Volume 77, Issue 9

The following 10 papers are selections from the 4th International Symposium on Chemistry and Biological Chemistry of Vanadium held 3-5 September 2004 in Szeged, Hungary. This conference attracted over 110 participants from 25 countries and 4 continents. Plenary and invited lectures as well as posters discussed the inorganic chemistry of vanadium, vanadium chemistry in catalysis and organic synthesis, and biological aspects of vanadium chemistry. A new feature was introduced: the presentation of the Vanadis Award. The purpose of the Vanadis Award is to recognize an outstanding contributor to the advancement of vanadium science. The award will be presented at each International Vanadium Symposium prior to a lecture to be given by the recipient. It is awarded on the basis of contributions to a discipline or combination of disciplines of vanadium science, and is presented to an investigator who has produced innovative research with impact on the direction of the field. The nominee is selected on the basis of the following criteria: (1) Innovative research: A history of development or expansion of techniques and procedures and discovery of new chemical, biochemical, biological, technological, or pharmaceutical systems; (2) Development of new applications in one or more of the following areas: chemistry, biochemistry, biology, pharmaceutical science, materials science, and nanotechnology; (3) Wide-ranging influence of the nominee's work on the research of others in one or more disciplines; (4) History of highquality and -impact publications; and (5) Service of the nominee to progress, application, and exploration of vanadium in science. The recipient of the first Vanadis Award is Prof. Debbie C. Crans of Colorado State University, whose award address is the first contribution to be presented herein. The additional contributions begin with papers covering various aspects of the inorganic chemistry of vanadium. These papers are followed by descriptions of recent results in the use of vanadium compounds to further organic synthesis, and on the catalytic behavior of interesting vanadium complexes. The final selection includes papers dealing with the role of vanadium in haloperoxidases, or as insulin-mimetic compounds, which may be orally administered replacements of insulin injections. A tremendous increase in studies of aqueous vanadium chemistry over the past decade has been driven by the need to comprehend the diverse biological effects of vanadium. Examples of the rich array of data and concepts needed to explain the biological role of vanadium are given by models of the vanadium-containing haloperoxidase enzyme activity. However, this selection of papers from the 4th International Vanadium Symposium indicates that basic inorganic studies and a wide range of applications of vanadium chemistry to fundamental chemical problems of synthesis, reactivity, and catalysis are not lacking. Indeed, we look forward to the 5th International Vanadium Symposium to be held in San Francisco, CA USA in the fall of 2006, where additional fundamental studies linked to the need to better understand vanadium nutritional essentiality, vanadium toxicity, vanadium therapy, and vanadium catalysis, including "green chemical" industrial applications will be presented. Kenneth Kustin and Tamas Kiss Conference Editors

The advances in vanadium chemistry over the past 15 years are discussed in the areas of solution chemistry, coordination chemistry, and bioinorganic chemistry and will be presented using the perspectives of "What exists in solution?", "What is its structure?", "How does it react?", and "What are its biological effects?". Current and future challenges will be described briefly.

Reaction of V IV OCl 2 in strongly acidic aqueous solution with either (NH 4 ) 2 SO 3 or Na 2 SO 3 and Bu 4 NBr at ~70°C in the pH range 2.5-4.5 gives the clusters (NH 4 ) 2 {[V 4 IV ( μ 4 -O) 2 ( μ 3 -OH) 2 ](V IV O) 2 ( μ 3 -SO 3 ) 4 O 4 (H 2 O) 2 } and ( n -Bu 4 N) 2 {[V 4 IV ( μ 4 -O) 2 ( μ 3 -OH) 2 ](V IV O) 2 ( μ 3 -SO 3 ) 4 O 4 (H 2 O) 2 }, respectively. Reaction of NH 4 V V O 3 with (NH 4 ) 2 SO 3 resulted in the isolation of the first compound. When the latter reaction is carried out in the presence of MgO, compound (NH 4 )[V IV O(SO 3 ) 1.5 H 2 O] ∞ .2.5H 2 O was isolated instead. Compound ( n -Bu 4 N) 2 {[V 4 IV ( μ 4 -O) 2 ( μ 3 -OH) 2 ](V IV O) 2 ( μ 3 -SO 3 ) 4 O 4 (H 2 O) 2 } and (NH 4 )[V IV O(SO 3 ) 1.5 H 2 O] ∞ .2.5H 2 O were characterized by X-ray structure analysis. The crystal structure of species ( n -Bu 4 N) 2 {[V 4 IV ( μ 4 -O) 2 ( μ 3 -OH) 2 ](V IV O) 2 ( μ 3 -SO 3 ) 4 O 4 (H 2 O) 2 } revealed a unprecedented hexanuclear cluster consisting of a cubane core [M 4 ( μ 4 -O) 2 ( μ 3 -OH) 2 ] connected to two other metal atoms through the core oxo-groups and four μ 3 -SO 3 bridges. Compound (NH 4 )[V IV O(SO 3 ) 1.5 H 2 O] ∞ .2.5H 2 O represents a rare example of an open-framework species prepared under mild conditions. Cyclic voltammetric examination of compound ( n -Bu 4 N) 2 {[V 4 IV ( μ 4 -O) 2 ( μ 3 -OH) 2 ](V IV O) 2 ( μ 3 -SO 3 ) 4 O 4 (H 2 O) 2 } revealed a redox process which was assigned to the oxidation of one core of vanadium(IV) to vanadium(V).

Oxovanadium(V) compounds serve as Lewis acids with oxidation capability and induce one-electron oxidative transformations of organosilicons, organotins, organoaluminums, organoborons, organozincs, and/or their ate complexes. Low-valent vanadium-catalyzed stereoselective reductive transformations, including dehalogenation, pinacol coupling, and the related radical reaction, have been developed by constructing a multicomponent redox system in combination with a coreductant and an additive.

(Schiff-base)vanadium(V) complexes catalyze the oxidation of Br - (formation of Br 2 ) and the stereoselective synthesis of functionalized tetrahydrofurans from substituted bishomoallylic alcohols. In both instances, tert -butyl hydroperoxide (TBHP) serves as primary oxidant. The oxidation of Br - was applied as the key step for stereo- and 6- endo -selectively constructing the 2,2,3,5,6,6-substituted tetrahydropyran nucleus of the marine natural product aplysiapyranoid A starting from an adequately substituted bishomoallylic alcohol. In the absence of Br - , 1-alkyl-, 1-vinyl-, and 1-phenyl-5,5-dimethyl-substituted bishomoallylic alcohols are selectively oxygenated to furnish 2,5- cis -configured tetrahydrofurans as major products. 2- Or 3-substituted ω,ω-dimethyl-substituted bishomoallylic alcohols afford trans -disubstituted tetrahydrofurans under these conditions. Oxidation of substituted 4-penten-1-ols, i.e., substrates with a terminal π-bond, proceeds with a preference for formation of trans -disubstituted tetrahydrofurans. According to data from (i) 51 V NMR spectroscopy, (ii) mass spectrometry, (iii) a structure-selectivity survey, (iv) competition kinetics, and (v) a stereochemical analysis, the oxygen atom transfer onto a bishomoallylic alcohol occurs in a peroxide- and alkenol-loaded (Schiff-base)vanadium(V) complex.

Oxybromination reaction of styrene was performed in a two-phase system of water/ionic liquids (ILs). The aim of the work was to make the mild and efficient two-phase system previously developed for the vanadium(V)-catalyzed oxybromination of alkenes, inspired by the activity of haloperoxidase enzymes, even more interesting from a sustainable point of view. As in that case, a brominating intermediate was formed from the metal catalyst, H 2 O 2 , and bromide ion in the acid aqueous phase, but chlorinated solvents were replaced with ILs. [bmim + ][PF 6 - ], [bm 2 im + ][PF 6 - ], [bmim + ][BF 4 - ], [bmim + ][CF 3 SO 3 - ], and [bmim + ][(CF 3 SO 2 ) 2 N - ] were tested. We report on interesting results in terms of reaction rates and selectivities.

The hydrolysis of vanadium(III) and the complex formation reactions between V(III) and weakly coordinating [glycine (GLY), DL-aspartic acid (ASP), D-penicillamine (PEN), DL-histidine (HIS)] or strongly coordinating [N,O] donor [picolinic (PIC) or 6-methylpicolinic acid (MePIC)] and [O,O] donor [maltol (MALT), 1,2-dimethyl-3-hydroxy-4-(1H)-pyridinone (DHP), tiron (TIR)] ligands were studied at 25.0 °C and an ionic strength of 0.20 M (KCl) in aqueous solution using combined pH-potentiometric and UV-vis spectroscopic techniques. Although some interaction between the amino acids and V(III) was found, we could not obtain reliable models for these systems owing to the intensive hydrolysis of the metal ion and the formation of polynuclear hydroxo complexes. With pyridine carboxylates or [O,O] donor ligands 1:1, 1:2 (in the latter case, also 1:3 species) were found to be present as major complexes in solution. The similarities and differences in binding V(III) by these ligands are discussed.

Vanadium-dependent haloperoxidases that catalyze the halogenation of organic substrates using hydrogen peroxide to oxidize halides are a rare class of enzymes which have an absolute requirement for vanadium. In this article, we describe studies using synthetic, small-molecule analogs of the vanadium(V) active site to functionally mimic the oxidation of bromide and thioethers. In addition, we describe computational studies using density functional theory that help describe the mechanism of catalysis.

The active center of vanadate-dependent peroxidases (VPOs) is represented by vanadate covalently attached to a histidine, with vanadium in a trigonal-bipyramidal environment. Protein phosphatases and kinases are inhibited by the phosphate analog vanadate [V V O 2 (OH) 2 - and V IV O(OH) 3 - ], which can be related to the coordination of vanadium to histidine or a hydroxide function as provided by tyrosinate or serinate. The vanadium centers in these proteins have been modeled by employing chiral ONO ligands. The penta-coordinated chiral complexes [VO(OMe)(L 1 )] (H 2 L 1 = substituted diethanolamine) are distorted trigonal-bipyramidal with the methoxy group and the amine-N in the axial positions. These structural models of VPO also mimic the sulfide-oxidation activity of the peroxidases. The complexes [VO(H 2 O)L 3 ] (H 2 L 3 = Schiff-base ligands based on salicylaldehyde derivatives ( o -vanillin; 2-hydroxy-naphthylaldehyde) and L- or D,L-tyrosine, or D,L-serine are tetragonal-pyramidal; the OH functions of the amino acid moieties are not directly coordinated to vanadium; they are involved, however, in complex hydrogen-bonding networks. The oxo/peroxo anion [VO(O 2 )(L 2 ) 2 ] 3- (H 2 L 2 = 2,5-dipicolinic acid) contains a slightly asymmetrically bonded O 2 2- , featuring structural characteristics of the peroxo/hydroperoxo intermediates of the peroxidases. XD structure results are reported for the following complexes: R , S - and R , R -[VO(OMe)(L 1 )], K 3 [VO(O 2 )(L 2 ) 2 ].4.5H 2 O, the Tyr derivatives L-[VO(H 2 O)L 3 ].MeOH and D,L-[VO(H 2 O)L 3 ].H 2 O, and the Ser derivative D,L-[VO(H 2 O)L 3 ].2H 2 O.

We report that oral administration of vanadium (+5) combined with L-glutamic acid γ-monohydroxamate at 1:2 stoichiometry [L-Glu(γ)HXM.VO 3 - ] is highly effective in reducing blood glucose levels (BGLs) in a wide variety of diabetic rodents. In streptozocin-treated rats, a single administration (0.28 mmol/kg body wt) decreased BGL from 490 to 360 mg/dl within 1 h of administration, keeping this reduced level for additional 22 h, and a daily dose of 0.14 mmol/kg was found optimal. In Zucker diabetic fatty (ZDF) rats, a single dose of 0.14 mmol/kg normalized BGL within 8 h of administration, and maintained normal value for additional two days. In db/db mice, a single L-Glu(γ)HXM.VO 3 - administration of 0.2 mmol/kg decreased BGL from 500 ± 50 to 240 ± 20 mg/dl at 2 h, but was less effective afterwards. In high-carbohydrate (CHO)-fed Psammomis obesus , a single oral dose (0.14 mmol/kg) normalized BGL over a period of two days, and a daily dose of 0.07 mmol/kg/d, at the time P. obesus was transferred from low- to high-CHO diet, fully arrested the development of hyperglycemia characterizing this diabetic rodent. Finally, we found that the index of toxicity of orally administered L-GLU(γ)HXM-vanadate in rodents is 5-7 times lower than that of free sodium vanadate.

The number of patients suffering from diabetes mellitus (DM) is increasing year by year throughout the world. In 2003, the world population was 6.3 billion, and the number of patients with DM in the adult population (20-79 years old) was 0.194 billion, which corresponded to 5.1 % of all disease incidence in that age range. In 2005, it is forecasted that the world population will increase to 8.0 billion and the ratio of DM to total disease incidence will increase to 6.3 %, with a disproportionate number of cases in Southeast Asia, the West Pacific, Central Asia, and North, Central, and South America. To treat Type 1 and Type 2 DM clinically, insulin preparations and synthetic drugs, respectively, have been used. However, these treatments are associated with some problems, such as several times of daily insulin injections following blood glucose monitoring and side effects in the case of the synthetic drugs. Consequently, a new class of therapeutic compounds is anticipated. After many trials, vanadium-containing complexes have been proposed to improve and treat both types of DM by in vivo experiments. We present an overview of insulinomimetic and antidiabetic vanadyl (+4 vanadium, V) complexes, and propose new candidates for dinuclear vanadyl complexes with naturally occurring ligands. The current state of research on the dinuclear vanadyl(IV)-tartrate complexes is described in regard to the physicochemical characteristics, in vitro insulinomimetic and in vivo blood-glucose-lowering effects of the prepared complexes.

Numerous areas of chemistry can benefit from the ongoing genomic revolution. Here, we discuss and highlight trends in chemistry in the postgenomic era. The areas of interest include combinatorial approaches in organic chemistry; design and analysis of proteins containing unnatural amino acids; trace element-containing proteins; design and characterization of new enzyme types; applications of postgenomic chemistry in drug design; identification of lipid networks and global characterization of lipid molecular species; development of recombinant and self-proliferating polymers; and applications in food chemistry and bioanalytical chemistry based on new nanoanalytical systems and novel recognition elements.