Department of Inorganic & Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
Molecules. 2022 Jul 21;27(14):4667. doi: 10.3390/molecules27144667.
A novel ambidentate dipeptide conjugate (H(L1)) containing N-donor atoms of the peptide part and an (O,O) chelate at the hydroxypyridinone (HP) ring is synthesized and characterized. It is hoped that this chelating ligand can be useful to obtain multitargeted Co(III)/Pt(II) dinuclear complexes with anticancer potential. The Pd(II) (as a Pt(II) model but with faster ligand exchange reactions) binding strength of the ligand was studied in an aqueous solution with the combined use of pH-potentiometry and NMR. In an equimolar solution, (L1) was found to bind Pd(II) via the terminal amino and increasing number of peptide nitrogens of the peptide backbone over a wide pH range. At a 2:1 Pd(II) to ligand ratio, the presence of [PdH(L1)] (x = 1-4) species, with high stability and with the coordination of the (O,O) chelating set of the ligand, was detected. The reaction of H(L1) with [Co(tren)] (tren = tris(2-aminoethyl)amine) indicated the exclusive binding of (L1) via its (O,O) donor atoms to the metal unit, while treatment of the resulting Co-complex with Pd(II) afforded the formation of a Co/Pd heterobimetallic complex in solution with an (NH, N) coordination of Pd(II). Shortening the peptide backbone in H(L1) by one peptide unit compared to the structurally similar ambidentate chelator consisting of three peptide bonds resulted in the slightly more favorable formation of the N-coordinated Pd(II) species, allowing the tailoring of the coordination properties.
一种新型的双齿肽缩合配体（H(L1)），其中包含肽部分的 N 供体原子和羟吡啶酮（HP）环上的（O,O）螯合。希望这种螯合配体能用于获得具有抗癌潜力的多靶点 Co(III)/Pt(II)双核配合物。使用 pH 电位法和 NMR 联合研究了配体与 Pd(II)（作为 Pt(II)模型，但配体的配体交换反应更快）的结合强度。在等摩尔溶液中，发现（L1）通过末端氨基和肽骨架上越来越多的肽氮结合 Pd(II)，在很宽的 pH 范围内。在 2:1Pd(II)与配体的比例下，检测到 [PdH(L1)]（x = 1-4）物种的存在，其具有高稳定性，并且配体的（O,O）螯合组配位。H(L1)与 [Co(tren)]（tren = 三（2-氨基乙基）胺）的反应表明（L1）通过其（O,O）供体原子与金属单元的排他性结合，而用 Pd(II)处理所得的 Co-配合物在溶液中形成 Co/Pd 异双核配合物，其中 Pd(II)具有（NH，N）配位。与由三个肽键组成的结构相似的双齿螯合剂相比，H(L1)中的肽骨架缩短一个肽单元导致更有利于形成 N 配位的 Pd(II)物种，从而可以调整配位性质。
