Acetylcholine Conformational Flexibility and Its Neutral Hydrolysis in Aqueous Solution. Issue 15 (17th April 2023)

• Record Type: Journal Article
• Authors: Fadilla, Rizka N.; Rusydi, Febdian; Madinah, Roichatul; Dipojono, Hermawan K.; Ahmad, Faozan; Mudasir, Mudasir; Puspitasari, Ira; Morikawa, Yoshitada
• Is Part Of: ChemistrySelect. Volume 8:Issue 15(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-04-17
• Subjects: acetylcholine -- Alzheimer's disease -- aqueous solution -- density functional calculations -- neutral hydrolysis; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202204151
• Languages: English
• ISSNs: 2365-6549

Abstract

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. 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.