The DP5 Probability, Quantification and Visualisation of Structural Uncertainty in Single Molecules

Abstract

Whenever a new molecule is made, a chemist will justify the proposed structure by analysing the NMR spectra. The widely-used DP4 algorithm will choose the best match from a series of possibilities, but draws no conclusions from a single candidate structure. Here we present the DP5 probability, a step-change in the quantification of molecular uncertainty: given one structure and one 13C NMR spectra, DP5 gives the probability of the structure being correct. We show the DP5 probability can rapidly differentiate between structure proposals indistinguishable by NMR to an expert chemist. We also show in a number of challenging examples the DP5 probability may prevent incorrect structures being published and later reassigned. DP5 will prove extremely valuable in fields such as discovery-driven automated chemical synthesis and drug development. Alongside the DP4-AI package, DP5 can help guide synthetic chemists when resolving the most subtle structural uncertainty. The DP5 system is available at https://github.com/Goodman-lab/DP5.

DU8ML: Machine Learning-Augmented Density Functional Theory Nuclear Magnetic Resonance Computations for High-Throughput In Silico Solution Structure Validation and Revision of Complex Alkaloids

“…With the new DU8ML method, the rms deviations for correct structures of NPs normally range from under 1.0 to 1.5 ppm. We are currently developing a DU8 implementation of Goodman’s absolute DP5 scheme to attach probabilistic values to potential candidate structures. However, in this paper, we will be using the rmsd values for 13 C chemical shifts as the primary criterion for our revisions or validations of the analyzed structures.…”

Identificação de novas moléculas orgânicas pelo uso combinado de experimentos de RMN e cálculos computacionais de DFT

“…Para solucionar esses casos, classicamente, havia duas estratégias: difração de raios X ou síntese total. A difração de raios X, ainda que forneça a informação estrutural a nível atômico e seja considerada a técnica mais confiável para determinação estrutural molecular, não pode ser utilizada nos casos em que não é possível obter um monocristal do produto natural (INOKUMA et al, 2013). A síntese total foi o processo mais utilizado pelos químicos durante os séculos XIX até a metade do século XX para a elucidação de produtos naturais.…”