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 H2O 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.

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

Lovison, Denise;Alessi, Dario;Allegri, Lorenzo;Ballico, Maurizio;Damante, Giuseppe
;
Melchior, Andrea;Baratta, Walter
2022-01-01

Abstract

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 H2O 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.
File in questo prodotto:
File Dimensione Formato  
Chemistry A European J - 2022 - Lovison - Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium II Complexes.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 3.94 MB
Formato Adobe PDF
3.94 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11390/1229130
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 9
social impact