Application of Quantum–Chemical Methods in the Forensic Prediction of Psychedelic Drugs’ Spectra (IR, NMR, UV–VIS, and MS): A Case Study of LSD and Its Analogs

Theoretical methods accurately predict the infrared, NMR, UV-VIS, and mass spectra of lysergic acid diethylamide (LSD) when compared with experimental data. Optimizing the molecular structure at the M05-2X/6-311++G(d,p) level of theory yielded bond lengths within 0.0436 Å and bond angles within 2.70° of crystallographic data. The computed C=O stretching vibration differed from experimental by less than 11 cm⁻¹. Predicted 13C NMR chemical shifts correlated with experimental values at 0.999, with a mean absolute error of 2.0 ppm. The calculated ground-to-excited-state energy difference of 330 nm matched the observed UV-VIS band. This approach was validated against a seized-sample GC-MS spectrum and by computing NMR spectra of common LSD analogs, demonstrating its potential for characterizing novel psychedelics.

Study at a glance

Abstract

Lysergic acid diethylamide (LSD) and its analogs are commonly encountered substances at crime scenes due to their misuse as hallucinogenic compounds. Modern methods have led to synthesizing different LSD analogs with pronounced physiological effects. Theoretical methods can be a valuable tool for predicting the spectra and stability of novel substances, especially when experimental data are partially available. The current work describes the application of theoretical methods in predicting IR, NMR, UV–VIS, and MS spectra of LSD based on the optimized structure at the M05-2X/6-311++G(d,p) level of theory. A suitable functional has been determined by comparison of the theoretically obtained geometrical parameters with the experimental ones based on the crystallographic structure. The MAE values for the structure optimized at M05-2X/6-311++G(d,p) level of theory were 0.0436 Å (bond lengths) and 2.70° (bond angles). The IR spectra of LSD and LSD tartrate have been described in detail, with the prominent bands being well reproduced (the difference between experimental and theoretical C=O stretching vibration wavenumbers was lower than 11 cm−1). Detailed assignment of 13C NMR spectra led to a high correlation factor (0.999) and low mean absolute error (2.0 ppm) between experimental and theoretical chemical shifts. Optimizing the ground and excited states allowed for the calculation of the energy difference of 330 nm, which reproduced the observed band position in the UV–VIS spectrum of LSD. The most abundant fragments in the experimental mass spectrum (at 323, 221, 207, 181, and 72 m/z) have been optimized, and their stability has been discussed from the structural point of view. This methodology has been validated by comparison with the experimental GC-MS spectra of sample seized at the crime screen and by structure optimization and computation of NMR spectra of common LSD analogs. The theoretical methods for the structure determination and prediction of spectra show great potential in the fast-developing world of new psychedelics.