A study on optical properties of various hot drug molecules by 2020

Advances in imaging technologies and imaging probes for in situ and real-time visualization of important analytes and biological events in humans are now extending the applications of imaging further into drug discovery, and have provided the potential to considerably accelerate the process of novel drug development. Currently, the research on developing activated molecules with excellent optical properties is minimal. In this contribution, we have systematically studied the optical properties of two small drug molecules among the top 200 pharmaceuticals by retail sales in 2020 with a combination of theoretical chemistry and experiment. The results suggested that compound 134 had a stronger fluorescence quantum yield (f = 7.1%) in organic solvent (phosphate buffer saline) due to its obvious planar geometry and p-A electron character. However, 134 displayed negligible HeLa cell fluorescence due to an inappropriate excitation wavelength. On the other hand, 18 exhibited a low fluorescence quantum yield (f = 0.3%) in phosphate buffer saline resulting from a smaller adiabatic energy difference (E-ad = 3.14 eV) and greater geometry relaxation between two electronic states (maximum HR factor of 98.47 in the low frequency regime) by methylpiperazine vibration and methyl rotation. However, surprisingly, 18 showed bright green fluorescence in HeLa cells, likely because of the complicated interaction between the methylpiperazine group in molecule 18 and cellar microenvironment that may restrict the molecular vibration, reducing non-radiative decay. We hope that this study could provide a powerful basis for finding existing molecules and developing novel compounds for integration of diagnosis and treatment of various diseases.