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The corresponding enantiomers 2<\/jats:bold>S<\/jats:bold><\/jats:italic><\/jats:sup>\u20104<\/jats:bold>S<\/jats:bold><\/jats:italic><\/jats:sup> have been obtained from 1<\/jats:bold>S<\/jats:bold><\/jats:italic><\/jats:sup> containing (S,S<\/jats:italic>)\u2010Skewphos. Reaction of 2<\/jats:bold>R<\/jats:bold><\/jats:italic><\/jats:sup> and 2<\/jats:bold>S<\/jats:bold><\/jats:italic><\/jats:sup> with (S<\/jats:italic>)\u2010cysteine and NaPF6<\/jats:sub> at pH=9 gives the diastereoisomers [Ru((S<\/jats:italic>)\u2010Cys)(CO)(PP)(phen)]PF6<\/jats:sub> (PP=(R,R<\/jats:italic>)\u2010Skewphos 2<\/jats:bold>R<\/jats:bold><\/jats:italic><\/jats:sup>\u2010Cys; (S,S<\/jats:italic>)\u2010Skewphos 2<\/jats:bold>S<\/jats:bold><\/jats:italic><\/jats:sup>\u2010Cys). The DFT energetic profile for 2<\/jats:bold>R<\/jats:bold><\/jats:italic><\/jats:sup> with (S<\/jats:italic>)\u2010cysteine in H2<\/jats:sub>O indicates that aquo and hydroxo species are involved in formation of 2<\/jats:bold>R<\/jats:bold><\/jats:italic><\/jats:sup>\u2010Cys. The stability of the ruthenium complexes in 0.9\u2009% w\/v NaCl solution, PBS and complete DMEM medium, as well as their n<\/jats:italic>\u2010octanol\/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505\u2005C, HCT\u2010116 and A549\u2005cell lines with EC50<\/jats:sub> values of 2.8\u20130.04\u2005\u03bc<\/jats:italic>M. The (R<\/jats:italic>,R<\/jats:italic>)\u2010Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4<\/jats:bold>R<\/jats:bold><\/jats:italic><\/jats:sup> (EC50<\/jats:sub>=0.04\u2005\u03bc<\/jats:italic>M) being 14 times more cytotoxic than 4<\/jats:bold>S<\/jats:bold><\/jats:italic><\/jats:sup> against the anaplastic thyroid cancer 8505\u2005C cell line.<\/jats:p>","DOI":"10.1002\/chem.202200200","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T07:23:03Z","timestamp":1649402583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1037-7384","authenticated-orcid":false,"given":"Denise","family":"Lovison","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Agroalimentari, Ambientali e Animali Universit\u00e0 di Udine Via Cotonificio 108 33100 Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1914-806X","authenticated-orcid":false,"given":"Dario","family":"Alessi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Agroalimentari, Ambientali e Animali Universit\u00e0 di Udine Via Cotonificio 108 33100 Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4053-7561","authenticated-orcid":false,"given":"Lorenzo","family":"Allegri","sequence":"additional","affiliation":[{"name":"Dipartimento di Area Medica - Istituto di Genetica Medica Universit\u00e0 di Udine Via Chiusaforte, F3 33100 Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1164-1316","authenticated-orcid":false,"given":"Federica","family":"Baldan","sequence":"additional","affiliation":[{"name":"Dipartimento di Area Medica - Istituto di Genetica Medica Universit\u00e0 di Udine Via Chiusaforte, F3 33100 Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6588-8037","authenticated-orcid":false,"given":"Maurizio","family":"Ballico","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Agroalimentari, Ambientali e Animali Universit\u00e0 di Udine Via Cotonificio 108 33100 Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2312-4009","authenticated-orcid":false,"given":"Giuseppe","family":"Damante","sequence":"additional","affiliation":[{"name":"Dipartimento di Area Medica - Istituto di Genetica Medica Universit\u00e0 di Udine Via Chiusaforte, F3 33100 Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilisa","family":"Galasso","sequence":"additional","affiliation":[{"name":"Centro di Ricerca LURM Laboratorio Interdipartimentale di Ricerca Medica Universit\u00e0 di Verona, Policlinico G.B. 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