Experimental and Computational Studies on the Interaction of DNA with Hesperetin Schiff Base CuII Complexes.

The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or L1H3), isoniazid (HIN or L2H3), or thiosemicarbazide (HTSC or L3H3) and their CuII complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLnH2(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV-Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants (Kb) of the Cu compounds with CT-DNA, in the range (2.3-9.2) × 106, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that π-π stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LnH2)(AcO)] and [Cu(LnH2)(H2O)]+, the tautomer that binds CuII, amido (am) and not imido (im), and the coordination mode of HTSC (O-, N, S), instead of (O-, N, NH2). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(L1H2am)(AcO)] > [Cu(L2H2am)(AcO)] ≈ TO ≈ L1H3 > [Cu(L3H2am)(AcO)], in line with the experimental Kb constants, obtained from the UV-Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(L1H2am)(AcO)] is larger than [Cu(L1H2am)(H2O)]+. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules.

Encapsulation and Biological Activity of Hesperetin Derivatives with HP-ß-CD.

The encapsulation of insoluble compounds can help improve their solubility and activity. The effects of cyclodextrin encapsulation on hesperetin's derivatives (HHSB, HIN, and HTSC) and the physicochemical properties of the formed complexes were determined using various analytical techniques. The antioxidant (DPPH•, ABTS•+ scavenging, and Fe2+-chelating ability), cytotoxic, and antibacterial activities were also investigated. The inclusion systems were prepared using mechanical and co-evaporation methods using a molar ratio compound: HP-ß-CD = 1:1. The identification of solid systems confirmed the formation of two inclusion complexes at hesperetin (CV) and HHSB (mech). The identification of systems of hesperetin and its derivatives with HP-ß-CD in solutions at pHs 3.6, 6.5, and 8.5 and at various temperatures (25, 37 and 60 °C) confirmed the effect of cyclodextrin on their solubility. In the DPPH• and ABTS•+ assay, pure compounds were characterized by higher antioxidant activity than the complexes. In the FRAP study, all hesperetin and HHSB complexes and HTSC-HP-ß-CD (mech) were characterized by higher values of antioxidant activity than pure compounds. The results obtained from cytotoxic activity tests show that for most of the systems tested, cytotoxicity increased with the concentration of the chemical, with the exception of HP-ß-CD. All systems inhibited Escherichia coli and Staphylococcus aureus.

Spectroscopic Characterization and Biological Activity of Hesperetin Schiff Bases and Their Cu(II) Complexes.

The three Schiff base ligands, derivatives of hesperetin, HHSB (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]isonicotinohydrazide), HIN (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]benzhydrazide) and HTSC (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]thiosemicarbazide) and their copper complexes, CuHHSB, CuHIN, and CuHTSC were designed, synthesized and analyzed in terms of their spectral characterization and the genotoxic activity. Their structures were established using several methods: elemental analysis, FT-IR, UV-Vis, EPR, and ESI-MS. Spectral data showed that in the acetate complexes the tested Schiff bases act as neutral tridentate ligand coordinating to the copper ion through two oxygen (or oxygen and sulphur) donor atoms and a nitrogen donor atom. EPR measurements indicate that in solution the complexes keep their structures with the ligands remaining bound to copper(II) in a tridentate fashion with (O-, N, Oket) or (O-, N, S) donor set. The genotoxic activity of the compounds was tested against model tumour (HeLa and Caco-2) and normal (LLC-PK1) cell lines. In HeLa cells the genotoxicity for all tested compounds was noticed, for HHSB and CuHHSB was the highest, for HTSC and CuHTSC-the lowest. Generally, Cu complexes displayed lower genotoxicity to HeLa cells than ligands. In the case of Caco-2 cell line HHSB and HTSC induced the strongest breaks to DNA. On the other side, CuHHSB and CuHTSC induced the highest DNA damage against LLC-PK1.

From the Physicochemical Characteristic of Novel Hesperetin Hydrazone to Its In Vitro Antimicrobial Aspects.

Microorganisms are able to give rise to biofilm formation on food matrixes and along food industry infrastructures or medical equipment. This growth may be reduced by the application of molecules preventing bacterial adhesion on these surfaces. A new Schiff base ligand, derivative of hesperetin, HABH (2-amino-N'-(2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene)benzohydrazide), and its copper complex, CuHABH [CuLH2(OAc)], were designed, synthesized and analyzed in terms of their structure and physicochemical properties, and tested as antibacterial agents. Their structures both in a solid state and in solution were established using several methods: FT-IR, 1H NMR, 13C NMR, UV-Vis, FAB MS, EPR, ESI-MS and potentiometry. Coordination binding of the copper(II) complex dominating at the physiological pH region in the solution was found to be the same as that detected in the solid state. Furthermore, the interaction between the HABH and CuHABH with calf-thymus DNA (CT-DNA) were investigated. These interactions were tracked by UV-Vis, CD (circular dichroism) and spectrofluorimetry. The results indicate a stronger interaction of the CuHABH with the CT-DNA than the HABH. It can be assumed that the nature of the interactions is of the intercalating type, but in the high concentration range, the complex can bind to the DNA externally to phosphate residues or to a minor/major groove. The prepared compounds possess antibacterial and antibiofilm activities against Gram-positive and Gram-negative bacteria. Their antagonistic activity depends on the factor-strain test system. The glass was selected as a model surface for the experiments on antibiofilm activity. The adhesion of bacterial cells to the glass surface in the presence of the compounds was traced by luminometry and the best antiadhesive action against both bacterial strains was detected for the CuHABH complex. This molecule may play a crucial role in disrupting exopolymers (DNA/proteins) in biofilm formation and can be used to prevent bacterial adhesion especially on glass equipment.

Structural and Spectral Investigation of a Series of Flavanone Derivatives.

Four flavanone Schiff bases (E)-1-(2-phenylchroman-4-ylidene)thiosemicarbazide (FTSC) (1), N',2-bis((E)-2-phenylchroman-4-ylidene)hydrazine-1-carbothiohydrazide (FTCH) (2), (E)-N'-(2-phenylchroman-4-ylidene)benzohydrazide (FHSB) (3) and (E)-N'-(2-phenylchroman-4-ylidene)isonicotinohydrazide (FIN) (4) were synthesized and evaluated for their electronic and physicochemical properties using experimental and theoretical methods. One of them, (2), consists of two flavanone moieties and one substituent, the rest of the compounds (1, 3, 4) comprises of a flavanone-substituent system in relation to 1:1. To uncover the structural and electronic properties of flavanone Schiff bases, computational simulations and absorption spectroscopy were applied. Additionally, binding efficiencies of the studied compounds to serum albumins were evaluated using fluorescence spectroscopy. Spectral profiles of flavanone Schiff bases showed differences related to the presence of substituent groups in system B of the Schiff base molecules. Based on the theoretically predicted chemical descriptors, FTSC is the most chemically reactive among the studied compounds. Binding regions within human and bovine serum albumins of the ligands studied are in the vicinity of the Trp residue and a static mechanism dominates in fluorescence quenching.

C5-Substituted 2-Selenouridines Ensure Efficient Base Pairing with Guanosine; Consequences for Reading the NNG-3' Synonymous mRNA Codons.

5-Substituted 2-selenouridines (R5Se2U) are post-transcriptional modifications present in the first anticodon position of transfer RNA. Their functional role in the regulation of gene expression is elusive. Here, we present efficient syntheses of 5-methylaminomethyl-2-selenouridine (1, mnm5Se2U), 5-carboxymethylaminomethyl-2-selenouridine (2, cmnm5Se2U), and Se2U (3) alongside the crystal structure of the latter nucleoside. By using pH-dependent potentiometric titration, pKa values for the N3H groups of 1-3 were assessed to be significantly lower compared to their 2-thio- and 2-oxo-congeners. At physiological conditions (pH 7.4), Se2-uridines 1 and 2 preferentially adopted the zwitterionic form (ZI, ca. 90%), with the positive charge located at the amino alkyl side chain and the negative charge at the Se2-N3-O4 edge. As shown by density functional theory (DFT) calculations, this ZI form efficiently bound to guanine, forming the so-called "new wobble base pair", which was accepted by the ribosome architecture. These data suggest that the tRNA anticodons with wobble R5Se2Us may preferentially read the 5'-NNG-3' synonymous codons, unlike their 2-thio- and 2-oxo-precursors, which preferentially read the 5'-NNA-3' codons. Thus, the interplay between the levels of U-, S2U- and Se2U-tRNA may have a dominant role in the epitranscriptomic regulation of gene expression via reading of the synonymous 3'-A- and 3'-G-ending codons.

Position Impact of Hydroxy Groups on Spectral, Acid-Base Profiles and DNA Interactions of Several Monohydroxy Flavanones.

Structure-related biological activities of flavanones are still considered largely unexplored. Since they exhibit various medicinal activities, it is intriguing to enter deeper into their chemical structures, electronic transitions or interactions with some biomolecules in order to find properties that allow us to better understand their effects. Little information is available on biological activity of flavanone and its monohydroxy derivatives in relation to their physicochemical properties as spectral profiles, existence of protonated/deprotonated species under pH changes or interaction with Calf Thymus DNA. We devoted this work to research demonstrating differences in the physicochemical properties of the four flavanones: flavanone, 2'-hydroxyflavanone, 6-hydroxyflavanone and 7-hydroxyflavanone and linking them to their biological activity. Potentiometric titration, UV-Vis spectroscopy were used to investigate influence of pH on acid-base and spectral profiles and to propose the mode of interaction with DNA. Cyclic voltammetry was applied to evaluate antioxidant potentiality and additionally, theoretical DFT(B3LYP) method to disclose electronic structure and properties of the compounds. Molecular geometries, proton affinities and pKa values have been determined. According to computational and cyclic voltammetry results we could predict higher antioxidant activity of 6-hydroxyflavanone with respect to other compounds. The values of Kb intrinsic binding constants of the flavanones indicated weak interactions with DNA. Structure-activity relationships observed for antioxidant activity and DNA interactions suggest that 6-hydroxyflavanone can protect DNA against oxidative damage most effectively than flavanone, 2'-hydroxyflavanone or 7-hydroxyflavanone.

Physicochemical, antioxidant, DNA cleaving properties and antimicrobial activity of fisetin-copper chelates.

Fisetin (3,3',4',7-tetrahydroxyflavone) metal chelates are of interest as this plant polyphenol has revealed broad prospects for its use as natural medicine in the treatment of various diseases. Metal interactions may change or enhance fisetin biological properties so understanding fisetin metal chelation is important for its application not only in medicine but also as a food additive in nutritional supplements. This work was aimed to determine and characterize copper complexes formed in different pH range at applying various metal/ligand ratios. Fisetin and Cu(II)-fisetin complexes were characterized by potentiometric titrations, UV-Vis (Ultraviolet-visible spectroscopy), EPR, ESI-MS, FTIR and cyclic voltammetry. Their effects on DNA were investigated by using circular dichroism, spectrofluorimetry and gel electrophoresis methods. The copper complex with the ratio of Cu(II)/fisetin 1/2 exhibited significant DNA cleavage activity, followed by complete degradation of DNA. The influence of copper(II) ions on antioxidant activity of fisetin in vitro has been studied using DPPH, ABTS and mitochondrial assays. The results have pointed out that fisetin or copper complexes can behave both as antioxidants or pro-oxidants. Antimicrobial activity of the compounds has been investigated towards several bacteria and fungi. The copper complex of Cu(II)/fisetin 1/2 ratio showed higher antagonistic activity against bacteria comparing to the ligand and it revealed a promising antifungal activity.

C5-substituents of uridines and 2-thiouridines present at the wobble position of tRNA determine the formation of their keto-enol or zwitterionic forms - a factor important for accuracy of reading of guanosine at the 3΄-end of the mRNA codons.

Modified nucleosides present in the wobble position of the tRNA anticodons regulate protein translation through tuning the reading of mRNA codons. Among 40 of such nucleosides, there are modified uridines containing either a sulfur atom at the C2 position and/or a substituent at the C5 position of the nucleobase ring. It is already evidenced that tRNAs with 2-thiouridines at the wobble position preferentially read NNA codons, while the reading mode of the NNG codons by R5U/R5S2U-containing anticodons is still elusive. For a series of 18 modified uridines and 2-thiouridines, we determined the pKa values and demonstrated that both modifying elements alter the electron density of the uracil ring and modulate the acidity of their N3H proton. In aqueous solutions at physiological pH the 2-thiouridines containing aminoalkyl C5-substituents are ionized in ca. 50%. The results, confirmed also by theoretical calculations, indicate that the preferential binding of the modified units bearing non-ionizable 5-substituents to guanosine in the NNG codons may obey the alternative C-G-like (Watson-Crick) mode, while binding of those bearing aminoalkyl C5-substituents (protonated under physiological conditions) and especially those with a sulfur atom at the C2 position, adopt a zwitterionic form and interact with guanosine via a 'new wobble' pattern.

DNA binding and cleavage studies of copper(II) complexes with 2'-deoxyadenosine modified histidine moiety.

This work is focused on the study of DNA binding and cleavage properties of 2'-deoxyadenosines modified with ester/amide of histidine (his(6)dA ester, his(6)dA amide) and their copper(II) complexes. To determine the coordination mode of the complex species potentiometric and spectroscopic (UV-visible, CD, EPR) studies have been performed. The analysis of electronic absorption and fluorescence spectra has been used to find the nature of the interactions between the compounds and calf thymus DNA (CT-DNA). There is significant influence of the -NH2 and -OCH3 groups on binding of the ligands or the complexes to DNA. Only amide derivative and its complex reveal intercalative ability. In the case of his(6)dA ester and Cu(II)-his(6)dA ester the main interactions can be groove binding. DNA cleavage activities of the compounds have been examined by gel electrophoresis. The copper complexes have promoted the cleavage of plasmid DNA, but none of the ligands exhibited any chemical nuclease activity. The application of different scavengers of reactive oxygen species provided a conclusion that DNA cleavage caused by copper complexes might occur via hydrolytic pathway.

Chelating ability and biological activity of hesperetin Schiff base.

Hydrazone hesperetin Schiff base (HHSB) - N-[(±)-[5,7-dihydroxy-2-(3-hydroxy-4-methoxy-phenyl)chroman-4-ylidene]amino]benzamide has been synthesized and its crystal structure was determined. This compound was used for the formation of Cu(II) complexes in solid state and in solution which were characterized using different spectroscopic methods. The analyses of potentiometric titration curves revealed that monomeric and dimeric complexes of Cu(II) are formed above pH7. The ESI-MS (electrospray ionization-mass spectrometry) spectra confirmed their formation. The EPR and UV-visible spectra evidenced the involvement of oxygen and nitrogen atoms in Cu(II) coordination. Hydrazone hesperetin Schiff base can show keto-enol tautomerism and coordinate Cu(II) in the keto (O(-), N, Oket) and in the enolate form (O(-), N, O(-)enol). The semi-empirical molecular orbital method PM6 and DFT (density functional theory) calculations have revealed that the more stable form of the dimeric complex is that one in which the ligand is present in the enol form. The CuHHSB complex has shown high efficiency in the cleavage of plasmid DNA in aqueous solution, indicating its potential as chemical nuclease. Studies on DNA interactions, antimicrobial and cytotoxic activities have been undertaken to gain more information on the biological significance of HHSB and copper(II)-HHSB chelate species.

Synthesis and characterization of V(IV)O complexes of picolinate and pyrazine derivatives. Behavior in the solid state and aqueous solution and biotransformation in the presence of blood plasma proteins.

Oxidovanadium(IV) complexes with 5-cyanopyridine-2-carboxylic acid (HpicCN), 3,5-difluoropyridine-2-carboxylic acid (HpicFF), 3-hydroxypyridine-2-carboxylic acid (H2hypic), and pyrazine-2-carboxylic acid (Hprz) have been synthesized and characterized in the solid state and aqueous solution through elemental analysis, IR and EPR spectroscopy, potentiometric titrations, and DFT simulations. The crystal structures of the complexes (OC-6-23)-[VO(picCN)2(H2O)]·2H2O (1·2H2O), (OC-6-24)-[VO(picCN)2(H2O)]·4H2O (2·4H2O), (OC-6-24)-Na[VO(Hhypic)3]·H2O (4), and two enantiomers of (OC-6-24)-[VO(prz)2(H2O)] (Λ-5 and Δ-5) have been determined also by X-ray crystallography. 1 presents the first crystallographic evidence for the formation of a OC-6-23 isomer for bis(picolinato) V(IV)O complexes, whereas 2, 4, and 5 possess the more common OC-6-24 arrangement. The strength order of the ligands is H2hypic ≫ HpicCN > Hprz > HpicFF, and this results in a different behavior at pH 7.40. In organic and aqueous solution the three isomers OC-6-23, OC-6-24, and OC-6-42 are formed, and this is confirmed by DFT simulations. In all the systems with apo-transferrin (VO)2(apo-hTf) is the main species in solution, with the hydrolytic V(IV)O species becoming more important with lowering the strength of the ligand. In the systems with albumin, (VO)(x)HSA (x = 5, 6) coexists with VOL2(HSA) and VOL(HSA)(H2O) when L = picCN, prz, with [VO(Hhypic)(hypic)](-), [VO(hypic)2](2-), and [(VO)4(µ-hypic)4(H2O)4] when H2hypic is studied, and with the hydrolytic V(IV)O species when HpicFF is examined. Finally, the consequence of the hydrolysis on the binding of V(IV)O(2+) to the blood proteins, the possible uptake of V species by the cells, and the possible relationship with the insulin-enhancing activity are discussed.

Fate of platinum metals in the environment.

For many years now automotive exhaust catalysts have been used to reduce the significant amounts of harmful chemical substances generated by car engines, such as carbon monoxide, nitrogen oxides, and aromatic hydrocarbons. Although they considerably decrease environmental contamination with the above-mentioned compounds, it is known that catalysts contribute to the environmental load of platinum metals (essential components of catalysts), which are released with exhaust fumes. Contamination with platinum metals stems mainly from automotive exhaust converters, but other major sources also exist. Since platinum group elements (PGEs): platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru) and iridium (Ir) seem to spread in the environment and accumulate in living organisms, they may pose a threat to animals and humans. This paper discusses the modes and forms of PGE emission as well as their impact on the environment and living organisms.

Formation in aqueous solution of a non-oxido V(IV) complex with VN6 coordination. Potentiometric, ESI-MS, spectroscopic and computational characterization.

The behaviour of the system formed by V(IV)O(2+) ion with all-cis-2,4,6-trimethoxycyclohexane-1,3,5-triamine (tmca) was characterized in aqueous solution through the combined application of electron paramagnetic resonance (EPR) and UV-Vis spectroscopy, electrospray ionization mass spectrometry (ESI-MS), pH-potentiometry and DFT methods. The formation of an unusual non-oxido [V(tmcaH-2)2] species with VN6 coordination, with the ligand in the bianionic form, was demonstrated. The geometry, EPR and UV-Vis spectra and electronic structure of [V(tmcaH-2)2] were simulated with Gaussian 09 and ORCA software and the results were compared with those of similar oxido and non-oxido vanadium(iv) species formed by other polyamine and polyol related ligands, such as 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci), 1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol (tdci), cis-inositol (ino) and 1,3,5-trideoxy-1,3,5-trimethoxy-cis-inositol (tmci). The results indicate that V(IV)O(2+) species are formed in acid and weakly basic solution and that [V(tmcaH-2)2] is observed above pH 10. In the non-oxido complex, DFT calculations suggest that the two -NH2 groups are in trans position and that the pre-organization of the ligands favours the metal complexation and the formation of the hexa-coordinated species with VN6 coordination.

Evaluation of polyphenols and anthocyanins contents in black chockeberry--Photinia melanocarpa (Michx.) fruits extract.

An evaluation of total polyphenols and anthocyanins contents in dietary supplements is important analysis in medical aspect of human and animal diets. The content of the mentioned compounds should be higher in 100 g of solid extracts than in 100 g of fruits. Thus, the presented work concerns the evaluation of total polyphenols and anthocyanins contents in black chockeberry--Photinia melanocarpa (Michx.) extract--dietary supplement (DS) available on market. The spectrophotometric analysis of DS were performed. The usage of certain conditions of measurements such as dilution factor, storage conditions and filtration, has the significance in the determination of the analyzed compounds in the extract.

Determination of nickel in Polish brands of margarines.

Nickel is used in the production of margarine as a catalyst for hydrogenation. This may lead to the presence of its residues in the products and could cause allergic reactions. Therefore, monitoring of this metal in foods is essential for consumers. The described liquid sampling AAS procedure allows product control. Nickel was determined in 10 brands of margarine, and only in 3 samples its content was below the acceptable limit of 0.2 mg kg(-1).

Impact of histidine residue on chelating ability of 2'-deoxyriboadenosine.

Copper(II) complexes with a new chelator-type nucleoside-histidine modified 2'-deoxyriboadenosine (N-[(9-ß-D-2'-deoxyribofuranosylpurin-6-yl)-carbamoyl]histidine) were studied by potentiometric and spectroscopic (UV-visible, CD, EPR) techniques, in conjunction with computer modeling optimization. The ligand can act as bidentate or tridentate depending on pH range. In acidic pH a very stable dimeric complex Cu(2)L(2) predominates with coordination spheres of both metal ions composed of oxygen atoms from carboxylic groups, one oxygen atom from ureido group and two nitrogen atoms derived from purine base and histidine ring. Above pH 5, deprotonation of carbamoyl nitrogens leads to the formation of CuL(2), Cu(2)L(2)H(-1) and Cu(2)L(2)H(-2) species. The CuL(2)H(-1) and CuL(2)H(-2) complexes with three or four nitrogens in Cu(II) coordination sphere have been detected in alkaline medium. Our findings suggest that N-[(9-beta-D-2'-deoxyribofuranosylpurin-6-yl)-carbamoyl]histidine chelates copper(II) ions very efficiently. The resulting complex might be used as an alternative base-pairing mode in which hydrogen-bonded base pairs present in natural DNA are replaced by metal-mediated ones.

Complex formation in aqueous solution and in the solid state of the potent insulin-enhancing V(IV)O2+ compounds formed by picolinate and quinolinate derivatives.

The complexation of V(IV)O(2+) ion with 10 picolinate and quinolinate derivatives, provided with the donor set (N, COO(-)), was studied in aqueous solution and in the solid state through the combined application of potentiometric (pH-titrations), spectroscopic (EPR, UV/vis and IR spectroscopy), and computational (density functional theory (DFT) calculations) methods. Such derivatives, that form potent insulin-enhancing V(IV)O(2+) compounds, are picolinic (picH), 6-methylpicolinic (6-mepicH), 3-methylpicolinic (3-mepicH), 5-butylpicolinic or fusaric (fusarH), 6-methyl-2,3-pyridindicarboxylic (6-me-2,3-pdcH(2)), 2-pyridylacetic (2-pyacH), 2-quinolinecarboxylic or quinaldic (quinH), 4-hydroxyquinoline-2-carboxylic or kynurenic (kynurH), 1-isoquinolinecarboxylic (1-iqcH) and 3-isoquinolinecarboxylic (3-iqcH) acid. On the basis of the potentiometric, spectroscopic, and DFT results, they were divided into the classes A, B, and C. The ligands belonging to class A (3-mepicH, 1-iqcH, 2-pyacH) form square pyramidal complexes in aqueous solution and in the solid state, and those belonging to class B (picH, fusarH, 3-iqcH) form cis-octahedral species, in which the two ligands adopt an (equatorial-equatorial) and an (equatorial-axial) arrangement and one water molecule occupies an equatorial site in cis position with respect to the V═O bond. Class C ligands (6-mepicH, 6-me-2,3-pdcH(2), quinH, kynurH) yield bis chelated species, that in water are in equilibrium between the square pyramidal and trans-octahedral form, where both the ligand molecules adopt an (equatorial-equatorial) arrangement and one water is in trans position with respect to the V═O group. The trans-octahedral compounds are characterized by an anomalous electron paramagnetic resonance (EPR) response, with A(z) value being reduced by about 10% with respect to the prediction of the "additivity rule". DFT methods allow to calculate the structure, (51)V hyperfine coupling constant (A(z)), the stretching frequency of V═O bond (ν(V═O)), the relative stability in aqueous solution, and the electronic structure and molecular orbital composition of bis chelated complexes. The results were used to explain the biotransformation of these potent insulin-enhancing compounds in blood serum.

Histamine modified 2'-deoxyriboadenosine--potential copper binding site in DNAzymes.

Copper(II) complexes of histamine modified 2'-deoxyriboadenosine (N-[(9-beta-D-2'-deoxyribofuranosylpurin-6-yl)-carbamoyl]histamine) ligand were studied by potentiometric, UV-visible and EPR techniques. The imidazole residue of the ligand was described as the main binding site forming mono-, bis-(ligand) and dimer complexes, but the interactions between adenosine nitrogen N(1) and carbamoyl nitrogen atoms and the copper(II) ion also were detected. This is the first report evaluating the coordinating ability of such a modified adenosine ligand towards copper(II) ion. Our findings suggest that histamine modified 2'-deoxyriboadenosine could chelate efficiently copper(II) ions if it were incorporated into DNAzyme sequence.