Breaking the DFT Energy Bias Caused by Intramolecular Hydrogen‐Bonding Interactions with MESSI, A Structural Elucidation Method Inspired by Wisdom of Crowd Theory**

Abstract

The use of quantum‐based NMR methods to complement and guide the connectivity and stereochemical assignment of natural and unnatural products has grown enormously. One of the unsolved problems is related to the improper calculation of the conformational landscape of flexible molecules that have functional groups capable of generating a complex network of intramolecular H‐bonding (IHB) interactions. Here the authors present MESSI (Multi‐Ensemble Strategy for Structural Identification), a method inspired by the wisdom of the crowd theory that breaks with the traditional mono‐ensemble approach. By including independent mappings of selected artificially manipulated ensembles, MESSI greatly improves the sense of the assignment by neutralizing potential energy biases.

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

“…The publication of tools featuring intuitive interfaces has greatly facilitated the adoption of in silico methodologies for structure elucidation purposes. Since the first DP4 applet, other informatics tools for structure elucidation have been published, each with varying degrees of ease and challenges in their utilization. ,,,,− Among them, DP4+ stands out not only for its exceptional performance but also for its widespread popularity owing to its seamless user experience. The isotropic shielding constants and the experimental chemical shifts can be effortlessly loaded into an Excel spreadsheet, thereby streamlining the entire process.…”

“…The most reliable correlation results are obtained using DP4+, so analysis should be concluded with this calculation using the top candidates identified during screening. It is also important to note that highly flexible polyhydroxy compounds are better tackled with specialized software like MESSI Choosing theory levels : The App admits the use of 60 validated levels of theory.…”

“…Inspired in Bayes′s theory, different statisticalbased methods have been developed, including DP4, 9 J-DP4, 10 ML-J-DP4, 11 DP4+, 12 DiCE, 13 and MESSI. 14 In addition, they were widely explored to determine the structure of both rigid cyclic compounds and conformationally flexible acyclic compounds, with variable levels of confidence. Among them, DP4+ stands out for its exceptional predictive capability across a broad range of molecules.…”

“…These methods are mostly based on the simulation of NMR parameters coupled with sophisticated techniques for data treatment. − One of the leading approaches involves the calculation of the probability associated with each structure from a set of two or more candidates. Inspired in Bayes′s theory, different statistical-based methods have been developed, including DP4, J -DP4, ML- J -DP4, DP4+, DiCE, and MESSI . In addition, they were widely explored to determine the structure of both rigid cyclic compounds and conformationally flexible acyclic compounds, with variable levels of confidence.…”

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

“…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…”