000152078 001__ 152078
000152078 005__ 20251017144622.0
000152078 0247_ $$2doi$$a10.1021/acs.inorgchem.1c00507
000152078 0248_ $$2sideral$$a126895
000152078 037__ $$aART-2021-126895
000152078 041__ $$aeng
000152078 100__ $$aRafols L.
000152078 245__ $$aPiano-Stool Ruthenium(II) Complexes with Delayed Cytotoxic Activity: Origin of the Lag Time
000152078 260__ $$c2021
000152078 5060_ $$aAccess copy available to the general public$$fUnrestricted
000152078 5203_ $$aWe have recently reported a series of piano-stool ruthenium(II) complexes of the general formula [RuCl2(¿6-arene)(P(1-pyrenyl)R2R3)] showing excellent cytotoxic activities (particularly when R2 = R3 = methyl). In the present study, new members of this family of compounds have been prepared with the objective to investigate the effect of the steric hindrance of a bulky phosphane ligand, namely diisopropyl(1-pyrenyl)phosphane (L), on exchange reactions involving the coordinated halides (X = Cl, I). Two ¿6-arene rings were used, i.e. ¿6-methyl benzoate (mba) and ¿6-p-cymene (p-cym), and four complexes were synthesized, namely [RuCl2(mba)(L)] (1Cl2iPr), [RuI2(mba)(L)] (1I2iPr), [RuCl2(p-cym)(L)] (2Cl2iPr), and [RuI2(p-cym)(L)] (2I2iPr). Unexpectedly, all of the complexes exhibited poor cytotoxic activities after 24 h of incubation with cells, in contrast to the related compounds previously reported. However, it was observed that aged DMSO solutions of 2I2iPr (from 2 to 7 days) exhibited better activities in comparison to freshly prepared solutions and that the activity improved over "aging"time. Thorough studies were therefore performed to uncover the origin of this lag time in the cytotoxicity efficiency. The data achieved clearly demonstrated that compounds 2I2iPr and 2Cl2iPr were undergoing a series of transformation reactions in DMSO (with higher rates for the iodido complex 2I2iPr), ultimately generating cyclometalated species through a mechanism involving DMSO as a coordinated proton abstractor. The cyclometalated complexes detected in solution were subsequently prepared; hence, pure [RuCl(p-cym)(¿2C-diisopropyl(1-pyrenyl)phosphane)] (3CliPr), [RuI(p-cym)(¿2C-diisopropyl(1-pyrenyl)phosphane)] (3IiPr), and [Ru(p-cym)(¿S-dmso)(¿2C-diisopropyl(1-pyrenyl)phosphane)]PF6 (3dmsoiPr) were synthesized and fully characterized. Remarkably, 3CliPr, 3IiPr, and 3dmsoiPr are all very efficient cytotoxic agents, exhibiting slightly better activities in comparison to the chlorido noncyclometalated complexes [RuCl2(¿6-arene)(P(1-pyrenyl)R2R3)] described in an earlier report. For comparison purposes, the iodido compounds [RuI2(mba)(dimethyl(1-pyrenyl)phosphane)] (1I2Me) and [RuI2(p-cym)(dimethyl(1-pyrenyl)phosphane)] (2I2Me), bearing the less hindered dimethyl(1-pyrenyl)phosphane ligand, have also been prepared. The cytotoxic and chemical behaviors of 1I2Me and 1I2Me were comparable to those of their chlorido counterparts reported previously.
000152078 536__ $$9info:eu-repo/grantAgreement/ES/MCIU/CTQ2015-65040-P$$9info:eu-repo/grantAgreement/ES/MCIU/CTQ2017-88446-R$$9info:eu-repo/grantAgreement/ES/MCIU/PGC2018-098630-B-I00$$9info:eu-repo/grantAgreement/ES/MCIU/PID2019-107006GB-C21$$9info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
000152078 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000152078 590__ $$a5.436$$b2021
000152078 591__ $$aCHEMISTRY, INORGANIC & NUCLEAR$$b5 / 46 = 0.109$$c2021$$dQ1$$eT1
000152078 592__ $$a1.121$$b2021
000152078 593__ $$aInorganic Chemistry$$c2021$$dQ1
000152078 593__ $$aChemistry (miscellaneous)$$c2021$$dQ1
000152078 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000152078 700__ $$aJosa D.
000152078 700__ $$aAguilà D.
000152078 700__ $$aBarrios L.A.
000152078 700__ $$0(orcid)0000-0003-2095-5843$$aRoubeau O.
000152078 700__ $$aCirera J.
000152078 700__ $$aSoto-Cerrato V.
000152078 700__ $$aPérez-Tomás R.
000152078 700__ $$aMartínez M.
000152078 700__ $$aGrabulosa A.
000152078 700__ $$aGamez P.
000152078 773__ $$g60, 11 (2021), 7974-7990$$pInorg. chem.$$tInorganic Chemistry$$x0020-1669
000152078 8564_ $$s3185240$$uhttps://zaguan.unizar.es/record/152078/files/texto_completo.pdf$$yVersión publicada
000152078 8564_ $$s3091256$$uhttps://zaguan.unizar.es/record/152078/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000152078 909CO $$ooai:zaguan.unizar.es:152078$$particulos$$pdriver
000152078 951__ $$a2025-10-17-14:22:08
000152078 980__ $$aARTICLE