Issue 7, 2023

Microhydrated clusters of a pharmaceutical drug: infrared spectra and structures of amantadineH+(H2O)n

Abstract

Solvation of pharmaceutical drugs has an important effect on their structure and function. Analysis of infrared photodissociation spectra of amantadineH+(H2O)n=1–4 clusters in the sensitive OH, NH, and CH stretch range by quantum chemical calculations (B3LYP-D3/cc-pVTZ) provides a first impression of the interaction of this pharmaceutically active cation with water at the molecular level. The size-dependent frequency shifts reveal detailed information about the acidity of the protons of the NH3+ group of N-protonated amantadineH+ (AmaH+) and the strength of the NH⋯O and OH⋯O hydrogen bonds (H-bonds) of the hydration network. The preferred cluster growth begins with sequential hydration of the NH3+ group by NH⋯O ionic H-bonds (n = 1–3), followed by the extension of the solvent network through OH⋯O H-bonds. However, smaller populations of cluster isomers with an H-bonded solvent network and free N–H bonds are already observed for n ≥ 2, indicating the subtle competition between noncooperative ion hydration and cooperative H-bonding. Interestingly, cyclic water ring structures are identified for n ≥ 3, each with two NH⋯O and two OH⋯O H-bonds. Despite the increasing destabilization of the N–H proton donor bonds upon gradual hydration, no proton transfer to the (H2O)n solvent cluster is observed up to n = 4. In addition to ammonium cluster ions, a small population of microhydrated iminium isomers is also detected, which is substantially lower for the hydrophilic H2O than for the hydrophobic Ar environment.

Graphical abstract: Microhydrated clusters of a pharmaceutical drug: infrared spectra and structures of amantadineH+(H2O)n

Supplementary files

Article information

Article type
Paper
Submitted
29 Sep 2022
Accepted
20 Jan 2023
First published
23 Jan 2023
This article is Open Access
Creative Commons BY license

Phys. Chem. Chem. Phys., 2023,25, 5529-5549

Microhydrated clusters of a pharmaceutical drug: infrared spectra and structures of amantadineH+(H2O)n

M. A. R. George and O. Dopfer, Phys. Chem. Chem. Phys., 2023, 25, 5529 DOI: 10.1039/D2CP04556G

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