Detecting multiple chirality centers in chiral molecules with high harmonic generation

TL;DR

This paper demonstrates that high harmonic generation driven by bi-chromatic lasers can sensitively detect and distinguish multiple chirality centers in molecules, enabling high-fidelity stereoisomer analysis with machine learning.

Contribution

It introduces a novel approach combining HHG spectroscopy with deep learning to analyze complex chiral molecules with multiple stereocenters.

Findings

HHG spectra encode information about molecular chirality.

Deep learning enables accurate stereoisomer reconstruction.

Single-shot HHG measurement can identify stereoisomer composition.

Abstract

Characterizing chirality is highly important for applications in the pharmaceutical industry, as well as in the study of dynamical chemical and biological systems. However, this task has remained challenging, especially due to the ongoing increasing complexity and size of the molecular structure of drugs and active compounds. In particular, large molecules with many active chirality centers are today ubiquitous, but remain difficult to structurally analyze due to their high number of stereoisomers. Here we theoretically explore the sensitivity of high harmonic generation (HHG) to the chirality of molecules with a varying number of active chiral centers. We find that HHG driven by bi-chromatic non-collinear lasers is a sensitive probe for the stereo-configuration of a chiral molecule. We first show through calculations (from benchmark chiral molecules with up to three chirality centers) that the HHG spectrum is imprinted with information about the handedness of each chirality center in the driven molecule. Next, we show that using both classical- and deep-learning-based reconstruction algorithms, the composition of an unknown mixture of stereoisomers can be reconstructed with high fidelity by a single-shot HHG measurement. Our work illustrates how the combination of non-linear optics and machine learning might open routes for ultra-sensitive sensing in chiral systems.