Vorobyeva Sofia N, Bautina Sof'ya A, Shekhovtsov Nikita A, Nikolaenkova Elena B, Sukhikh Taisiya S, Golubeva Yuliya A, Klyushova Lyubov S, Krivopalov Viktor P, Rakhmanova Marianna I, Gourlaouen Christophe, Bushuev Mark B
Nikolaev Institute of Inorganic Chemistry, Siberian Branch of Russian Academy of Sciences, 3, Acad. Lavrentiev Ave., Novosibirsk 630090, Russia.
Novosibirsk State University, 1, Pirogova str., Novosibirsk 630090, Russia.
Dalton Trans. 2024 May 14;53(19):8398-8416. doi: 10.1039/d4dt00824c.
The impact of isomerism of pyrimidine-based ligands and their rhodium(III) complexes with regard to their structures and properties was investigated. Two isomeric ligands, 4-(3,5-dimethyl-1-pyrazol-1-yl)-2,5-diphenylpyrimidine (HL2,5) and 4-(3,5-dimethyl-1-pyrazol-1-yl)-2,6-diphenylpyrimidine (HL2,6), were synthesized. The ligands differ by the degree of steric bulk: the molecular structure of HL2,5 is more distorted due to presence of pyrazolyl and phenyl groups in the neighbouring positions 4 and 5 of the pyrimidine ring. The complexation of HL2,5 and HL2,6 with RhCl leads to the sp C-H bond activation, resulting in the isolation of two complexes, [RhL2,5(Solv)Cl2]·nEtOH and [RhL2,6(Solv)Cl2]·nEtOH (Solv = HO, EtOH), with the deprotonated forms of the pyrazolylpyrimidine molecules which coordinate the Rh ion as N^N^C-tridentate ligands. According to DFT modelling, the mechanism of the deprotonation involves (i) the C-H bond breaking in the 2-phenyl group followed by the coordination of the C atom to the Rh atom, (ii) the protonation of coordinated chlorido ligand, (iii) the ejection of the HCl molecule and (iv) the coordination of the HO molecule. The ligand isomerism has an impact on emission properties and cytotoxicity of the complexes. Although the excited states of the complexes effectively deactivate through S/T and S/S crossings associated with the cleavage of the weak HO ligands upon excitation, the [RhL2,5(Solv)Cl2]·nEtOH complex appeared to be emissive in the solid state, while [RhL2,6(Solv)Cl2]·nEtOH is non-emissive at all. The complexes show significant cytotoxic activity against cancerous HepG2 and Hep2 cell lines, with the [RhL2,6(Solv)Cl2]·nEtOH complex being more active than its isomer [RhL2,5(Solv)Cl2]·nEtOH. On the other hand, noticeable cytotoxicity of the latter against HepG2 is supplemented by its non-toxicity against non-cancerous MRC-5 cells.
研究了嘧啶基配体及其铑（III）配合物的异构现象对其结构和性质的影响。合成了两种异构配体，4-（3,5-二甲基-1-吡唑-1-基）-2,5-二苯基嘧啶（HL2,5）和4-（3,5-二甲基-1-吡唑-1-基）-2,6-二苯基嘧啶（HL2,6）。这两种配体的空间位阻程度不同：由于嘧啶环的4位和5位相邻位置存在吡唑基和苯基，HL2,5的分子结构扭曲程度更大。HL2,5和HL2,6与RhCl的络合导致sp C-H键活化，从而分离出两种配合物，[RhL2,5（溶剂）Cl2]·nEtOH和[RhL2,6（溶剂）Cl2]·nEtOH（溶剂 = HO，EtOH），其中吡唑基嘧啶分子的去质子化形式作为N^N^C三齿配体与Rh离子配位。根据密度泛函理论（DFT）建模，去质子化机制包括：（i）2-苯基中的C-H键断裂，随后C原子与Rh原子配位；（ii）配位氯配体的质子化；（iii）HCl分子的逸出；（iv）HO分子的配位。配体异构现象对配合物的发射性质和细胞毒性有影响。尽管配合物的激发态通过与激发时弱HO配体的裂解相关的S/T和S/S交叉有效地失活，但[RhL2,5（溶剂）Cl2]·nEtOH配合物在固态下表现出发射性，而[RhL2,6（溶剂）Cl2]·nEtOH完全无发射性。这些配合物对肝癌HepG2和喉癌Hep2细胞系显示出显著的细胞毒性活性，[RhL2,6（溶剂）Cl2]·nEtOH配合物比其异构体[RhL2,5（溶剂）Cl2]·nEtOH更具活性。另一方面，后者对HepG2的显著细胞毒性由其对非癌性MRC-5细胞的无毒性补充。
