Aqueous V(V)-peroxo-amino acid chemistry. Synthesis, structural and spectroscopic characterization of unusual ternary dinuclear tetraperoxo vanadium(V)-glycine complexes.

Vanadium participation in cellular events entails in-depth comprehension of its soluble and bioavailable forms bearing physiological ligands in aqueous distributions of binary and ternary systems. Poised to understand the ternary V(V)-H(2)O(2)-amino acid interactions relevant to that metal ion's biological role, we have launched synthetic efforts involving the physiological ligands glycine and H(2)O(2). In a pH-specific fashion, V(2)O(5), glycine, and H(2)O(2) reacted and afforded the unusual complexes (H(3)O)(2)[V(2)(O)(2)(mu(2):eta(2):eta(1)-O(2))(2)(eta(2)-O(2))(2)(C(2)H(5)NO(2))] x 5/4 H(2)O (1) and K(2)[V(2)(O)(2)(mu(2):eta(2):eta(1)-O(2))(2)(eta(2)-O(2))(2)(C(2)H(5)NO(2))] x H(2)O (2). 1 crystallizes in the triclinic space group P1, with a = 7.805(4) A, b = 8.134(5) A, c = 12.010(7) A, alpha = 72.298(9) degrees, beta = 72.991(9) degrees, gamma = 64.111(9) degrees, V = 641.9(6) A(3), and Z = 2. 2 crystallizes in the triclinic space group P1, with a = 7.6766(9) A, b = 7.9534(9) A, c = 11.7494(13) A, alpha = 71.768(2) degrees, beta = 73.233(2) degrees, gamma = 65.660(2) degrees, V = 610.15(12) A(3), and Z = 2. Both complexes 1 and 2 were characterized by UV/visible, LC-MS, FT-IR, Raman, NMR spectroscopy, cyclic voltammetry, and X-ray crystallography. The structures of 1 and 2 reveal the presence of unusual ternary dinuclear vanadium-tetraperoxo-glycine complexes containing [(V(V)=O)(O(2))(2)](-) units interacting through long V-O bonds and an effective glycinate bridge. The latter ligand is present in the dianionic assembly as a bidentate moiety spanning both V(V) centers in a zwitterionic form. The collective physicochemical properties of the two ternary species 1 and 2 project the chemical role of the low molecular mass biosubstrate glycine in binding V(V)-diperoxo units, thereby stabilizing a dinuclear V(V)-tetraperoxo dianion. Structural comparisons of the anions in 1 and 2 with other known dinuclear V(V)-tetraperoxo binary anionic species provide insight into the chemical reactivity of V(V)-diperoxo species in key cellular events such as insulin mimesis and antitumorigenicity, potentially modulated by the presence of glycinate and hydrogen peroxide.

pH-specific synthetic chemistry and solution studies in the binary system of iron(III) with the alpha-hydroxycarboxylate substrate quinic acid: potential relevance to iron chemistry in plant fluids.

Iron is an essential metal ion in plant growth and development. Mobilization and further use of that metal by cellular structures in metabolic pathways entails the existence of soluble forms complexed with indigenous organic substrates, such as the low molecular mass d-(-)-quinic acid. In an effort to understand the relevant aqueous chemistry involving well-defined forms of iron, research efforts were carried out on the binary Fe(III)-quinic acid system. pH-specific reactions of FeCl(3).6H(2)O with quinic acid in a molar ratio 1:3 led to the isolation of the mononuclear Fe(III)-quinate complexes, K[Fe(C(7)H(11)O(6))(3)].(OH).3H(2)O (1), (NH(4))[Fe(C(7)H(11)O(6))(3)].(OH) (2), and Na[Fe(C(7)H(11)O(6))(3)].(OH).8H(2)O (3). Compounds 1-3 were characterized by analytical, spectroscopic techniques (UV/vis, FT-IR, Electron Paramagnetic Resonance (EPR), and Mossbauer spectroscopy), cyclic voltammetry, and magnetic susceptibility measurements. Compound 1 crystallizes in P2(1)3, with a = 15.1693(9) A, V = 3490.6(4) A(3), and Z = 4. Compound 2 crystallizes in P2(1)3, with a = 15.2831(9) A, V = 3569.7(4) A(3), and Z = 4. Compound 3 crystallizes in P2(1)3, with a = 15.6019(14) A, V = 3797.8(6) A(3), and Z = 4. The X-ray crystal structures of 1-3 reveal a mononuclear Fe(III) ion bound by three quinates in an octahedral fashion. Each quinate ligand binds Fe(III) through the alpha-hydroxycarboxylate group as a singly deprotonated moiety, retaining the alcoholic hydrogen. EPR measurements in solution suggest that 1 dissociates, releasing free quinate. Solution speciation studies of the binary system (a) unravel the aqueous species distribution as a function of pH and reagent molar ratio, and (b) corroborate the EPR results proposing the existence of a neutral Fe(III)-quinate complex form. The collective physicochemical properties of 1-3 formulate a well-defined profile for the Fe(III) assembly in aqueous media and project structural features consistent with solubilized Fe(III)-hydroxycarboxylate binary forms potentially mobilized into plant (bio)chemical processes.

Assessment of PTEN tumor suppressor activity in nonmammalian models: the year of the yeast.

Model organisms have emerged as suitable and reliable biological tools to study the properties of proteins whose function is altered in human disease. In the case of the PI3K and PTEN human cancer-related proteins, several vertebrate and invertebrate models, including mouse, fly, worm and amoeba, have been exploited to obtain relevant functional information that has been conserved from these organisms to humans along evolution. The yeast Saccharomyces cerevisiae is an eukaryotic unicellular organism that lacks a canonical mammalian-like PI3K/PTEN pathway and PIP3 as a physiological second messenger, PIP2 being essential for its life. The mammalian PI3K/PTEN pathway can be reconstituted in S. cerevisiae, generating growth alteration phenotypes that can be easily monitored to perform in vivo functional analysis of the molecular constituents of this pathway. Here, we review the current nonmammalian model systems to study PTEN function, summarize our knowledge of PTEN orthologs in yeast species and propose the yeast S. cerevisiae as a sensitive biological sensor of PI3K oncogenicity and PTEN tumor suppressor activity.