ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Importance of the shape of the linker between two quaternary pyridinium rings on reactivation process in oximes: in vitro and in silico study

Kamil Kuca, Joyce Sobreiro Francisco Diz, Tanos Celmar Costa França, Eugenie Nepovimova, and Rafael Dolezal

Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic

E-mail: kamil.kuca@uhk.cz

Received: 23 November 2025  Accepted: 9 June 2026

Abstract:

Acetylcholinesterase (AChE) reactivators are essential antidotes for treating intoxication caused by nerve agents. Among the available candidates, the oxime K203 has recently attracted significant attention due to its strong reactivation efficacy demonstrated in both in vitro and in vivo studies. In this work, we investigated three structurally related oxime reactivators that differ from K203 only in the nature of the linker connecting their two quaternary nitrogen atoms. Although this linker is often regarded as a passive structural component, our results show that its composition plays a meaningful role in modulating reactivation performance. The combined in vitro findings and molecular modeling analyses consistently highlight the linker as a key contributor to the overall reactivation efficacy of these compounds.

Keywords: Oxime K203; Reactivator; Nerve agent; Acetylcholinesterase; Broad-spectrum; Antidote

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-05190-w

Chemical Papers 80 (11) 13435–13443 (2026)