Enrico Leporati

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.

Palladium(II) complexes containing a P, N chelating ligand Part II. Synthesis and characterisation of complexes with different hydrazinic ligands. Catalytic activity in the hydrogenation of double and triple C-C bonds

Abstract Palladium(II) complexes of the type Pd(PNO)Y (PNO = 2-(diphenylphosphino)benzaldehyde picolinhydrazone, nicotinhydrazone, isonicotinhydrazone; Y = CH3CO2, Cl, I) and Pd(PNS)Y (PNS = 2-(diphenylphosphino)benzaldehyde thiosemicarbazone; Y = CH3CO2, Cl, I) were synthesised and characterised by spectroscopic methods. The X-ray structure of an iodo complex was also determined. The catalytic activity of all the complexes in the homogeneous hydrogenation of terminal double and triple bonds was tested with particular regards to the chemoselectivity from triple to double bond. A correlation between the catalytic activity and the nature of the ligand and Y group was established. In the hydrogenation of phenylacetylene using acetato complexes as catalysts, stable phenylethynylpalladium(II) complexes were recovered and characterised by spectroscopic methods. A facile route of synthesis of alkynyl complexes was also determined.

4-Amino-3-methyl-1,2,4-Δ2-triazoline-5-thione: an example of thione-thiol tautomerism and stabilization of Cu(I) and Au(I) complexes☆

Two complexes of Cu(I) (1) and Au(I) (2) with the ligand 4-amino-3-methyl-1,2,4-Δ2-triazoline-5-thione (HL) have been prepared. Potentiometric and spectrophotometric studies on the ligand show that the thiol is the prevalent form in solution while in the solid state the thione form is present. Preliminary ab initio calculations of the molecular electrostatic potential maps for the ligand HL are in good agreement with reactivity and studies in solution. Both compounds crystallize in the monoclinic system, 1 in the P21/m space group with unit cell parameters a = 6.829(2), b = 6.218(2), c = 8.540(3) A, β = 105.68(2)°, Dcalc = 2.180 g cm−3 and V = 349.1(2) A3 or Z = 2, 2 in the C2/m space group with unit cell parameters a = 15.902(6), b = 6.606(5), c = 6.707(3) A, β = 109.37(2)°, Dcalc = 2.462 g cm−3 and V = 664.7(6) A3 for Z = 2.5563 and 742 observed reflections for 1 and 2, respectively, were used in the refinement which converged to R and Rw values of 0.0388 and 0.0528 for 1 and 0.0432 and 0.0540 for 2. The structure of complex 1 presents an unusual phenomenon of disorder with the Cu atoms statistically distributed in two independent positions and the complex can be described as assuming a non-molecular cationic structure. The crystal structure of 2 consists of discrete [Au(HL)2]+ and Cl− ions.

Organotin complexes with pyrrole-2-carboxaldehyde monoacylhydrazones. Synthesis, spectroscopic properties, antimicrobial activity, and genotoxicity

A series of organotin complexes with pyrrole-2-carboxaldehyde 2-hydroxybenzoylhydrazone (H3mfps) and pyrrole-2-carboxaldehyde 2-picolinoylhydrazone (H2mfpp) was investigated. The IR, 1H, and 119Sn nuclear magnetic resonance spectroscopic characterization of all the compounds is reported and discussed in connection with the ligand behaviour of the hydrazone and the structure of the organotin complex. Complexes exhibit antibacterial properties higher than those of the corresponding ligands but they turn out to be less potent than the parent organotin compounds. Sn(H3mfps) (C6H5)2Cl2.2H2O and Sn(Hmfpp)(n-C4H9)2Cl are the most active antibacterial compounds showing MIC values between 3-6 micrograms/ml against Bacillus subtilis and Staphylococcus aureus and between 6-25 micrograms/ml against Escherichia coli; the first compound also strongly inhibits the growth of Aspergillus niger. All the ligands and complexes are devoid of DNA-damaging activity in the Bacillus subtilis rec-assay. H2mfpp and its complexes Sn(Hmfpp)(C2H5)2Cl and Sn3(Hmfpp)(mfpp) (C6H5)3Cl6 are shown by the Salmonella-microsome assay to be mutagenic substances in the presence of a metabolic activation system. The obtained results are discussed on the basis of structure-activity relationships.

Structural researches on copper(II) complexes with vitamin B6 derivatives: X-ray structures of bis(N-t-butyl-pyridoxylideneiminato)copper(II) and bis(N-t-butyl-pyridoxylideneiminato)copper(II)methanol (1:1/3)

Abstract The structures of bis(N-t-butyl-pyridoxylideneiminato)copper(II) (compound I) and bis(N-t-butyl-pyridoxylideneiminato)copper(II)methanol (1:1/3) (compound II) were determined from three-dimensional X-ray data collected by counter methods. Crystals (I) are monoclinic, space group C 2/c with Z = 8 in a unit cell of dimensions a = 11.19(1), b = 20.06(2), c = 23.99(2) A, β = 99.7(1)°. Crystals (II) are trigonal, space group R 3 c with Z = 18 and cell dimensions a = 16.82(3), c = 48.59(5) A . Compound (I) was refined to a final conventional R factor of 0.0403 for 2150 reflections with I ⩾ 2σ( I ) and compound (II) to a final R ( F ) of 0.0475 for 543 reflections with F ⩾ 6σ( F ). Both compounds show a C 2 symmetry but in (II) only, the copper atom lies on a crystallographic two-fold axis; the metal atom is chelated to two pyridoxylidene ligands through the imino N and the phenolato O in a flattened tetrahedral coordination with a θ value of 52.9(3)° for (I) and 47.1(7)° for (II). In (I) the OH⋯N hydrogen bonds form layers while in (II) they determine a trimeric unit which hosts a methanol molecule as guest. The layers or the trimers are held together by weak Van der Waals interactions.

Protonation equilibria in aqueous solutions of thiocarbohydrazide and thiosemicarbazide

Abstract The equilibria in aqueous solutions of thiocarbohydrazide have been potentiometrically at 25.0±0.1°C and compared with those found in solutions of thiosemicarbazide. In acidic media a two-step protonation equilibrium has been found for thiocarbohydrazide and a one-step protonation equilibrium for thiosemicarbazide; this corresponds to the number of hydrazinic radicals of the two molecules, thus suggesting that the protons are attached to the -NH-NH 2 group also in thiosemicarbazide. The dependence of the cumulative protonation constants β n upon the ionic strength up to μ = 2 M is that typical for cation acids for both compounds. In alkaline media both compounds present a two-step protonation equilibrium. The dependence on the ionic strength of the protonation constants β n * in alkaline media is that typical for anions bases. These anions derive from thio-enolic forms of the molecules. The existence of cation acids and anion bases in the solutions has been checked also by electrophoretic tests. The stepwise constants for both compounds show a regular decreases as expected for polyprotic acids.

Complexes of thiocarbohydrazide with divalent metals: Stability constants in aqueous solutions

Abstract The association equilibria of thiocarbohydrazide, SC (NHNH2)2, with divalent ions Co2+, Ni2+, Zn2+ have been determined potentiometrically at 25.0±0.1°C in 0.5 M KCl solution. The following stability constants have been obtained: for Co2+, log K1 = 2.969(18), log K2 = 2.689(18); for Ni2+, log K1 = 4.404(8), log K2 = 3.700(8), log K3 = 3.113(8); for Zn2+, log K1 = 2.526(23). A method for the calculation of the estimated standard deviations is given. The stability constants obtained are comparable, for number of steps as well as values, with the stability constants of carbohydrazide, O=C(NHNH2)2, with the same metals. For both ligands, complexes with five-membered ring chelates can be postulated, the donor atoms being N,S and N,O respectively. The constants for thiocarbohydrazide are slightly higher than the corresponding constants of the oxygenated analog, except for zinc where the reverse occurs. Therefore, in agreement with the classification of Ahrland, ZnII confirms to be an (A)-acceptor, and NiII a (B)-acceptor.

Pattern of transition-metal chelates with biological activity. Complex formation equilibria between α-amino-N-hydroxy-1H-imidazole-4-propanamide and cobalt(II), nickel(II), copper(II), and hydrogen lons in aqueous solution

The complex-formation equilibria between CoII, NiII, and CuII and α-amino-N-hydroxy-1H-imidazole-4-propanamide (ahip) have been investigated by potentiometric titrations in 0.5 mol dm–3 KCl solution at 25°C. Their acid–base and metal–ligand reaction stoicheiometrics have been determined, and the equilibrium constants of the corresponding proton and metal ion association constants have been calculated from potentiometric data with the aid of the programs BETAREF and SUPERQUAD. The parameters relating to potentiometric calibration curves and the equilibrium chemical models are selected on the basis of a critical evaluation of the least-squares results and of a statistical analysis of the weighted residuals. Protonated and hydrolysed complexes were formed in the pH range 3.0–11.0. The following cumulative formation constants βpqr=[MpHqLr]/[M]p[H]q[L]r were obtained: ahip, log β011= 8.942(2), log β021= 16.009(2), log β031= 21.400(4); CoII–ahip, log β111= 14.036(23), log β122= 26.633(45), log β112= 20.861(30), log β102= 12.784(50); NiII–ahip, log β111= 15.009(7), log β122= 28.821(17), log β112= 22.793(12), log β101= 9.27(7), log β102= 15.644(13), log β1 – 12= 4.961(17); CuII–ahip, log β111= 16.916(12), log β122= 29.15(9), log β112= 22.08(9), log β101= 10.698(38), log β102= 13.73(8), log β1 – 12= 3.34(8). The probable structures of the chelated compounds formed in aqueous solution were deduced and their protonation and stability constants compared with those of analogous co-ordination compounds. The ligand is bound to the metal ion via N(3) of the imidazole ring, the α-amino nitrogen, and the hydroxyl oxygen of the deprotonated NHO– group. Equilibrium constants for their formation and visible spectra of the Cu2+–ahip system are discussed in terms of the metal chelates structures and their possible significance to biological systems.

Chelating behaviour of methyl 2-pyridyl ketone carbono- and thiocarbonohydrazones in copper(II) and zinc(II) complexes

The compounds bis(methyl 2-pyridyl ketone) carbono-(H2L1) and thiocarbono-hydrazone (H2L2) have been synthesized, their protonation constants obtained through spectrophotometric studies and their crystal structures determined by X-ray diffractometry. Their complexation behaviour has been studied towards copper and zinc chloride and acetate. The results indicate that they are able to form bimetallic complexes with both copper salts used and zinc acetate; this is confirmed by an X-ray analysis carried out on [Cu2(HL1)Cl3(OH2)]·1.5H2O.

Complex formation equilibria between 2-amino-N-hydroxyacetamide and 2–amino-N-hydroxypentanamide and cobalt (II), nickel(II), copper(II), and hydrogen ions in aqueous solutions

The formation constants of the complexes formed between H+, Co2+, Ni2+, and Cu2+ and 2-amino-N-hydroxyacetamide (aha) and 2-amino-N-hydroxypentanamide (ahp) have been measured at 25 °C and I= 0.5 mol dm–3(KCl) using potentiometric techniques. Their acid–base and metal–ligand reaction stoicheiometries have been determined, and the equilibrium constants of the corresponding proton and metal ion association constants have been calculated from potentiometric data with the aid of the program SUPERQUAD. The equilibrium chemical models are selected on the basis of a critical evaluation of the least-squares results and of a statistical analysis of the weighted residuals. Interpretation of the results was facilitated by visible spectrophotometry of solutions containing metal ions (M), and aha or ahp (HL) at various pH. All metals form the mononuclear ([ML]+ and [ML2]) and hydroxo complexes with both ligands, whereas with copper(II) polynuclear species are also present. The ligands are bound to the metals through co-ordination of the aminohydroxamate moiety, via the N atom of the amino group, and by the deprotonated NHO– group; the square-planar complexes are probably held together by quite strong intermolecular hydrogen bonds involving the unco-ordinated ketonic oxygen atom.