Preparation of organometallic ruthenium-arene-diaminotriazine complexes as binding agents to DNA.

The reactions of two diami- notriazine ligands 2,4-diamino-6-(2-pyr- idyl)-1,3,5-triazine (2-pydaT) and 6- phenyl-2,4-diamino-1,3,5-triazine (PhdaT) with ruthenium-arene precur- sors led to a new family of rutheniu- m(II) compounds that were spectro- scopically characterized. Four of the complexes were cationic, with the gen- eral formula ((h 6 -arene)Ru(k 2 -N,N-2- pydaT)Cl)X (X = BF4, TsO; arene = p- cymene: 1·BF4, 1·TsO; arene = ben- zene: 2·BF4, 2·TsO). The neutral cyclo- metalated complex ((h 6 -p-cymene)R- u(k 2 -C,N-PhdaT*)Cl) (3) was also iso- lated. The structures of complexes 2·BF4 and 3·H2O were determined by X-ray diffraction. Complex 1·BF4 un- derwent a partial reversible-aquation process in water. UV/Vis and NMR spectroscopic measurements showed that the reaction was hindered by the addition of NaCl and was pH-con- trolled in acidic solution. At pH 7.0 (sodium cacodylate) Ru-Cl complex 1·BF4 was the only species present in solution, even at low ionic strength. However, in alkaline medium (KOH), complex 1·BF4 underwent basic hydrol- ysis to afford a Ru-OH complex (5). Fluorimetric studies revealed that the interaction of complex 1·BF4 with DNA was not straightforward; instead, its main features were closely linked to ionic strength and to the (DNA)/com- plex ratio. The bifunctional complex 1·BF4 was capable of interacting con- currently through both its p-cymene and 2-pydaT groups. Cytotoxicity and genotoxicity studies showed that, con- trary to the expected behavior, the complex species was biologically inac- tive; the formation of a Ru-OH com- plex could be responsible for such be- havior.