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

The catalytic and biological properties of dirhodium tetracarboxylates ([Rh 2 (μ-O 2 CR) 4 L 2 ], L = axial ligand and R = CH 3 -, CH 3 CH 2 -, etc .) largely depend on the nature of bridging carboxylate equatorial μ-O 2 CR ligands, which can be easily exchanged by solvent molecules when R is CF 3 ( i.e. μ-O 2 CR is trifluoroacetate, tfa). Here, we prepared the [Rh 2 (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 [Rh 2 (OAc) 4 ] and [ cis -Rh 2 (OAc) 2 (tfa) 2 ]. UV-vis absorption spectroscopy and 19 F nuclear magnetic resonance studies indicate that [Rh 2 (OAc)(tfa) 3 ] rapidly loses tfa ligands and interacts with the proteins. Crystallographic data demonstrate that the reaction of [Rh 2 (OAc)(tfa) 3 ] with proteins can lead to products that are significantly different when compared to those obtained with [Rh 2 (OAc) 4 ] and [ cis -Rh 2 (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 [Rh 2 (OAc) 4 ] and [ cis -Rh 2 (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 -Rh 2 (OAc) 2 (tfa) 2 ] and [Rh 2 (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.