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

Abstract

Catalytic and biological properties of dirhodium tetracarboxylates ([Rh2(μ-O2CR)4L2], L=axial ligand, R=CH3-, CH3CH2-, etc) largely depend on the nature of the bridging carboxylate equatorial μ-O2CR ligands, which can be easily exchanged...

Effect of Equatorial Ligand Substitution on the Reactivity with Proteins of Paddlewheel Diruthenium Complexes: Structural Studies

“…Overall, these data indicate that Ru–Ru bonds remain stable upon reaction with HEWL regardless of the experimental conditions used. Interestingly, the structures of the adducts of HEWL with dirhodium tetraacetate and derivatives under the same conditions show breakage of the Rh–Rh bond. ,, …”

“…Interestingly, the structures of the adducts of HEWL with dirhodium tetraacetate and derivatives under the same conditions show breakage of the Rh−Rh bond. 36,38,39 In conclusion, here we have studied the reactivity of [Ru 2 Cl(D-p-FPhF)(O 2 CCH 3 ) 3 ] with HEWL under different experimental conditions. Our data unambiguously demonstrate that the compound binds the protein, forming adducts with dimetallic moieties bound to the Asp side chains upon the release of an acetate ligand.…”

“…Nevertheless, the axial coordination of dimetallic compounds to both a residue side chain and a carbonyl oxygen in the solid state was already observed in the adducts formed upon the reaction of dirhodium compounds with proteins. [36][37][38][39][40]44 In structure 4 (Figure 3D), binding of the dimetallic center occurs at the level of the side chains of Asp101 (Figure 4H), Asp119 (Figure 4I), and Arg125 (Figure 4J). However, in this structure, especially close to the side chain of Asp101 (Figure 4H), interpretation of the map is complicated by conformational disorder, by the presence of multiple conformations of the diruthenium center, and by the presence of a high concentration of chloride ions, which could replace the diruthenium ligands.…”

“…Interestingly, the structures of the adducts of HEWL with dirhodium tetraacetate and derivatives under the same conditions show breakage of the Rh–Rh bond. 36 , 38 , 39 …”

Kinetics of Reactions of Dirhodium and Diruthenium Paddlewheel Tetraacetate Complexes with Nucleophilic Protein Sites: Computational Insights

“…The dirhodium tetraacetate complex [Rh 2 (μ-O 2 CCH 3 ) 4 ] includes a Rh­(II)–Rh­(II) bond with four carboxylates playing the role of bridging ligands arranged in a lantern-like form around the central bimetal unit, whereas neutral solvent molecules (L) occupy the axial coordination sites. Although causing toxic side effects, this complex has a proven activity against several cancer types, such as sarcoma 180, P388 leukemia, L1210 tumors, and Ehrlich-Lettre ascites carcinoma. − Nevertheless, its mode of action is not yet disentangled despite several studies on its interaction with various proteins, − although it is hypothesized that its biomolecular targets are single- and double-stranded DNA, proteins, − peptides, , and amino acids. − Moreover, interaction of dirhodium compounds with peptides and proteins was investigated in the framework of protein modification with the aim of designing artificial metalloenzymes. , Usually, Rh-based complexes are coordinated to proteins either via the covalent linkage, involving direct binding of these metal complexes to proteins, , or via the dative anchoring which is based on the formation of noncovalent interactions between protein atoms and Rh ligands as well as coordinative bonds between protein side chains and Rh centers . There are experimental pieces of evidence of the Rh-complex selectivity toward side chains of Asn, Asp, His, Lys, and the C-terminal carboxylate. ,, …”