The challenges of trafficking hydrolysis prone metals and ascidians as an archetype

Some of the metal ions that are required, exploited, or simply managed in biological systems are susceptible to hydrolysis and to hydrolytic precipitation in the aqueous, aerobic environment of much of biology. Organisms have evolved exquisite mechanisms for handling these metal ions, offering striking examples of biological control over inorganic coordination chemistry. This year marks the one hundredth anniversary of the discovery of remarkably high vanadium concentrations in the blood cells of the ascidian. In the ensuing years, these marine invertebrates were established as masters of the biological chemistry of very hydrolysis-prone metals, with various ascidian species accumulating high concentrations of iron, vanadium, and titanium, among others. These three metals have very different histories of biological relevance, and many questions remain about how, and ultimately why, these organisms sequester them. This Perspective addresses the aqueous coordination chemistry that organisms like ascidians must control if they are to manipulate hydrolysis-prone metal ions, and describes some of the ascidian biomolecules that have been implicated in this phenomenon. The recently available genome sequence for one ascidian species offers a glimpse into its metal-management arsenal. It offers the opportunity to map the relatively well-studied paradigm of iron management onto the genome of an organism that is intermediate in evolution between invertebrates and vertebrates. The ascidians have much to teach us about how to manage metals like iron, titanium, and vanadium and how that ability evolved.     

A non‐oxo methanolate‐bridged divanadium(IV) complex with tris(2‐sulfanidylphenyl)phosphane ligands: synthesis,structural characterization and magnetic investigation

Vanadium chemistry is of interest due its biological relevance and medical applications. In particular, the interactions of high‐valent vanadium ions with sulfur‐containing biologically important molecules, such as cysteine and glutathione, might be related to the redox conversion of vanadium in ascidians, the function of amavadin (a vanadium‐containing anion) and the antidiabetic behaviour of vanadium compounds. A mechanistic understanding of these aspects is important. In an effort to investigate high‐valent vanadium–sulfur chemistry, we have synthesized and characterized the non‐oxo divanadium(IV) complex salt tetraphenylphosphonium tri‐μ‐<!?tlsb=‐0.11pt>methanolato‐κ⁶O:O‐bis({tris[2‐sulfanidyl‐3‐(trimethylsilyl)phenyl]phosphane‐κ⁴P,S,S′,S′′}vanadium(IV)) methanol disolvate, (C₂₄H₂₀P)[V^IV₂(μ‐OCH₃)₃(C₂₇H₃₆PS₃)₂]·2CH₃OH. Two V^IV metal centres are bridged by three methanolate ligands, giving a C2‐symmetric V₂(μ‐OMe)₃ core structure. Each V^IV centre adopts a monocapped trigonal antiprismatic geometry, with the P atom situated in the capping position and the three S atoms and three O atoms forming two triangular faces of the trigonal antiprism. The magnetic data indicate a paramagnetic nature of the salt, with an S = 1 spin state.     

REVIEW: SPECTROSCOPIC STUDIES OF OXOVANADIUM COORDINATION COMPOUNDS

Abstract

In this review we present selected examples of our studies of oxovanadium(IV) and oxovanadium(V) complexes relevant for the bioinorganic chemistry of vanadium. Some of the investigated complexes are good models for different steps of vanadium metabolism or for a better understanding of the structural and electronic peculiarities of the coordination spheres of these oxocations in biomolecules. The investigated systems include ligands such as nucleotides, carbohydrates, phosphates, amino acids, oxine derivatives, porphine-like cores and other simple organic and inorganic ligands. All these complexes have been systematically investigated by means of vibrational (infrared and Raman) and electronic spectroscopy and, in some cases, also by thermal and electrochemical behavior. The potentialities and possibilities of the spectroscopic methodologies are illustrated and discussed and some general trends, useful for the structural characterization of these and similar systems, are emphasized.     

Bioanorganische Chemie des Vanadiums. Leben ohne Vanadium?

Vanadium is used by microorganisms as an electron acceptor in respiration, and as an essential transition metal in enzymatic reactions. An example for the employment in respiratory function is the soil bacterium Shewanella, which reduces vanadate(V) to oxidovanadium(IV). Examples for enzymatic reactions are the nitrogen fixation (by the proteobacterium Azotobacter and the cyanobacterium Anabaena), and the two‐electron oxidation of halide X^– to a species {X⁺} by marine macro‐algae, fungi and lichen. In vanadium nitrogenase, vanadium is constituent of a {Fe₇VS₉} cluster, in vanadate‐dependent haloperoxidases it is present in the form of H₂VO₄^– bound to a histidyl residue of the protein matrix. Mushrooms of the genus Amanita store vanadium in the form of amavadin, a “bare” (non‐oxo) vanadium(IV) complex. Several sea squirts and fan worms accumulate vanadium from sea water and store it as an aqua complex of vanadium(III). “Tailored” vanadium complexes with organic ligands have been shown to be active as insulin‐mimics in vivo and in vitro: They are able to stimulate the cellular uptake of glucose and to inhibit the degradation of lipids. These functions are related to the phosphate‐vanadate antagonism.     

Polyoxometalate Chemistry: An Old Field with New Dimensions in Several Disciplines

Inorganic metal–oxygen cluster anions form a class of compounds that is unique in its topological and electronic versatility and is important in several disciplines. Names such as Berzelius, Werner, and Pauling appear in the early literature of the field. These clusters (so-called isopoly- and heteropolyanions) contain highly symmetrical core assemblies of MO_x units (M = V, Mo, W) and often adopt quasi-spherical structures based on Archimedean and Platonic solids of considerable topological interest. Understanding the driving force for the formation of high-nuclearity clusters is still a formidable challenge. Polyoxoanions are important models for elucidating the biological and catalytic action of metal–chalcogenide clusters, since metal–metal interactions in the oxo clusters range from very weak (virtually none) to strong (metal–metal bonding) and can be controlled by choice of metal (3d, 4d, 5d), electron population (degree of reduction), and extent of protonation. Mixed-valence vanadates, in particular, show novel capacities for unpaired electrons, and the magnetic properties of these complexes may be tuned in a stepwise manner. Many vanadates also act as cryptands and clathrate hosts not only for neutral molecules and cations but also for anions, whereby a remarkable “induced self-assembly process” often occurs. Polyoxometalates have found applications in analytical and clinical chemistry, catalysis (including photocatalysis), biochemistry (electron transport inhibition), medicine (antitumoral, antiviral, and even anti-HIV activity), and solid-state devices. These fields are the focus of much current research. Metal–oxygen clusters are also present in the geosphere and possibly in the biosphere. The mixed–valence vanadates contribute to an understanding of the extremely versatile geochemistry of the metal. The significant differences between the chemistry of the polyoxoanions and that of the thioanions of the same elements is of relevance to heterogeneous catalysis, bioinorganic chemistry, and veterinary medicine.     

History of Solution Chemistry of Japan

A historical view of the solution chemistry of Japan is described for a wide range of fields of solution chemistry, which relates to physical chemistry, inorganic chemistry, analytical chemistry, biochemistry and bioinorganic chemistry, and colloid and polymer chemistry. The works by pioneers of Japanese solution chemistry are introduced, some of which are not well recognized internationally. The influences of Japanese solution chemistry on the world and vice versa are discussed on the basis of a rather personal viewpoint. Recent activities of Japanese solution chemists at the national and international levels are also reviewed.     

钒化合物抗糖尿病作用的研究进展*

在糖尿病的治疗研究中,体内和体外的研究表明,钒化合物可以降低I型和II型糖尿病血糖,促进葡萄糖转运和糖原合成,具有“类胰岛素作用”。本文综述了近年来钒化合物在降低和改善糖尿病症状的生物效应及其通过胰岛素信号通路在降糖作用的分子机制的研究进展。     

硒化合物诱导细胞凋亡的信号转导机制

从硒化合物诱导细胞凋亡及其机理阐明硒防治肿瘤的生物功能,是当今硒的生物无机化学与相关学科交叉的前沿。本文通过作者的研究工作及国内外有关工作介绍了活性氧（ROS）介导的硒化合物诱导细胞凋亡的信号转导机制,阐述了ROS作为信号分子的特性及硒化合物与ROS作用的化学基础。     

Chemical oscillation of vanadium complexes: Simple and aperiodic systems

An oscillatory chemical reaction is an intriguing phenomenon subject to various and often uncontrollable factors. Many oscillatory systems consist of a strong acid, metal ion and an additional species with accessible oxidation states, and restrictive temperature conditions. Thus, an oscillatory system in which all the factors are understood would be useful. In this paper, we describe the first such system based on vanadium chemistry. The V(IV) complex (pale green color) turns dark orange with the production of a V(V) complex. This reaction is affected by many factors such as oxygen, ultraviolet (UV) irradiation, visible irradiation, and aldehyde addition. This oscillation reaction occurs only in a dichloromethane solution, suggesting that the solvent intervenes in the reaction. Examination of the gas phase during the oscillation reaction revealed the formation of carbon monoxide, carbon dioxide, hydrogen chloride, and phosgene. Based on these observations, we propose a plausible oscillation reaction mechanism.The results of this study contribute to the field of nonlinear dynamics. Additionally, this work offers new insights into vanadium chemistry because this oscillation phenomenon is strongly correlated with the electron transfer reaction of the vanadium complex. Moreover, studies using vanadium complexes may help in understanding vanadium-mediated electron transfer systems in vivo, such as vanadium accumulation and storage observed in marine organisms.     

Antivitamins B12—Some Inaugural Milestones

The recently delineated structure- and reactivity-based concept of antivitamins B₁₂ has begun to bear fruit by the generation, and study, of a range of such B₁₂-dummies, either vitamin B₁₂-derived, or transition metal analogues that also represent potential antivitamins B₁₂ or specific B₁₂-antimetabolites. As reviewed here, this has opened up new research avenues in organometallic B₁₂-chemistry and bioinorganic coordination chemistry. Exploratory studies with antivitamins B₁₂ have, furthermore, revealed some of their potential, as pharmacologically interesting compounds, for inducing B₁₂-deficiency in a range of organisms, from hospital resistant bacteria to laboratory mice. The derived capacity of antivitamins B₁₂ to induce functional B₁₂-deficiency in mammalian cells and organs also suggest their valuable potential as growth inhibitors of cancerous human and animal cells.     

Schwingungsspektren und strukturchemie von heterometall-komplexen und -clustern mit thiometallat-liganden

The thioanions of the early transition metals, e.g. MoOS₃^2?, WOS₃^2?, MoS₄^2? and WS₄^2?, form hetero-metal complexes, which are interesting because of their electronic properties and their relevance to problems of bioinorganic chemistry. Their vibrational spectra are discussed in relation to the molecular structure of the compounds and especially to the wide variety of the coordination types of the thiometalate ligands. It is demonstrated that vibrational spectroscopy (especially Raman and resonance Raman) is a powerful tool for the determination of the local symmetry of the thioanions in polynuclear coordination compounds.     

Anticancer diaminotris(phenolato) vanadium(V) complexes: Ligand-metal interplay

Abstract

Vanadium complexes are attractive candidates for anticancer chemotherapy, although often suffering from rich aqueous chemistry and hydrolytic instability. We have introduced an LVO family of vanadium oxo complexes, L being a diaminotris(phenolato) chlelating ligand, demonstrating high hydrolytic stability in water along with promising in vitro and in vivo efficacy. Herein we analyzed mechanistic aspects of the reactivity of such complexes in cellular environment. A representative complex exhibited high activity toward all lines in the NIH NCI-60 panel, with an average GI₅₀ value of 0.7 ± 0.5 μM, and with a unique reactivity pattern implying a distinct mechanism. Free ligands demonstrated cytotoxicity similar to that of their vanadium complexes, were identified in cells treated with the complex, and induced apoptosis as did the parent complex, all implying their participation as active species. Cell cycle studies pointed to possible arrest mostly at the S phase, with some variations for the complex and ligand on the two lines analyzed. Nevertheless, the vanadium ion apparently accelerated cellular entry, as the activity was evident following markedly shorter periods of incubation with the extracellular complex when compared with the free ligand. The results displayed herein overall highlight the role of the vanadium complex as a pro-drug.     

Preparation of polyethylene in solution

Polyethylene was prepared in a homogeneous system at 120°C. Several catalytic systems were employed, all using a soluble vanadium compound. The first consisted of an alkylaluminum compound in conjunction with the vanadium compound and a “promoter.” This promoter, which is believed to act as an oxidizing agent to reactivate dead catalyst sites, was a polyhalo compound with esters of trichloroacetic acid preferred. The promoter was added continuously throughout the polymerization. Polyethylene so produced had a narrow M?_w/M?_n ratio close to the theoretical ratio of 2.0 for a single catalyst site. Up to 266 polymer chains were produced per vanadium atom. In the second system, the cocatalyst was an AlBr₃(AlCl₃)–(C₆H₅)₄Sn[(C₆H₅)₃Bi] combination. The continuous addition of a promoter such as methyl trichloroacetate was necessary, presumably to reactivate dead catalytic sites. By this procedure, yields up to 6.6 kg of polymer per millimole of vanadium and 30–60 chains per vanadium atom were achieved. The product had a narrow M?_w/M?_n ratio of 2.4 by gel-permeation chromatography (GPC). A study of the interactions of the catalyst compounds indicated that CCl₃COOR does oxidize di- and trivalent vanadium.     

Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone

The review is focused on recent developments of chemistry of synthetic analogs of natural compounds, isoflavone and homoisoflavone. The possible synthetic strategies to access heterocyclic analogs of these compounds starting from readily available 3-formylchromone and its derivatives (3-cyanochromone, 2-amino-3-formylchromone) and products of its condensation with simplest C- and N-nucleophiles are discussed. The structural features of the reaction products that depend on the nature of the reaction medium, structure of the starting compounds, and reagent ratio are considered. Particular attention is given to the application of the modern strategies of organic synthesis, namely green chemistry approaches, click reactions, domino reactions, etc. Examples of compounds of this group most promising for clinical application due to wide and pronounced pharmacological effects are given.

     

History of Solution Chemistry of Japan

An historical view of solution chemistry of Japan is described for a wide range of fields of solution chemistry, which relates to physical chemistry, inorganic chemistry, analytical chemistry, biochemistry and bioinorganic chemistry, and colloid and polymer chemistry. The works by pioneers of Japanese solution chemistry are introduced, some of which are not well recognized internationally. The influences of Japanese solution chemistry on the world and vice versa are discussed on the basis of a rather personal viewpoint. Recent activities of Japanese solution chemists at the national and international levels are also reviewed.     

Application of HPLC to measure vanadium in environmental,biological and clinical matrices

Vanadate and vanadium compounds exist in many environmental, biological and clinical matrices, and despite the need only limited progress has been made on the analysis of vanadium compounds. The vanadium coordination chemistry of different oxidation states is known, and the result of the characterization and speciation analysis depends on the subsequent chemistry and the methods of analysis. Many studies have used a range of methods for the characterization and determination of metal ions in a variety of materials. One successful technique is high performance liquid chromatography (HPLC) that has been used mainly for measuring total vanadium level and metal speciation. Some cases have been reported where complexes of different oxidation states of vanadium have been separated by HPLC. Specifically reversed phase (RP) HPLC has frequently been used for the measurement of vanadium. Other HPLC methods such as normal phase, anion-exchange, cation-exchange, size exclusion and other RP-HPLC modes such as, ion-pair and micellar have been used to separate selected vanadium compounds. We will present a review that summarizes and critically analyzes the reported methods for analysis of vanadium salts and vanadium compounds in different sample matrices. We will compare various HPLC methods and modes including sample preparation, chelating reagents, mobile phase and detection methods. The comparison will allow us to identify the best analytical HPLC method and mode for measuring vanadium levels and what information such methods provide with regard to speciation and quantitation of the vanadium compounds.     

Solution structure of Vanabin2, a vanadium(IV)-binding protein from the vanadium-rich ascidian Ascidia sydneiensis samea

Ascidians belonging to the suborder Phlebobranchia are known to accumulate high levels of a transition metal, vanadium, in their blood cells, called vanadocytes, although the mechanism for this biological phenomenon remains unclear. Recently, we identified vanadium(IV)-binding proteins, designated as Vanabins, from vanadium-accumulating ascidians. Here, we report the first 3D structure of Vanabin2 from an ascidian, Ascidia sydneiensis samea, in an aqueous solution. The structure revealed a novel bow-shaped conformation, with four alpha-helices connected by nine disulfide bonds. There are no structural homologues reported so far. The 15N heteronuclear single-quantum coherence (HSQC) perturbation experiments of Vanabin2 indicated that vanadyl cations, which are exclusively localized on the same face of the molecule, are coordinated by amine nitrogens derived from amino acid residues such as lysines, arginines, and histidines, as suggested by the electron paramagnetic resonance (EPR) results. The present NMR studies provide information that will contribute toward elucidating the mechanism of vanadium accumulation in ascidians.     

Oxovanadium(IV,V) Complexes with 2‐Acetylpyridine‐2‐furanoylhydrazone (Hapf) as Ligand. X‐Ray Crystal Structures of [VO2(apf)] and [V2O2(μ‐O)2(apf)2]

The preparation of oxovanadium(IV, V) coordination compounds with 2‐acetylpyridine‐2‐furanoylhydrazone (Hapf) is described. [VO(apf)(acac)] was prepared from oxovanadium(IV) diacetylacetonate [VO(acac)₂] by reaction with Hapf in methanol or dichloromethane. The complex is paramagnetic and its EPR spectrum is consistent with an octahedral coordination for the vanadium(IV) atom. Voltammetry studies of [VO(apf)(acac)] indicate an irreversible oxidation, in agreement with the chemical behavior of the compound in solution. The vanadium(IV) complex undergoes slow oxidation in alcoholic solution, losing the acetylacetonate ligand to form [VO₂(apf)] and [V₂O₂(μ‐O)₂(apf)₂]. The crystal structures of these last compounds were determined by X‐ray diffraction methods. [V₂O₂(μ‐O)₂(apf)₂] crystallizes monoclinic [P2₁/c, Z = 2, a = 817.400(10), b = 1650.90(3), c = 984.70(2) pm, β = 112.7190(10)°]. The crystal structure consists of dimeric units, in which two μ‐oxo ligands subtend asymmetric bridges between the vanadium atoms in a very distorted octahedral coordination. In the crystal of [VO₂(apf)], orthorhombic [Pnma, Z = 4, a = 1630.000(10), b = 675.10(4), c = 1136.40(2) pm], the vanadium(V) atom is pentacoordinated.