Volume 8, Issue 15 e202204151
Research Article

Acetylcholine Conformational Flexibility and Its Neutral Hydrolysis in Aqueous Solution

Rizka N. Fadilla

Rizka N. Fadilla

Department of Precision Engineering, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan

Research Center for Quantum Engineering Design, Faculty of Science and Technology, Universitas Airlangga, Jl. Mulyorejo, Surabaya, 60115 Indonesia

Contribution: Formal analysis (lead), ​Investigation (lead), Methodology (supporting), Writing - original draft (lead), Writing - review & editing (lead)

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Dr. Febdian Rusydi

Corresponding Author

Dr. Febdian Rusydi

Research Center for Quantum Engineering Design, Faculty of Science and Technology, Universitas Airlangga, Jl. Mulyorejo, Surabaya, 60115 Indonesia

Department of Physics, Faculty of Science and Technology, Universitas Airlangga, Jl. Mulyorejo, Surabaya, 60115 Indonesia

Contribution: Conceptualization (lead), Methodology (lead), Writing - review & editing (equal)

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Roichatul Madinah

Roichatul Madinah

Research Center for Quantum Engineering Design, Faculty of Science and Technology, Universitas Airlangga, Jl. Mulyorejo, Surabaya, 60115 Indonesia

Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia

Contribution: ​Investigation (equal)

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Prof. Hermawan K. Dipojono

Prof. Hermawan K. Dipojono

Advanced Functional Materials Research Group, Department of Engineering Physics, Faculty of Industrial Technology, Institut Teknologi Bandung, Jl. Ganesha no. 10, Bandung, 40132 Indonesia

Contribution: Formal analysis (equal)

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Dr. Faozan Ahmad

Dr. Faozan Ahmad

Department of Physics, Faculty of Mathematics and Science, IPB University, Bogor, 16680 Indonesia

Contribution: ​Investigation (supporting)

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Prof. Mudasir Mudasir

Prof. Mudasir Mudasir

Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta, 55281 Indonesia

Contribution: Formal analysis (supporting)

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Dr. Ira Puspitasari

Dr. Ira Puspitasari

Research Center for Quantum Engineering Design, Faculty of Science and Technology, Universitas Airlangga, Jl. Mulyorejo, Surabaya, 60115 Indonesia

Information System Study Program, Faculty of Science and Technology, Universitas Airlangga, Jl. Mulyorejo, Surabaya, 60115 Indonesia

Contribution: ​Investigation (supporting), Resources (lead)

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Prof. Yoshitada Morikawa

Prof. Yoshitada Morikawa

Department of Precision Engineering, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan

Research Center for Precision Engineering, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, 565-0871 Osaka, Japan

Contribution: Writing - review & editing (equal)

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First published: 17 April 2023

Graphical Abstract

Acetylcholine, a neurotransmitter in the brain, has several conformers with ttg as the most populated one. The ttg conformer's role in molecular recognition has been known, while its properties related to neutral hydrolysis in aqueous solution is discussed in this work based on a reliable model.

Abstract

Enzymatic hydrolysis is the main target to deal with ACh depletion. However, a recent study indicates that the non-enzymatic one may contribute to the depletion. This study highlights the necessity of considering possible conformers, discrete-continuum models, and dispersive effects for investigating the neutral (non-enzymatic) hydrolysis of flexible molecules in aqueous solution. We systematically built the possible conformers within the first-principles framework. The results confirm the reactivity of high-energy ACh conformer towards neutral hydrolysis. We proposed that conformational changes occur before the hydrolysis. The calculated activation and reaction energy shows that the discrete-continuum solvation model gives the closest result to experimental observations. This study also shows that neglecting dispersive effects brings unreliable structures in the initial state, which leads to unreliable activation energy.

Conflict of interest

There are no conflicts to declare.

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.