A DFT Study towards the Amide cis‐trans Isomerization Process of the Myc‐Max Inhibitor Mycro 3 and Its Photophysical Properties; Synthesis and NMR Studies of the trans‐Conformation. Issue 25 (1st July 2022) - Mamalis, Dimitrios
Abstract: Mycro 3 is a synthetic pyrazolo[1, 5‐ a ]pyrimidine amide with interesting bioactivity having exhibited promising results in in vivo studies against pancreatic cancer. Even though it is a known compound, no data concerning its conformations have been reported before. The aim of this work is to investigate the formation of its trans ‐ and cis ‐ isomers, the photophysical processes of the isomerization, and the solvent effect via a DFT study. We found that this isomerization is a thermodynamically favourable reaction, having a small barrier of 10.3 kcal/mol in DMSO. Additionally, the calculated 1 H and 13 C NMR spectra of the two isomers revealed measurable differences. Furthermore, the S0 →S1 excitation was found in vis area at 413 nm ( trans ‐isomer), while the S2 →S0 and S1 →S0 excitations are charge trans fer (CT) and partially CT state in near‐infrared and vis spectra, showing that mycro 3 also has the potential to be used as a photosensitizer. Finally, its synthesis and its NMR analysis revealed a good agreement with the proposed trans conformation. Abstract : Cis‐trans isomerization and photophysical properties of the isomers have been examined via DFT calculations. The isomerization barrier is slightly affected by the solvent effect. Absorption and emission spectra of the isomers showed that mycro3 has the potential to be used as a photosensitizer additionally to its potential as an inhibitor of the MYC oncoprotein. Synthesis and NMR experiments are in good agreement with theoretical data.