Sulfonatocalix[4]arene-Based Scavengers for V-Type Nerve Agents with Enhanced Detoxification Activity.

Autor: Gaß P; Fachbereich Chemie - Organische Chemie, RPTU Kaiserslautern-Landau, Erwin-Schrödinger-Str. 54, 67663, Kaiserslautern, Germany., Casalino S; Fachbereich Chemie - Organische Chemie, RPTU Kaiserslautern-Landau, Erwin-Schrödinger-Str. 54, 67663, Kaiserslautern, Germany., Worek F; Institut für Pharmakologie und Toxikologie der Bundeswehr, Neuherbergstraße 11, 80937, München, Germany., Kubik S; Fachbereich Chemie - Organische Chemie, RPTU Kaiserslautern-Landau, Erwin-Schrödinger-Str. 54, 67663, Kaiserslautern, Germany.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Dec 13, pp. e202404321. Date of Electronic Publication: 2024 Dec 13.
DOI: 10.1002/chem.202404321
Abstrakt: Synthetic small molecule scavengers that rapidly detoxify nerve agents in vivo allow (pre)treatment of nerve agent poisoning. However, scavengers that detoxify persistent V-type nerve agents at pH 7.4 and 37 °C with sufficient efficiency are still unknown. The most promising compound to date is a monosubstituted sulfonatocalix[4]arene containing a hydroxamic acid group. This compound was used to investigate the effect of structural modifications on detoxification activity. While none of the monosubstituted calixarene derivatives considered in this context possessed higher activity than the parent compound, the disubstituted derivatives were very active, exhibiting half-lives of detoxification under the conditions of an established in vitro assay of <1.5 min. The rate of detoxification decreased with decreasing scavenger concentration, but even at a fourfold molar excess of the scavenger, complete detoxification of 2.5 μM solutions of some nerve agents could be achieved within one hour. These disubstituted calixarene derivatives thus bring synthetic scavengers for V-type nerve agents closer to application.
(© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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