Physical-Chemistry Seminar: UNDERSTANDING THE PHOTOISOMERIZATION OF AZOARENES IN COMPLEX ENVIRONMENTS USING MULTISCALE SIMULATIONS
04/06/2023
Chemistry Faculty Seminar Room
12:30
Dr. Jonathan R. Church Fritz Haber Center for Molecular Dynamics Research, Institute of Chemistry, The Hebrew University
Understanding the Photoisomerization of Azoarenes in Complex Environments Using Multiscale Simulations
Azoarenes exhibit unique photochemical properties that make them promising candidates for applications in materials science, nanotechnology, and medicine. These molecules can undergo a reversible trans to cis photoisomerization, enabling them to act as photoswitches in technical applications. For example, they have been utilized as targeted drug delivery systems that release a drug in direct response to light. 1 A current limitation is that many azoarenes require UV light for photoactivation and have poor photoproduct yields. Active research aims to tune their absorption maximum to longer wavelengths while also improving their photoswitching properties, such as faster switching rates and greater thermal stability. Understanding the isomerization process at an atomistic level can be obtained from computer simulations which provide guidance for experimental design. However, treatment of the environment raises the complexity of the simulation and increases the computational cost. To overcome this, multiscale simulations such as the hybrid quantum mechanical/molecular mechanics (QM/MM) method can be employed. In this talk I will present results of QM/MM simulations of azoarenes in two environments: (1) encapsulated in supramolecular cages, and (2) inside a tubulin protein acting as a photoswitch for controlled drug release. 2,3 Using these simulations, I was able to understand the unusual involvement of triplet states in the photoisomerization mechanism of azoarenes encapsulated in a supramolecular cage with triplet energy sensitizers. Meanwhile, in the case of azoarenes embedded in tubulin I was able to use non-adiabatic dynamics to gain mechanistic insights into the isomerization mechanism inside a protein environment.
References:
(1) Sheldon, J. E.; Dcona, M. M.; Lyons, C. E.; et al. Photoswitchable Anticancer Activity via Trans-Cis Isomerization of a Combretastatin A-4 Analog. Org. Biomol. Chem. 2016, 14 (1), 40. https://doi.org/10.1039/C5OB02005K.
(2) Wranik, M.; Weinert, T.; Slavov, C.; et al Watching the Release of a Photopharmacological Drug from Tubulin Using Time-Resolved Serial Crystallography. Nat. Commun. 2023 141 2023, 14 (1), 1–12. https://doi.org/10.1038/s41467-023-36481- 5. (3) Gemen, J.; Church, J. R.; Ruoko, T.-P.; et al. Disequilibrating Azoarenes by Visible-Light Sensitization under Confinement. 2023. https://doi.org/10.26434/CHEMRXIV-2023- GQ2H0.