Department of Chemical Sciences, University of Naples Federico II, 80126 Napoli, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia, 3-13, 50019 Sesto Fiorentino, Florence, Italy.
Int J Mol Sci. 2021 Feb 2;22(3):1496. doi: 10.3390/ijms22031496.
The structures of the adducts formed upon reaction of the cytotoxic paddlewheel dirhodium complex [Rh(μ-OCCH)] with the model protein hen egg white lysozyme (HEWL) under different experimental conditions are reported. Results indicate that [Rh(μ-OCCH)] extensively reacts with HEWL:it in part breaks down, at variance with what happens in reactions with other proteins. A Rh center coordinates the side chains of Arg14 and His15. Dimeric Rh-Rh units with Rh-Rh distances between 2.3 and 2.5 Å are bound to the side chains of Asp18, Asp101, Asn93, and Lys96, while a dirhodium unit with a Rh-Rh distance of 3.2-3.4 Å binds the C-terminal carboxylate and the side chain of Lys13 at the interface between two symmetry-related molecules. An additional monometallic fragment binds the side chain of Lys33. These data, which are supported by replicated structural determinations, shed light on the reactivity of dirhodium tetracarboxylates with proteins, providing useful information for the design of new Rh-containing biomaterials with an array of potential applications in the field of catalysis or of medicinal chemistry and valuable insight into the mechanism of action of these potential anticancer agents.
报道了在不同实验条件下，细胞毒性桨轮二铑配合物[Rh(μ-OCCH)]与模型蛋白鸡卵清溶菌酶（HEWL）反应形成的加合物的结构。结果表明，[Rh(μ-OCCH)]与 HEWL 广泛反应：它部分分解，与与其他蛋白质反应不同。一个 Rh 中心配位 Arg14 和 His15 的侧链。二聚 Rh-Rh 单元的 Rh-Rh 距离在 2.3 至 2.5 Å 之间，与 Asp18、Asp101、Asn93 和 Lys96 的侧链结合，而 Rh-Rh 距离为 3.2-3.4 Å 的二铑单元与 C 末端羧酸盐和 Lys13 的侧链结合在两个对称相关分子之间的界面处。另外一个单金属片段与 Lys33 的侧链结合。这些数据得到了重复结构测定的支持，阐明了二铑四羧酸盐与蛋白质的反应性，为设计具有多种潜在应用（如催化或药物化学领域）的新型含 Rh 生物材料提供了有用的信息，并深入了解这些潜在抗癌药物的作用机制。
