The silver(I) N‐heterocyclic carbene (NHC) complex bis(1‐(anthracen‐9‐ylmethyl)‐3‐ethylimidazol‐2‐ylidene) silver chloride ([Ag(EIA)2]Cl), bearing two anthracenyl fluorescent probes, has been synthesized and characterized. [Ag(EIA)2]Cl is stable in organic solvents and under physiological conditions, and shows potent cytotoxic effects in vitro toward human SH‐SY5Y neuroblastoma cells. The interactions of [Ag(EIA)2]Cl with a few model biological targets have been studied as well as its ability to be internalized in cells. The in vitro anticancer activity is apparently related to the level of drug internalization. Notably, [Ag(EIA)2]Cl does not react with a few model proteins, but is capable of binding the C‐terminal dodecapeptide of thioredoxin reductase hTrxR(488–499) and to strongly inhibit the activity of this enzyme. Binding occurs through an unconventional process leading to covalent binding of one or two carbene ligands to the C‐terminal dodecapeptide with concomitant release of the silver cation. To the best of our knowledge, this mode of interaction is reported here for the first time for Ag(NHC)2 complexes.

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Three pseudohalide analogues of the established gold drug Auranofin (AF hereafter), of general formula Au(PEt 3 )X, i.e. Au(PEt 3 )CN, Au(PEt 3 )SCN and Au(PEt 3 )N 3 (respectively denoted as AFCN, AFSCN and AFN 3 ), were prepared and characterized. The crystal structure was solved for Au(PEt 3 )SCN highlighting the classical linear geometry of the 2-coordinate gold(I) center. The solution behaviour of the compounds was then comparatively analysed through 31 PNMR providing evidence for an acceptable stability under physiological-like conditions. Afterward, the reaction of these gold compounds with bovine serum albumin (BSA) and consequent adduct formation was investigated by 31 PNMR. For all the studied gold compounds, the [Au(PEt 3 )] + moiety was identified as the reactive species in metal/protein adducts formation. The cytotoxic effects of the complexes were subsequently

Oxidative stress due to excess superoxide anion ( ) produced by dysfunctional mitochondria is a key pathogenic event of aging and ischemia-reperfusion diseases. Here, a new -scavenging Mn II complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing 2 quinoline units (MnQ2), designed to improve complex stability and cell permeability, was compared to parental Mn II complex with methyls replacing quinolines (MnM2). MnQ2 was more stable than MnM2 (log K = 19.56(8) vs. 14.73(2) for the equilibrium Mn 2+ + L 2− , where L = Q2 and M2) due to the involvement of quinoline in metal binding and to the hydrophobic features of the ligand which improve metal desolvation upon complexation. As oxidative stress model, H9c2 rat cardiomyoblasts were subjected to hypoxia-reoxygenation. MnQ2 and MnM2 (10 μmol L −1 ) were added at reoxygenation for 1 or 2 h. The more lipophilic MnQ2 showed more rapid cell and mitochondrial penetration than MnM2. Both MnQ2 and MnM2 abated endogenous ROS and mitochondrial , decreased cell lipid peroxidation, reduced mitochondrial dysfunction, in terms of efficiency of the respiratory chain and preservation of membrane potential (Δψ) and permeability, decreased the activation of pro-apoptotic caspases 9 and 3, and increased cell viability. Of note, MnQ2 was more effective than MnM2 to exert cytoprotective anti-oxidant effects in the short term. Compounds with redox-inert Zn II replacing the functional Mn II were ineffective. This study provides clues which further our understanding of the structure-activity relationships of Mn II -chelates and suggests that Mn II -polyamino-polycarboxylate macrocycles could be developed as new anti-oxidant drugs.

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