Therapeutic use of hyaluronan

Hyaluronan used today as a therapeutic agent in human and animal medicine must be in a highly purified form, free of immunologically active protein molecules, from endotoxin and from inflammatory molecules originating from the tissues or bacterial cultures—the source of hyaluronan. All hyaluronans, whether in liquid or in covalently crosslinked gel form, must have certain elastoviscous properties to be usable for current therapeutic applications. Elastoviscous properties are especially important in the ophthalmic viscosurgical use. The metabolism of hyaluronan is very fast in most tissues, except in the vitreus. The ability of injected hyaluronan with a short half-life time in the joint to accomplish long-lasting analgesia represents a challenge for the design of the various products. The history of the therapeutic use of hyaluronan and its present status is described, with emphasis on its use in ophthalmic surgery and for a long-lasting analgesia in arthritic joints in humans and animals. The use of hyaluronan gels is described in viscoaugmentation as injected into the dermal layer of the skin. Hyaluronan gels were also used as viscosupplements injected into sphincter muscles to improve their function in aging or disease. The use of hyaluronan and its gel for drug delivery was suggested several decades ago, and is also mentioned.     

The role of hyaluronan in the structure and function of the biomatrix of connective tissues

This review focuses on the only polysaccharide compartment of the biomatrix of connective tissues: hyaluronan. This pure polysaccharide is present in the largest amount and highest concentration in three connective tissues of the adult vertebrate body: the vitreus of the eye, the synovial fluid of the joint, and the dermis of the rooster comb. The molecular properties, weight average molecular weight, polydispersity, and elastoviscous properties of hyaluronan, as well as its distribution in these biomatrices, are presented. The differences and similarities in the biological function of this polysaccharide in the biomatrix are discussed. The effect of aging on the hyaluronan content of the vitreus, synovial fluid, and the dermis of human skin is also presented.

Stability against aggregation of bovine casein micelles in the presence of acidic and alkaline gelatin

The effect of the presence of colloidal dispersed and molecular dispersed acidic (type A) and alkaline (type B) gelatins with similar molecular weight and size but different isoelectric points (7.9 and 4.9) on the stability against aggregation of bovine casein micelles was investigated by turbidimetric titration and laser techniques, over a wide range of biopolymers concentrations, gelatin/casein ratio in the initial mixture (0.03–20), pH (4.9–6.7) and ionic strength (10⁻³(milk salts)–1.0 NaCl), using glucono-δ-lactone (GL) as acidifier. Aggregates of acid gelatin A interact with the oppositely charged micellar casein at an ionic strength of around 10⁻³(milk salts) and pH 6.7 resulting in the formation of an electroneutral complex by ionic bonds between the carboxyl groups of casein and the amino groups of the gelatin molecules. The complexes obtained are polynuclear, the aggregation of which is not as sensitive to pH as that of free casein micelles. Aggregation of such complexes is the result of bridging flocculation. The “molar” ratio gelatin aggregates/casein micelles in the mixed aggregates is 4/1. The complexes are formed and stabilised via electrostatic interaction rather than through hydrogen bonds or hydrophobic interaction. In the presence of an excess of gelatin molecules in the initial mixture a charged gelatin–casein complex forms and some dissociation of casein micelles occurs and, as a consequence, soluble complexes are obtained. During the addition of alkaline gelatin B aggregates to the micellar casein solution and subsequent acidification of the mixture by GL, no effect of the presence of gelatin B on the stability of micellar casein was observed. Received: 28 March 2000 Accepted: 5 October 2000     

Supramolecular Proteoglycan Aggregate Mimics: Cyclodextrin‐Assisted Biodegradable Polymer Assemblies for Electrostatic‐Driven Drug Delivery

Self‐assembled, noncovalent polymeric biodegradable materials mimicking proteoglycan aggregates were synthesized from inclusion complexes of cationic surfactants with γ‐cyclodextrin and the natural anionic polymer hyaluronan. The amorphous structure of this ternary system was proven by X‐ray diffraction and thermal analysis. Light‐scattering measurements showed that there was a competition between hyaluronic acid and the surfactant for the cyclodextrin cavity. These self‐assembled supramolecular matrices were loaded with both hydrophilic and lipophilic drug substances for dissolution studies. The release of the entrapped drugs was found to be controlled by cations in the surrounding media and by biodegradation. Slow drug release in an ion‐free medium became faster in physiological salt solution in which the macroscopic polymer matrix was disassembled. In contrast, the enzymatic degradation of hyaluronan was hindered in the polymeric matrix. The supramolecular systems consisting of γ‐cyclodextrin as a macrocyclic host, a cationic surfactant guest, and hyaluronic acid as the anionic polymer electrostatically cross‐linked by the inclusion complex of the first two was found to be a novel drug‐delivery system for the controlled release of traditional drugs such as curcumin and ketotifen and proteins such as bovine serum albumin.     

The network gel polymer electrolyte based on poly(acrylate-co-imide) and its transport properties in lithium ion batteries

Poly (acrylate-co-imide)-based gel polymer electrolytes are synthesized by in situ free radical polymerization. Infrared spectroscopy confirms the complete polymerization of gel polymer electrolytes. The ionic conductivity of gel polymer electrolytes are measured as a function of different repeating EO units of polyacrylates. An optimal ionic conductivity of the poly (PEGMEMA₁₁₀₀-BMI) gel polymer electrolyte is determined to be 4.8 × 10^–3 S/cm at 25 °C. The lithium transference number is found to be 0.29. The cyclic voltammogram shows that the wide electrochemical stability window of the gel polymer electrolyte varies from −0.5 to 4.20 V (vs. Li/Li⁺). Furthermore, we found the transport properties of novel gel polymer electrolytes are dependent on the EO design and are also related to the rate capability and the cycling ability of lithium polymer batteries. The relationship between polymer electrolyte design, lithium transport properties and battery performance are investigated in this research.     

The complexation efficiency

Studies have shown that cyclodextrins form both inclusion and non-inclusion complexes and that several different types of complexes can coexist in aqueous solutions. In addition, both cyclodextrins and cyclodextrin complexes are known to form aggregates and it is thought that these aggregates are able to solubilize drugs through micellar-type mechanism. Thus, stability constants determined from phase-solubility profiles are rarely true stability constants for of some specific drug/cyclodextrin complexes. A more precise method for evaluation of the solubilizing effects of cyclodextrins is to determine their complexation efficiency (CE). CE can be determined by measuring the solubility of a given drug at 2–3 cyclodextrin concentrations in pure water or a medium constituting the pharmaceutical formulation such as parenteral solution or aqueous eye drop formulation. Based on the CE value the drug:cyclodextrin ratio in the complexation medium can be determined as well as the increase in the formulation bulk in a solid dosage form. Determination of CE is a simple method for quick evaluating the solubilizing effects of different cyclodextrins and/or the effects of excipients on the solubilization. Here we report the CE of 43 different drugs with mainly 2-hydroxypropyl-β-cyclodextrin but also with randomly methylated β-cyclodextrin as well as few other cyclodextrins. Calculation of CE, drug:cyclodextrin molar ratio and the increase in the formulation bulk is discussed, as well as the influence of the intrinsic solubility and drug lipophilicity on the CE.     

Oxorhenium(V) complexes with tetradentate NSNO pyridylthioazophenolates: syntheses, spectral and electrochemical studies

A family of oxorhenium(V) complexes of newly designed pyridylthioazophenolate ligands has been synthesized and isolated in pure form. The solid state structure of an organic compound (HL1) has been established by X-ray crystallography. The molecular structure observed in the solid state is that the two molecules of the ligand (HL1) in the asymmetric unit have similar geometries, except for the orientation of the pyridine ring. This series of organic moieties acts as tetradentate monobasic NSNO donor chelators in oxorhenium(V) complexes which has been characterized by elemental analyses, IR, ¹H-NMR, UV–Vis. The complexes are 1:1 electrolytes in nature in MeOH solution, the counter anion being ClO ₄ ⁻ . The electrochemical studies of the [Re^VO(L)Cl]ClO₄ complexes in MeCN using TBAP as supporting electrolyte exhibit quasi-reversible voltammogram showing one-electron couple for [Re^VIO(L)Cl]²⁺−[Re^VO(L)Cl]⁺ in the 1.11–1.29 V vs SCE range.     

Phototransformations of selected pharmaceuticals under low-energy UVA–vis and powerful UVB–UVA irradiations in aqueous solutions—the role of natural dissolved organic chromophoric material

The kinetics of simulated low-energy daylight (UVA–vis) and powerful combined ultraviolet B and A (UVB–UVA) induced direct and indirect phototransformations of four pharmaceuticals, i.e., ibuprofen, metoprolol, carbamazepine, and warfarin, which were investigated in dilute solutions of pure laboratory and natural humic waters. The results strengthen the essential function of natural chromophores in dissolved organic material (CDOM) as principal photosensitizer toward indirect phototransformations of pharmaceuticals in natural conditions under available low-energy UVA–vis and slight UVB radiations. The results confirmed that organic micropollutants are able to undergo a direct photolysis if their absorbance spectra overlap the spectral range of the available radiation but only if the radiation is strong enough, e.g., ibuprofen is able to undergo only indirect photolysis via different pathways in all realistic conditions. The action of nitrate anions as photosensitizers in the applied conditions proved to be of little importance. High-performance size-exclusion chromatographic experiments verified that the rate constants obtained under the low-energy UVA–vis and powerful UVB–UVA irradiations for the decreased amounts of the two largest molecular size fractions of CDOM were quite close to the rate constants detected for the increased amounts of the next five molecular size fractions with smaller molecular sizes. The decreased contents of the two largest molecular size fractions correlated quite well with the decreased contents of the studied pharmaceuticals under the low-energy UVA–vis irradiation process but somewhat less under the powerful UVB–UVA irradiation. The photochemically induced decomposition of the CDOM aggregates appears to increase the amounts of smaller molecular size fractions and simultaneously produce via CDOM-stimulated radical reactions indirect structural transformations of pharmaceuticals. Apparent quantum yields were estimated for the transformation–degradation of the two largest molecular-size CDOM aggregates under low-energy UVA–vis and powerful UVB–UVA irradiations. Figure Structural difference between CDOM and pharmaceuticals studies     

Cationic conjugated polymers for homogeneous and sensitive fluorescence detection of hyaluronidase

The cationic charged water-soluble polyfluorenes containing 2,1,3-benzothiadiazole (BT) units (P1–3) have been synthesized and characterized. These polymers demonstrate intramolecular energy transfer from the fluorene units to the BT sites when oppositely charged hyaluronan is added due to the formation of electrostatic complexes, followed by a shift in emission color from blue to green or brown. Upon adding hyaluronidase, the hyaluronan is cleaved into fragments. The relatively weak electrostatic interactions of hyaluronan fragments with polyfluorenes keep their main chains separated and energy transfer from the fluorene units to the BT sites is inefficient, and the polyfluorenes recover their blue emissions. The complexes of conjugated polymers/hyaluronan can be utilized as probes for sensitive and facile fluorescence assays for hyaluronidase. The new assay method interfaces with the aggregation and light harvesting properties of conjugated polymers. Supported by the “100 Talents” Program of Chinese Academy of Sciences, the National Natural Science Foundation of China (Grant Nos. 20725308 & 20721061), and 973 Project (Grant Nos. 2006CB806200 & 2006CB932100)     

Study of the Ternary Complex Formation Between Vanadium(III), Dipicolinic Acid and Small Blood Serum Bioligands

Ternary complex formation reactions were studied between vanadium(III), dipicolinic acid and small molecular weight blood serum components: lactic, oxalic, citric and ortophosphoric acids. The electromotive force measurement permitted us to determine the chemical speciation of the complexes formed. In the vanadium(III)–dipicolinic acid–lactic acid system the complexes detected were: V(dipic)(lac), V(dipic)(lac)(OH)⁻ and V(dipic)(lac)(OH)₂^2-(\mathrm{OH})_{2}^{2-}. In the vanadium(III)–dipicolinic acid–oxalic acid system the observed complexes were: V(dipic)(ox)⁻, V(dipic)(ox)(Hox)²⁻ and V(dipic)(ox)₂^3-(\mathrm{ox})_{2}^{3-}. In the vanadium(III)–dipicolinic acid–citric acid system the complexes V(dipic)(Hcit)⁻, V(dipic)(cit)²⁻, V(dipic)(cit)(OH)³⁻, V(dipic)(cit)(OH)₂^4-(\mathrm{OH})_{2}^{4-} and V(dipic)(cit)(OH)₃^5-(\mathrm{OH})_{3}^{5-} were detected. Finally in the vanadium(III)–dipicolinic acid–phosphoric acid system the complexes V(dipic)(H₂PO₄) and V(dipic)(HPO₄)⁻ were observed. The UV-vis spectra allowed us to perform a qualitative characterization of the complexes formed in aqueous solution.     

Free energy calculations offer insights into the influence of receptor flexibility on ligand–receptor binding affinities

Docking algorithms for computer-aided drug discovery and design often ignore or restrain the flexibility of the receptor, which may lead to a loss of accuracy of the relative free enthalpies of binding. In order to evaluate the contribution of receptor flexibility to relative binding free enthalpies, two host–guest systems have been examined: inclusion complexes of α-cyclodextrin (αCD) with 1-chlorobenzene (ClBn), 1-bromobenzene (BrBn) and toluene (MeBn), and complexes of DNA with the minor-groove binding ligands netropsin (Net) and distamycin (Dist). Molecular dynamics simulations and free energy calculations reveal that restraining of the flexibility of the receptor can have a significant influence on the estimated relative ligand–receptor binding affinities as well as on the predicted structures of the biomolecular complexes. The influence is particularly pronounced in the case of flexible receptors such as DNA, where a 50% contribution of DNA flexibility towards the relative ligand–DNA binding affinities is observed. The differences in the free enthalpy of binding do not arise only from the changes in ligand–DNA interactions but also from changes in ligand–solvent interactions as well as from the loss of DNA configurational entropy upon restraining.     

Preparing undoped and Mn-doped ZnO nanoparticles: a comparison between sol–gel and gel-combustion methods

Undoped and Mn doped ZnO nanoparticles were synthesized by two wet chemical techniques: sol–gel and gel-combustion. We were able to prepare Mn-doped ZnO nanoparticles free from the second phases at calcining temperatures 400 and 500 °C using sol–gel and gel combustion, respectively. Complete crystallization occurs in both methods, but it is found that the crystallization is better performed in the ZnO based solid solution prepared by the sol–gel method. TEM images show that the average size of the nanoparticles synthesized by gel-combustion is smaller than that of prepared by sol–gel method. Optical characterizations such as vibrational properties, lattice dynamical parameters, absorption edges and optical band gap energies were also carried out by FTIR and UV–Vis spectroscopies. The quantitative estimations led to the conclusion that the effects of the method on the particle size and the optical band gap energy of the prepared samples are very significant.     

Dynamics of hyaluronan aqueous solutions as assessed by fast field cycling NMR relaxometry

Fast field cycling (FFC) NMR relaxometry has been used to study the conformational properties of aqueous solutions of hyaluronan (HYA) at three concentrations in the range 10 to 25 mg mL^–1. Results revealed that, irrespective of the solution concentration, three different hydration layers surround hyaluronan. The inner layer consists of water molecules strongly retained in the proximity of the HYA surface. Because of their strong interactions with HYA, water molecules in this inner hydration layer are subject to very slow dynamics and have the largest correlation times. The other two hydration layers are made of water molecules which are located progressively further from the HYA surface. As a result, decreasing correlation times caused by faster molecular motion were measured. The NMRD profiles obtained by FFC-NMR relaxometry also showed peaks attributable to ¹H–¹⁴N quadrupole interactions. Changes in intensity and position of the quadrupolar peaks in the NMRD profiles suggested that with increasing concentration the amido group is progressively involved in the formation of weak and transient intramolecular water bridging adjacent hyaluronan chains. In this work, FFC-NMR was used for the first time to obtain deeper insight into HYA–water interactions and proved itself a powerful and promising tool in hyaluronan chemistry.     

Influence of coagulant and free stabilizer on formation of aggregates in magnetic fluids

The influence of coagulant (isopropanol) and free oleic acid on the formation of quasi-spherical aggregates in a colloidal magnetite solution in kerosene is studied experimentally. It is revealed that the mean sizes of these aggregates fit the 60–90-nm range and are independent of the concentrations of coagulant and free oleic acid provided that these concentrations do not exceed 10–12 vol %. The independence of the mean sizes of aggregates on temperature and disperse composition of particles is considered as a supplementary argument in favor of hypothesis that the main reason for their formation are the defects of protective layers, whereas magnetodipole interactions play a secondary role. It is shown that an excess of oleic acid causes a disproportional decrease in the initial susceptibility of magnetic fluid that is interpreted as a result of the formation of droplet aggregates with characteristic sizes of a few micrometers or more. Apparently, isopropanol leads to an analogous effect, but only at low temperatures.     

Separation and characterization of aggregated species of amyloid-beta peptides

We have investigated the use of isoelectric focusing and immunodetection for the separation of low molecular weight species of amyloid-beta (Aβ) peptides from their aggregates. From solutions of Aβ_1–40 or Aβ_1–42 monomeric peptides, low molecular weight material appeared at a pI value of ca. 5, while the presence of aggregates was detected as bands, observed at a pI of 6–6.5. The formation of Aβ aggregates (protofibrils) was verified by a sandwich ELISA, employing the protofibril conformation-selective antibody mAb158. In order to study the aggregation behavior when using a mixture of the monomers, we utilized the IEF separation combined with Western blot using two polyclonal antisera, selective for Aβ_1–40 and Aβ_1–42, respectively. We conclude that both monomers were incorporated in the aggregates. In a further study of the mixed aggregates, we used the protofibril conformation-selective antibody mAb158 for immunoprecipitation, followed by nanoelectrospray mass spectrometry (IP-MS). This showed that the Aβ_1–42 peptide is incorporated in the aggregate in a significantly larger proportion than its relative presence in the original monomer composition. IP-MS with mAb158 was also performed, and compared to IP-MS with the Aβ-selective antibody mAb1C3, where a monomeric Aβ_1–16 peptide was added to the protofibril preparation. Aβ_1–16 is known for its poor aggregation propensity, and acted therefore as a selectivity marker. The results obtained confirmed the protofibril conformation selectivity of mAb158.     

Investigation of DNA cleavage activities of new oxime-type ligand complexes and molecular modeling of complex-DNA interactions

Nucleolytic activities of some new oxime-type ligand complexes were investigated by neutral agarose gel electrophoresis. Analysis of the cleavage products in agarose gel indicated that all complexes used converted supercoiled pUC18 plasmid DNA to its nicked or linear form. It was found that nucleolytic activities of the complexes depend on the complex concentration, reaction time and the presence of a cooxidant (magnesium monoperoxyphthalate, MMPP) in the reaction mixture. However, the complexes cleaved pUC18 plasmid DNA at all investigated pH values. Nucleolytic activities of complexes were investigated for different complex concentrations (0.1–100 μmol L⁻¹), pH values (6.0–10.0) and reaction times (0–60 min). Molecular modeling studies performed by the Hyperchem Software together with DNA-binding studies showed that planar sites of the complexes intercalated into double stranded DNA. It can be concluded that all oxime-type ligand complexes used can be evaluated as nuclease mimics.     

Strong emitting sol–gel materials based on interaction of luminescence dyes and lanthanide complexes with silver nanoparticles

We show here how luminescence of fluorescent dyes and lanthanide complexes in sol–gel matrix can be intensified as a result of interaction of the species with silver nanoparticles. Preparation of silver nanoparticles in sol–gel composite precursor is outlined and their structural characterization are presented. Zirconia-glymo and Glymo-polyurethane-silica were used as host matrices for silver nanoparticles and the fluorescence species. The intensification of fluorescence was demonstrated by steady state spectroscopy.     

Influence of ligand binding on the conformation of Torpedo californica acetylcholinesterase

With the aim of identifying structural changes in acetylcholinesterase, induced by ligand binding, we use a completely automatic procedure to analyse the differences between the backbone conformation of the free enzyme and those in eight complexes of Torpedo californica acetylcholinesterase, with various quaternary ammonium ligands, and with the protein inhibitor fasciculin. In order to discriminate between structural changes due to ligand binding and those arising from model imprecision, we also examine protein–ligand and protein–water contacts. Except for the peptide flip in the complex with huperzine A, the backbones of other complexes with quaternary ammonium ligands display negligible changes relative to the free enzyme. Another exception is the complex with the bisquaternary ammonium ligand decamethonium, where several loops display above average deformations, but only two, those spanning residues 334–348 and residues 277–304, seem to move as a result of ligand binding. Movement of the ω loop (residues 61–95) is detected only in the complex with the protein fasciculin. Received: 21 July 2000 / Accepted: 18 September 2000 / Published online: 28 February 2001     

Mass spectrometric identification and characterization of antimony complexes with ribose-containing biomolecules and an RNA oligomer

Mass spectrometric techniques have been used to study the interaction of inorganic Sb(V) with biomolecules containing a ribose or deoxyribose moiety. Electrospray (ES) mass spectra of reaction mixtures containing inorganic Sb(V) and one of several biomolecules (adenosine, cytidine, guanosine, uridine, adenosine-5′-monophosphate, adenosine-3′,5′-cyclic monophosphate, ribose, or 2′-deoxyadenosine) afforded high-mass antimony-containing ions corresponding to Sb(V)–biomolecule complexes of stoichiometry 1:1, 1:2, or 1:3. The complexes were characterized by collision-induced dissociation (CID) tandem mass spectrometry (MS) using ion-trap multistage MS. The CID results revealed that Sb(V) binds to the ribose or deoxyribose moiety. Structures are proposed for the Sb–biomolecule complexes. Analysis of the reaction mixtures by reversed-phase chromatography coupled on-line to either inductively coupled plasma (ICP) MS or ES–MS showed that in solution Sb(V) forms complexes with all the analyzed biomolecules with vicinal cis hydroxyl groups. Evidence (from size-exclusion chromatography ICP–MS and direct infusion ES–MS) of complexation of Sb(V) with an RNA oligomer, but not with a DNA oligomer, supports the suggestion that the presence of vicinal cis hydroxyl groups is critical for complexation to occur. This is the first direct evidence of complexation of Sb(V) with RNA. Results obtained by studying the effect of changing reaction conditions, i.e. pH, reaction time, and Sb/biomolecule molar ratio, on the extent of Sb–biomolecule formation suggest the reaction may be of physiological importance. Selected reaction monitoring (SRM) and precursor-ion-scanning tandem MS were investigated to determine their potential to detect trace levels of the Sb–biomolecule complexes in biological samples. Application of SRM MS–MS in combination with high-performance liquid chromatography enabled successful detection of an Sb–adenosine complex that had been spiked into a complex biological matrix (liver homogenate).Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Speciation of the Ternary Complexes of Vanadium(III)–Dipicolinic Acid and the Amino Acids Cysteine,Histidine, Aspartic and Glutamic Acids in 3.0 mol⋅dm<Superscript>−3</Superscript> KCl at 25 °C

In this work we present results for the speciation of the ternary complexes formed in the aqueous vanadium(III)–dipicolinic acid and the amino acids cysteine (H₂cys), histidine (Hhis), aspartic acid (H₂asp) and glutamic acid (H₂glu) systems (25 °C; 3.0 mol⋅dm⁻³ KCl as ionic medium), determined by means of potentiometric measurements. The potentiometric data were analyzed with the least-squares program LETAGROP, taking into account the hydrolysis of vanadium(III), the acid-base reactions of the ligands, and the binary complexes formed. Under the experimental conditions (vanadium(III) concentration = 2–3 mmol⋅dm⁻³ and vanadium(III): dipicolinic acid: amino acid molar ratio 1:1:1, 1:1:2 and 1:2:1), the following species [V(dipic)(H₂asp)]⁺, [V(dipic)(Hasp)], [V(dipic)(asp)]⁻, [V(dipic)(asp)(OH)]²⁻, and [V(dipic)(asp)(OH)₂]³⁻ were found in the vanadium(III)–dipicolinic acid–aspartic acid system. In the vanadium(III)–dipicolinic acid–glutamic acid system [V(Hdipic)(H₂glu)]²⁺, [V(dipic)(H₂glu)]⁺, [V(dipic)(Hglu)], [V(dipic)(Hglu)(OH)]⁻, and [V(dipic)(Hglu)(OH)₂]²⁻ were observed. In the vanadium(III)–dipicolinic acid–cysteine system the complexes [V(dipic)(H₂cys)]⁺, [V(dipic)(Hcys)], [V(dipic)(cys)]⁻, and [V(dipic)(cys)(OH)]²⁻ were present. And finally, in the vanadium(III)–dipicolinic acid–histidine system the complexes [V(Hdipic)(Hhis)]²⁺, [V(dipic) (Hhis)]⁺[\mathrm{V}(\mathrm{dipic}) (\mathrm{Hhis})]^{+}, [V(dipic)(his)], [V(dipic)(his)(OH)]⁻, and [V(dipic)(his)(OH)₂]²⁻ were observed. The stability constants of these complexes were determined. The species distribution diagrams as a function of pH are briefly discussed.