Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells (original) (raw)

Chemistry – A European Journal

The chiral cationic complex [Ru(η 1-OAc)(CO)((R,R)-Skewphos)(phen)]OAc (2 R), isolated from reaction of [Ru(η 1-OAc)(η 2-OAc)(R,R)-Skewphos)(CO)] (1 R) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)-Skewphos)(phen)]Y (X = Y = OPiv 3 R ; X = SAc, Y = OAc 4 R). The corresponding enantiomers 2 S-4 S have been obtained from 1 S containing (S,S)-Skewphos. Reaction of 2 R and 2 S with (S)-cysteine and NaPF 6 at pH = 9 gives the diastereoisomers [Ru((S)-Cys)(CO)(PP)(phen)]PF 6 (PP = (R,R)-Skewphos 2 R-Cys; (S,S)-Skewphos 2 S-Cys). The DFT energetic profile for 2 R with (S)cysteine in H 2 O indicates that aquo and hydroxo species are involved in formation of 2 R-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 EC 50 values of 2.8-0.04 μM. The (R,R)-Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4 R (EC 50 = 0.04 μM) being 14 times more cytotoxic than 4 S against the anaplastic thyroid cancer 8505 C cell line.

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