Azobenzene/Tetraethyl Ammonium Photochromic Potassium Channel Blockers: Scope and Limitations for Design of Para-Substituted Derivatives with Specific Absorption Band Maxima and Thermal Isomerization Rate

• Published in: International journal of molecular sciences 2021-12, Vol.22 (23), p.13171
• Main Authors: Strashkov, Daniil M, Mironov, Vladimir N, Nikolaev, Dmitrii M, Panov, Maxim S, Linnik, Stanislav A, Mereshchenko, Andrey S, Kochemirovsky, Vladimir A, Vasin, Andrey V, Ryazantsev, Mikhail N
• Format: Article
• Language: English
• Subjects: Absorption spectra; Ammonium; Azo compounds; Azo Compounds - chemistry; azobenzene; azobenzene thermal isomerization rate; Biological activity; Chemical Phenomena; Equilibrium; Flash photolysis; Functional groups; Isomerization; Isomers; Kinetics; Light; Maxima; Pain perception; photochromic ion channel blockers; Photochromism; photopharmacology; Potassium; Potassium Channel Blockers - chemistry; Quantum Theory; red-shifting azobenzenes; Signal transduction; Solvents; spectral tuning of azobenzene photoswitches; Spectroscopy; Spectrum analysis; Stereoisomerism; Tetraethylammonium - chemistry; Thermodynamics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222313171

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 and isomers of ATPLs, the thermal lifetime of their 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.