Cirila Djordjevic

Antitumor activity and toxicity of peroxo heteroligand vanadates(V) in relation to biochemistry of vanadium

A selected set of 14 V(V) complexes was tested for toxicity and antitumor activity against L1210 murine leukemia, to examine the biological properties of peroxoheteroligand vanadates(V) of the formula (NH4)4[O(VO(O2)2)2], M3I[VO(O2)2C2O4], and MI[VO(O2)L], L = malate, citrate, iminodiacetate, nitrilotriacetate, and EDTA. The x-ray structure is known for five of these compounds. A relationship has been found between the chemical composition and the biological activity (antitumor activity-toxicity) of these complexes. Activity in the L1210 system is defined as greater than or equal to 25% increase in life span, and this was seen with (NH4)4[O(VO(O2)2)2]; M3[VO(O2)2(C2O4)]2H2O, M = K, NH4; and NH4[VO(O2)Malato]H2O. These observations are important for the biochemistry of vanadium. The special nature of electron transfer within the V(V)-peroxo moiety is proposed to be responsible for this phenomenon. Peroxo heteroligand vanadates(V) therefore represent a model system for studying some biochemical interactions of vanadium in living matter.

Peroxo malato vanadates(V): syntheses, spectra and structure of the (NH4)2[VO(O2)(C4H4O5)]22H2O dimer with a rhomboidal V2O2(hydroxyl) bridging core

Crystalline peroxo malato vanadates(V) of the formula M[VO(O2)(C4H4O5)]H2O, where M = Na, K, NH4, Cs, obtained from aqueous solutions and characterized by IR and UV spectroscopy are described. X-ray structure analysis of (NH4)2[VO(O2)(C4H4O5)]22H2O shows that the complex crystallizes in the triclinic space group, P1, with a = 9.157(4), b = 9.662(5), c = 14.203(5) A, ga = 104.58(3), β = 90.52(3), γ = 115.50(2)°, V=1088 A3, Z=2. The structure contains a dimer with a novel tridentate coordination of the malato ion. Two bridging hydroxyl oxygens enclose a symmetrical rhomboidal V2O2 plane, binding two distorted pentagonal bipyramidal vanadium polyhedra. The peroxo groups, with OO bond lengths of 1.442(2) A, are located in the equatorial plane across from the bridging hydroxyl oxygens, and the fifth side of the pentagonal plane is occupied by the oxygen of the vicinal carboxylic group. The second carboxylic group is coordinated at the apical position, trans to the oxo group. In the UV spectra all the compounds show the typical broad [monoperoxo → vanadium] charge transfer band at a λmax=425 nm. Characteristic very strong IR bands were assigned by comparison with the spectra of malic acid and numerous other heteroligand peroxo vanadates(V). The v(OO) stretch appears in the vicinity of 922 cm−1, and the v(V = O) band near 977 cm−1. The stereochemistry and the relationship of these compounds to the biochemistry of vanadium are discussed.

Peroxo heteroligand vanadates(V): Synthesis, spectra-structure relationships, and stability toward decomposition

Effect of heteroligands (L) on the properties of vanadium peroxides was investigated by preparing a number of peroxovanadium complexes, which were characterized by analysis, IR, UV/V and NMR spectra. X-ray structures for some were obtained. The vanadates(V) contain the cation M(I)=Na, K, NH4, Rb or Cs. Diperoxo complexes include M(I)[VO(O2)2L], where L=dipyridyl, o-phenanthroline; M(I)3[VO(O2)2(C2O4)]; K2[(nicotinic acid) {VO(O2)2}2]H2O;M(I)4[O{VO(O2)2}2 cystine]2H2O; H4[O{VO(O2)2(adenine)2)2]2H2O; and K2H2[O{VO(O2)2(adenosine)}2]2H2O. Monoperoxo vanadates(V) correspond to the formula M(I)2[VO(O2)L]2 for L=citrate and malate; M(I)2[VO(O2)L] for L=nitrilotriacetate; M(I)[VO(O2)L] for L=iminodiacetate, tartrate and EDTA; and [HVO2(O2)(adenosine)]2H2O. Syntheses of these heteroligand peroxovanadium compounds are sensitive to pH, temperature and the concentration of the components. The stability towards decomposition in solid state, mother-liquid and pure water solutions depends upon the heteroligand. Characteristic (V=O) and (O-O) stretching frequency bands in IR can be correlated with the corresponding bond lengths and the [peroxo≈V(V)] charge transfer bands in UV/V spectra. Intramolecular one-electron transfer in peroxo vanadates(V) can trigger the generation of radicals, and its dependency upon the nature of the heteroligand is discussed.

Synthesis and properties of peroxo α-amino acid complexes of molybdenum(VI). The structures of MoO(O2)2(HAA)(H2O), HAA= glycine, proline

Le complexe avec la glycine cristallise dans P2 1 /c avec Z=4; R=0,022. Le complexe avec la proline cristallise dans P2 1 2 1 2 1 avec Z=4; R=0,027

Peroxo aminopolycarboxylato vanadate(V) of an unusually low toxicity: synthesis and structure of the very stable K2[VO(O2)(C6H6NO6)]·2H2O

The synthesis and structure of a monoperoxo vanadate(V) of the formula K2[VO(O2)NTA]·2H[2O, where NTA = C6H6NO6 3−, the nitrilotriacetate, is described. This stable compound crystallizes in the orthorhombic system (space group Pna21): a = 7.621(1), b = 13.002(3), c = 13.155(1) A. A tetradentate NTA encloses vanadium in a distorted pentagonal bipyramid with an apical V = O group. Cis to it, in the pentagonal plane, a non-symmetrically coordinated peroxo group is located with an (OO) bond length of 1.438(4) A. Complex IR spectra display rich absorption due to coordinated NTA, in addition to the characteristic V = O and (OO) stretching vibrations. Aqueous solutions of the complex show a (peroxo → V(V)) charge transfer band at γmax = 425 nm.

Synthesis and properties of molybdenum(VI) peroxo compounds with imidazole and the X-ray structure of (C3H5N2)2[O{MoO(O2)2H2O}2], a novel imidazolium peroxo complex containing a μ-oxo bridged dimer

Abstract Crystalline peroxo molybdate(VI) complexes with imidazole are reported: (C3H5N2) 2[O{MoO(O2)2H2O}2] (1), MoO2(O2)(C3H4N2)2H2O (2) and K2MoO2(O2)2 (C3H4N2)4H2O (3). They represent the first peroxo metal compounds containing imidazole. IR spectra display characteristic ν(MoO) between 967 and 955 cm−1, and ν(OO) between 892 and 853 cm−1. The X-ray crystal structure of (1) shows the presence of a μ-oxo group bridging two pentagonal bipyramidal {MoO(O2)2H2O} moieties, each hydrogen bonded to an essentially planar imidazolium cation via one of the oxygens of a coordinated peroxo group.

Conversion of malonate and malate to oxalate in aqueous peroxo molybdate(VI) solutions. Synthesis and structure of potassium oxodiperoxooxalatomolybdate(VI)

Etude de la conversion catalytique de 2 ions dicarboxylato utilises comme heterocoordinats dans des systemes aqueux de peroxomolybdate(VI). Etude RX de la structure de [MoO(O 2 ) 2 (C 2 O 4 )] 2−

Co-ordination complexes of niobium and tantalum. Part XV. Sulphoxide complexes of oxobis(oxalato)niobates(V)

The preparation and properties of crystalline colourless complexes of the composition MI[NbO(C2O4)2(dmso)2](M = NH4, K, Rb, or Cs; dmso = dimethyl sulphoxide), and MI[NbO(C2O4)2(tmso)2](M = NH4, K, Rb; tmso = tetramethylene sulphoxide) are described. The complexes were prepared by dissolving the corresponding MI salts of oxobis(oxalato)aquoniobates in dmso and tmso, respectively. Stability trends and i.r. spectra of these oxobis-(oxalato) bis(sulphoxide)niobate(V) series of complexes are discussed. According to chemical and i.r. evidence the complexes contain two oxygen-bonded sulphoxide ligands and the presence of seven-co-ordinate niobium(V) in these complexes is assumed.

Oxodiperoxovanadate(V) complexes with bidentate ligands

Crystalline oxodiperoxovanadate(V) complexes containing co-ordinated 2·2′-bipyridine(bipy), 1,10-phenanthro-line(phen), and oxalato-groups, C2O42–(ox), M[VO(O2)2L],nH2O (M = Na, K, or NH4; L = bipy or phen; n= 2–5) and M3[VO(O2)2(ox)],2H2O (M = K or NH4), have been prepared. The complexes are formed in hydrogen peroxide solutions of trioxovanadate(V) ions in the presence of corresponding ligands. They are soluble in water, where molar conductivity measurements indicate the presence of 1 : 1 and 1 : 3 electrolytes, respectively. With large excesses of the bidentate nitrogen ligands, complexes are obtained, of simplest formula LH2[V2O2(O2)4L2],6H2O (L = bipy or phen), which do not contain a monomeric peroxovanadate(V) group. The oxodiperoxovanadate(V) complexes are not analogous nor isomorphous with eight-co-ordinate triperoxoniobate(V) and -tantalate(V) complexes containing the same bidentate ligands and prepared under similar conditions.

Peroxides of vanadium and related metals in biological and medicinal chemistry

Ions of vanadium and other transition metals of do or low dn electron configuration are present in substantial amount in selected human tissues and blood. Vanadium is one of the elements recently recognised as essential for mammals [1]. In a very low concentration [2] it is thought to be widely distributed in tissues, but its biological function remains unknown. Complexes of vanadium and related metals with peroxo group, stabilized in specific ligand fields [3], exist in solid state and aqueous solutions. Such compounds of biologically important metals can help us understand the metal interactions with dioxygen moiety in living matter [4]. We have prepared and characterized a number of peroxo complexes of vanadium, niobium, tantalum and lanthanides, some containing various heteroligands (e.g., oxalates, amino-carboxylates). Antitumor activity (ILS 25–32%), using L1210 murine leukemia test systems, have been found for some of these vanadium complexes [5]. They represent a new type of antitumor metal agents, quite different from a previously reported vanadocene dichloride [6]. A change in toxicity have been observed among analogous peroxo and nonperoxo niobate complexes. The relationship between the chemical properties of these compounds and their biological effects is studied by observing properties of complex peroxo species in aqueous solutions. Proton and 13C NMR spectra of heteroligands offer an indirect evidence for peroxo group presence in the metal ligand sphere. Individual resonance patterns and specific chemical shifts are observed in saturated deuterium oxide solutions for particular complex polyhedra present in the solid state. Peroxo → metal charge transfer band is pH dependent and distinct for different spheres. Redox potentials measured upon oxidation by various oxidants depend upon the type of the complex, showing significant differences (⩾300 mV). Vanadium complexes are particularly interesting in this respect because of a conceivable intramolecular redox process [7]. Under proper tuning by heteroligands the reactivity of coordinated peroxo group is expected to be modified, and eventually undergo one electron oxidation. Antitumor activity and toxicity of vanadium complexes can accordingly be associated with free radical processes [8], in addition to previously observed perturbation of enzymes involving phosphate metabolism, and perhaps sodium pump. For such speculations more reliable analyses of vanadium in tissue are of primary importance [9].