A Trishistidine Pseudopeptide with Ability to Remove Both Cu and Cu from the Amyloid-β Peptide and to Stop the Associated ROS Formation.

The pseudopeptide L, derived from a nitrilotriacetic acid scaffold and functionalized with three histidine moieties, is reminiscent of the amino acid side chains encountered in the Alzheimer's peptide (Aβ). Its synthesis and coordination properties for Cu and Cu are described. L efficiently complex Cu in a square-planar geometry involving three imidazole nitrogen atoms and an amidate-Cu bond.

XAS Investigation of Silver(I) Coordination in Copper(I) Biological Binding Sites.

Silver(I) is an unphysiological ion that, as the physiological copper(I) ion, shows high binding affinity for thiolate ligands; its toxicity has been proposed to be due to its capability to replace Cu(I) in the thiolate binding sites of proteins involved in copper homeostasis. Nevertheless, the nature of the Ag(I)-thiolate complexes formed within cells is poorly understood, and the details of Ag(I) coordination in such complexes in physiologically relevant conditions are mostly unknown. By making use of X-ray absorption spectroscopy (XAS), we characterized the Ag(I) binding sites in proteins related to copper homeostasis, such as the chaperone Atox1 and metallothioneins (MTs), as well as in bioinspired thiolate Cu(I) chelators mimicking these proteins, in solution and at physiological pH.

Cancer cell cytotoxicity of cyclometalated compounds obtained with osmium(II) complexes.

A library of 29 organoosmium compounds has been built up with known and novel cyclometalated compounds obtained with C-N, N(∧)C(∧)N, and C(∧)N(∧)N ligands. All compounds have been tested for their in vitro cytotoxic properties against A172, a tumor cell line derived from a human glioblastoma, this affording a contrasted picture of the activities of the compounds gathered in this study. Some compounds displayed good to excellent activities, some of them showing IC50 in the nanomolar range.

Library of second-generation cycloruthenated compounds and evaluation of their biological properties as potential anticancer drugs: passing the nanomolar barrier.

A library of 32 organoruthenium compounds has been synthesised. Known and novel C-N cyclometalated compounds as well as N-C-N and N-N-C pincer derivatives of this metal have been used in this purpose. Most of the compounds have been tested for their in vitro antitumoral behaviours, good to excellent activities have thus been found.