Electronegativity Effects on Conformational Stability Using Bent's Rule: From Simple Molecules to Acetylcholine

Febdian Rusydi

doi:10.11113/mjfas.v20n5.3635

Authors

Febdian Rusydi ᵃDepartment of Physics, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia ᵇResearch Center for Quantum Engineering Design, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia

DOI:

https://doi.org/10.11113/mjfas.v20n5.3635

Keywords:

Acetylcholine, Alzheimer’s disease, Bent’s rule, Conformational stability, DFT calculations.

Abstract

Hybridization and electronegativity are fundamental concepts in chemistry connected by Bent's rule. This rule explains many aspects of the structural chemistry and reactivity of organic and inorganic compounds. Over decades, the application of Bent's rule has expanded, demonstrating its wide-ranging utility in elucidating molecular stability due to the substitution of highly electronegative atoms. This study successfully leverages Bent's rule to explain conformational energy difference in acetylcholine case using density-functional calculations. We used butane (Group 2) and butanone (Group 3) families to model the head of ACh⁺ and substituted one of the carbons with highly electronegative atoms: B, C, N, and O. This enabled us to evaluate the effects of electronegativity, as well as the presence of carbonyl groups, on their conformational stability and s character. There were three highlighted results. First, our calculations result in the s character are consistent with Bent's rule. Second, the high conformational energy differences can be attributed to the changes of s character in C2–Z bond: linear in Group 2 and exponential in Group 3, indicating the strong contribution of the carbonyl group. Third, the key determining factor in ACh⁺ conformational stability is the carbonyl group, which also strongly contributes to the solute-solvent interactions. Therefore, our study can be further applied to other similar molecules, potentially leading to broader applications in chemistry, especially for understanding ACh⁺stability for Alzheimer’s Disease treatment.

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