 10(-6) s(-1) for ruthenium and osmium complexes, respectively, and the estimated rate constants of isomerization at room temperature are of ca. 10(-10) s(-1). The activation parameters, which have been obtained from fitting the reaction rates at different temperatures to the Eyring equation for ruthenium [ΔH(cis-trans)‡ = 122.8 ± 1.3; ΔH(trans-cis)‡ = 138.8 ± 1.0 kJ/mol; ΔS(cis-trans)‡ = -18.7 ± 3.6; ΔS(trans-cis)‡ = 31.8 ± 2.7 J/(mol·K)] and osmium [ΔH(cis-trans)‡ = 200.7 ± 0.7; ΔH(trans-cis)‡ = 168.2 ± 0.6 kJ/mol; ΔS(cis-trans)‡ = 142.7 ± 8.9; ΔS(trans-cis)‡ = 85.9 ± 3.9 J/(mol·K)] reflect the inertness of these systems. The entropy of activation for the osmium complexes is highly positive and suggests the dissociative mechanism of isomerization. In the case of ruthenium, the activation entropy for the cis to trans isomerization is negative [-18.6 J/(mol·K)], while being positive [31.0 J/(mol·K)] for the trans to cis conversion. The thermodynamic parameters for cis to trans isomerization of [RuCl4(NO)(Hind)]-, viz. ΔH° = 13.5 ± 1.5 kJ/mol and ΔS° = -5.2 ± 3.4 J/(mol·K) indicate the low difference between the energies of cis and trans isomers. The theoretical calculation has been carried out on isomerization of ruthenium complexes with DFT methods. The dissociative, associative, and intramolecular twist isomerization mechanisms have been considered. The value for the activation energy found for the dissociative mechanism is in good agreement with experimental activation enthalpy. Electrochemical investigation provides further evidence for higher reactivity of ruthenium complexes compared to that of osmium counterparts and shows that intramolecular electron transfer reactions do not affect the isomerization process. A dissociative mechanism of cis↔trans isomerization has been proposed for both ruthenium and osmium complexes.

Striking difference in antiproliferative activity of ruthenium- and osmium-nitrosyl complexes with azole heterocycles.

Ruthenium nitrosyl complexes of the general formulas (cation)(+)[cis-RuCl4(NO)(Hazole)](-), where (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (Hind) (1c), (cation)(+) = (H2pz)(+), Hazole = 1H-pyrazole (Hpz) (2c), (cation)(+) = (H2bzim)(+), Hazole = 1H-benzimidazole (Hbzim) (3c), (cation)(+) = (H2im)(+), Hazole = 1H-imidazole (Him) (4c) and (cation)(+)[trans-RuCl4(NO)(Hazole)](-), where (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (1t), (cation)(+) = (H2pz)(+), Hazole = 1H-pyrazole (2t), as well as osmium analogues of the general formulas (cation)(+)[cis-OsCl4(NO)(Hazole)](-), where (cation)(+) = (n-Bu4N)(+), Hazole =1H-indazole (5c), 1H-pyrazole (6c), 1H-benzimidazole (7c), 1H-imidazole (8c), (cation)(+) = Na(+); Hazole =1H-indazole (9c), 1H-benzimidazole (10c), (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (11c), (cation)(+) = H2pz(+), Hazole = 1H-pyrazole (12c), (cation)(+) = (H2im)(+), Hazole = 1H-imidazole (13c), and (cation)(+)[trans-OsCl4(NO)(Hazole)](-), where (cation)(+) = n-Bu4N(+), Hazole = 1H-indazole (5t), 1H-pyrazole (6t), (cation)(+) = Na(+), Hazole = 1H-indazole (9t), (cation)(+) = (H2ind)(+), Hazole = 1H-indazole (11t), (cation)(+) = (H2pz)(+), Hazole = 1H-pyrazole (12t), have been synthesized. The compounds have been comprehensively characterized by elemental analysis, ESI mass spectrometry, spectroscopic techniques (IR, UV-vis, 1D and 2D NMR) and X-ray crystallography (1c·CHCl3, 1t·CHCl3, 2t, 3c, 6c, 6t, 8c). The antiproliferative activity of water-soluble compounds (1c, 1t, 3c, 4c and 9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c) in the human cancer cell lines A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma) has been assayed. The effects of metal (Ru vs Os), cis/trans isomerism, and azole heterocycle identity on cytotoxic potency and cell line selectivity have been elucidated. Ruthenium complexes (1c, 1t, 3c, and 4c) yielded IC50 values in the low micromolar concentration range. In contrast to most pairs of analogous ruthenium and osmium complexes known, they turned out to be considerably more cytotoxic than chemically related osmium complexes (9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c). The IC50 values of Os/Ru homologs differ by factors (Os/Ru) of up to ~110 and ~410 in CH1 and SW480 cells, respectively. ESI-MS studies revealed that ascorbic acid may activate the ruthenium complexes leading to hydrolysis of one M-Cl bond, whereas the osmium analogues tend to be inert. The interaction with myoglobin suggests nonselective adduct formation; i.e., proteins may act as carriers for these compounds.

Versatile chemical transformations of benzoxazole based ligands on complexation with 3d-metal ions.

Two benzoxazoles derivative ligands were synthesized from the condensation of 3,5-di-tert-butyl-o-benzoquinone (DTBBQ) with ethanolamine or 1,3-diamino-2-hydroxypropane in methanol. Condensation of DTBBQ with ethanolamine gives the expected 5,7-di-tert-butyl-2-methylenhydroxylbenzoxazole (HL1) while with 1,3-diamino-2-hydroxypropane it gives (2-hydroxyethyl-2-{2,4-bis(1,1-dimethylethyl)-1-phenol-6 amino}-2{5,7-di-tert-butyl-benzoxazole}) (H(2)L2) with only one benzoxazole ring instead of the symmetric bis-benzoxazole derivative. The structure of HL1 and H(2)L2 were confirmed by NMR-spectroscopy and X-ray diffraction on a single crystal for HL1. The reaction of HL1 with CuCl(2) gives a mononuclear [Cu(II)(HL1)(2)Cl(2)] (1) complex for which the crystal structure shows that HL1 is preserved. In contrast, upon reaction with nickel(II), cobalt(II), and manganese(II) H(2)L2 is further oxidized and transformed in new ligands HL3 in mononuclear complexes [M(II)(L3)(2)] (M = Ni(II) (2); M = Co(II) (3)) and H(2)L4 in tetranuclear complex [Mn(II)(4)(HL4)(4)Cl(4)] (4) as found from the crystal structures of complexes 2-4. Electrochemical studies for complexes 2 and 3 evidence complicated redox properties. [Mn(II)(4)(HL4)(4)Cl(4)] (4) has a cubane-like structure with a "4 + 2" fashion The magnetic susceptibility of 4 is well fitted considering one Mn---Mn interaction J(a)(Mn(II)-Mn(II)) = -0.50(1) cm(-1) with g = 2.00(7).