Enzyme inhibition,radical scavenging,and spectroscopic studies of vanadium(IV)–hydrazide complexes

Spectroscopic, enzyme-inhibition, and free-radical scavenging properties of a series of hydrazide ligands and their vanadium(IV) complexes have been investigated. Analytical and spectral data indicate the presence of a dimeric unit with two oxovanadium(IV) ions (VO²⁺) coordinated with two hydrazide ligands along with two water molecules. All complexes are stable in the solid state, but exhibit varying degrees of stability in solution. Binding of the coordinating solvent such as DMSO is indicated at the 6th position of vanadium in the dimeric unit followed by conversion to a monomeric intermediate species, [VOL(DMSO)3]1+ (L = hydrazide ligand). The free hydrazide ligands are inactive against snake venom phosphodiesterase I (SVPD), whereas oxovanadium(IV) complexes of these ligands show varying degrees of inhibition and are found to be non-competitive inhibitors. The superoxide and nitric oxide radical scavenging properties have been determined. Hydrazide ligands are inactive against these free radicals, whereas their V(IV) complexes show varying degrees of inhibition. Structure–activity relationship studies indicate that the electronic and/or steric factors that change the geometry of the complexes play an important role in their inhibitory potential against SVPD and free radicals.     

Chemistry, urease inhibition, and phytotoxic studies of binuclear vanadium(IV) complexes

Vanadium plays an important role in biological systems and exhibits a variety of bioactivities. In an effort to uncover the chemistry and biochemistry of vanadium with nitrogen- and oxygen-containing ligands, we report herein the synthesis and spectroscopic characterization of vanadium(IV) complexes with hydrazide ligands. Substituents on these ligands exhibit systematic variations of electronic and steric factors. Elemental and spectral data indicate the presence of a dimeric unit with two vanadium(IV) ions coordinated with two hydrazide ligands along with two H(2)O molecules. The stability studies of these complexes over time in coordinating solvent, DMSO, indicates binding of the solvent molecules to give [V2O2L2(H2O)2(DMSO)2]2+ (L=hydrazide ligand) and then conversion of it to a monomeric intermediate species, [VOL(DMSO)3]1+. Hydrazide ligands are inactive against urease, whereas vanadium(IV) complexes of these ligands show significant inhibitory potential against this enzyme and are found to be non-competitive inhibitors. These complexes also show low phytotoxicity indicating their usefulness for soil ureases. Structure-activity relationship studies indicate that the steric and/or electronic effects that may change the geometry of the complexes play an important role in their inhibitory potential and phytotoxicity.     

Spectroscopic characterization of amino acid and amino acid ester-Schiff-base complexes of oxovanadium and their catalysis in sulfide oxidation

α-Amino acid Schiff-base complexes of oxovanadium(IV), whose ligands have amino acid side chains with coordinating functional groups, retained coordination geometries in which the amino acid side chains were probably coordinated in the axial position with a phenolate oxygen, a carboxylate oxygen, an imine nitrogen, and a solvent being bound in the equatorial plane. As for amino acid ester Schiff-base complexes, the amino acid side chains were coordinated in the equatorial plane in the place of the carboxyl group in the case of the amino acid Schiff-base complexes. The amino acid Schiff-base complexes of oxovanadium(V) were present as dimers in dichloromethane. Peroxo complexes prepared from the Schiff-base complexes of oxovanadium(V) converted methyl phenyl sulfide to the corresponding sulfoxide in 80-90% yield in CDCl₃ and in 30-70% yield in CD₃OD in 30 min. They converted the sulfide in a stereoselective manner yielding the sulfoxide in small enantiomeric excess (5-20%).     

Atropisomeric amides: Achiral ligands with chiral conformations

A new class of achiral ligands with atropisomeric conformations has been coordinated to titanium(IV). The ligands are ortho-hydroxy benzamide derivatives which are deprotonated on reaction with titanium tetraisopropoxide to furnish Ti(L)(2)(O-iPr)(2) complexes (L=ortho-phenoxy benzamide). In these octahedral titanium compounds, the ortho-phenoxy benzamide ligands chelate to titanium, bonding through the phenoxide oxygen and the amide carbonyl oxygen. The benzamide ligands adopt atropisomeric conformations with an angle between the aryl and amide groups of approximately 35 degrees. The ligand precursor, ligand, and titanium complexes have been characterized by X-ray crystallography. Only one diastereomer of each titanium complex was observed in the solid state structures.     

Platinum(II) complexes of 4-methoxy- and 4-chlorobenzoic acid hydrazides. Synthesis, characterization, and cytotoxic effect

The complexes [Pt(NH₃)(pmbah)Cl₂], [Pt(NH₃)(pcbah)Cl₂], [Pt(pmbah₂X₂] and [Pt(pcbah)₂X₂] (pmbah = 4-methoxybenzoicacid hydrazide, pcbah = 4-chlorobenzoic acid hydrazide; X = Cl, Br, I) have been synthesized and characterized by elemental analysis, electric conductivity, ¹H NMR, IR, and electronic spectra. A cis-square planar structure with hydrazide ligands coordinated via the NH₂ groups has been proposed for these compounds. The complexes, but not the free ligands, have shown a strong growth inhibitory effect in Friend leukemia cells in vitro, most of which are more active than cisplatin.     

Synthesis, structure, and nuclease properties of several binary and ternary complexes of copper(II) with norfloxacin and 1,10 phenantroline

Three new binary Cu(II) complexes of norfloxacin have been synthesized and characterized. We also report the synthesis, characterization and X-ray crystallographic structures of a new binary compound, [Cu(HNor)(2)]Cl(2).2H(2)O (2) and two new ternary complexes norfloxacin-copper(II)-phen, [Cu(Nor)(phen)(H(2)O)](NO(3)).3H(2)O (4), and [Cu(HNor)(phen)(NO(3))](NO(3)).3H(2)O (5). The structure of 2 consists of two crystallographically independent cationic monomeric units of [Cu(HNor)(2)](2+), chloride anions, and uncoordinated water molecules. The Cu(II) ion is placed at a center of symmetry and is coordinated to two norfloxacin ligands which are related through the inversion center. The structures of 4 and 5 consist of cationic units ([Cu(Nor)(phen)(H(2)O)](+) for 4 and [Cu(HNor)(phen)(NO(3))](+) for 5), nitrate counteranions, and lattice water molecules that provide crystalline stability through a network of hydrogen-bond interactions. The complexes exhibit a five coordinated motif in a square pyramidal environment around the metal center. The ability of compounds 4 and 5 to cleave DNA has also been studied. Mechanistic studies with different inhibiting reagents reveal that hydroxyl radicals, singlet oxygen, and superoxide radicals are all involved in the DNA scission process mediated by these compounds.     

Synthesis, spectroscopy, electrochemistry and thermal study of vanadyl unsymmetrical Schiff base complexes

The new tetradentate unsymmetrical N₂O₂ Schiff base ligands and VO(IV) complexes were synthesised and characterized by using IR, UV-Vis and elemental analysis. The electrochemical properties of the vanadyl complexes were investigated by means of cyclic voltammetry. The oxidation potentials are increased by increasing the electron-withdrawing properties of functional groups of the Schiff base ligands according to the trend of MeO < H < Br < NO₂. The thermogravimetry (TG) and differential thermoanalysis (DTA) of the VO(IV) complexes were carried out in the range of 20-700 °C. The complexes were decomposed in two stages. Also decomposition of synthesised complexes is related to the Schiff base characteristics. The thermal decomposition of the studied reactions was first order.     

Self-assembled pentagonal bipyramidal and skew trapezoidal organotin(IV) complexes of substituted benzoic acids: Their antibacterial, antifungal, cytotoxic, insecticidal and urease inhibition activities

Fourteen di- and triorganotin(IV) derivatives with pentagonal bipyramidal and skew trapezoidal geometries have been synthesized and characterized. Dimethylstannyl bis[3-amino-4-chlorophenylcarboxylate] (1), bis[3-amino-4-chlorophenylcarboxylato] tetraethyldistannoxane] (2) and bis[3,5-dinitro-4-chlorophenylcarboxylato] tetra-n-butyldistannoxane (10) are dinuclear and tetranuclear complexes of bidentate ligands. The crystal structure of (1) is dimeric in which each Sn atom is seven coordinated. Study of weak intramolecular Sn?O interactions is very important to decide geometry around tin. Furthermore, it has been investigated that these compounds exhibit fairly good antibacterial, antifungal, cytotoxic, insecticidal and antiurease activities.     

Vanadium(V) complexes with hydrazides and their spectroscopic and biological properties

The present study explores the synthesis and inhibitory potential of vanadium(V) complexes of hydrazides (1c–12c) against oxidative enzymes including xanthine oxidase and lipoxygenase (LOX). In addition, non-enzymatic radical scavenging activities of these complexes were also determined. On the basis of spectral, elemental and physical data, synthesized vanadium(V) complexes are tentatively assigned to have an octahedral geometry with two hydrazide ligands and two oxo groups forming a negatively charged sphere complex with ammonium as counter ion. This is further verified by the conductivity studies of the complexes. Results show that hydrazide ligands (1–12) and their respective vanadium(V) complexes (1c–12c) posses scavenging and inhibition potential against DPPH and LOX, respectively. However, contrary to that uncoordinated ligands showed no activity against nitric oxide, superoxide and xanthine oxidase whereas their complexes showed varying degree of activity. These studies indicate that geometry of complex, nature and position of substituent groups play a vital role in scavenging and inhibition potential of these compounds.     

Vanadium(IV/V) speciation of pyridine-2,6-dicarboxylic acid and 4-hydroxy-pyridine-2,6-dicarboxylic acid complexes: potentiometry,EPR spectroscopy and comparison across oxidation states

Evaluation of stability of vanadium(IV) and (V) complexes under similar conditions is critical for the interpretation and assessment of bioactivity of various vanadium species. Detailed understanding of the chemical properties of these complexes is necessary to explain differences observed their activity in biological systems. These studies are carried out to link the chemistry of both vanadium(IV) and (V) complexes of two ligands, 2,6-pyridinedicarboxylic acid (dipicolinic acid, H(2)dipic) and 4-hydroxy-2,6-pyridinedicarboxylic acid (H(2)dipic-OH). Solution speciation of the two 2,6-pyridinedicarboxylic acids with vanadium(IV) and vanadium(V) ions was determined by pH-potentiometry at I=0.2 M (KCl) ionic strength and at T=298 K. The stability and the metal affinities of the ligands were compared. Vanadium(V) complexes were found to form only tridentate coordinated 1:1 complexes, while vanadium(IV) formed complexes with both 1:1 and 1:2 stoichiometries. The formation constant reflects hindered coordination of a second ligand molecule, presumably because of the relatively small size of the metal ion. The most probable binding mode of the complexes was further explored using ambient and low temperature EPR spectroscopy for vanadium(IV) and 51V NMR spectroscopy for vanadium(V) systems. Upon complex formation the pyridinol-OH in position 4 deprotonates with pK approximately 3.7-4.1, which is approximately 6 orders of magnitude lower than that of the free ligand. The deprotonation enhances the ligand metal ion affinity compared to the parent ligand dipicolinic acid. In the light of the speciation and stability data of the metal complexes, the efficiency of the two ligands in transporting the metal ion in the two different oxidation states are assessed and discussed.     

Chloro-substituted dipicolinate vanadium complexes: Synthesis, solution, solid-state, and insulin-enhancing properties

Three vanadium complexes of chlorodipicolinic acid (4-chloro-2,6-dipicolinic acid) in oxidation states III, IV, and V were prepared and their properties characterized across the oxidation states. In addition, the series of hydroxylamido, methylhydroxylamido, dimethylhydroxylamido, and diethylhydroxylamido complexes were prepared from the chlorodipicolinato dioxovanadium(V) complex. The vanadium(V) compounds were characterized in solution by ⁵¹V and ¹H NMR and in the solid-state by X-ray diffraction and ⁵¹V NMR. Density Functional Theory (DFT) calculations were performed to evaluate the experimental parameters and further describes the electronic structure of the complex. The small structural changes that do occur in bond lengths and angles and partial charges on different atoms are minor compared to the charge features that are responsible for the majority of the electric field gradient tensor. The EPR parameters of the vanadium(IV) complex were characterized and compared to the corresponding dipicolinate complex. The chemical properties of the chlorodipicolinate compounds are discussed and correlated with their insulin-enhancing activity in streptozoticin (STZ) induced diabetic Wistar rats. The effect of the chloro-substitution on lowering diabetic hyperglycemia was evaluated and differences were found depending on the compounds oxidation state similar as was observed for the vanadium III, IV and V dipicolinate complexes (P. Buglyo, D.C. Crans, E.M. Nagy, R.L. Lindo, L. Yang, J.J. Smee, W. Jin, L.-H. Chi, M.E. Godzala III, G.R. Willsky, Inorg. Chem. 44 (2005) 5416-5427). However, a linear correlation of oxidation states with efficacy was not observed, which suggests that the differences in mode of action are not simply an issue of redox equivalents. Importantly, our results contrast the previous observation with the vanadium-picolinate complexes, where the halogen substituents increased the insulin-enhancing properties of the complex (T. Takino, H. Yasui, A. Yoshitake, Y. Hamajima, R. Matsushita, J. Takada, H. Sakurai, J. Biol. Inorg. Chem. 6 (2001) 133-142).     

Synthesis and characterization of new dinuclear complexes of molybdenum(V) with β′-hydroxy-β-enaminones

New dinuclear molybdenum(V) complexes have been obtained by the reaction of [Mo₂O₃(acac)₄] (acac=acetilacetonate ion) with the polydentate ligands, β′-hydroxy-β-enaminones. All prepared complexes consist of Mo₂O₄ ²⁺ core coordinated by two ligands as in the β-diketonates only through two donor oxygen atoms. Such bonding gives the opportunity for the sixth coordination place around molybdenum to be completed by the monodentate solvent molecule D. All compounds have been characterized by means of elemental analyses, one- and two-dimensional NMR spectroscopy, IR spectroscopy as well as by thermal analyses. The molecular and crystal structures of the molybdenum(V) complexes 1a and 1b coordinated by two different isomeric ligands as well as of the isomer a itself have been determined by a single crystal X-ray diffraction method.     

Binuclear copper(II) complexes of 5-N-(beta-ketoen)amino-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranoses: synthesis, structure, and catecholoxidase activity

The synthesis of 5-amino-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranose (8) was carried out via 5-azido-5-deoxy-1,2:3,4-O-diisopropylidene-alpha-D-glucofuranose (6), its reduction with Raney-Nickel and deprotection. 5-N-(beta-Ketoen)amino-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranoses (8a-f) were synthesized from 5-amino-5-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranose and beta-ketoenolethers leading to ligands with symmetrically substituted double bonds (8a, 8b) and e/z isomeric mixtures with unsymmetrical substitution (8c-f). Reaction of the ligands with Cu(II) ions leads to binuclear complexes of the general formula Cu2L2. In contrast to copper(II) complexes which are not derived from amino carbohydrates the metal centers in the compounds saturate their coordination sphere by complexation of additional solvent molecules, interaction with neighboring complex molecules, or free hydroxyl groups of the own ligand. Residues of the ketoen moiety, R1 and R2, also influence the electronic properties of the metal centers. The combination of factors leads to different catalytic properties of the complexes in catecholoxidase-like reactions.     

Mono and oligonuclear vanadium complexes as catalysts for alkane oxidation: synthesis, molecular structure, and catalytic potential

A series of mono- and oligonuclear vanadium(V) and vanadium(IV) complexes containing various chelating N,O-, N₃-, and O₂-ligands have been prepared. The biphasic reaction of an aqueous solution of ammonium vanadate and a dichloromethane solution of hexamethylphosphoramide (hmpa) and pyrazine-2-carboxylic acid (pcaH) or pyrazine-2,5-dicarboxylic acid (pdcaH₂) or pyridine-2,5-dicarboxylic acid (pycaH₂) yields yellow crystals of [VO₂(pca)(hmpa)] (1), [(VO₂)₂(pdca)(hmpa)₂] (2), and [VO₂(pycaH)(hmpa)] (3), respectively. The single-crystal X-ray structure analyses reveal 1 and 3 to be mononuclear vanadium(V) complexes, in which a VO₂ unit coordinates to one nitrogen and one oxygen atom of a pca or pycaH chelating ligand, and 2 to be a dinuclear vanadium(V) complex, in which two VO₂ units are coordinated through one nitrogen and one oxygen atom of a pdca bridging ligand; in the three complexes the vanadium atoms also coordinate to the oxygen atom of a hmpa ligand. The reaction of N,N,N^′,N^′-tetrakis(2-benzimidazolylmethyl)-2-hydroxo-1,3-diaminopropane (hptbH) and VOSO₄ in methanol gives the cationic complex [(VO)₄(hptb)₂(μ-O)]⁴⁺ (4), which can be crystallized as the perchlorate salt. In this tetranuclear complex, two dinuclear vanadium(IV) units are held together by a μ-oxo bridge. The known complex [VOCl₂(tmtacn)] (5) was synthesized from the reaction of 1,4,7-trimethyl-1,4,7-triazacyclononane (tmtacn) and VCl₃ in acetonitrile; the reaction of tetrabutylammonium vanadate with pyro-cathecol (catH₂) in acetonitrile gives the known anionic complex [V(cat)₃]⁻ (6), in which the vanadium(V) center is bonded to three cat chelating ligands through the oxygen atoms, obtained as the tetrabutylammonium salt. All compounds synthesized are highly efficient oxidation catalysts for the reaction of cyclohexane with air and hydrogen peroxide in the presence of four equivalents of pcaH per vanadium, although the catalytic activity of the complexes containing bulky chelating ligands 4 and 5 is somewhat lower in the initial period of the reaction. During this period the active species are formed from the complexes and final turnover numbers are high. The catecholate ligands of complex 6 may reduce from V(V) to V(IV) in the beginning of the process, thus providing very high initial oxidation rates.     

Synthesis, characterization, electrochemical and spectroscopic investigation of cobalt(III) Schiff base complexes with axial amine ligands: The layered crystal structure of [Co(salophen)(4-picoline)2]ClO4 · CH2Cl2

Cobalt(III) complexes with potentially tetradentate salophen (H₂salophen = N,N′-bis(salicylidene)-1,2-phenylenediamine) as equatorial ligand and with different axial amine ligands (NH₃, cyclohexylamine, aniline, 4-picoline and pyridine) were synthesized and characterized by IR, ¹H NMR, elemental analysis. Electronic spectra and electrochemical properties of the complexes were studied in DMF solutions. The lowest energy transitions, which occur between 464.8 and 477 nm, are attributed mainly to the intraligand charge transfer, confirmed by Zindo/S electronic structure calculations. The reduction potentials of Co(III)/Co(II) are more affected than those of Co(II)/Co(I) by the axial amine ligands. The crystal structure of the [Co^III(salophen)(4- picoline)₂]ClO₄ · CH₂Cl₂ was determined, indicating that the cobalt(III) center is six coordinated surrounded by the tetradentate salophen ligand and two 4-picoline ligands. The crystal packing of the complex shows a layered structure, in which the perchlorate counter ions and also the lattice solvent molecules are intercalated between the bc planes of the complex cations.     

Unusual reactivity of cytotoxic cis-dihydrazide Pt(II) complexes in aqueous solution

Complexes of the general structure cis-[PtX(2)(hydrazide)(2)] and cis-[PtX(2)NH(3)(hydrazide)], where X=Cl(-), Br(-) and I(-), and hydrazide=cyclohexylcarboxylic acid hydrazide (chcah), cyclopentylcarboxylic acid hydrazide (cpcah), 3-aminocyclohexanspiro-5-hydantoin (achsh) and 3-aminocyclopentanspiro-5-hydantoin (acpsh), were investigated with respect to aqueous stability, DNA platination rates and cytotoxic activity on a panel of seven human cancer cell lines as well as a cisplatin-resistant cell line. Stabilities in aqueous solution, determined by RP-HPLC and UV-Vis methods, were highly dependent on the type of halide ligand, with stability decreasing in the order I(-)>Cl(-)>Br(-). Added chloride (100 mM) only stabilized the dichloro-Pt(II) complexes containing the hydrazide as part of a hydantoin ring (i.e., achsh). Platination of calf thymus DNA determined by AAS was most rapid with dichloro-Pt(II) complexes containing achsh ligand. The mixed-amine dichloro-Pt(II) complexes with either chcah or cpcah ligands also platinated DNA >80%, but at a slower rate, while dihydrazide dichloro-Pt(II) complexes with either chcah or cpcah ligands resulted in <25% DNA platination at 24 h. cis-[PtX(2)(hydrazide)(2)], where hydrazide=chcah or cpcah, were the most potent compounds (chcah>cpcah), but activity was independent of the halide ligand (I(-)=Cl(-)=Br(-)). These complexes showed no cross-resistance with cisplatin, but they also showed little differentiation in potency over the seven cell lines. Complexes with the hydantoin ligands achsh and acpsh were inactive in all cell lines. Thus, neither stability in aqueous media nor covalent binding to DNA are correlated with biological activity, suggesting that cis-dihydrazide Pt(II) complexes act by a unique mechanism of action.     

The permeability and cytotoxicity of insulin-mimetic vanadium (III,IV,V)-dipicolinate complexes

Vanadium (III,IV,V)-dipicolinate complexes with different redox properties were selected to investigate the structure-property relationship of insulin-mimetic vanadium complexes for membrane permeability and gastrointestinal (GI) stress-related toxicity using the Caco-2 cell monolayer model. The cytotoxicity of the vanadium complexes was assayed with 3-(4,5-dimethylthiazoyl-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assays and the effect on monolayer integrity was measured by the trans-epithelial electric resistance (TEER). The three vanadium complexes exhibited intermediate membrane permeability (P(app) = 1.4-3.6x10(-6) cm/s) with low cellular accumulation level (<1%). The permeability of all compounds was independent of the concentration of vanadium complexes and excess picolinate ligands. Both V(III) and V(V)-dipicolinate complexes induced 3-4-fold greater reactive oxygen and nitrogen species (RONS) production than the V(IV)-dipicolinate complex; while the vanadium (III)-dipicolinate was 3-fold less damaging to tight junction of the Caco-2 cell monolayer. Despite the differences in apparent permeability, cellular accumulation, and capacity to induce reactive oxygen and nitrogen species (RONS) levels, the three vanadium complexes exhibited similar cytotoxicity (IC50 = 1.7-1.9 mM). An ion pair reagent, tetrabutylammonium, increased the membrane apparent permeability by 4-fold for vanadium (III and IV)-dipicolinate complexes and 16-fold for vanadium (V)-dipicolinate as measured by decrease in TEER values. In addition, the ion pair reagent prevented damage to monolayer integrity. The three vanadium (III,IV,V)-dipicolinate complexes may pass through caco-2 monolayer via a passive diffusion mechanism. Our results suggest that formation of ion pairs may influence compound permeation and significantly reduce the required dose, and hence the GI toxicity of vanadium-dipicolinate complexes.     

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.     

Syntheses and structures of four antimony complexes with planar tridentate pyridine ligands

The syntheses and structures of four antimony chloride complexes with tridentate N,N,O Schiff base ligands are reported. The tridentate ligands derived from 2-acetylpyridine and various acid hydrazides all lost a proton upon coordination. The ligand was either negative or zwitterionic depending on the acid hydrazide. The complexes are water soluble although a hydrolysis reaction can occur. The appearance of the μ-dichloro-μ-oxo-tetrachlorodiantimonate(III) anion in one of the complexes was unexpected but appears to be related to the temperatures used in the synthesis. The variation in the distances in the various complexes and the anion are discussed using bond valence sum calculations.     

Mixed-ligand rhenium-188 complexes with tetradentate/monodentate NS3/P ('4 + 1') coordination: relation of structure with antioxidation stability

Development of new radiopharmaceuticals based on rhenium-188 depends on finding appropriate ligands able to give complexes with high in vivo stability. Rhenium(III) mixed-ligand complexes with tetradentate/monodentate ('4 + 1') coordination of the general formula [Re(NS(3))(PRR'R' ')] (NS(3) = tris(2-mercaptoethyl)amine and derivatives thereof, PRR'R' ' = phosphorus(III) ligands) appear to be among the promising tools to achieve this goal. According to this approach, we synthesized and characterized a series of rhenium model complexes. In vitro stabilities of the corresponding rhenium-188 complexes were determined by incubating 2-3 MBq or alternatively 37 MBq of the complexes in phosphate buffer, human plasma, and rat plasma, respectively, at 22 degrees C or 37 degrees C, followed by checking the amount of (188)ReO(4)(-) formed after 1 h, 24, and 48 h by thin-layer chromatography. The rate of perrhenate formation varied over a wide range, depending primarily on the nature of the phosphorus(III) ligand. Physicochemical parameters of the corresponding nonradioactive rhenium complexes were analyzed in detail to find out the factors influencing their different stability and furthermore to design new substitution-inert '4 + 1' complexes. Tolman's cone angle of phosphorus(III) ligands and the lipophilic character of the inner coordination sphere were found to be crucial factors to build up stable rhenium '4 + 1' complexes. Additional information useful to describe electronic and steric properties of these compounds were selected from electronic spectra (wavelength of the Re-->S charge-transfer band), cyclovoltammetric measurements (E degrees of the Re(III)/Re(IV) couple), and NMR investigations ((31)P chemical shift of coordinated P(III) ligands).