A unique ternary Ce(III)-quercetin-phenanthroline assembly with antioxidant and anti-inflammatory properties.

Quercetin is one of the most bioactive and common dietary flavonoids, with a significant repertoire of biological and pharmacological properties. The biological activity of quercetin, however, is influenced by its limited solubility and bioavailability. Driven by the need to enhance quercetin bioavailability and bioactivity through metal ion complexation, synthetic efforts led to a unique ternary Ce(III)-quercetin-(1,10-phenanthroline) (1) compound. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetric analysis (TGA), UV-Visible, NMR, Electron Spray Ionization-Mass Spectrometry (ESI-MS), Fluorescence, X-rays) revealed its solid-state and solution properties, with significant information emanating from the coordination sphere composition of Ce(III). The experimental data justified further entry of 1 in biological studies involving toxicity, (Reactive Oxygen Species, ROS)-suppressing potential, cell metabolism inhibition in Saccharomyces cerevisiae (S. cerevisiae) cultures, and plasmid DNA degradation. DFT calculations revealed its electronic structure profile, with in silico studies showing binding to DNA, DNA gyrase, and glutathione S-transferase, thus providing useful complementary insight into the elucidation of the mechanism of action of 1 at the molecular level and interpretation of its bio-activity. The collective work projects the importance of physicochemically supported bio-activity profile of well-defined Ce(III)-flavonoid compounds, thereby justifying focused pursuit of new hybrid metal-organic materials, effectively enhancing the role of naturally-occurring flavonoids in physiology and disease.

The aqueous structural speciation of binary thallium-hydroxycarboxylic acid systems. Structure-chemical (bio)reactivity correlations.

Among transition and non-transition metals, thallium is a unique case of an element which, despite its known toxicity, provides interesting challenges through its biology and chemistry linked to diagnosis of human pathophysiologies. Poised to investigate in-depth the structural and electronic aspects of thallium involvement in physiological processes, the synthetic exploration of aqueous binary systems of Tl(I) with physiological binders from the family of hydroxycarboxylic acids (glycolic, lactic, mandelic and citric acid) was pursued in a pH-specific fashion. The isolated crystalline coordination polymers, emerging from that effort, were physicochemically characterized through elemental analysis, FT-IR, ESI-MS, 1H-/13C-NMR, and X-ray crystallography. The coordination environment of thallium in each molecular Tl(I) assembly, along with lattice dimensionality (2D3D), reflects the contributions of the ligands, collectively exemplifying interactions probed into though BVS and Hirshfeld surface analysis. The results portray a well-defined solid-state and solution profile for all species investigated, thereby providing the basis for their subsequent selection into in vitro biological studies involving the (patho)physiological cell lines 3T3-L1, Saos-2, C2C12, and MCF-7. Biotoxicity profiles, encompassing cell viability, morphology, and cell growth support clearly a concentration-, time-, and cell tissue-specific behavior for the chosen Tl(I) compounds in a structure-specific fashion. Collectively, the chemical experimental data support the biological results in formulating a structure-specific behavior for Tl(I)-hydroxycarboxylato species with respect to biotoxicity mechanisms in a (patho)physiological environment. The accrued knowledge stands as the foreground for further investigation into the relevant biological chemistry of Tl(I) and molecular technologies targeting its sequestration and removal from cellular media.

Ciprofloxacin conjugated to diphenyltin(IV): a novel formulation with enhanced antimicrobial activity.

The metalloantibiotic of formula Ph2Sn(CIP)2 (CIPTIN) (HCIP = ciprofloxacin) was synthesized by reacting ciprofloxacin hydrochloride (HCIP·HCl) (an antibiotic in clinical use) with diphenyltin dichloride (Ph2SnCl2DPTD). The complex was characterized in the solid state by melting point, FT-IR, X-ray Powder Diffraction (XRPD) analysis, 119Sn Mössbauer spectroscopy, X-ray Fluorescence (XRF) spectroscopy, and Thermogravimetry/Differential Thermal Analysis (TG-DTA) and in solution by UV-Vis, 1H NMR spectroscopic techniques and Electrospray Ionisation Mass Spectrometry (ESI-MS). The crystal structure of CIPTIN and its processor HCIP was also determined by X-ray crystallography. The antibacterial activity of CIPTIN, HCIP·HCl, HCIP and DPTD was evaluated against the bacterial species Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZs). CIPTIN shows lower MIC values than those of HCIP·HCl (up to 4.2-fold), HCIP (up to 2.7-fold) or DPTD (>135-fold), towards the tested microbes. CIPTIN is classified into bactericidal agents according to MBC/MIC values. The developing IZs are 40.8 ± 1.5, 34.0 ± 0.8, 36.0 ± 1.1 and 42.7 ± 0.8 mm, respectively which classify the microbes P. aeruginosa, E. coli, S. aureus and S. epidermidis to susceptible ones to CIPTIN. These IZs are greater than the corresponding ones of HCIP·HCl by 1.1 to 1.5-fold against both the tested Gram negative and Gram positive bacteria. CIPTIN eradicates the biofilm of P. aeruginosa and S. aureus more efficiently than HCIP·HCl and HCIP. The in vitro toxicity and genotoxicity of CIPTIN were tested against human skin keratinocyte cells (HaCaT) (IC50 = 2.33 µM). CIPTIN exhibits 2 to 9-fold lower MIC values than its IC50 against HaCaT, while its genotoxic effect determined by micronucleus assay is equivalent to the corresponding ones of HCIP·HCl or HCIP.

Binary-ternary Cd(II)-(hydroxycarboxylic acid)-(aromatic chelator) systems exhibit in vitro cytotoxic selectivity in a tissue-specific manner.

Cadmium is a metallotoxin, amply encountered in the environment and derived through physical and anthropogenic activities. Its entry in various organisms leads through water and the food chain to humans, thereby inducing a plethora of pathophysiologies. Delineation of the interactive role of cadmium with physiological and physiologically relevant substrates, requires well-defined forms of cadmium arising from such interactions along with the ensuing chemical reactivity amounting to toxic manifestations and health aberrations. To implement such efforts, low molecular mass substrate metal ion binders are needed, forming species with enhanced solubility and bioavailability. To that end, α-hydroxy isobutyric acid (HIBAH2) was used in pH-specific synthetic efforts involving bulky aromatic chelators 2,2'-bipyridine (2,2'-bipy) and 1,10-phenanthroline (phen), thus leading to new crystalline materials [Cd(C4H7O3)2]n(1), [Cd(C4H7O3)2(H2O)2](2), [{Cd2(C4H7O3)2(C10H8N2)2(H2O)2}(NO3)2]n·nH2O(3), and [{Cd2(C4H7O3)2(C12H8N2)2(H2O)2}(NO3)2]n·2nH2O(4), which were physicochemically characterized (elemental analysis, FT-IR, NMR, ESI-MS, and X-ray crystallography) in the solid state and solution. Their physicochemical characteristics led to their employment in tissue-specific biological toxicity studies in three different cell lines. Their toxicity profile (cell viability, morphology, chemotacticity) was correlated through genetic biomarkers to apoptotic-necrotic processes, thereby shedding light on cadmium cellular toxicity processes. Finally, the cytoprotective action of specific chelators was examined, lending credence to the notion that appropriately structured chelators and antioxidants may be used as effective deterrent to cadmium toxicity. Collectively, structure-specificity linked to tissue-specific toxicity profiling in well-defined binary-ternary Cd(II)-HIBAH2 systems exemplifies that metal ion's aberrant interactions in the cellular milieu, meriting further probing into the development of efficient chelators in cadmium detoxification.

In-depth synthetic, physicochemical and in vitro biological investigation of a new ternary V(IV) antioxidant material based on curcumin.

Curcumin is a natural product with a broad spectrum of beneficial properties relating to pharmaceutical applications, extending from traditional remedies to modern cosmetics. The biological activity of such pigments, however, is limited by their solubility and bioavailability, thereby necessitating new ways of achieving optimal tissue cellular response and efficacy as drugs. Metal ion complexation provides a significant route toward improvement of curcumin stability and biological activity, with vanadium being a representative such metal ion, amply encountered in biological systems and exhibiting exogenous bioactivity through potential pharmaceuticals. Driven by the need to optimally increase curcumin bioavailability and bioactivity through complexation, synthetic efforts were launched to seek out stable species, ultimately leading to the synthesis and isolation of a new ternary V(IV)-curcumin-(2,2'-bipyridine) complex. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetry (TGA), UV-Visible, NMR, ESI-MS, Fluorescence, X-rays) portrayed the solid-state and solution properties of the ternary complex. Pulsed-EPR spectroscopy, in frozen solutions, suggested the presence of two species, cis- and trans-conformers. Density Functional Theory (DFT) calculations revealed the salient features and energetics of the two conformers, thereby complementing EPR spectroscopy. The well-described profile of the vanadium species led to its in vitro biological investigation involving toxicity, cell metabolism inhibition in S. cerevisiae cultures, Reactive Oxygen Species (ROS)-suppressing capacity, lipid peroxidation, and plasmid DNA degradation. A multitude of bio-assays and methodologies, in comparison to free curcumin, showed that it exhibits its antioxidant potential in a concentration-dependent fashion, thereby formulating a bioreactivity profile supporting development of new efficient vanado-pharmaceuticals, targeting (extra)intra-cellular processes under (patho)physiological conditions.

In vitro structure-specific Zn(II)-induced adipogenesis and structure-function bioreactivity correlations.

The advent of Zn(II) metallodrugs in metabolic syndrome pathologies generates a strong challenge toward synthetic endeavors targeting well-defined, atoxic and biologically active binary/ternary species of Zn(II). Proper formulation of that metal ion's coordination sphere sets the stage for construction of appropriately configured Schiff ligands based on tromethamine and variably modified vanillin core components. The arising Schiff ligands react with Zn(II) in a defined stoichiometry, thereby delivering new binary Zn(II)-L species with defined physicochemical properties. Analytical (elemental), spectroscopic (FT-IR, Thermogravimetric Analysis) and crystallographic techniques attest to the distinct nature of the derived binary-ternary materials, bearing defined Zn(II):L molecular stoichiometry, variable nuclearity, charge, bulk and balance mix of hydrophilicity-hydrophobicity, thereby providing the physicochemical profile based on which biological studies could ensue. The structurally based selection of species was applied onto in vitro 3T3-L1 cultures, essentially exploring toxicity, migration, morphology, cell differentiation and maturation. The systematic effort toward comparative work on appropriately defined Zn(II) species and insulin in inducing adipogenesis reveals the salient structural features in the Schiff family of ligands configuring Zn(II) so as to promote complex formation sufficient to engage biomolecular targets during the process of initiation and maturation. Molecular targets of importance in adipogenesis were examined under the influence of Zn(II) and their expression levels suggest the structural composition that a Zn(II) ion might have to optimally pursue cell differentiation. Thus, a well-defined selection of binary Zn(II)-L species is tightly associated with the incurred bioactivity, thereby setting the stage for the development of efficient Zn(II) metallodrugs to combat Diabetes mellitus II.

Synthetic endeavors on cadmium species bearing glycolate and aromatic chelators with structure-specific biotoxic correlations in vitro.

Cadmium is a well-known metallotoxin widespread in the environment and easily reaching cellular targets in lower and higher organisms, including humans. The form(s) of that metal ion through which it interacts with biomolecular targets in a cellular milieu are critical in cell survival. Poised to investigate the structure-specific activity of Cd(II) in a cellular environment and delve into the associated biotoxic processes, binary and ternary systems of that metal ion in the presence of the physiological α-hydroxycarboxylic acid glycolic acid and aromatic (N,N')-binders 2,2'-bipyridine (2,2'-bipy) and 4,4'-bipyridine (4,4'-bipy) were examined synthetically in aqueous media and a pH-specific fashion. The arising new materials [Cd(C2H3O3)2]n (1), [Cd(C2H3O3)(C10H8N2)(NO3)]n·nH2O (2), and {[Cd(C2H3O3)(C10H8N2)(H2O)](NO3)}n·2nH2O (3) project coordination polymers, which were physicochemically characterized through elemental analysis, FT-IR, NMR, luminescence and X-ray crystallography. The distinct spectroscopic features of 1-3, with luminescence exemplifying distinct behavior (2,3), further corroborated by crystallographic analysis, lend credence to a structure-specific selection of species employed in ensuing in vitro biological studies. The emerging results in two different cell lines (3T3-L1, Saos-2) reveal a concentration-dependent, structure-specific and cell line-specific toxicity profile of Cd(II), reflecting its coordination composition and formulation, rendering it soluble and bioavailable (1,2). Mechanistic information riding on caspase-dependent investigation unravels that metal ion's specific behavior compromising cell survival and integrity. Employment of ethylenediamine tetraacetic acid (EDTA) a) shows efficient sequestration of Cd(II) away from its toxic reactivity denoting the strength of interactions involved, and b) lends credence to further development of appropriately configured organic binders, selectively providing molecular protection from Cd(II) toxicity.

Synthetic investigation, physicochemical characterization and antibacterial evaluation of ternary Bi(III) systems with hydroxycarboxylic acid and aromatic chelator substrates.

Due to its physical and chemical properties, bismuth (Bi(III)) is widely used in the treatment of several gastrointestinal and skin diseases, and infections caused by bacteria. Herein, its known antimicrobial potential was taken into consideration in the synthesis of two new hybrid ternary materials of Bi(III) with the physiological α-hydroxycarboxylic glycolic acid and 1,10-phenanthroline (phen), [Bi2(C2H2O3)2(C2H3O3)(NO3)]n. nH2O (1) and [Bi(C12H8N2)(NO3)4](C10H8N4) (2), aiming at improving its antibacterial properties. Their physicochemical characterization was carried out through elemental analysis, FT-IR, atomic absorption spectroscopy, single crystal X-ray diffraction, thermogravimetric analysis (TGA), photoluminescence, and 13C MAS-NMR techniques. The antimicrobial activity of the title complexes was directly linked to Bi(III) coordination environment and the incipient aqueous chemistry. For their antibacterial assessment, minimum inhibitory concentration (MIC), zone of inhibition (ZOI), and bacteriostatic-bacteriocidal activity were determined in various Gram positive (Staphylococcus aureus, Bacillus subtilis and Bacillus cereus) and Gram negative (Escherichia coli and Xanthomonas campestris) bacterial cultures, in reference to a positive control (ampicillin), encompassing further comparisons with literature data. The findings reveal that the new hybrid bismuth materials have significant antimicrobial effects against the employed bacteria. Specifically, 2 exhibits better antimicrobial properties than free Bi(NO3)3 and phen. On the other hand, 1 is bacteriostatic toward four microorganisms except X. campestris, with 2 being bacteriocidal toward four microorganisms except B. cereus. Collectively, the new hybrid, well-defined, and two of the rarely crystallographically characterized Bi(III) materials a) exhibit properties reflecting their physicochemical nature and reactivity, and b) are expected to contribute to the development of efficient metallodrugs against drug-resistant bacterial infections.

Copper(I) halide complexes of 2,2,5,5-tetramethyl-imidazolidine-4-thione: Synthesis, structures, luminescence, thermal stability and interaction with DNA.

Five neutral mononuclear copper(I) halide complexes containing 2,2,5,5-tetramethylimidazolidine-4-thione (tmimdtH) and triphenylphosphane (PPh3) or tri-o-tolylphosphane (totp) have been prepared and structurally characterized by X-ray single-crystal analysis. The complexes containing PPh3 adopt the usual distorted tetrahedral geometry, while the presence of the bulkier totp forces the formation of three-coordinated trigonal planar species. The interaction of the compounds with calf-thymus DNA was monitored directly via UV-vis spectroscopy, DNA-viscosity measurements and indirectly via its competition with ethidium bromide for DNA studied by fluorescence emission spectroscopy. Intercalation was revealed as the most possible mode of binding. Furthermore, luminescent properties and thermal stabilities of the complexes were investigated.

Structure-specific adipogenic capacity of novel, well-defined ternary Zn(II)-Schiff base materials. Biomolecular correlations in zinc-induced differentiation of 3T3-L1 pre-adipocytes to adipocytes.

Among the various roles of zinc discovered to date, its exogenous activity as an insulin mimetic agent stands as a contemporary challenge currently under investigation and a goal to pursue in the form of a metallodrug against type 2 Diabetes Mellitus. Poised to investigate the adipogenic potential of Zn(II) and appropriately configure its coordination sphere into well-defined anti-diabetic forms, (a) a series of new well-defined ternary dinuclear Zn(II)-L (L=Schiff base ligands with a variable number of alcoholic moieties) compounds were synthesized and physicochemically characterized, (b) their cytotoxicity and migration effect(s) in both pre- and mature adipocytes were assessed, (c) their ability to effectively induce cell differentiation of 3T3-L1 pre-adipocytes into mature adipocytes was established, and (d) closely linked molecular targets involving or influenced by the specific Zn(II) forms were perused through molecular biological techniques, cumulatively delineating factors involved in Zn(II)-induced adipogenesis. Collectively, the results (a) reveal the significance of key structural features of Schiff ligands coordinated to Zn(II), thereby influencing its (a)toxicity behavior and insulin-like activity, (b) project molecular targets influenced by the specific forms of Zn(II) formulating its adipogenic potential, and (c) exemplify the interwoven relationship between Zn(II)-L structural speciation and insulin mimetic biological activity, thereby suggesting ways of fine tuning structure-specific zinc-induced adipogenicity in future efficient antidiabetic drugs.

Design, synthesis and characterization of novel binary V(V)-Schiff base materials linked with insulin-mimetic vanadium-induced differentiation of 3T3-L1 fibroblasts to adipocytes. Structure-function correlations at the molecular level.

Among the various roles of vanadium in the regulation of intracellular signaling, energy metabolism and insulin mimesis, its exogenous activity stands as a contemporary challenge currently under investigation and a goal to pursue as a metallodrug against Diabetes mellitus II. In this regard, the lipogenic activity of vanadium linked to the development of well-defined anti-diabetic vanadodrugs has been investigated through: a) specifically designing and synthesizing Schiff base organic ligands L, bearing a variable number of terminal alcohols, b) a series of well-defined soluble binary V(V)-L compounds synthesized and physicochemically characterized, c) a study of their cytotoxic effect and establishment of adipogenic activity in 3T3-L1 fibroblasts toward mature adipocytes, and d) biomarker examination of a closely-linked molecular target involving or influenced by the specific V(V) forms, cumulatively delineating factors involved in potential pathways linked to V(V)-induced insulin-like activity. Collectively, the results a) project the importance of specific structural features in Schiff ligands bound to V(V), thereby influencing the emergence of its (a)toxicity and for the first time its insulin-like activity in pre-adipocyte differentiation, b) contribute to the discovery of molecular targets influenced by the specific vanadoforms seeking to induce glucose uptake, and c) indicate an interplay of V(V) structural speciation and cell-differentiation biological activity, thereby gaining insight into vanadium's potential as a future metallodrug in Diabetes mellitus.

Silver(I) complexes of N-methylbenzothiazole-2-thione: synthesis, structures and antibacterial activity.

Three silver(I) complexes containing N-methylbenzothiazole-2-thione (mbtt) have been prepared and structurally characterized by X-ray single-crystal analysis. Silver(I) nitrate, and silver(I) triflate react with mbtt to give homoleptic complexes of formula [(mbtt)2Ag(µ-mbtt)2Ag(mbtt)2](NO3)2 (1) and [Ag(mbtt)3](CF3SO3) (2) respectively, while silver(I) chloride gives the binuclear halide-bridged [(mbtt)2Ag(µ2-Cl)2Ag(mbtt)2] (3). In the binuclear complex 1 the two metal ions, separated by 3.73 Å from each other, are doubly bridged by the exocyclic S-atoms of two mbtt ligands, with the tetrahedral environment around each silver ion being completed by the S-atoms of two terminally bonded mbtt units. Compound 2 is mononuclear with the metal ion surrounded by the exocyclic S-atoms of three mbtt ligands in a nearly ideal trigonal planar arrangement. The new complexes showed significant in vitro antibacterial activity against certain Gram-positive and Gram-negative bacterial strains.

Copper(I) halide complexes of 5-carbethoxy-2-thiouracil: synthesis, structure and in vitro cytotoxicity.

5-Carbethoxy-2-thiouracil (eitotH2) reacts with copper(I) halides CuX (X = Cl, Br, I) to give dinuclear complexes of the formula [CuX(eitotH2)2]2 while mononuclear mixed-ligand complexes of the formula [CuX(PPh3)2(eitotH2)] result when the reactions are performed in the presence of two equivalents of triphenylphosphine (PPh3). The molecular structures of representative compounds from each of the above types of complexes, namely [CuI(eitotH2)2]2, [CuCl(PPh3)2(eitotH2)] and [CuBr(PPh3)2(eitotH2)] have been established by single-crystal X-ray diffraction. The new copper(I) complexes were evaluated for in vitro antitumor properties against two tumor cell lines, A549 (human pulmonary carcinoma cell line) and HeLa (human epithelial carcinoma cell line) and one normal immortalized cell line MRC5 (human fetal lung fibroblast). The mixed-ligand complexes possessing triphenylphosphine were found to be highly cytotoxic in contrast to the phosphine-free ones which inhibited cell proliferation only in relatively high concentrations.

Copper(I) halide complexes of N-methylbenzothiazole-2-thione: synthesis, structure, luminescence, antibacterial activity and interaction with DNA.

The reactions of copper(I) halides, CuX (X=Cl, Br, I) with N-methylbenzothiazole-2-thione (mbtt), independent of the molar ration chosen (1:2 or 1:3), led to the formation of dinuclear complexes of the formula [CuX(mbtt)2]2, whereas the reactions of CuX and mbtt in the presence of two equivalents of triphenylphosphine (PPh3) afforded mononuclear mixed-ligand complexes of the formula [CuX(PPh3)2(mbtt)]. The molecular structure of a representative compound from each of the two above types of complexes, namely [CuCl(mbtt)2]2 and [CuI(PPh3)2(mbtt)] have been established by single-crystal X-ray diffraction. The new complexes are strongly emissive both in the solid state and in solution. The complexes were also screened for antibacterial activity and their ability to interact with native calf thymus DNA (CT-DNA) in vitro. Both types of complexes showed significant activities against all the bacteria tested as compared to that of standard antibiotic ampicillin, however, the three mixed-ligand complexes including triphenylphosphane as ligand exhibited perceptibly stronger antibacterial activity than the three homoleptic ones possessing only the mbtt ligand. DNA electrophoretic mobility experiments showed that all complexes bind to CT-ds DNA resulting in high molecular weight complexes ending in DNA degradation.

Gitelman syndrome: first report of genetically established diagnosis in Greece.

Gitelman syndrome is an inherited renal tubular disorder characterized by hypokalemic metabolic alkalosis. It is distinguished from other hypokalemic tubulopathies, such as Bartter syndrome, by the presence of both hypomagnesemia and hypocalciuria. We report a case of Gitelman syndrome in a 10-year-old girl who presented for examination of persistent unexplained hypokalemia. She had no severe clinical symptoms but she had typical laboratory findings including hypokalemia, hypomagnesemia and normocalcemic hypocalciuria. Molecular analysis revealed a mutation in the exon 21 of the SLC12A3 gene which encodes the thiazide-sensitive sodium-chloride co-transporter expressed in the distal convoluted tubule (a guanine to adenosine substitution at nucleotide 2538). She was treated with oral potassium and magnesium supplements. This is the first report of genetically established diagnosis in Greece. Gitelman syndrome should be considered as a cause of persistent hypokalemia and genetic analysis might be a useful tool to confirm the diagnosis.

Solid and solution behavior of sulphonylurea complexes with ions of IIA group metals. Molecular modeling of K[Zn(ClCH4SO2NCONHC3H7)3] and action of zinc-sulphonylurea complexes as hypoglycemic agents.

Complexes of Zn2+ with deprotonated suphonylurea as ligands have been synthesized and characterized. Deprotonated sulphonylurea act as bidentate ligands using one nitrogen and one oxygen atom (the ureido oxygen) to bind Zn2+ forming K[Zn(suphonylurea)3]. Using the MMX89 program, a model for K[Zn(ClC6H4SO2NCONHC3H7)3] compound is proposed. Conductometric and potentiometric studies in methanol, for d10 metal-sulphonylurea complexes, demonstrated that zinc, cadmium and silver complexes are 1:1 electrolytes and are protonated in the range 4.2-5.6 pH. UV-Vis study shows no interaction between metal and protonated sulphonylureas in methanol solutions. At 7.34 pH the form of Zn complexes which act as a hypoglycemic agent is [ZnL3]-. Test for hypoglycemic activity reduced glycemia to a statistically significant degree compared to the corresponding free ligands.