Design and evaluation of light-responsive ruthenium complexes for neurotransmitter release: synthesis, characterization, DFT and gene regulation studies.

Neurotransmitters are critical biomolecules involved in the mediation of synaptic transmission and the control of many neurophysiological processes. Their therapeutic potential, however, is usually limited by fast degradation, off-target action, and absence of spatial targeting. Photoactivated chemotherapy (PACT) offers a potential solution for spatially and temporally controlled delivery of bioactive molecules. In this paper, neurotransmitters were encapsulated in light-sensitive ruthenium (II) polypyridyl caged complexes, which would be inert in the dark and release upon irradiation with 465 nm blue light through photolysis. The complexes were prepared and thoroughly characterized by UV-VIS spectroscopy, FTIR, ESI-MS, NMR, CHNS elemental analysis, and ICP-MS, establishing coordination and structural integrity. Photorelease of neurotransmitters was verified by time-resolved UV-VIS and mass spectrometric investigations. To assess the biological relevance of light-induced release, gene expression analysis was conducted, demonstrating upregulation of the important neuronal markers after irradiation. The findings prove the efficiency of ruthenium-based cages in light-regulated neurotransmitter delivery and justify their possible application in neurotherapeutic PACT platforms.