Ionic Exchange Resins and Hydrogels for Capturing Metal Ions in Selected Sweet Dessert Wines.

Samples of sweet and dessert wines, Vin Santo (VSR) from Malvasia grapes, and Granello (GR) from Sauvignon grapes were collected and analyzed for the content of selected macro- and micro-nutrients (Na, K, Mg, Ca, Mn, Fe, Cu and Zn) and of Pb. GR wines had low levels for Fe, Cu and Zn, when compared to VSR and in particular Zn was two orders of magnitude lower. Methods to decrease the content of Zn and Cu in VSR, as well as those for reducing, at the same time, the concentrations of Ca, Mg and K in both VSR and GR, to avoid the formation of opalescence and depots of metal tartrates, were studied. Synthetic hydrogels containing l-histidine residue were tested. The overall relative lowering effects were by ca 4, 23, and 12% for K, Mg and Ca contents, and ca 6, 27 and 10%, for Mn, Cu and Zn contents, in GR wine samples. Commercial ion exchange resin Lanxess Lewatit L-207 and L-208 were then assayed, being legally allowed in the agro-food industry. The L-207 resin revealed great lowering effects on the concentrations of Mn, Cu and Zn, being 75, 91 and 97%, respectively, in VSR wines and 77, 76 and 92%, respectively, in GR wines. The content of Zn was reduced from 49.3 ± 1.2 mg/L in the original wine, down to 1.1 ± 0.1 mg/L, within 48 h soaking. The effects on the character of the dessert wines by the resin L-207 was also taken under control, measuring pH and color index. The color index changed by ca 15% and pH by ca 6% upon treatment of VSR wine with L-207 resins (48 h).

{Ru(CO)x}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo.

The reaction of [Ru(CO)6Cl2], 1, with N[combining low line]3-methylbenzimidazole (MBI) and 5,6-dimethylbenzimidazole (DMBI) afforded two new complexes with the general formula fac-[RuII(CO)3Cl2L], L = MBI (2) or DMBI (4). Crystals of cis,trans-[RuII(CO)2Cl2(N[combining low line]3-MBI)2], 3, were also obtained from the mother liquor that produced 2. In the presence of water, the dissociation of Ru-N, Ru-Cl and Ru-CO bonds occurred as a function of time, water content and pH. Density functional theory structure simulations/optimizations were carried out at the Becke3LYP level of theory for evaluating the relative stability of possible conformers. ESI-MS studies revealed the ability of the complexes to link model proteins, such as lysozyme, bovine pancreatic ribonuclease and cytochrome c, with the partial release of the heteroaromatic base, chlorido and carbonyl ligands. X-ray diffraction studies on crystals grown from a solution of HEWL and 2 showed the partial removal of chloride and CO. Cytotoxicity tests yielded two-digit micromolar IC50 values in CH1/PA-1 and SW480 cancer cells. In contrast to CORM-3 and 2, a significantly reduced tumor growth was observed with 4 in the murine colon cancer CT-26 model in vivo.

Synthesis, spectroscopic and DFT structural characterization of two novel ruthenium(III) oxicam complexes. In vivo evaluation of anti-inflammatory and gastric damaging activities.

The reactions of ruthenium(III) chloride trihydrate with piroxicam (H2PIR) and tenoxicam (H2TEN), two widely used non-steroidal anti-inflammatory drugs, afforded [Ru(III)Cl2(H2PIR)(HPIR)],·1, and [Ru(III)Cl2(H2TEN)(HTEN)],·2. Both compounds were obtained as pure green solids through purification via flash column chromatography. Characterizations were accomplished through UV-vis and IR spectroscopy, potentiometry and HPLC. Quantum mechanics and density functional computational methods were applied to investigate their respective molecular structures. The experimental and computational results are in agreement with a pseudo-octahedral coordination where the two chlorido ligands are in trans positions (apical) and the two trans-N,O chelating oxicam ligands occupy the equatorial sites. Both compounds revealed an acceptable solubility and stability profile upon dissolution in a standard buffer at physiological pH. Nonetheless, the addition of biologically occurring reducing agents caused spectral changes. The two complexes manifested a poor reactivity with the model proteins cytochrome c and lysozyme: no evidence for adduct formation was indeed obtained based on a standard ESI MS analysis; in contrast, some significant reactivity with serum albumin was proved spectrophotometrically. Remarkably, both study compounds revealed pronounced anti-edema effects in vivo suggesting that the pharmacological actions of the ligands are mostly retained; in addition, they were less irritating than piroxicam on the gastric mucosa when the coordination compounds and free oxicam were administered at the same overall molar concentration of the ligand. Overall, the present results point out that ruthenium coordination may represent an effective strategy to improve the pharmacological properties of oxicam drugs reducing their undesired side effects.

Copper(I)-alkyl sulfide and -cysteine tri-nuclear clusters as models for metallo proteins: a structural density functional analysis.

After having set up the computational methodology for Cu(I)-sulfur systems as models for copper proteins, namely using the simple ligands H(2)S, HS(-), CH(3)SH, and CH(3)S(-), the Cu(I)-Cysteine systems have been investigated: [Cu(I)( S -H(2)Cys) (n) ](+) (H(2)Cys, cysteine, NH(2),SH,COOH) [Cu(I)( S -HCys) (n) ](1-) (n) (NH(2),S(-),COOH). Finally, the structures for bi-nuclear [Formula: see text] (Et, CH(2)CH(3)), [Formula: see text] and tri-nuclear [Cu(I)( S -SH)](3), [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] (NH(2),SH,COOH), [Formula: see text] (NH(2),S(-),COOH, and NH(2),SH,COO(-)), as well as [Formula: see text] (NH(2),S(-),COO(-)), were also optimized to mimic the active center for a metallo-chaperone copper transport protein (CopZ). The X-ray structures for the biomolecules were matched fairly well as regards the Cu-S bond distances and Cu…Cu contact distances in the case the model cysteine S atom is deprotonated. Upon protonation of ligand S atoms, the conformation of clusters is altered and might bring about the di- and tri-nuclear core breakage. These findings suggest that subtle protonation/deprotonation steps, i.e. small and/or local pH changes play a significant role for copper transport processes.

X-ray structural characterization of the bis-guanine derivative of a cisplatin analogue having just one proton on each coordinated nitrogen and a head-to-head conformation: [Pt{(+/-)-N,N'-dimethyl-2,3-diaminobutane}(9-ethyl-guanine)2]dinitrate.

The X-ray structural and NMR characterization of a bis-guanine derivative of a cisplatin analogue designed to reduce the rate of the Pt-N7 rotation of the coordinated guanine nucleobases by more than 1-million-fold is reported. The [Pt{(+/-)-Me(2)dab}(9-EtG)(2)](NO(3))(2) (Me(2)dab = N,N'-dimethyl-2,3-diaminobutane, 9-EtG = 9-ethyl-guanine) complex crystallizes in the P2(1)/n space group, and the crystal contains a racemic mixture of complex molecules. The data were collected at 120 +/- 2 K, and the crystal and molecular structure (comprising one disordered nitrate) were resolved and refined to conventional agreement factors of R1 = 0.0270 and wR2 = 0.0565. The guanine ligands assume the less common head-to-head (HH) orientation, disclosing full details of the intramolecular relationships between cis guanines and between guanine and cis amine. Moreover, an understanding has been gained of the steric factors determining induction of asymmetry (from carbons to adjacent nitrogen atoms) and puckering of the chelate ring (delta or lambda for R,S,S,R or S,R,R,S configurations at the N,C,C,N chelate-ring atoms, respectively) within the Me(2)dab ligand. The chemical shift separation between H8 signals of the two HT atropisomers and between the two H8 signals of the single HH atropisomer can be explained in terms of canting of the nucleobases relative to the coordination plane and in terms of the different relationships between the H8 proton of one guanine and the shielding zone of the cis guanine. Furthermore, for each configuration of the Me(2)dab ligand (R,S,S,R or S,R,R,S), the NMR data indicate that the handedness of canting is similar for the two guanines in all three (two HT and one HH) conformers (R canting for R,S,S,R and L canting for S,R,R,S configuration).

New platinum-oxicam complexes as anti-cancer drugs. Synthesis, characterization, release studies from smart hydrogels, evaluation of reactivity with selected proteins and cytotoxic activity in vitro.

The reaction of aqueous cis-[Pt(NH(3))(2)(H(2)O)(2)](NO(3))(2) with Na(+)HMEL(-) (H(2)MEL, meloxicam, 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide), and Na(+)HISO(-) (H(2)ISO, isoxicam, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) at pH 7 produced micro-crystalline cis-[Pt(NH(3))(2)(N(1')-HMEL)(2)], 5 and cis-[Pt(NH(3))(2)(N(1')-HISO)(2)], 6. The X-ray diffraction structure of 5 shows two HMEL(-) anions donating through the thiazole nitrogen atoms and adopting a head-to-tail (HT) conformation. The (1)H NMR spectrum for 5 from DMSO-d(6) shows inertness of the complex up to at least 24h. Delivery studies for 5 and 6 from vinyl hydrogel based on L-phenylalanine (pH 6.5, 25 degrees C) show that concentrations of complexes ranging between 2.5 and 5 microM can be reached after a day. Compounds 5 and 6 show strong anti-proliferative effects on CH1 cells (ovarian carcinoma, human) in vitro, IC(50) values being 0.60 and 0.37 microM, respectively (0.16 microM for reference, cis-diamminodichloridoplatinum(II), cisplatin). ESI-MS measurements clearly documented that both 5 and 6 form adducts with the three model proteins ubiquitin (UBI), cytochrome c (CYT C) and superoxide dismutase (SOD), the HISO(-) complex being significantly more effective than the HMEL(-) one. Density functional methods help in finding rationale for the easiest dissociation of Pt-H(2)ISO/HISO bonds when compared to the Pt-N(1)(')-H(2)MEL/N(1)(')-HMEL linkages.

fac-{Ru(CO)(3)}(2+) selectively targets the histidine residues of the beta-amyloid peptide 1-28. Implications for new Alzheimer's disease treatments based on ruthenium complexes.

The reaction of the ruthenium(II) complex fac-[Ru(CO)(3)Cl(2)(N(1)-thz)] (I hereafter; thz = 1,3-thiazole) with human beta-amyloid peptide 1-28 (Abeta(28)) and the resulting {Ru(CO)(3)}(2+) peptide adduct was investigated by a variety of biophysical methods. (1)H NMR titrations highlighted a selective interaction of {Ru(CO)(3)}(2+) with Abeta(28) histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of Abeta(28); electrospray ionization mass spectrometry (ESI-MS) suggested a prevalent 1:1 metal/peptide stoichiometry and disclosed the nature of peptide-bound metallic fragments. Notably, very similar ESI-MS results were obtained when I was reacted with Abeta(42). The implications of the above findings for a possible use of ruthenium compounds in Alzheimer's disease are discussed.

X-ray structure and density functional theory studies of an unexpected product: trans-bis{2-[(2-cyanoethyl)iminomethyl]phenolato}copper(II).

The title compound, [Cu(C(10)H(9)N(2)O)(2)] or [Cu(II)(CYMB)(2)], (I), was obtained in an attempt to reduce trans-bis(2-{[3,5-bis(trifluoromethyl)phenyl]iminomethyl}phenolato)copper(II), [Cu(TIMB)(2)], (II), with bis(pentamethylcyclopentadienyl)cobalt(II) [decamethylcobaltocene, Cp*(2)Co, (III)]. The molecular structure of (I) has the Cu(II) centre located on an inversion centre of the C2/c space group. A density functional theory (DFT) analysis at the B3LYP/Lanl2dz(CuF);6-31G**(CHNO) level performed in order to optimize the structures of the free ligands CYMB(-) and TIMB(-), and the metal complexes [Cu(I/II)(CYMB)(2)](-/0) and [Cu(I/II)(TIMB)(2)](-/0), reproduced well the X-ray diffraction structure and allowed us to infer the insertion of the cyanomethide anion on the 3,5-bis(trifluoromethyl)phenyl system from an evaluation of the Mulliken atomic charges and the electronic energies.

Cisplatin/hydrogel complex in cancer therapy.

Hydrogels containing alpha-amino acid residues (L-phenylalanine, L-histidine) were used to complex the chemotherapeutic agent cisplatin. The release of the drug in phosphate buffer solution showed an initial burst effect, followed by a near zero-order release phase over the seven days of reported period. Unlike the nonreleasing pattern of the hydrogel poly(N-acryloyl-L-phenylalanine-co-N-isopropylacrylamide) (CP2), the homopolymer poly(N-acryloyl-L-phenylalanine) (P9) hydrogel showed a released amount of cisplatin loaded from a water/DMSO mixture that was three times greater than that loaded from simple water. The hydrogel P9 formed with cisplatinum(II) complex species of well-defined stoichiometry; the drug species was released by a chemically controlled process. The Pt(II)/L (L is the monomeric unit of the polymer) stoichiometric molar ratio of 0.5, corresponding to two close carboxylate groups per Pt(II), was found by the viscometric data on the soluble polymer analogue. The platinum species released from cisplatin-loaded (from water) hydrogel retained its cytotoxic activity toward Me665/2/21 human melanoma cell line, in the same manner shown by the native cisplatin. On the contrary, the platinum species released from cisplatin-loaded (from water/DMSO) hydrogel was devoid of any cytotoxic effect.

Release studies from smart hydrogels as carriers for piroxicam and copper(II)-oxicam complexes as anti-inflammatory and anti-cancer drugs. X-ray structures of new copper(II)-piroxicam and -isoxicam complex molecules.

Piroxicam H(2)PIR (H(2)PIR, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide), [Cu(HPIR)(2)(H(2)O)(2)] previously prepared and tested from this laboratory and at National Institute of Health, National Cancer Institute, Developmental Therapeutic Program, NIH-NCI-DTP, USA [R. Cini, G. Tamasi, S. Defazio, M.B. Hursthouse, J. Inorg. Biochem. 101 (2007) 1140-1152, and references cited therein], [Cu(HMEL)(2)(DMF)] (H(2)MEL, 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide; DMF, N,N-dimethylformamide), [Cu(HISO)(2)] (H(2)ISO, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide), and [Cu(HTEN)(2)(H(2)O)(2)] (H(2)TEN, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-thieno[2,3-e][1,2]thiazine-3-carboxamide 1,1-dioxide), were loaded on CMH2 hydrogel (co-1:10-poly(N-methacryloyl-L-histidine-co-N-isopropylacrylamide) cross-linked with N,N'-ethylene-bis-acrylamide (EBA) 2%) and the kinetics of release of Cu-HPIR species in several media were studied. The release of Cu(HPIR)(2) in DMSO from CMH2 hydrogel after swelling and loading from DMSO followed a diffusion controlled process. The release of Cu(HPIR)/Cu(HPIR)(2) from dried CMH2 hydrogel after swelling and loading from THF solution, then soaking into water/DMSO 95:5 v/v (pH 5.6) followed a relaxation controlled and diffusion controlled mechanism. The amount of Cu(HPIR)(2) released in the medium reached 0.03 microg Cu/mg gel/mL, i.e. ca 0.8 microM within 48 h that compares well with the IC(50) values reported for metal based drugs like carboplatin (diammino(1,1-cyclobutandicarboxylato)platinum(II)) against certain human tumor cell lines. The release studies performed by monitoring both the absorbance values at 362 nm (sensitive to metal-bound HPIR(-)) and the content of Cu via AAS, showed an excellent agreement with the Cu(HPIR)(2) or Cu(HPIR)(2) stoichiometry, depending on the delivery medium. Corresponding studies were performed for other Cu(oxicam-H)(2) species in different delivery media.

[RuII(NO+)]3+-core complexes with 4-methyl-pyrimidine and ethyl-isonicotinate: synthesis, X-ray structure, spectroscopy, and computational and NO-release studies upon UVA irradiation.

The reaction of RuCl(3)(NO).H(2)O with 4-methylpyrimidine (MePYM) and ethylisonicotinate (EINT), in absolute ethanol at 40-55 degrees C afforded crystalline trans-[RuCl(3)(NO)L(2)] complexes. Structural studies via X-ray diffraction, and spectroscopic methods (NMR, IR, UV-visible (UV-Vis)) revealed that the molecular structures have the two Ls in trans positions (axial) and the chloride anions and the NO(+) cation as equatorial ligands; pyrimidine...pyrimidine pairing pattern via two weak C-H...N interactions occur. The molecular structures for the EINT derivative was inferred from spectroscopy and computations. Under irradiation at 366 nm several solutions of the title compounds deliver NO via first order processes. Visible light (420-700 nm) does not produce significant NO release from CH(2)Cl(2) and CH(3)CN solutions within 24h.

NMR and X-ray structural characterization of a cisplatin analogue able to slow down the Pt-N7 rotation of a coordinated guanine base by a billion-fold times: 2,2'-bipiperidine(dimethylmalonato)platinum(II) complex.

The synthesis and the NMR and X-ray structural characterization of a cisplatin analogue designed to reduce the Pt-N7 rotation of a coordinated guanine base by a billion times are reported. The [Pt(dmm){(+/-)-bip}] (dmm=dimethylmalonato; bip=2,2'-bipiperidine) complex crystallizes in the C2/m space group, which contemplates a mirror plane bisecting the bip and dmm ligands. Because the bip moiety (R, R or S, S configuration at the 2,2'-carbon atoms) does not have planes of symmetry, the requirements of the crystal symmetry are satisfied by a statistical disorder made of bip molecules of R, R or S, S configurations alternating at the same crystallographic site. Such an unexpected arrangement has been permitted by a "quasi planarity" of the bip ligand [maximum deviation from the mean plane through the C and N atoms of 0.2927(9) A], which allows bip molecules of different chiralities to fit in the same space. The bip array of heavy atoms is overlaid, from both sides, by a layer of "quasi axial" (C)H and (N)H atoms (six per side). Those on one side are hydrogen-bonded to the dmm oxygen atoms of another complex molecule joined in a pair. The distance between the average platinum coordination planes is as short as 3.498(1) A, comparable to those found in crystals of the [PtCl 2(bipy)] complex (bipy=2,2'-bipyridine) and of graphite, in which, however, all atoms of each unit are rigorously coplanar and there are no out-of-plane hydrogen atoms. The NMR data show a net chemical shift separation between geminal methylene protons, with the "quasi axial" protons being always at higher field with respect to the "quasi equatorial" ones. This is in accordance with a rigid bip ligand frame and the inability of the bip methylene protons adjacent to the coordinated nitrogen to rotate away from a cis-G base (G=guanine) during G rotation around the Pt-N7 bond.

Unusual coordinating behavior by three non-steroidal anti-inflammatory drugs from the oxicam family towards copper(II). Synthesis, X-ray structure for copper(II)-isoxicam, -meloxicam and -cinnoxicam-derivative complexes, and cytotoxic activity for a copper(II)-piroxicam complex.

Cytotoxic tests recently performed at National Cancer Institute, NCI (USA), on [Cu(HPIR)(2)(DMF)(2)], 1, (H(2)PIR=piroxicam, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) a widely used non-steroidal anti-inflammatory drug, NSAID [see R. Cini, G. Giorgi, A. Cinquantini, C. Rossi, M. Sabat, Inorg. Chem. 29 (1990) 5197-5200, for synthesis and structural characterization, DMF=dimethylformamide] (NSC #624662) by using a panel of ca. 50 human cancer cells, showed growth inhibition factor GI(50) values as low as 20microM against several cancer lines, with an average value 54.4microM. The activity of 1 is larger against ovarian cancer cells, non-small lung cancer cells, melanoma cancer cells, and central nervous system cancer cells. The widely used anticancer drug carboplatin (cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)) (NSC #241240) has average GI(50) value of 102microM. The reactions of copper(II)-acetate with other NSAIDs from the oxicam family were tested and crystalline complexes were obtained and characterized. Isoxicam (H(2)ISO=4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HISO)(2)].0.5DMF, 2.0.5DMF (DMF=dimethylfomamide). The coordination arrangement is square-planar and the HISO(-) anions behave as ambi-dentate chelators via O(amide),N(isoxazole) and O(enolate),O(amide) donors. Meloxicam (H(2)MEL=4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HMEL)(2)(DMF)].0.25H(2)O, 3.0.25H(2)O. The coordination arrangement is square-pyramidal, the equatorial donors being O(amide),N(thiazole) from two HMEL(-) anions and the apical donor being O(DMF). Unexpectedly, cinnoxicam (HCIN=2-methyl-1,1-dioxido-3-[(pyridin-2-ylamino)carbonyl]-2H-1,2-benzothiazin-4-yl-(3-phenylacrylate)) produced [Cu(MBT)(2)(PPA)(2)] (MBT=3-(methoxycarbonyl)-2-methyl-2H-1,2-benzothiazin-4-olate 1,1-dioxide, PPA=3-phenyl-N-pyridin-2-ylacrylamide).

fac-{Ru(CO)3}2+-core complexes and design of metal-based drugs. synthesis, structure, and reactivity of Ru-thiazole derivative with serum proteins and absorption-release studies with acryloyl and silica hydrogels as carriers in physiological media.

The reaction of [Ru2(CO)6Cl4], 1, with excess THZ (1,3-thiazole) in absolute ethanol at 55 degrees C produces fac-[Ru(CO)3Cl2(THZ)], 2, in high yield. [Ru(CO)2Cl2(THZ)2], 3, is formed at higher temperature (ca 70 degrees C) and higher concentration of THZ. The X-ray structures of the new compounds have been determined, and density functional studies performed at the hybrid B3LYP/(Lanl2DZ, Ru; 6-311+G**, CHClNOS) level allowed the estimation of the structures of several conformers as well as that of their relative total electronic energies. Compound 2 is soluble (slowly) in aqueous media, where it reacts with the transport proteins bovine serum albumin (BSA) and human apotransferrin (HTF), and at a lower extent with calf thymus DNA (CT-DNA) and with guanosine-5'-monophosphate (GMP). The complex molecule is adsorbed by certain synthetic acryloyl polymers that have terminal carboxylate functions and is embedded in silica gels when these latter are prepared in the presence of a solution of 2. Ruthenium species are slowly released from the loaded gels into physiological solutions at pH 7.4. The reactivity of 2 with biomolecules and synthetic hydrogels makes it a compound of interest for anticancer and antimetastases tests.

The first pure LambdaHT rotamer of a complex with a cis-[metal(nucleotide)2] unit: a cis-[Pt(amine)2(nucleotide)2] LambdaHT rotamer with unique molecular structural features.

cis-[PtA2(nucleotide)2] complexes (A2 stands for two amines or a diamine) have been extensively investigated as model compounds for key cisplatin-DNA adducts. All cis-[metal(nucleotide/nucleoside)2] complexes with guanine and related purines characterized in the solid state thus far have the DeltaHT conformation (head-to-tail orientation of the two bases and right-handed chirality). In sharp contrast, the LambdaHT conformation (left-handed chirality) dominates in acidic and neutral aqueous solutions of cis-[PtA2(5'-GMP)2] complexes. Molecular models and solution experiments indicate that the LambdaHT conformer is stabilized by 5'-phosphate/N1H hydrogen-bond interactions between cis nucleotides with the normal anti conformation. However, this evidence, while compelling, is indirect. At last, conditions have been defined to allow crystallization of this elusive conformer. The structure obtained reveals three unique features not present in all other cis-[PtA2(nucleotide)2] solid-state structures: a LambdaHT conformation, very strong hydrogen-bond interactions between the phosphate and N1H of cis nucleotides, and a very small dihedral angle between the planes of the two guanines lying nearly perpendicular to the coordination plane. These new results indicate that, because there are no local base-base repulsions precluding the LambdaHT conformer, global forces rather than local interactions account for the predominance of the DeltaHT conformer over the LambdaHT conformer in the solid state and in both inter- and intrastrand HT crosslinks of oligonucleotides and DNA.

Structural study of ribonucleotide reductase inhibitor hydrazones. Synthesis and X-ray diffraction analysis of a copper(II)-benzoylpyridine-2-quinolinyl hydrazone complex.

Single crystals as yellow needles of N-(4,8-dimethyl-quinolin-2-yl)-N'-(1-pyridin-2-yl-ethylidene)-hydrazine, HL(1), 1, and N-(4-methyl-quinolin-2-yl)-N'-(phenyl-pyridin-2-yl-methylene)-hydrazine, HL(2), 2, were obtained from methanol (MeOH) and analyzed via X-ray diffraction (XRD). HL(2) reacted with copper(II) acetate to produce a dark red powder that gave single crystals of [Cu(L(2))(OOCCH(3))].0.9C(6)H(5)CH(3), 3.0.9C(6)H(5)CH(3) when recrystallized from toluene. The conformation of the N(quinolinyl,q)-C(q)-N(H)-N(imine,i)-C-C(pyridine,p)-N(p) grouping is trans,trans,trans,trans or tttt, and ttcc for 1 and 2, respectively, at the solid state, as revealed via single crystal X-ray diffraction. Thus, the structure of 1 has the methyl (hydrazone) group syn to the N-H bond and syn to the N(q) and N(p) atom. On the other side, the structure of 2 is stabilized by a strong intra-molecular N-H...N hydrogen bond which involves the pyridyl nitrogen atom. The molecule 1 is almost planar, the torsion angles do not deviate more than 4 degrees from the idealized values of 0 degrees and 180 degrees . In the structure of 2 the pyridyl ring is almost coplanar with the N(q)-C(q)-NH-N(i)-C system, whereas the phenyl (Ph) ring is twisted by ca. 55 degrees . The structure of 3 has the L(2) ligand as deprotonated at the N-N function and in a cttc conformation as opposite to the ttcc one found for pure 2. The metal center is coordinated through N(q), N(i), N(p) and through an oxygen atom from a carboxylate anion. The molecular modeling analysis of 1 and 2 (semi-empirical molecular orbital at Zerner's intermediate neglect of differential overlap (ZINDO/1) level and density functional theory (DFT) methods) gave good agreement with the X-ray structures. Semi-empirical quantum mechanics analysis of 3 allowed to assign the UV-Vis spectrum that is characterized by strong absorptions in the visible, UVA and UVB regions. Owing to the ribonucleotide reductase inhibitory activity of the ligand, to the ascertained anticancer activity shown previously by related copper(II)-hydrazone complexes, and to the oxygen radical scavenger activity of several copper(II)-complexes, 3 is potentially anticancer and anti-inflammatory.

Complexes having the fac-[M(CO)3]+ core (M=Tc, Re) useful in radiopharmaceuticals: X-ray and NMR structural characterization and density functional calculations of species containing two sp3 N donors and one sp3 O donor.

Radiopharmaceuticals containing the "fac-[M(CO)3]+ " core (M=99mTc, 186Re, or 188Re) have potential as diagnostic or therapeutic agents. Complexes with this core with sp3 amine donors have received little attention. We have studied adducts formed by ENDACH2 (HO2CCH2NHCH2CH2NHCH2CO2H) and ENACH (NH2CH2CH2NHCH2CO2H). Re(CO)3(ENDACH)-A (1A) and Re(CO)3(ENDACH)-B (1B) isomers were obtained by the reaction of ENDACH2 with Re(CO)5Cl. Re(CO)3(ENAC) (2) was obtained by the reaction of ENACH with aqueous [Re(CO)3(H2O)3]+. From single-crystal X-ray data, the three new neutral complexes, 1A, 1B, and 2, have a six-coordinate, pseudo-octahedral Re center with facially coordinated carbonyl ligands. ENDACH- and ENAC- bind facially to Re through both amine nitrogens and one carboxyl oxygen, forming two five-membered chelate rings. The Re(CO)3(ENDACH) isomers have an uncoordinated, dangling -CH2CO2H group, which is an ideal coupling site for attachment to biomolecules. The isomers differ by the configuration of the NH center bearing this dangling group. The H atom of the amine (N2) is endo (near the carbonyl ligands in the basal plane) in 1A and exo (away from carbonyl ligands) in isomer 1B. Isomers reach equilibrium (1A:1B, 70:30) after 3 days at high pH. Density functional structure optimizations were performed for isolated molecules of the type Tc(I)/Re(I)(CO)3(N2O): [Re(CO)3(NH3)2(H2O)]+, [Tc(CO)3(NH3)2(H2O)]+, [Re(CO)3(EN)(H2O)]+ (EN, ethylenediamine), [Tc(CO)3(EN)(H2O)]+, and various models for 1A, 1B, and 2. The computed structures are in good agreement with the X-ray structures. The theoretical and experimental Re-N bond distances usually agree within 0.045 A. The total electronic energy values for the computed 1A and 1B models differ by 0.815 kcal mol(-1), giving an isomer ratio of 80:20, in good agreement with the 1A/1B ratio (70:30) found.

Heavy metals in drinking waters from Mount Amiata (Tuscany, Italy). Possible risks from arsenic for public health in the Province of Siena.

Concentrations of As, Al and some heavy metals (V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, Pb) were measured in drinking waters from Siena and Grosseto districts, South Tuscany, Italy. The analysis, performed mostly by electrothermal activated atomic absorption spectroscopy equipped with graphite furnace, and in some cases high-resolution inductively coupled plasma mass spectrometry, indicated that concentrations of the elements were generally far below the maximum allowed concentration (MAC). However, the concentration of As in some of the waters at sources or at the terminals of the water webs was relatively high (largest value, 14.4(2) microg/l) when compared to the MAC(As) value (10 microg/l, December 25, 2003; Italian Law). Relatively high concentrations of some metals had been detected in a few samples from the ends of the distribution webs, when compared to values at sources. These effects are probably due to leaching from metal pipes. A general 'metal index' (MI) for drinking water, which takes into account possible additive effects of N heavy metals on the human health that helps to quickly evaluate the overall quality of drinking waters, is introduced in this paper as MI=?(i=1,N)[C(i)/(MAC)(i)]. Samples from Ermicciolo spring and Siena water web had MI values of 1.1 and 1.3, respectively, showing that the quality of drinking water in town is somewhat worse than that at one of the main sources, at least regarding the 12 elements taken into account.

X-ray structure and circular dichroism of pure rotamers of bis[guanosine-5'-monophosphate(-1)](N,N,N',N'-tetramethylcyclohexyl-1,2-diamine)platinum(II) complexes that have R,R and S,S configurations at the asymmetric diamine.

The use of a sterically hindered diamine ligand (Me(4)DACH) has allowed for the first time, the isolation and characterization, both in the solid state (X-ray crystallography) and in solution (circular dichroism), of pure DeltaHT rotamers of [Pt(Me(4)dach)(5'-GMP)(2)] (compounds 1 and 2 for R,R and S,S configurations of the Me(4)DACH ligand, respectively). Comparison of the CD spectra obtained for each rotamer, which differ only in the chirality of the Me(4)DACH ligand (R,R or S,S) or in the chirality of the HT conformation (Delta or Lambda), allowed us to conclude that, in the 200-350 nm range, the contributions to the overall CD spectrum that stem from diamine chirality and diamine-induced chirality of platinum d--d transitions or from sugar chirality are negligible relative to the exciton chiral coupling that occurs for pi-pi* transitions of the cis guanines. Accurate molecular structures of 1.10 D(2)O and 2.14 D(2)O (conventional crystallographic agreement indexes R(1) convergent to 2.07 % and 2.18 %, respectively) revealed that the crystallized rotamers have a DeltaHT conformation that is in agreement with all previously reported X-ray structures of [Pt(diamine)(nucleos(t)ide)(2)] complexes. This conformation allows the 5'-phosphate to be located in proximity to the Me(4)DACH ligand so that (P)O...HC(N) hydrogen-bond interactions exists in both complexes. For both structures, the canting of the guanine planes on the coordination plane is right-handed (R; canting angle (Phi) of 80.9 degrees and 73.2 degrees, respectively); this indicates that the canting direction is driven by the HT conformation chirality (Delta for both compounds) and not by the chirality of the carrier ligand (different for the two compounds). Density functional theory analysis of the conformational space as a function of Phi indicated a good agreement between the computed and experimental structures. The increase in energy for Phi values below 65 degrees and 55 degrees (for 1 and 2, respectively) is mainly due to the short intramolecular contacts between C(8)H and the cis N-Me groups on the same side of the platinum coordination plane.