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

Abstract

The catalytic and biological properties of dirhodium tetracarboxylates ([Rh₂(μ-O₂CR)₄L₂], L = axial ligand and R = CH₃-, CH₃CH₂-, etc.) largely depend on the nature of bridging carboxylate equatorial μ-O₂CR ligands, which can be easily exchanged by solvent molecules when R is CF₃ (i.e. μ-O₂CR is trifluoroacetate, tfa). Here, we prepared the [Rh₂(OAc)(tfa)₃] compound and investigated its interaction with bovine pancreatic ribonuclease and lysozyme under the same conditions used to study the reactivity of these proteins with [Rh₂(OAc)₄] and [cis-Rh₂(OAc)₂(tfa)₂]. UV-vis absorption spectroscopy and ¹⁹F nuclear magnetic resonance studies indicate that [Rh₂(OAc)(tfa)₃] rapidly loses tfa ligands and interacts with the proteins. Crystallographic data demonstrate that the reaction of [Rh₂(OAc)(tfa)₃] with proteins can lead to products that are significantly different when compared to those obtained with [Rh₂(OAc)₄] and [cis-Rh₂(OAc)₂(tfa)₂]: 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 [Rh₂(OAc)₄] and [cis-Rh₂(OAc)₂(tfa)₂]. 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 [cis-Rh₂(OAc)₂(tfa)₂] and [Rh₂(OAc)(tfa)₃] 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.