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Open Access 18-12-2023 | Original Article

Determination of 3- and 4-chloromethcathinone interactions with plasma proteins: study involving analytical and theoretical methods

Authors: Piotr Holowinski, Michal P. Dybowski

Published in: Forensic Toxicology | Issue 2/2024

Abstract

Purpose

The purpose of this paper was to determine 3- and 4-chloromethcathinone (3- and 4-CMC) binding degree and possible binding interaction modes with human serum albumin (HSA) using analytical and theoretical methods.

Methods

Experimental determination of 3- and 4-CMC binding degree with HSA was performed using gas chromatography–tandem mass spectrometry preceded by the equilibrium dialysis (ED) and ultrafiltration (UF). Nuclear magnetic resonance (NMR) spectroscopy was used to determine 3- and 4-CMC epitope-binding maps and possible binding sites in HSA. The molecular docking and molecular dynamics were employed to obtain detailed information about binding modes of 3- and 4-CMC enantiomers in HSA.

Results

As follows from the presented data, the degree of binding of 3- and 4-CMC is at a similar level of approx. 80%. This indicates a relatively strong binding of CMC to plasma proteins. The model studies employing the NMR spectroscopy and molecular simulations indicate that both CMCs bind to HSA. The whole 3- and 4-CMC molecules are embedded in the binding sites, with aromatic moieties being in the closest contact with the HSA residues. Moreover, conducted experiments show that Sudlow site II is the main binding center for 3- and 4-CMC and Sudlow site I acts as the secondary binding site.

Conclusions

Although many studies describe pharmacological and toxicological properties of synthetic cathinones (SC), the data taking SCs binding in plasma into consideration are scarce. To our knowledge, this is the first report presenting comprehensive experimental and theoretical characterization of 3- and 4-CMC binding with plasma proteins.

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Title: Determination of 3- and 4-chloromethcathinone interactions with plasma proteins: study involving analytical and theoretical methods
Authors: Piotr Holowinski
Michal P. Dybowski
Publication date: 18-12-2023
Publisher: Springer Nature Singapore
Published in: Forensic Toxicology / Issue 2/2024
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-023-00677-7

2024 ESC Congress

Springer Medicine

Determination of 3- and 4-chloromethcathinone interactions with plasma proteins: study involving analytical and theoretical methods

Abstract

Purpose

Methods

Results

Conclusions

2024 ESC Congress

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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