Towards Red Light Control of Ion Channel Blockers

Photoswitchable ion channel blockers reported previously have proven effective for modulating the activity of voltage-gated potassium (KV) channels. One limitation of previously reported azobenzene-based blockers was that the wavelength needed to promote trans-to-cis isomerization ranged from ultraviolet (UV) to blue. Light in this wavelength range poorly penetrates tissues and is cytotoxic, which limits the utility of these photoswitchable compounds for in vivo studies of KV channel activity. We designed, synthesized and ran preliminary patch-clamp experiments on analogous ion channel blockers bearing the tetra-ortho-methoxy (TOM) substitution pattern to bathochromically shift the absorption spectrum to permit long-wavelength photo-control. In combination with a bis-para-amino functionality, these blockers can form azonium ions under physiological conditions, which absorb red light strongly and undergo trans-to-cis isomerization. Red-light effectively penetrates tissues, allowing for in vivo studies of biological systems. We also report synthesis and initial characterization of a novel, further red-shifted dioxane ortho-methoxy (DOM) azobenzene substitution pattern.M.Sc.2017-11-17 00:00:0