Effect of Electron-donating Group on NO Photolysis of {RuNO}6 Ruthenium Nitrosyl Complexes with N2 O2 Lgands Bearing π-Extended Rings.

In this study, we introduced the electron-donating group (-OH) to the aromatic rings of Ru(salophen)(NO)Cl (0) (salophenH2 =N,N'-(1,2-phenylene)bis(salicylideneimine)) to investigate the influence of the substitution on NO photolysis and NO-releasing dynamics. Three derivative complexes, Ru((o-OH)2 -salophen)(NO)Cl (1), Ru((m-OH)2 -salophen)(NO)Cl (2), and Ru((p-OH)2 -salophen)(NO)Cl (3) were developed and their NO photolysis was monitored by using UV/Vis, EPR, NMR, and IR spectroscopies under white room light. Spectroscopic results indicated that the complexes were diamagnetic Ru(II)-NO+ species which were converted to low-spin Ru(III) species (d5 , S=1/2) and released NO radicals by photons. The conversion was also confirmed by determining the single-crystal structure of the photoproduct of 1. The photochemical quantum yields (ΦNO s) of the photolysis were determined to be 0>1, 2, 3 at both the visible and UV excitations. Femtosecond (fs) time-resolved mid-IR spectroscopy was employed for studying NO-releasing dynamics. The geminate rebinding (GR) rates of the photoreleased NO to the photolyzed complexes were estimated to be 0≃1, 2, 3. DFT and TDDFT computations found that the introduction of the hydroxyl groups elevated the ligand π-bonding orbitals (π (salophen)), resulting in decrease of the HOMO-LUMO gaps in 1-3. The theoretical calculations suggested that the Ru-NNO bond dissociations of the complexes were mostly initiated by the ligand-to-ligand charge transfer (LLCT) of π(salophen)→π*(Ru-NO) with both the visible and UV excitations and the decreasing ΦNO s could be explained by the changes of the electronic structures in which the photoactivable bands of 1-3 have relatively less contribution of transitions related with Ru-NO bond than those of 0.

In vitro and in vivo leishmanicidal activity of a ruthenium nitrosyl complex against Leishmania (Viannia) braziliensis.

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. There are many complications presented by the current treatment, as high toxicity, high cost and parasite resistance, making the development of new therapeutic agents indispensable. The present study aims to evaluate the leishmanicidal potential of ruthenium nitrosyl complex cis-[Ru(bpy)2(SO3)(NO)](PF6) against Leishmania (Viannia) braziliensis. The effect of this metal complex on parasite-host interaction was evaluated by in vitro efficacy test in dermal fibrobast cells in the presence of different concentrations (1, 10, 50 and 100 µM) and by in vivo efficacy tests performed in the presence of two different concentrations of complex (100 µg/kg/day or 300 µg/kg/day) evaluating its effect on the size of the lesion and the number of parasites present in the draining lymph nodes in hamsters. Even at the lowest concentration of 1 µM of ruthenium complex, it was observed a significant decrease of the infected cells, after 24 h exposure in vitro, with total reduction at 50 µM of the ruthenium complex. In the in vivo cutaneous infection model, administration of daily doses of 300 µg/kg/day of complex reduced significantly lesion size by 51% (p < 0.05), with a 99.9% elimination of the parasites found in the lymph nodes (p < 0.001). The results suggest a promising leishmanicidal effect by that ruthenium nitrosyl complex against L. (V.) braziliensis.