Computation-Guided Support to Experiments by the Exploration of Reaction Mechanisms: Organic Synthesis, Natural Products and Environmental Issues

Abstract

Humankind has experienced a remarkable development since it began to design and optimize chemical reactions to achieve valuable compounds. The key to accomplish these tasks is the proper understanding of how chemical transformations occur at a molecular level, that is, their reaction mechanisms. Based on a suitable mechanistic proposal, experimentalists choose a given chemical protocol to optimize experimental conditions, design new synthetic routes, and circumvent competing reactions. In this context, computational chemistry has become a valuable ally for mechanistic elucidation. We present herein a review of complementary collaborations between experimentalists and theoretical chemists to rationalize processes at the molecular level, focusing mainly on the fields of organic synthesis, natural product chemistry, and systems with environmental interest. Throughout this review, we highlight the ability of computational evaluations to provide answers to questions raised from experiments in a clear and direct way, indicating to experimentalists alternative paths to help them solve their problems.

Going beyond structural effects: explicit solvation influence on the rotational isomerism of C-glycosylated flavonoids

“…60 The adequate description of explicit solvent effects stands as a bottleneck in the simulation of chemical phenomena due to the high computational cost and complexity of the models representing the condensed phase simulation. 26,62,63 Combining implicit-explicit solvation models can be a simple and efficient strategy for computing solvation effects. 64 The implicit solvation models account for the solvent effects by simulating it as a continuum of a bulk property (such as dielectric).…”

“…The solvent arrangement around the solute can be obtained by a top-down approach starting with a condensed phase simulation (using molecular dynamics or Monte Carlo calculations), and only a few explicit solvent molecules are selected for a DFT level evaluation. 23,26,63,64 Herein, we combine both models, known as the hybrid cluster-continuum model, to simulate solvent effects (DMSO and H 2 O) on the rotational isomerism. We chose the simulated solvent compatible to experimental available data.…”

“…This quantum method can access the transition state of bond rotation and dispersive interactions along the flavonoid backbone that can influence the isomerism. 26 A set of C-glycosyl flavonoids (Fig. 1) was explored, rationally chosen to explore the substituent effects that exhibit (1-3, 5) [11][12][13][14][15][16] and do not exhibit (4) 17 NMR signal duplication using DMSO (for 2-5) and H 2 O (for 1) as solvents.…”

Exploring borderline SN1–SN2 mechanisms: the role of explicit solvation protocols in the DFT investigation of isopropyl chloride

“…9,10 While extensive efforts have been devoted to unraveling the intricate effects of solvation in chemical processes, accounting for precise solvent effects into quantum simulations of chemical reactions remains a substantial challenge. 11–13 An efficient strategy to describe these processes at the atomic level combines explicit and implicit solvation methods. 14,15 There are two main methodologies for defining the solvent arrangement around a particular solute: top-down and bottom-up.…”

Mechanistic Insights into the Efficiency of Formaldehyde-Based Compounds and Glyoxal as H2S Scavengers

“…Sulfur compounds represent one of the major problems to the oil and gas industry, being regarded as impurities that imparts undesirable characteristics to both the matrix and final products . Among these compounds, hydrogen sulfide, H 2 S, poses a significant challenge to the industry due to its notorious toxicity, corrosiveness, and ability to contaminate catalysts. − Most of the hydrogen sulfide present in oil and gas comes from anthropogenic actions during the refinement process, such as the hydrodesulfurization (HDS), employed to convert sulfur compounds into hydrocarbon, releasing H 2 S. − …”