Mechanistic Basis for Red Light Switching of Azonium Ions

Azonium ions formed by the protonation of tetra-ortho-methoxy-substituted aminoazobenzenes photoisomerize with red light under physiological conditions. This property makes them attractive as molecular tools for the photocontrol of physiological processes, for example, in photopharmacology. However, a mechanistic understanding of the photoisomerization process and subsequent thermal relaxation is necessary for the rational application of these compounds as well as for guiding the design of derivatives with improved properties. Using a combination of sub-ps/ns transient absorption measurements and quantum chemical calculations, we show that the absorption of a photon by the protonated E–H⁺ form of the photoswitch causes rapid (ps) isomerization to the protonated Z–H⁺ form, which can also absorb red light. Proton transfer to solvent then occurs on a microsecond time scale, leading to an equilibrium between Z and Z–H⁺ species, the position of which depends on the solution pH. Whereas thermal isomerization of the neutral Z form to the neutral E form is slow (∼0.001 s^–1), thermal isomerization of Z–H⁺ to E–H⁺ is rapid (∼100 s^–1), so the solution pH also governs the rate at which E/E–H⁺ concentrations are restored after a light pulse. This analysis provides the first complete mechanistic picture that explains the observed intricate photoswitching behavior of azonium ions at a range of pH values. It further suggests features of azonium ions that could be targeted for improvement to enhance the applicability of these compounds for the photocontrol of biomolecules.