ABSTRACT
Tetrazole/tetrazolate monocyclopentadienyliron(II) and ruthenium(II) compounds of general formulas [(η5-C5H5)M(dppe)(N4(H)CC6H4NO2)][PF6]/[(η5-C5H5)M(dppe)(N4CC6H4NO2)] were investigated for their pH-switching second-order nonlinear optical (SONLO) properties. Compounds [(η5-C5H5)M(dppe)(N4CC6H4NO2)] (M = Fe, Ru) and compound [(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)][PF6] were fully characterized by (1H-, 13C-, 31P-) NMR, cyclic voltammetry, and elemental analysis, and compounds [(η5-C5H5)Fe(dppe)(N4CC6H4NO2)] and [(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)][PF6] were further characterized by single-crystal X-ray diffraction; the synthesis of [(η5-C5H5)Fe(dppe)(N4(H)CC6H4NO2)][PF6] was unsuccessful. Time-dependent density functional theory calculations were performed using PBE0 and CAM-B3LYP functionals to evaluate the first hyperpolarizability (ßtot) of the tetrazole/tetrazolate complexes and for a detailed analysis of the experimental data. Both functionals predict (i) high first hyperpolarizabilities for the tetrazolate complexes [(η5-C5H5)M(dppe)(N4CC6H4NO2)], with ßtot[Ru] ≈ 1.2ßtot[Fe], and (ii) a 3-fold reduction in ßtot[Ru] upon protonation, in complex [(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)]+, forecasting [(η5-C5H5)Ru(dppe)(N4CC6H4NO2)]/[(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)]+ complexes as on/off, pH-switchable SONLO forms.
ABSTRACT
Eight ruthenium(ii) compounds of the general formula [(η(5)-C5H5)Ru(N-N)(PPh3)][PF6] were rationally designed, exhibiting high cytotoxicity against HCT116 human colon cancer cells, with IC50 between 14.56 and 1.56 µM; importantly, compounds 5Ru and 6Ru are the first reported ruthenium glycoconjugates exploiting glucose transporters, widely overexpressed in cancer, for cellular uptake.
Subject(s)
Antineoplastic Agents/therapeutic use , Carbohydrates/chemistry , Colonic Neoplasms/drug therapy , Coordination Complexes/therapeutic use , Monosaccharide Transport Proteins/metabolism , Ruthenium Compounds/chemistry , Antineoplastic Agents/chemistry , Biological Transport , Colonic Neoplasms/pathology , Coordination Complexes/chemistry , HCT116 Cells , Humans , Models, MolecularABSTRACT
New ruthenium(II) and iron(II) organometallic compounds of general formula [(η(5)-C5H5)M(PP)Lc][PF6], bearing carbohydrate derivative ligands (Lc), were prepared and fully characterized and the crystal structures of five of those compounds were determined by X-ray diffraction studies. Cell viability of colon cancer HCT116 cell line was determined for a total of 23 organometallic compounds and SAR's data analysis within this library showed an interesting dependency of the cytotoxic activity on the carbohydrate moiety, linker, phosphane coligands, and metal center. More importantly, two compounds, 14Ru and 18Ru, matched oxaliplatin IC50 (0.45 µM), the standard metallodrug used in CC chemotherapeutics, and our leading compound 14Ru was shown to be significantly more cytotoxic than oxaliplatin to HCT116 cells, triggering higher levels of caspase-3 and -7 activity and apoptosis in a dose-dependent manner.
