Photopharmacology is a field of medicine and pharmacology that uses light to selectively activate or deactivate pharmaceutical agents. This approach significantly enhances and localizes the drug action and, therefore, reduces its side effects. Apart from the bioactive moiety, any photopharmacological compound should contain a photoactive group that must absorb light at the desired wavelength and reorganize the molecular structure after photoactivation. The design of an effective photopharmacological compound requires careful tuning of physical, chemical, and biological properties. The present review summarizes and analyzes the main approaches to the molecular design of photopharmacological drugs based on azobenzene or azoheteroarenes. The main ideas and methods used for tuning spectral and photochemical properties of compounds of this class are discussed. A comparative analysis of main computational methods for their in silico screening is carried out; the most common approaches to the synthesis of azobenzenes and azoheteroarenes derivatives are systematized. Special attention is given to the methods and approaches that are specific to the molecular design of photopharmacological compounds with required physicochemical and photochemical properties. The bibliography includes 212 references.

In this paper, we propose a fast and simple approach for the fabrication of the electrocatalytically active ruthenium-containing microstructures using a laser-induced metal deposition technique. The results of scanning electron microscopy and electrical impedance spectroscopy (EIS) demonstrate that the fabricated ruthenium-based microelectrode had a highly developed surface composed of 10 μm pores and 10 nm zigzag cracks. The fabricated material exhibited excellent electrochemical properties toward non-enzymatic dopamine sensing, including high sensitivity (858.5 and 509.1 μA mM−1 cm−2), a low detection limit (0.13 and 0.15 μM), as well as good selectivity and stability.

Azobenzene-based quaternary ammonium compounds provide optical control of ion channels and are considered promising agents for regulation of neuronal excitability and for restoration of the photosensitivity of retinal cells. However, the selectivity of the action of these compounds remains insufficiently known. We studied the action of DENAQ (diethylamine-azobenzene-quaternary ammonium) and DMNAQ (dimethylamine-azobenzene-quaternary ammonium) on ionotropic glutamate receptors in rat brain neurons. In the dark, both compounds applied extracellularly caused fast and reversible inhibition of NMDA (N-methyl-D-aspartate) receptor-mediated currents with IC 50 values of 10 and 5 μM, respectively. Light-induced transformation of DENAQ and DMNAQ to their cis forms caused the IC 50 values to increase to 30 and 27 μM, respectively. Detailed analysis of this action revealed a complex nature consisting of fast inhibitory and slower potentiating effects. The AMPA (α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid) receptors were only weakly affected independently on illumination. We conclude that, in addition to their long-lasting intracellular action, which persists after washout, azobenzene-based quaternary ammonium compounds should affect glutamatergic transmission and synaptic plasticity during treatment. Our findings also extend the list of soluble photoswitchable inhibitors of NMDA receptors. While the site(s) and mechanisms of action are unclear, the effect of DENAQ demonstrates strong pH dependence. At acidic pH values, DENAQ potentiates both NMDA and AMPA receptors.

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Azobenzene/tetraethyl ammonium photochromic ligands (ATPLs) are photoactive compounds with a large variety of photopharmacological applications such as nociception control or vision restoration. Absorption band maximum and lifetime of the less stable isomer are important characteristics that determine the applicability of ATPLs. Substituents allow to adjust these characteristics in a range limited by the azobenzene/tetraethyl ammonium scaffold. The aim of the current study is to find the scope and limitations for the design of ATPLs with specific spectral and kinetic properties by introducing para substituents with different electronic effects. To perform this task we synthesized ATPLs with various electron acceptor and electron donor functional groups and studied their spectral and kinetic properties using flash photolysis and conventional spectroscopy techniques as well as quantum chemical modeling. As a result, we obtained diagrams that describe correlations between spectral and kinetic properties of ATPLs (absorption maxima of E and Z isomers of ATPLs, the thermal lifetime of their Z form) and both the electronic effect of substituents described by Hammett constants and structural parameters obtained from quantum chemical calculations. The provided results can be used for the design of ATPLs with properties that are optimal for photopharmacological applications.