Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, via Cinthia 21, 80126 Naples, Italy.
Department of Chemical, Materials and Production Engineering, University of Naples Federico II, P.le V. Tecchio 80, 80125 Naples, Italy.
Dalton Trans. 2022 Mar 1;51(9):3695-3705. doi: 10.1039/d2dt00082b.
Dirhodium complexes of general formula [Rh(OCR)]L are a well-known class of bimetallic compounds that are used as efficient catalysts for a variety of reactions and have been shown to be potent antibacterial and anticancer agents. The catalytic and biological properties of these complexes largely depend on the nature of the bridging carboxylate ligands. Trifluoroacetate (tfa)-containing dirhodium compounds have been used to build artificial metalloenzymes upon reaction with peptides and have been shown to be more cytotoxic than dirhodium tetraacetate. However, there is no structural information on the interaction between these compounds and proteins. Here, -Rh(μ-OCCH)(μ-OCCF) ([-Rh(OAc)(tfa)]) has been synthesized and its reaction with bovine pancreatic ribonuclease (RNase A) and hen egg white lysozyme (HEWL) was analyzed using a combination of different techniques, including Fluorine-19 nuclear magnetic resonance spectroscopy and macromolecular X-ray crystallography, with the aim to unveil the differences in the reactivity of tfa-containing dihrodium complexes with proteins when compared to [Rh(OAc)]. [-Rh(OAc)(tfa)] and [Rh(OAc)] bind the N atoms of His side chains of RNase A at the axial position; however the fluorine-containing compound rapidly loses its tfa ligands, while [Rh(OAc)] can retain the acetate ligands upon protein binding. The reactivity of [-Rh(OAc)(tfa)] with HEWL is slightly distinct when compared to that of [Rh(OAc)] under the same experimental conditions; however, both [-Rh(OAc)(tfa)] and [Rh(OAc)] degrade when soaked within HEWL crystals. These results provide a structural-based guide for the design of new heterogenous chiral dirhodium/peptide and dirhodium/protein adducts with application in the fields of organic synthesis and asymmetric catalysis.
[Rh(OCR)]L 的二铑配合物是一类众所周知的双金属化合物，它们可用作各种反应的高效催化剂，并已被证明具有很强的抗菌和抗癌活性。这些配合物的催化和生物性质在很大程度上取决于桥连羧酸配体的性质。含三氟乙酸根（tfa）的二铑化合物在与肽反应后被用来构建人工金属酶，并且被证明比二乙酸根二铑更具细胞毒性。然而，目前还没有关于这些化合物与蛋白质相互作用的结构信息。在这里，合成了[Rh(μ-OCCH)(μ-OCCF)]（[-Rh(OAc)(tfa)]），并使用包括氟-19 核磁共振波谱和大分子 X 射线晶体学在内的多种技术对其与牛胰腺核糖核酸酶（RNase A）和鸡卵清溶菌酶（HEWL）的反应进行了分析，目的是揭示含 tfa 的二铑配合物与蛋白质的反应性与[Rh(OAc)]的差异。[-Rh(OAc)(tfa)]和[Rh(OAc)]与 RNase A 的轴向位置上的 His 侧链的 N 原子结合；然而，含氟化合物迅速失去其 tfa 配体，而[Rh(OAc)]在与蛋白质结合时可以保留醋酸盐配体。与相同实验条件下的[Rh(OAc)]相比，[-Rh(OAc)(tfa)]与 HEWL 的反应性略有不同；然而，当浸泡在 HEWL 晶体中时，[-Rh(OAc)(tfa)]和[Rh(OAc)]都会降解。这些结果为设计具有应用于有机合成和不对称催化领域的新型异质手性二铑/肽和二铑/蛋白质加合物提供了结构基础。
