Dataset Information

Does Steric Hindrance Actually Govern the Competition between Bimolecular Substitution and Elimination Reactions?

ABSTRACT: Bimolecular nucleophilic substitution (S_N2) and elimination (E2) reactions are prototypical examples of competing reaction mechanisms, with fundamental implications in modern chemical synthesis. Steric hindrance (SH) is often considered to be one of the dominant factors determining the most favorable reaction out of the S_N2 and E2 pathways. However, the picture provided by classical chemical intuition is inevitably grounded on poorly defined bases. In this work, we try to shed light on the aforementioned problem through the analysis and comparison of the evolution of the steric energy (E_ST), settled within the IQA scheme and experienced along both reaction mechanisms. For such a purpose, the substitution and elimination reactions of a collection of alkyl bromides (R-Br) with the hydroxide anion (OH^-) were studied in the gas phase at the M06-2X/aug-cc-pVDZ level of theory. The results show that, generally, E_ST recovers the appealing trends already anticipated by chemical intuition and organic chemistry, supporting the role that SH is classically claimed to play in the competition between S_N2 and E2 reactions.

SUBMITTER: Gallegos M

PROVIDER: S-EPMC8958592 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Does Steric Hindrance Actually Govern the Competition between Bimolecular Substitution and Elimination Reactions?

Gallegos Miguel M Costales Aurora A Martín Pendás Ángel Á

The journal of physical chemistry. A 20220315 11

Bimolecular nucleophilic substitution (S<sub>N</sub>2) and elimination (E2) reactions are prototypical examples of competing reaction mechanisms, with fundamental implications in modern chemical synthesis. Steric hindrance (SH) is often considered to be one of the dominant factors determining the most favorable reaction out of the S<sub>N</sub>2 and E2 pathways. However, the picture provided by classical chemical intuition is inevitably grounded on poorly defined bases. In this work, we try to s ...[more]

PMID: 35290051

Similar Datasets

Project description:BackgroundIn computational structural biology, structure comparison is fundamental for our understanding of proteins. Structure comparison is, e.g., algorithmically the starting point for computational studies of structural evolution and it guides our efforts to predict protein structures from their amino acid sequences. Most methods for structural alignment of protein structures optimize the distances between aligned and superimposed residue pairs, i.e., the distances traveled by the aligned and superimposed residues during linear interpolation. Considering such a linear interpolation, these methods do not differentiate if there is room for the interpolation, if it causes steric clashes, or more severely, if it changes the topology of the compared protein backbone curves.ResultsTo distinguish such cases, we analyze the linear interpolation between two aligned and superimposed backbones. We quantify the amount of steric clashes and find all self-intersections in a linear backbone interpolation. To determine if the self-intersections alter the protein's backbone curve significantly or not, we present a path-finding algorithm that checks if there exists a self-avoiding path in a neighborhood of the linear interpolation. A new path is constructed by altering the linear interpolation using a novel interpretation of Reidemeister moves from knot theory working on three-dimensional curves rather than on knot diagrams. Either the algorithm finds a self-avoiding path or it returns a smallest set of essential self-intersections. Each of these indicates a significant difference between the folds of the aligned protein structures. As expected, we find at least one essential self-intersection separating most unknotted structures from a knotted structure, and we find even larger motions in proteins connected by obstruction free linear interpolations. We also find examples of homologous proteins that are differently threaded, and we find many distinct folds connected by longer but simple deformations. TM-align is one of the most restrictive alignment programs. With standard parameters, it only aligns residues superimposed within 5 Ångström distance. We find 42165 topological obstructions between aligned parts in 142068 TM-alignments. Thus, this restrictive alignment procedure still allows topological dissimilarity of the aligned parts.ConclusionsBased on the data we conclude that our program ProteinAlignmentObstruction provides significant additional information to alignment scores based solely on distances between aligned and superimposed residue pairs.

Dataset Information

Does Steric Hindrance Actually Govern the Competition between Bimolecular Substitution and Elimination Reactions?

Publications

Does Steric Hindrance Actually Govern the Competition between Bimolecular Substitution and Elimination Reactions?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets