The Influence of Some Axial Ligands on Ruthenium-Phthalocyanine Complexes: Chemical, Photochemical, and Photobiological Properties.

This work presents a new procedure to synthesize ruthenium-phthalocyanine complexes and uses diverse spectroscopic techniques to characterize trans-[RuCl(Pc)DMSO] (I) (Pc = phthalocyanine) and trans-[Ru(Pc)(4-ampy)2] (II) (4-ampy = 4-aminopyridine). The triplet excited-state lifetimes of (I) measured by nanosecond transient absorption showed that two processes occurred, one around 15 ns and the other around 3.8 µs. Axial ligands seemed to affect the singlet oxygen quantum yield. Yields of 0.62 and 0.14 were achieved for (I) and (II), respectively. The lower value obtained for (II) probably resulted from secondary reactions of singlet oxygen in the presence of the ruthenium complex. We also investigate how axial ligands in the ruthenium-phthalocyanine complexes affect their photo-bioactivity in B16F10 murine melanoma cells. In the case of (I) at 1 µmol/L, photosensitization with 5.95 J/cm2 provided B16F10 cell viability of 6%, showing that (I) was more active than (II) at the same concentration. Furthermore, (II) was detected intracellularly in B16F10 cell extracts. The behavior of the evaluated ruthenium-phthalocyanine complexes point to the potential use of (I) as a metal-based drug in clinical therapy. Changes in axial ligands can modulate the photosensitizer activity of the ruthenium phthalocyanine complexes.

Photobiomodulation combined with photodynamic therapy using ruthenium phthalocyanine complexes in A375 melanoma cells: Effects of nitric oxide generation and ATP production.

Light irradiation has been used in clinical therapy for several decades. In this context, photobiomodulation (PBM) modulates signaling pathways via ROS, ATP, Ca2+, while photodynamic therapy (PDT) generates reactive oxygen species by excitation of a photosensitizer. NO generation could be an important tool when combined with both kinds of light therapy. By using a metal-based compound, we found that PBM combined with PDT could be a beneficial cancer treatment option. We used two types of ruthenium compounds, ([Ru(Pc)], Pc = phthalocyanine) and trans-[Ru(NO)(NO2)(Pc)]. The UV-vis spectra of both complexes displayed a band in the 660 nm region. In the case of 0.5 µM trans-[Ru(NO)(NO2)(Pc)], light irradiation at the Q-band reduced the percentage of viable human melanoma (A375) cells to around 50% as compared to [Ru(Pc)]. We hypothesized that these results were due to a synergistic effect between singlet oxygen and nitric oxide. Similar experiments performed with PDT (660 nm) combined with PBM (850 nm) induced more photocytotoxicity using both [Ru(Pc)] and trans-[Ru(NO)(NO2)(Pc)]. This was interpreted as PBM increasing cell metabolism (ATP production) and the consequent higher uptake of the ruthenium phthalocyanine compounds and more efficient apoptosis. The use of metal-based photosensitizers combined with light therapy may represent an advance in the field of photodynamic therapy.