0000000000699927
AUTHOR
Nazzareno Re
Probing the Paradigm of Promiscuity for N‐Heterocyclic Carbene Complexes and their Protein Adduct Formation
Metal complexes can be considered a "paradigm of promiscuity" when it comes to their interactions with proteins. They often form adducts with a variety of donor atoms in an unselective manner. We have characterized the adducts formed between a series of isostructural N-heterocyclic carbene (NHC) complexes with Ru, Os, Rh, and Ir centers and the model protein hen egg white lysozyme by X-ray crystallography and mass spectrometry. Distinctive behavior for the metal compounds was observed with the more labile Ru and Rh complexes targeting mainly a surface l-histidine moiety through cleavage of p-cymene or NHC co-ligands, respectively. In contrast, the more inert Os and Ir derivatives were detec…
Two mixed valence diruthenium(ii,iii) isomeric complexes show different anticancer properties
In this paper it is demonstrated that the nature of the ligands of two Ru2(II,III) paddlewheel complexes dramatically affects the overall anticancer properties in cells. Herein, the complex [Ru2(EB776)4Cl] was found to be more active against a glioblastoma model with respect to its isomer [Ru2(EB106)4Cl]. These different effects depend on the steric hindrance, on the allowed conformations of the complexes and on the presence of hydrophilic regions in [Ru2(EB776)4Cl], which overall lead to a lower “steric protection”.
Multilayered Modelling of the Metallation of Biological Targets
The unique property of metals – the remarkable ability to modulate the electronic structure of both metal center and bound ligands – is the reason for their omnipresence in enzymes and in metal-coordinating biological factors. Modern metallodrug chemistry began with the serendipitous unveiling of the antitumour properties of cisplatin, followed by an avalanche of synthesized novel metallodrugs. The metallation of biological targets has then become a new paradigm in the field of bioinorganic chemistry, and a plethora of computational approaches have been developed and utilized to ease the detailed comprehension of its mechnisms with a focus on medical applications. Studies of the electronic …
Reactivity of antitumor coinage metal-based N-heterocyclic carbene complexes with cysteine and selenocysteine protein sites
Abstract The reaction of the antitumor M(I)-bis-N-heterocyclic carbene (M(I)-NHC) complexes, M = Cu, Ag, and Au, with their potential protein binding sites, i.e. cysteine and selenocysteine, was investigated by means of density functional theory approaches. Capped cysteine and selenocysteine were employed to better model the corresponding residues environment within peptide structures. By assuming the neutral or deprotonated form of the side chains of these amino acids and by considering the possible assistance of an external proton donor such as an adjacent acidic residue or the acidic component of the surrounding buffer environment, we devised five possible routes leading to the binding o…