Can Graph Machines Accurately Estimate ¹³C NMR Chemical Shifts of Benzenic Compounds?

Abstract

NMR spectroscopy, which is based on the phenomenon of nuclear magnetic resonance, has been widely popularized by its application in medical imaging under the name of MRI. In the organic laboratory, the 13C NMR spectrum of a newly synthetized compound remains an essential step in elucidating its structure. For the chemist, the interpretation of such a spectrum, which is a set of chemical shift values, is made easier if he has a tool capable of predicting with sufficient accuracy the carbon shift values from the structure he intends to prepare. As there are few open source methods for accurately estimating this property, we applied our graph machine approach to build models capable of predicting the chemical shifts of carbons. For this study, we have focused on benzene compounds building an optimized model derived from training a database of 10577 chemical shifts originating from 2026 structures which contain up to ten types of atoms other than carbon, namely H, O, N, S, P, Si and halogens. It provides a training root mean squared relative error (RMSRE) of 0.5 %, i.e. a root mean squared error (RMSE) of 0.6 ppm, and a mean absolute error (MAE) of 0.4 ppm for estimating the chemical shifts of the 10k carbons. The predictive capability of the graph machine model is also compared with that of three commercial software on a data set of 171 original benzenic structures (1012 chemical shifts). The graph machine model proves very efficient in predicting chemical shifts with an RMSE of 0.9 ppm, and compares favorably with the RMSEs of 3.4, 1.8 and 1.9 ppm computed with ChemDraw, ACD and MestReNova softwares respectively. Finally, a Docker-based tool is proposed to predict the carbon chemical shifts of benzenic compounds solely from their SMILES codes.