Structural Studies on the Interactions between Metal Ions and Biological Macromolecules

The essential role of metal ions in biology is stressed by structural investigations on two metalloenzymes: human carbonic anhydrase (CA) and Cu, Zn superoxide dismutase (SOD). The X-ray structure of CA complex with histamine affords a satisfactory explanation of the mechanism of activation of CA. The high resolution (1.02 Å) crystal structure of a mutant monomeric Cu, Zn superoxide dismutase gives relevant information on the mechanism of the catalytic activity of the native dimeric enzyme and on the reduced activity of the monomer

Structural Studies on the Interactions between Metal Ions and Biological Macromolecules

The essential role of metal ions in biology is stressed by structural investigations on two metalloenzymes: human carbonic anhydrase (CA) and Cu, Zn superoxide dismutase (SOD). The X-ray structure of CA complex with histamine affords a satisfactory explanation of the mechanism of activation of CA. The high resolution (1.02 Å) crystal structure of a mutant monomeric Cu, Zn superoxide dismutase gives relevant information on the mechanism of the catalytic activity of the native dimeric enzyme and on the reduced activity of the monomer

Comparative Analysis of [Au(en)2]3+ and [Pt(en)2]2+ non Covalent Binding to Calf Thymus DNA

Reactions of the complexes bisethylendiammine gold(III) and bisethylendiammine platinum(II) with calfthymus DNA were comparatively analysed. Both complexes bind DNA non-covalently most probably on the basis of electrostatic interactions. Binding of either complex at low ratios results into modest modifications of B-type DNA conformations, as detected by CD. Far larger CD alterations are observed at high ratios. The gold(III) chromophore is scarcely perturbed by DNA addition Binding of [Au(en)2]Cl3 to calf thymus DNA is reversed by sodium cyanide. By analogy with the case of [Pt(en)2]Cl2 it is suggested that Auen acts as a minor groove binder

Structure and Cytotoxic Properties of Some Selected Gold(III) Complexes

We prepared four representative square planar gold(III) complexes - [AuCl3(Hpm)], [AuCl2(esal)], [AuCl(dien)]Cl2 and [Au(en)2]Cl3 -and characterized them both in the solid state and in solution. Thereafter, the cytotoxicity of these compounds was evaluated in vitro against the A2780 human ovarian tumor cell line that was used as the reference cell line. Remarkably, ali these gold(III) complexes showed significant cytotoxic effects, [AuCl2(esal)] showing a potency comparable to cisplatin. The present gold(III) complexes were also tested on the corresponding cisplatin-resistant line and revealed they were able to overcome resistance to cisplatin to a large extent. The implications of these findings for the development of new gold(III) complexes to be tested as antitumor agents are discussed

Gold(III) Compounds as New Family of Anticancer Drugs

Gold(III) complexes are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents. This renewed interest is the result of recent studies in which various gold(III) complexes have been shown to be stable under physiological conditions and to manifest relevant antiproliferative properties against selected human tumor cell lines. The pharmacological investigation of some representative gold(III) complexes has been extended to consider their effects on the cell cycle and to reveal induction of apoptosis. Remarkably, preliminary studies suggest that the interactions in vitro of gold(Ill) complexes with calf thymus DNA are weak whereas significant binding to model proteins takes place. Our findings imply that the mechanism of action of cytotoxic gold(Ill) complexes might be substantially different from that of clinically established platinum compounds

Crystal and molecular structure of the ternary complex Zn(II)–ATP–2,2′-bipyridyl

A series of microcrystalline compounds between adenosine 5′-triphosphoric acid (ATP), 22′-bipyridyl and some 3d metal ions, such as Mn(II), Co(II), Cu(II) and Zn(II), have been obtained in 1:1 ratio [1]. Crystal suitable for X-ray analysis were obtained for the zinc compound. Diffractometer data, collected on one of these crystals, gave the following results: a = 11.105(3), b = 25.223(7), c = 1.539(3) Å, β = 91.34(4)°, monoclinic, space group P21. 1617 reflections with intensity greater then twice their standard deviation were used for the structure determination and refinement (R = 0.098). The structure of the compound consists of dimeric molecules in which two zinc atoms are held together by two –OPO– bridges from the γ-phosphate groups of two ATP molecules (Fig. 1). Both zinc atoms show a distorted octahedral coordination, formed by two oxygen atoms from different γ-phosphate groups, one oxygen atom from the β-phosphate group and the two nitrogen atoms of the bipyridyl ligand. The sixth position is completed by an α-phosphate oxygen atom which is only weakly bound. ZnN and ZnO distances average respectively 2.15(4) and 2.0293) Å. The structure is held together by strong intermolecular bipyridyl–purine and bipyridyl–bipyridyl stacking interactions. Weaker bipyridyl–purine intramolecular stacking is also observed. The molecule provides a possible model for ATP transport and phosphate group transfer mechanism

Macrocyclic polyphosphane ligands: cobalt(II) and nickel(II) complexes of 1,10-dipropyl-4RS, 7SR, 13SR, 16RS-tetraphenyl-1,10-diaza-4,7,13,16-tetraphospha-cyclooctadecane and crystal structure of the cobalt tetraphenylborate monohydrate complex

The X-ray crystal structure of the title compound has been carried out. The crystals are triclinic, space group P1, a = 13.252(2), b = 13.943(2), c = 24.316(5) Å, α = 70.660(14), β = 75.219(14), γ = 69.231(13)° for Z = 2. The structure has been refined to an R factor of 0.069 by the least-squares technique. The cobalt atom is five-coordinated by the four phosphorus atoms of the macrocycle and by a water molecule forming a distorted square-pyramidal geometry. The stereochemistry of some cobalt(II) and nickel(II) complexes of the same ligand were investigated, in the solid state and in solution, by electronic spectroscopy. © 1984