TY - JOUR

T1 - Azobenzene/tetraethyl ammonium photochromic potassium channel blockers

T2 - Scope and limitations for design of para-substituted derivatives with specific absorption band maxima and thermal isomerization rate

AU - Strashkov, Daniil M.

AU - Mironov, Vladimir N.

AU - Nikolaev, Dmitrii M.

AU - Panov, Maxim S.

AU - Linnik, Stanislav A.

AU - Mereshchenko, Andrey S.

AU - Kochemirovsky, Vladimir A.

AU - Vasin, Andrey V.

AU - Ryazantsev, Mikhail N.

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/12/6

Y1 - 2021/12/6

N2 - 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.

AB - 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.

KW - Azobenzene

KW - Azobenzene thermal isomerization rate

KW - DENAQ

KW - Photochromic ion channel blockers

KW - Photopharmacology

KW - Red-shifting azobenzenes

KW - Spectral tuning of azobenzene photoswitches

UR - http://www.scopus.com/inward/record.url?scp=85120625287&partnerID=8YFLogxK

U2 - 10.3390/ijms222313171

DO - 10.3390/ijms222313171

M3 - Article

AN - SCOPUS:85120625287

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 23

M1 - 13171

ER -