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

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. ; Nature 2023, 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.