Efficient Simulation of Raman Optical Activity Spectra via Molecular Tailoring Approach

Raman Optical Activity (ROA) is an indispensable tool to investigate the chiral characteristics of molecular systems; however, its quantum mechanical modeling remains computationally demanding for large systems. Moreover, standard ab initio packages often become ineffective in such cases. Against this backdrop, we report the application of the fragment-based Molecular Tailoring Approach (MTA) to enable ROA spectra simulations of complex systems (up to 407 atoms) in both gas and solvent phases using density functional theory. The grafting-assisted MTA-based ROA spectra exhibit excellent agreement with the full conventional calculations and successfully reproduce key spectral features. Furthermore, for selected systems, the consistency with the experimental data further validates the effectiveness of the method. Given its accuracy, substantial computational speed-up, and compatibility with off-the-shelf hardware, the present study provides a cost-effective strategy for investigating ROA spectra of large molecular systems.