Antonios G. Hatzidimitriou

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.

Alkaline Earth Metal Ion/Dihydroxy–Terephthalate MOFs: Structural Diversity and Unusual Luminescent Properties

Alkaline earth (group 2) metal ion organic frameworks (AEMOFs) represent an important subcategory of MOFs with interesting structures and physical properties. Five MOFs, namely, [Mg2(H2dhtp)2(μ-H2O)(NMP)4] (AEMOF-2), [Mg2(H2dhtp)1.5(DMAc)4]Cl·DMAc (AEMOF-3), [Ca(H2dhtp)(DMAc)2] (AEMOF-4), [Sr3(H2dhtp)3(DMAc)6]·H2O (AEMOF-5), and [Ba(H2dhtp)(DMAc)] (AEMOF-6) (H4dhtp = 2,5-dihydroxy-terepthalic acid; DMAc = N,N-dimethylacetamide; NMP = N-methylpyrrolidone), are presented herein. The reported MOFs display structural variety with diverse topologies and new structural features. Interestingly, AEMOF-6 is the first example of a Ba(2+)-H2dhtp(2-) MOF, and AEMOF-5 is only the second known Sr(2+)-H2dhtp(2-) MOF. Detailed photoluminescence studies revealed alkaline earth metal ion-dependent fluorescence properties of the materials, with the heavier alkaline earth metal ions exhibiting red-shifted emission with respect to the lighter ions at room temperature. A bathochromic shift of the emission was observed for the MOFs (mostly for AEMOF-3 and AEMOF-4) at 77 K as a result of excited state proton transfer (ESIPT), which involves an intramolecular proton transfer from a hydroxyl to an adjacent carboxylic group of the H2dhtp(2-) ligand. Remarkably, AEMOF-6 displays rare yellow fluorescence at room temperature, which is attractive for solid state lighting applications. To probe whether the alkaline earth metal ions are responsible for the unusual luminescence properties of the reported MOFs, the potential energy surfaces (PESs) of the ground, S0, and lowest energy excited singlet, S1, states of model complexes along the intramolecular proton transfer coordinate were calculated by DFT and TD-DFT methods.

Neutral and cationic manganese(II)–diclofenac complexes: structure and biological evaluation

The interaction of MnCl2 with the non-steroidal anti-inflammatory drug sodium diclofenac in the presence of 2,2′-bipyridine and pyridine resulted in the formation of cationic and neutral mononuclear complexes [Mn(diclofenac)(2,2′-bipyridine)(H2O)2] (diclofenac) (1) and [Mn(diclofenac)2(pyridine)2(H2O)2] (2), respectively. The structure of 1 was characterized by X-ray crystallography. In a preliminary attempt to evaluate the biological properties and possible application, the interaction of the complexes with calf-thymus DNA and human or bovine serum albumins was monitored. Additionally, the ability of the compounds to scavenge radicals such as 1,1-diphenyl-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and hydroxyl radicals was evaluated; the complexes were more potent scavengers than free sodium diclofenac.

Synthesis, characterization and biological evaluation of 99m Tc/Re–tricarbonyl quinolone complexes

New rhenium(I) tricarbonyl complexes with the quinolone antimicrobial agents oxolinic acid (Hoxo) and enrofloxacin (Herx) and containing methanol, triphenylphosphine (PPh3) or imidazole (im) as unidentate co-ligands, were synthesized and characterized. The crystal structure of complex [Re(CO)3(oxo)(PPh3)]∙0.5MeOH was determined by X-ray crystallography. The deprotonated quinolone ligands are bound bidentately to rhenium(I) ion through the pyridone oxygen and a carboxylate oxygen. The binding of the rhenium complexes to calf-thymus DNA (CT DNA) was monitored by UV spectroscopy, viscosity measurements and competitive studies with ethidium bromide; intercalation was suggested as the most possible mode and the DNA-binding constants of the complexes were calculated. The rhenium complex [Re(CO)3(erx)(im)] was assayed for its topoisomerase IIα inhibition activity and was found to be active at 100μM concentration. The interaction of the rhenium complexes with human or bovine serum albumin was investigated by fluorescence emission spectroscopy (through the tryptophan quenching) and the corresponding binding constants were determined. The tracer complex [(99m)Tc(CO)3(erx)(im)] was synthesized and identified by comparative HPLC analysis with the rhenium analog. The (99m)Tc complex was found to be stable in solution. Upon injection in healthy mice, fast tissue clearance of the (99m)Tc complex was observed, while both renal and hepatobiliary excretion took place. Preliminary studies in human K-562 erythroleukemia cells showed cellular uptake of the (99m)Tc tracer with distribution primarily in the cytoplasm and the mitochondria and less in the nucleus. These preliminary results indicate that the quinolone (99m)Tc/Re complexes show promise to be further evaluated as imaging or therapeutic agents.

Copper(II) complexes of salicylaldehydes and 2-hydroxyphenones: synthesis, structure, thermal decomposition study and interaction with calf-thymus DNA and albumins

The neutral mononuclear copper(II) complexes with substituted salicylaldehyde (X-saloH), or 2-hydroxyphenone (ketoH) ligands, having the formula [Cu(L)2(S)n] (where S = solvent CH3OH or H2O and n = 0, 1 or 2) have been prepared and characterized, and their interaction with DNA and albumins was studied. The ligands are chelated to the metal ion through the phenolate and carbonyl oxygen atoms. The crystal structures of [Cu(5-NO2-salo)2(CH3OH)2] (3), [Cu(5-Cl-salo)2] (4), [Cu(bpo)2] (6) and [Cu(mpo)2]·2H2O (7·2H2O) have been determined by X-ray crystallography. The thermal stability of the copper complexes has been investigated by a simultaneous TG/DTG-DTA technique. Spectroscopic (UV), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques have been employed in order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA while competitive studies with ethidium bromide (EB) performed by fluorescence spectroscopy have revealed the ability of the complexes to displace the DNA-bound EB. In conclusion intercalation is the most possible mode of interaction of the complexes with CT DNA. The interaction of the complexes with serum albumin proteins has been studied by fluorescence emission spectroscopy and the determined binding constants exhibit relatively high values.

The structural and electronic impact on the photophysical and biological properties of a series of CuI and AgI complexes with triphenylphosphine and pyrimidine-type thiones

Four CuI and three AgI mixed–ligand complexes containing a heterocyclic pyrimidine-type thione (pymtH = pyrimidine-2-thione or dmpymtH = 4,6-dimethyl-pyrimidine-2-thione) and triphenylphosphine (PPh3) have been synthesized and structurally characterized. All copper and two of the silver compounds, namely [Cu(PPh3)2(pymtH)2]BF4 (1), [Cu(PPh3)3(pymtH)]BF4 (2), [Cu(PPh3)2(dmpymtH)2]BF4 (3), [Cu(PPh3)3(dmpymtH)]BF4 (4), [Ag(PPh3)3(pymtH)]NO3 (5) and [Ag(PPh3)3(dmpymtH)]NO3 (6), reveal a tetrahedral coordination environment while [Ag(PPh3)2(pymtH)]NO3 (7) preferentially adopts a trigonal planar arrangement. The stoichiometry of the isolated silver complexes does not always follow the respective stoichiometries of the synthetic procedures. The photophysical properties of all the isolated products have been evaluated. In solution, phosphine derived emission is detected while in the solid state only [Cu(PPh3)3(dmpymtH)]BF4 (4) emits from a state of different parentage. All of the complexes were also tested for in vitro antibacterial activity against four bacterial strains and for anti-inflammatory activity by measuring lipoxygenase inhibition activity.

Copper(II)-loaded HEU-type zeolite crystals: characterization and evidence of surface complexation with N,N-diethyldithiocarbamate anions

Abstract Copper(II)-loaded HEU-type zeolite crystals (CuHEU) formed by wet-chemical procedures were studied through powder X-ray diffraction (PXRD), scanning electron microscopy–energy dispersive spectroscopy (SEM–EDS), electron paramagnetic resonance (EPR), diffuse reflectance UV–Vis spectroscopy [DRS(UV–Vis)], X-ray photoelectron spectroscopy (XPS) and extended X-ray absorption fine structure (EXAFS) techniques. The copper in the non-stoichiometric and non-homoionic CuHEU crystals was identified as six-coordinated cupric ions, the ligating atoms being both oxygen atoms of the framework basic Lewis sites and water molecules. The resulting Cu(II) complexes adopt a tetragonally distorted octahedral symmetry. Treating the CuHEU material with an aqueous solution of N,N-diethyldithiocarbamato ligands (Et2dtc−) results in the product CuHEU–Et2dtc, the structure and properties of which were studied by means of PXRD, SEM–EDS, DRS(UV–Vis), EPR and XPS techniques. The spectroscopic investigation of the material revealed the presence of both CuS and CuO coordination bonds in a novel type of coordination sphere around the Cu2+ ions forming a complex with the Et2dtc ligands supported on the surface of the zeolitic substrate. The surface complexation process does not affect either the oxidation state or the tetragonally distorted octahedral symmetry of the copper(II) grafted onto the zeolitic material. Strong evidence exists indicating that the coordination process involves the nucleophilic substitution of primary coordinated water molecules by the stronger σ-donor Et2dtc− ligands.

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 vanadiums potential as a future metallodrug in Diabetes mellitus.

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.

Nickel(II)–naproxen mixed-ligand complexes: synthesis, structure, antioxidant activity and interaction with albumins and calf-thymus DNA

The nickel(II) complexes with the non-steroidal anti-inflammatory drug naproxen (Hnap) were prepared in the absence or presence of the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), 2,2′-bipyridylamine (bipyam), 2,2′-dipyridylketone oxime (Hpko) or pyridine (py) and were characterized by diverse techniques. The crystal structures of complexes [Ni(nap-O)(nap-O,O′)(bipy)(MeOH)], 2 and [Ni(nap-O)(nap-O,O′)(phen)(H2O)] 3 were determined by X-ray crystallography. The antioxidant activity of the complexes was evaluated in vitro by examining their ability to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase. The ability of the complexes to intercalate to calf-thymus DNA was monitored by diverse techniques (UV-vis spectroscopy, cyclic voltammetry, viscosity measurements) and competitive studies with ethidium bromide. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the corresponding binding constants were calculated. The bio-activity of the complexes was compared to previously reported metal–naproxen complexes and the structural factors responsible for enhanced activity are discussed.