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

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 S 0 !S 1 excitation was found in vis area at 413 nm (transisomer), while the S 2 !S 0 and S 1 !S 0 excitations are charge transfer (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.