Nitric oxide (NO) is an endogenously produced small molecule involved in neural transmission, immune response, and blood pressure regulation. The radical nature of NO has also been studied for its ability to increase radiation damage in hypoxic cells, thus improving radiation chemotherapy. In this vein, we are committed to generating molecules that utilize an external trigger to allow for controlled release of NO in biology.
Photochemical release of NO allows for specific location, timing, and dosage of a drug and has the potential to limit wide spread side-effects common to chemotherapy treatments. Several novel ruthenium nitrosyls have been synthesized and studied for their photoactive nitric oxide release. Compounds were characterized by mass spectroscopy, NMR, UV-visible spectra, IR, elemental analysis, photochemical reactivity and ability to release NO. Quantum yields and efficiency measurements were conducted by monitoring the moles of NO produced due to light irradiation. The release of NO was detected by a Nitric Oxide Analyzer in real time.
Two major compounds will be discussed, a water soluble, water stable ruthenium nitrosyl for applications in biological systems and a hydrophobic ruthenium nitrosyl variant which was infused into a polymer matrix with up-converting nanoparticles (UCNP). The water soluble compound Ru(NO)(salen-CO2H)Cl 1, has been studied for its photochemistry, cytotoxicity on a murine melanoma cancer cell line, and vasodilation in murine aortic rings. The hydrophobic compound, Ru(NO)(salophen)Cl, was loaded into a polymer matrix with UCNP, utilizing unique properties of UCNPs to shift the excitation wavelength into the near infrared region, where there is better tissue penetration of light. This document contains the synthetic, photochemical, and studies on the efficiency of NO release for each compound.