Spectral Analysis on Cuba-Lumacaftor: Cubane as Benzene Bioisosteres of Lumacaftor

Dongdong Wang; Xiaohong Lyu; Mengtao Sun; Yongqiang Liang

doi:10.1021/acsomega.3c07532

Spectral Analysis on Cuba-Lumacaftor: Cubane as Benzene Bioisosteres of Lumacaftor

ACS Omega. 2023 Nov 3;8(45):43332-43340. doi: 10.1021/acsomega.3c07532. eCollection 2023 Nov 14.

Authors

Dongdong Wang¹, Xiaohong Lyu¹, Mengtao Sun², Yongqiang Liang³

Affiliations

¹ Department of Radiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121004, China.
² School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China.
³ Department of Central Sterile Supply, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121004, China.

Abstract

In this paper, we theoretically investigate the electronic structure and physical properties of cuba-lumacaftor, cubane as benzene bioisosteres of lumacaftor, stimulated by recent experimental reports [Wiesenfeldt M. P.; Nature2023, 618, 513-518]. The permanent electric dipole moments of cuba-lumacaftor in neutral, acidic, and alkaline environments are significantly enlarged than that of lumacaftor, significantly promoting the interaction between cuba-lumacaftor and surrounding polar solvent environments and resulting in pH-independent high solubility and pharmacological activity. Furthermore, electronic circular dichroism (ECD) spectra reveal that the chirality of cuba-lumacaftor is much decreased compared to that of lumacaftor. Raman spectra and resonance Raman spectra combined with polarizability also reveal the vibrational information on cuba-lumacaftor. Our results promote a deeper understanding of better pharmacological activity.