Digging into protein metalation differences triggered by fluorine containing-dirhodium tetracarboxylate analogues.

The catalytic and biological properties of dirhodium tetracarboxylates ([Rh(μ-OCR)L], L = axial ligand and R = CH-, CHCH-, .) largely depend on the nature of bridging carboxylate equatorial μ-OCR ligands, which can be easily exchanged by solvent molecules when R is CF ( μ-OCR is trifluoroacetate, tfa). Here, we prepared the [Rh(OAc)(tfa)] compound and investigated its interaction with bovine pancreatic ribonuclease and lysozyme under the same conditions used to study the reactivity of these proteins with [Rh(OAc)] and [-Rh(OAc)(tfa)]. UV-vis absorption spectroscopy and F nuclear magnetic resonance studies indicate that [Rh(OAc)(tfa)] rapidly loses tfa ligands and interacts with the proteins. Crystallographic data demonstrate that the reaction of [Rh(OAc)(tfa)] with proteins can lead to products that are significantly different when compared to those obtained with [Rh(OAc)] and [-Rh(OAc)(tfa)]: the dirhodium centre can bind the side chain of His residues at both axial and equatorial sites, at variance with what is found in the case of [Rh(OAc)] and [-Rh(OAc)(tfa)]. These data indicate that the hydrolysis of dirhodium tetracarboxylates plays a significant role in defining their reaction with proteins allowing the formation of unexpected reaction products. These results suggest that [-Rh(OAc)(tfa)] and [Rh(OAc)(tfa)] can be used to obtain different dirhodium/peptide and dirhodium/protein adducts with distinct catalytic properties and can explain the different cytotoxicity exhibited by tfa-containing dirhodium tetracarboxylates.