Cisplatin Binding to Proteins: Molecular Structure of the Ribonuclease A Adduct

The crystal structure of the main adduct formed in the reaction between cisplatin and bovine pancreatic ribonuclease is reported here. Notably, in both of the protein molecules present in the asymmetric unit, platinum­(II) binding takes place exclusively at the level of Met29. In one of the two molecules, the Gln28 side chain completes the platinum coordination sphere, anchoring the cisplatin fragment to the protein in a bidentate fashion. These results contain interesting implications for understanding the biological chemistry of this important drug

Protein Recognition of Gold-Based Drugs: 3D Structure of the Complex Formed When Lysozyme Reacts with Aubipy^c

The structure of the adduct formed in the reaction between Aubipy^c, a cytotoxic organogold­(III) compound, and the model protein hen egg white lysozyme (HEWL) has been solved by X-ray crystallography. It emerges that Aubipy^c, after interaction with HEWL, undergoes reduction of the gold­(III) center followed by detaching of the cyclometalated ligand; the resulting naked gold­(I) ion is found bound to the protein at Gln121. A direct comparison between the present structure and those previously solved for the lysozyme adducts with other gold­(III) compounds demonstrates that coordinated ligands play a key role in the protein–metallodrug recognition process. Structural data support the view that gold­(III)-based antitumor prodrugs are activated through metal reduction

Structure−Function Relationships within Keppler-Type Antitumor Ruthenium(III) Complexes: the Case of 2-Aminothiazolium[<i>trans</i>-tetrachlorobis(2-aminothiazole)ruthenate(III)]

Keppler-type ruthenium(III) complexes exhibit promising antitumor properties. We report here a study of 2-aminothiazolium[trans-tetrachlorobis(2-aminothiazole)ruthenate(III)], both in the solid state and in solution. The crystal structure has been solved and found to exhibit classical features. Important solvatochromic effects were revealed. Notably, we observed that introduction of an amino group in position 2 greatly accelerates chloride hydrolysis compared to the thiazole analogue; this latter finding may be of interest for a fine-tuning of the reactivity of these novel metallodrugs

Structural Features of a New Dinuclear Platinum(II) Complex with Significant Antiproliferative Activity

A novel dinuclear platinum(II) complex, [Pt2-N,N‘-bis(2-dimethylaminoethyl oxamide)Cl4], showing peculiar structural features, has been prepared and characterized. X-ray diffraction data reveal that the two platinum ions are simultaneously bound to the N,N‘-bis(2-dimethylaminoethyl) oxamide ligand, on opposite sides. The coordination environment of both platinum centers is square planar, with identical NOCl2 donor sets. The complex is poorly soluble within a physiological buffer but moderately soluble in DMSO. Preliminary in vitro studies point out that this dinuclear platinum complex exhibits significant growth-inhibiting properties on a panel of cultured human tumor cell lines, although less pronounced than those of cisplatin

Structure of a Terbium(III)−Quinizarine Complex: The First Crystallographic Model for Metalloanthracyclines

The crystal structure of a complex of terbium(III) with quinizarine 2-sulfonate has been solved by single-crystal X-ray diffraction methods. The metal cation is coordinated by two adjacent phenolate and quinone oxygens of the anthraquinone moiety of a quinizarine sulfonate anion and by six water molecules. To our knowledge, this is the first structure of a metal complex of the 1,4-dihydroxy anthraquinone ligand. On the basis of strict similarities in the spectroscopic features of the terbium adducts with either doxorubicin or quinizarine 2-sulfonate, the present structure is proposed as a model for the metal complexes of anthracyclines

Decomposition of Ascorbic Acid in the Presence of Cadmium Ions Leads to Formation of a Polymeric Cadmium Oxalate Species with Peculiar Structural Features

Slow decomposition of l-ascorbic acid, carried out under aerobic conditions and in the presence of cadmium ions, results in formation of a crystalline product that is highly insoluble in water. This compound has been identified as a cadmium oxalate polymeric species with formula Cd(C2O4)·3H2O. The crystal structure of this compound is described. Relevant crystal data are the following:  C4H12O14Cd2, fw = 508.94; triclinic; space group P1 (No. 1); a = 6.010(1) Å, b = 6.668(1) Å, c = 8.498(1) Å; α = 74.64(1)°, β = 74.25(1)°, γ = 80.91(1)°; V = 314.7(5) Å3; Z = 1

Decomposition of Ascorbic Acid in the Presence of Cadmium Ions Leads to Formation of a Polymeric Cadmium Oxalate Species with Peculiar Structural Features

Slow decomposition of l-ascorbic acid, carried out under aerobic conditions and in the presence of cadmium ions, results in formation of a crystalline product that is highly insoluble in water. This compound has been identified as a cadmium oxalate polymeric species with formula Cd(C2O4)·3H2O. The crystal structure of this compound is described. Relevant crystal data are the following:  C4H12O14Cd2, fw = 508.94; triclinic; space group P1 (No. 1); a = 6.010(1) Å, b = 6.668(1) Å, c = 8.498(1) Å; α = 74.64(1)°, β = 74.25(1)°, γ = 80.91(1)°; V = 314.7(5) Å3; Z = 1

Promising <i>in Vitro</i> anti-Alzheimer Properties for a Ruthenium(III) Complex

Metal complexes represent today an attractive class of experimental anti-Alzheimer agents with the potential of blocking β-amyloid 1–42 aggregation and scavenging its toxicity. Three representative ruthenium­(III) complexes, namely NAMI A, KP1019, and PMRU20, were specifically evaluated to this end in an established <i>in vitro</i> model of AD relying on primary cortical neurons. Notably, PMRU20 turned out to be highly effective in protecting cortical neurons against Aβ 1–42 toxicity, while the other tested ruthenium compounds were poorly active or even inactive; we also found that PMRU20 is virtually devoid of any significant toxicity <i>in vitro</i> at the applied concentrations. Interestingly, PMRU20 was neuroprotective even against the toxicity induced by Aβ 25–35. The direct reaction of PMRU20 with Aβ 1–42 was explored through ESI MS analysis and some adduct formation evidenced. In addition, thioflavin T assays revealed that PMRU20 greatly reduces Aβ 1–42 aggregation. The implications of these findings are discussed in relation to emerging treatment strategies for the Alzheimer’s disease

Synthesis, Structural Characterization, Solution Chemistry, and Preliminary Biological Studies of the Ruthenium(III) Complexes [TzH][<i>trans</i>-RuCl₄(Tz)₂] and [TzH][<i>trans</i>-RuCl₄(DMSO)(Tz)]·(DMSO), the Thiazole Analogues of Antitumor ICR and NAMI-A

Two ruthenium(III) complexes bearing the thiazole ligand, namely, thiazolium (bisthiazole) tetrachlororuthenate (I, TzICR) and thiazolium (thiazole, DMSO) tetrachlororuthenate (II, TzNAMI) were prepared and characterized. The crystal structures of both complexes were solved by X-ray diffraction methods and found to match closely those of the corresponding imidazole complexes. The behavior in aqueous solution of bothTzICR and TzNAMI was analyzed spectroscopically. The time-dependent spectrophotometric profiles resemble closely those of the related ICR and NAMI-A anticancer compounds, respectively. It is observed that replacement of imidazole with thiazole, a less basic ligand, produces a significant decrease of the ligand exchange rates in the case of the NAMI-like compound. The main electrochemical features of these ruthenium(III) thiazole complexes were determined and compared to those of ICR and NAMI-A. Moreover, some preliminary data were obtained on their biological properties. Notably, both complexes exhibit higher reactivity toward serum albumin than toward calf thymus DNA; cytotoxicity is negligible in line with expectations. A more extensive characterization of the pharmacological properties in vivo is presently in progress

Clioquinol, a Drug for Alzheimer's Disease Specifically Interfering with Brain Metal Metabolism: Structural Characterization of Its Zinc(II) and Copper(II) Complexes

Clioquinol, a 8-hydroxyquinoline derivative, is producing very encouraging results in the treatment of Alzheimer's disease (AD). Its biological effects are most likely ascribed to complexation of specific metal ions, such as copper(II) and zinc(II), critically associated with protein aggregation and degeneration processes in the brain. We report here, for the first time, a structural characterization of the zinc(II) and copper(II) complexes of clioquinol. A ligand to metal stoichiometry of 2:1 is found in both cases, though in the presence of quite different coordination polyhedra. The present findings are discussed in the frame of modern approaches to AD treatment