Giovanna Gasparri Fava

SYNTHESIS, SPECTROSCOPIC AND STRUCTURAL CHARACTERIZATION, AND BIOLOGICAL ACTIVITY OF AQUACHLORO(PYRIDOXAL THIOSEMICARBAZONE) COPPER(II) CHLORIDE

The synthesis, spectroscopic studies, x-ray crystal structure, and biological properties of the complex [Cu(H2L)(OH2)Cl]Cl (1) (H2L = pyridoxal thiosemicarbazone) are reported. The compound crystallizes in space group P2(1)/n, a = 12.128(2), b = 9.096(2), c = 13.592(2) A, beta = 108.65(2) degrees, U = 1420.7 A3, and Z = 4. The molecular structure consists of discrete cations [Cu(H2L)(OH2)Cl]+ and Cl- anions. Each copper atom is in an approximately square pyramidal environment involving the phenolic oxygen, the imine nitrogen, the sulphur, and a water oxygen in the equatorial positions, while a chlorine atom occupies the axial position. The structure of this complex is compared to that of the dimeric [(Cu(HL)(OH2))2]Cl2.2H2O (2) obtained under different experimental conditions, to that of a Co(III) complex with the same ligand [Co(HL)L].4.5H2O (3) and to that of the free ligand H2L, especially in relation to its biological activity. Compounds 1 and 2 have not antiviral action in vitro with respect to RNA viruses, show an inductive effect on Friend erythroleukemia cells (FLC), erythroid differentiation and a suppressive effect regarding FLC proliferation. Complex 3 and the free ligand do not have biological activity.

Synthesis, characterization and biological activity of two new polymeric copper(II) complexes with α-ketoglutaric acid thiosemicarbazone

In this paper we describe the synthesis of new copper complexes with alpha-ketoglutaric acid thiosemicarbazone. The crystal structures of the two compounds: [Cu(H(2)ct)Cl](n) [(Cu(H(2)ct)Cl)(2)] (1) and [Cu(Hct)](n).3nH(2)O (2) (H(3)ct=alpha-ketoglutaric acid thiosemicarbazone) have been determined by X-ray and spectroscopic methods. In 1 two independent copper atoms are present. Cu(1), in a nitrogen- and oxygen-bridged polymer, is a six-coordinated (4+2), Cu(2), five coordinated (4+1), is a chlorine-bridged dimer. In 2 the copper atom presents a penta-coordination, polymeric chains form layers and the -CH(2)CH(2)COO(-) groups bridge copper atoms. In 1 a monodentate and in 2 a syn-anti bidentate bridging carboxylate are present. The biological properties of 1 and 2 and also of the free ligand (H(3)ct) were tested in vitro and compared on Friend erythroleukemia cells (FLC) and on human leukemia cell lines K562 and U937. On the FLC cells the free ligand does not inhibit cell growth, but increases the DNA synthesis; complex 1 inhibits cell proliferation and increases the DNA synthesis; complex 2 inhibits cell growth, but induces a decrement of DNA synthesis and increases the reverse transcriptase activity. Regarding the human cell lines, both complexes show proliferation inhibition through an apoptosis mechanism on cell line U937, while they have no effects on the K562 line.

Synthesis, spectroscopic and structural characterization of chlorobis(methyl pyruvate thiosemicarbazone)copper(I) and chlorobis(triphenylphosphine) (methyl pyruvate thiosemicarbazone)copper(I) toluene solvate (2/1)

Abstract Two new compounds, chlorobis(methyl pyruvate thiosemicarbazone)copper(I), [Cu(Hmpt)2Cl] (A), and chlorobis(triphenylphosphine)(methyl pyruvate thiosemicarbazone)copper(I) toluene solvate (2/1), [Cu(PPh3)2(Hmpt)Cl]·0.5C7H8 (B) have been synthesized and characterized using spectroscopic studies and single-crystal X-ray diffraction methods at 293 K. Compound A crystallizes in space group C2/c, with a = 14.695(1), b = 13.775(1), c = 10.251(1) A, β = 113.38(1)°, V= 1904.7 A3; compound B crystallizes in space group P 1 , with a=17.871(7), b=10.681(2), c=11.695(7) A, α=74.90(1), β=86.65(4), γ=83.66(2)°, V=2141 A3. The crystal structures were solved by the heavy-atom method for A and by direct methods for B and refined to R values of 0.053 for both compounds. In A the copper and chlorine atoms lie on a crystallographic two-fold axis and the trigonal coordination around copper involves, besides chlorine, two sulfur atoms from two Hmpt molecules. In B the copper is tetrahedrally four-coordinated involving a chlorine atom, a sulfur atom from the Hmpt molecule and the phosphorus atoms of the two PPh3 molecules. In both compounds the ligand is neutral, monodentate through the sulfur atom and shows the configuration Z E Z about the C(2)N(3), C(1)N(2) and C(2)C(3) bonds (with respect to possible donating centres O(1), N(3) and S). The main vibrational bands are also reported and discussed.

SYNTHESIS, CHARACTERISATION AND BIOLOGICAL ACTIVITY OF THREE COPPER(II) COMPLEXES WITH A MODIFIED NITROGENOUS BASE : 5-FORMYLURACIL THIOSEMICARBAZONE

Three Cu(II) co-ordination compounds with a novel ligand, 5-formyluracil thiosemicarbazone (H3ut), have been synthesised and characterised by single-crystal X-ray diffraction and subsequently tested in vitro on human leukemic cells. The crystal structures revealed, in all three cases, a square pyramidal co-ordination geometry of the copper atom with the ligand lying on the basal plane and behaving as an SNO terdentate ligand. These three compounds have been tested on human leukemic cell line K562 and CEM. In these experiments the complexes have demonstrated to inhibit cell growth and one of them to induce apoptosis. In the paper we also report the spectrophotometric characterization of the free ligand.

Transition-metal complexes of isatin-β-thiosemicarbazone. X-ray crystal structure of two nickel complexes

Manganese, iron, cobalt, nickel, copper and zinc complexes of isatin-beta-thiosemicarbazone (H2L) have been synthesized and spectroscopically characterized The X-ray crystal structures of two nickel complexes, namely [Ni(HL)2]. EtOH (1) and [Ni(HL)2]. 2DMF (2), reveal a distorted octahedral coordination with the monodeprotonated ligand that behaves as an O,N,S terdentate. Different packing interactions are determined by the presence of different crystallization solvents, i.e., ethanol in 1 and dimethylformamide (DMF) in 2. 1H and 13C NMR studies of the ligand and zinc complexes in solution were carried out and a complete assignment for the ligand was made by homodecoupling, gradient assisted 2D 1H-13C HMQC and HMBC NMR spectroscopy. Biological studies, carried out in vitro on human leukaemic cell lines U937, have shown that the free ligand and the copper (II) complex are more active in the inhibition of cell proliferation than the nickel complexes. No compound was able to induce apoptosis.

Acenaphthenequinone thiosemicarbazone and its transition metal complexes: Synthesis, structure, and biological activity☆

The reaction of iron, nickel, copper, and zinc chlorides or acetates with acenaphthenequinone thiosemicarbazone, Haqtsc leads to the formation of novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the free ligand Haqtsc 1 and of the compound [Ni(aqtsc)2].DMF 2, have also been determined by X-ray methods from diffractometer data. In 1, the conformation of the two nonequivalent molecules is governed by intramolecular hydrogen bonds, while an intermolecular hydrogen bond is responsible for dimer-like groups formation. In 2, the coordination geometry about nickel is distorted octahedral, and the two ligand molecules are terdentate monodeprotonated. Biological studies have shown that, for the first time at least up the used doses, a free ligand is active both in the inhibition of cell proliferation and in the induced differentiation on Friend erythroleukemia cells (FLC).

2,6-DIACETYLPYRIDINE BIS(THIOSEMICARBAZONES) ZINC COMPLEXES: SYNTHESIS, STRUCTURE, AND BIOLOGICAL ACTIVITY

The reaction of zinc chloride, acetate, or perchlorate with two bis(thiosemicarbazones) of 2,6-diacetylpyridine [H2daptsc = 2,6-diacetylpyridine bis(thiosemicarbazone) and H2dapipt = 2,6-diacetylpyridine bis(hydrazinopyruvoylthiosemicarbazone)] leads to the formation of four novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the two compounds--[Zn(daptsc)]2.2DMF (1) and [Zn(H2dapipt)(OH2)2](CIO4)2.3H2O (2)--also have been determined by x-ray methods from diffractometer data. Compound (1) is dimeric and the two zinc atoms have a distorted octahedral coordination. The ligand is deprotonated. In compound (2), the coordination geometry about zinc is pentagonal--bipyramidal and the ligand is in the neutral form. The molecular structure of (2) consists of cations [Zn(H2dapipt)(OH2)]2+, CIO4- disordered anions, and three water molecules of solvation. Biological studies have shown that the ligands and the complexes Zn(daptsc).1/2EtOH and Zn(H2daptsc)Cl2 have an effect in vitro on cell proliferation and differentiation (inhibition); both are concentration dependent. [Zn(daptsc)]2.2DMF (1) shows the effects at lower concentration values with respect to other compounds.

The four-carbon elongation of three-carbon chiral synthons using 2-(trimethylsiloxy)furan: highly stereocontrolled entry to enantiomerically pure seven-carbon α,β-unsaturated 2,3-dideoxy-aldonolactones

Abstract The BF3-promoted addition of 2-(trimethylsiloxy)furan to three carbon synthons derived from D- and L-glyceraldehyde, D- and L-serinal, and imines thereof furnishes C7 α,β-unsaturated 2,3-dideoxy-aldonolactone derivatives in high yield, with very high level of diastereoselection. In all the cases, compounds having 4,5-threo:5,6-erythro relative stereodisposition preferentially emerge from the reactions, accompanied by only marginal amounts of 4,5-erythro:5,6-erythro epimers. An empirical rule for the rapid assigment of the configuration at C-4 (γ-carbon) of γ- substituted unsaturated and saturated γ-butyrolactones is given, based upon the sign of the optical rotation values.

Total synthesis of 1,5-dideoxy-1,5-iminoalditols

Abstract Enantiomerically pure 1,5-dideoxy-1,5-imino-D-glycero-D-allo-heptitol (10) has been synthesized in ca. 9% overall yield by utilizing 2,3-O-isopropylidene-D-glyceraldehyde-N-benzylimine (1) as a chiral source and 2-(trimethylsiloxy)furan (2) as a homologative reactant. The opening move was the preparation of properly protected seven-carbon butenolide 4, followed by diastereoselective anti, cis-dihydroxylation of the lactone double bond and furanose-to-azapyranose ring expansion. This generated a piperidine intermediate 7, the stereochemistry of which was secured by a single crystal X-ray analysis of its diacetate 9.

Total synthesis of both enentiomers of trans-β-hydroxyppecolic acid

Abstract trans-β-Hydroxypipecolic acids of both l - and d -series, l -1 and d -1, have been straightforwardly prepared in 14% and 15% yields, respectively, starting from glyceraldehyde imines d -7 and l -7 as useful three-carbon chirons. The key feature of these parallel syntheses lies on the highly diastereoselective character of the initial coupling manoeuver between silyloxy furan TBSOF and imines 7, which ultimately accounts for the relative, and hence absolute configuration of the target pipecolic acids.