Molecular Recognition of Nerve Agents and Their Organophosphorus Surrogates: Toward Supramolecular Scavengers and Catalysts.
Molecular Recognition of Nerve Agents and Their Organophosphorus Surrogates: Toward Supramolecular Scavengers and Catalysts.
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DOI：
10.1002/chem.202101532
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发表时间：
2021-09-20
期刊：
影响因子：
--
通讯作者：
Badjić JD
中科院分区：
文献类型：
--
作者：
Finnegan TJ;Gunawardana VWL;Badjić JD
神经毒剂是上个世纪发展起来的四面体有机磷化合物（OP），其不可逆地抑制乙酰胆碱酯酶（AChE），从而阻碍生物体的神经信号传导。接触OP会导致症状迅速发展，从过度流涎、鼻塞和胸痛到抽搐和窒息，如果不加以治疗，可能导致死亡。这些强效毒素是用廉价的原料大规模制备的，使恐怖组织或国家能够对军事和平民使用它们。现有的解毒剂提供有限的保护，难以应用于大量受影响的个体。虽然目前正在开发新的药物，但仍然需要能够预防和逆转OP中毒作用的治疗剂。在这篇综述中，我们描述了分子识别科学如何扩展快速安全隔离神经毒剂的工具托盘。神经毒剂是一种致命的有机磷化合物，对军事和平民构成严重威胁。尽管数十年来投资于开发解毒系统作为解毒剂或治疗剂，但进展不足。在这篇评论中，我们认为研究神经毒剂的分子识别将有助于构建更有效的OP清除剂。含有机磷的神经毒剂和农药因其毒性强、作用迅速而成为解毒剂和解毒剂的重要靶标。在这篇综述中，我们探讨了非生物宿主在这些强效毒素的螯合和分离领域。我们强调了各种分子主机，已被证明结合和失活OP，以及提供策略，他们的设计。我们希望这篇评论能激励社区中的其他人创造新的工具来对抗OP的威胁。
Nerve agents are tetrahedral organophosphorus compounds (OPs) that were developed in the last century to irreversibly inhibit acetylcholinesterase (AChE) and therefore impede neurological signaling in living organisms. Exposure to OPs leads to a rapid development of symptoms from excessive salivation, nasal congestion and chest pain to convulsion and asphyxiation which if left untreated may lead to death. These potent toxins are prepared on a large scale from inexpensive staring materials, making it feasible for terrorist groups or states to use them against military and civilians. The existing antidotes provide limited protection and are difficult to apply to a large number of affected individuals. While new prophylactics are currently being developed, there is still need for therapeutics capable of both preventing and reversing the effects of OP poisoning. In this review, we describe how the science of molecular recognition can expand the pallet of tools for rapid and safe sequestration of nerve agents. Nerve agents are lethal organophosphorus compounds (OPs), posing a serious threat to military and civilians. In spite of decades invested toward developing detoxifying systems acting as prophylactics or therapeutics, there has been insufficient progress. In this critical review, we posit that examining molecular recognition of nerve agents shall help constructing more effective scavengers of OPs. The extreme toxicity and rapid action of organophosphorus (OP) containing nerve agents and pesticides make them a vital target for the development of antidotes and prophylactics. In this review, we explore the realm of abiotic hosts in the sequestration and isolation of these potent toxins. We highlight a variety of the molecular hosts that have shown to bind and deactivate OPs, as well provide strategies for their design. We hope that this review inspires others in the community to create novel tools to combat the threat of OPs.
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