Biological studies of chalcogenolato-bridged dinuclear half-sandwich complexes.
A series of cationic chalcogenolato-bridged diruthenium complexes [(η(6)-p-MeC6H4Pr(i))2Ru2(μ-EC6H5)3](+) (E = S, 1; E = Se, 2; E = Te, 3) has been obtained in ethanol from the reaction of (η(6)-p-MeC6H4Pr(i))2Ru2(μ-Cl)2Cl2 with benzenethiol, benzeneselenol, and sodium tellurophenolate, respectively. The thiolato and selenolato derivatives are isolated in good yield as the chloride salts, while the tellurolato analogue is isolated as the hexafluorophosphate salt. Similarly, the dinuclear pentamethylcyclopentadienyl (C5Me5) rhodium and iridium complexes (η(5)-C5Me5)2M2(μ-Cl)2Cl2 react with benzenethiol, benzeneselenol, and sodium tellurophenolate in ethanol to give the corresponding cationic dinuclear complexes of the general formula [(η(5)-C5Me5)2M2(μ-EC6H5)3](+) (M = Rh, E = S, 4; E = Se, 5; E = Te, 6; M = Ir, E = S, 7; E = Se, 8; E = Te, 9). In addition, cationic dinuclear complexes with mixed thiolato-selenolato and thiolato-tellurolato bridges have been prepared, [(η(6)-p-MeC6H4Pr(i))2Ru2(μ-EC6H5)(μ-SCH2C6H4-p-Bu(t))2](+) (E = Se, 10; E = Te, 11) and [(η(5)-C5Me5)2M2(μ-EC6H5)(μ-SCH2C6H5)2](+) (M = Rh, E = Se, 12; E = Te, 13; M = Ir, E = Se, 14; E = Te, 15), starting from the neutral dinuclear complexes (η(6)-p-MeC6H4Pr(i))2Ru2Cl2(μ-SCH2C6H4-p-Bu(t))2 and (η(5)-C5Me5)2M2Cl2(μ-SCH2C6H5)2. All complexes are highly cytotoxic showing activity in the submicromolar range. The nature of the chalcogenolato bridges seems to have an impact on the activity, while the nature of the metal center plays a minor role. Among the complexes tested, the dinuclear complexes 1, 4, and 7 with the thiolato bridges show the highest activity on cancer cells and the best affinity for CT-DNA as demonstrated by cell biology and biophysical experiments.
Institut de Chimie, Université de Neuchâtel , Avenue de Bellevaux 51, CH-2000 Neuchâtel, Switzerland.
Justin P
JP
Johnpeter
Gajendra
G
Gupta
Jerald Mahesh
JM
Kumar
Gunda
G
Srinivas
Narayana
N
Nagesh
Bruno
B
Therrien
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018011:Chalcogens / Q000737:chemistry* / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018011:Chalcogens; D056831:Coordination Complexes; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA