手性阳离子络合物[Ru(η1-OAc)(CO)((R,R)-Skewphos)(phen)]OAc(2R),从[Ru(η1-OAc)(η2-OAc)(R,R)-Skewphos)(CO)](1R)带phen,与NaOPiv和KSAc反应得到[RuX(CO)((R,R)-Skewphos)(phen)]Y(X=Y=OPiv3R;X=SAc,Y=OAc4R)。相应的对映体2S-4S已从含1S(S,S)-Skewphos。在pH=9时,2R和2S与(S)-半胱氨酸和NaPF6反应得到非对映异构体[Ru((S)-Cys)(CO)(PP)(phen)]PF6(PP=(R,R)-Skewphos2R-Cys;(S,S)-Skewphos2S-Cys)。H2O中具有(S)-半胱氨酸的2R的DFT能量谱表明,水和羟基物种参与2R-Cys的形成。钌配合物在0.9%w/vNaCl溶液中的稳定性,PBS和完整的DMEM培养基,以及它们的正辛醇/水分配系数(logP),已被评估。手性复合物对SW1736、8505℃、HCT-116和A549细胞系的EC50值为2.8-0.04μM。(R,R)-Skewphos衍生物与它们的对映异构体相比显示出更高的细胞毒性,4R(EC50=0.04μM)对间变性甲状腺癌8505C细胞系的细胞毒性是4S的14倍。
The chiral cationic complex [Ru(η1 -OAc)(CO)((R,R)-Skewphos)(phen)]OAc (2R ), isolated from reaction of [Ru(η1 -OAc)(η2 -OAc)(R,R)-Skewphos)(CO)] (1R ) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)-Skewphos)(phen)]Y (X=Y=OPiv 3R ; X=SAc, Y=OAc 4R ). The corresponding enantiomers 2S -4S have been obtained from 1S containing (S,S)-Skewphos. Reaction of 2R and 2S with (S)-cysteine and NaPF6 at pH=9 gives the diastereoisomers [Ru((S)-Cys)(CO)(PP)(phen)]PF6 (PP=(R,R)-Skewphos 2R -Cys; (S,S)-Skewphos 2S -Cys). The DFT energetic profile for 2R with (S)-cysteine in H2 O indicates that aquo and hydroxo species are involved in formation of 2R -Cys. The stability of the ruthenium complexes in 0.9 % w/v NaCl solution, PBS and complete DMEM medium, as well as their n-octanol/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505 C, HCT-116 and A549 cell lines with EC50 values of 2.8-0.04 μM. The (R,R)-Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4R (EC50 =0.04 μM) being 14 times more cytotoxic than 4S against the anaplastic thyroid cancer 8505 C cell line.