DP4+App: Finding the Best Balance between Computational Cost and Predictive Capacity in the Structure Elucidation Process by DP4+. Factors Analysis and Automation

Abstract

DP4+ is one of the most popular methods for the structure elucidation of natural products using NMR calculations. While the method is simple and easy to implement, it requires a series of procedures that can be tedious, coupled with the fact that its computational demand can be high in certain cases. In this work, we made a substantial improvement to these limitations. First, we deeply explored the effect of molecular mechanics architecture on the DP4+ formalism (MM-DP4+). In addition, a Python applet (DP4+App) was developed to automate the entire process, requiring only the Gaussian NMR output files and a spreadsheet containing the experimental NMR data and labels. The script is designed to use the statistical parameters from the original 24 levels of theory (employing B3LYP/6-31G* geometries) and the new 36 levels explored in this work (over MMFF geometries). Furthermore, it enables the development of customizable methods using any desired level of theory, allowing for a free choice of test molecules.

Study of heavy atom influence on poly-halogenated compounds using DP4/MM-DP4+/DP4+: insights and trends

“…An energy cutoff window of 5 kcal mol −1 was selected to ensure good conformational diversity. For DP4 14 and MM-DP4+, 18 the MMFF geometries were used as inputs for GIAO NMR calculations at the B3LYP/6-31G** and SMD/ωB97XD/6-31+G** levels, respectively. For DP4+ calculations, 15 the MMFF geometries were re-optimized at the B3LYP/6-31G* level of theory (gas phase), prior to the GIAO NMR calculations at the PCM/mPW1PW91/6-31+G** level of theory (the recommended one for general applications).…”

“…A leading strategy entails the use of Bayes's theory to calculate the probability associated with each structural motif. From the pioneering DP4, 14 several toolboxes have been developed, including DP4+, 15 J -DP4, 16 ML- J -DP4, 17 MM-DP4+, 18 and MESSI. 19…”