A Molecular Probe for the Highly Selective Chromogenic Detection of DFP, a Mimic of Sarin and Soman Nerve Agents
A Molecular Probe for the Highly Selective Chromogenic Detection of DFP, a Mimic of Sarin and Soman Nerve Agents
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DOI：
10.1002/chem.201102241
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发表时间：
2011-10-01
影响因子：
4.3
通讯作者：
Sancenon, Felix
中科院分区：
文献类型：
--
作者：
Gotor, Raul;Costero, Ana M.;Sancenon, Felix
化学战剂在恐怖主义中的使用证明，需要发展可靠和准确的方法来检测这些致命的化合物。[1]在化学武器中，神经毒剂特别危险，联合国将其归类为大规模杀伤性武器。神经毒剂能够通过抑制乙酰胆碱酯酶来干扰神经系统的活动，导致乙酰胆碱在突触连接处积聚;这阻碍了肌肉的放松。[2]从化学观点来看，神经性毒剂是具有良好离去基团的有机膦酸酯。目前的神经代理监测方法主要基于生物传感器，[3]离子迁移谱，[4]光子晶体，[5]电化学，[6]微悬臂梁，[7]和光纤阵列[8]，并显示出一定的局限性，如低便携性和复杂性。最近，作为这些经典方法的替代，荧光和显色探针的发展已被证明是有用的识别这些化学品在溶液和气相中。[9]显色系统是特别有吸引力的，因为使用广泛可用的仪器和肉眼检测。然而，用于检测这些衍生物的选择性和灵敏的显色荧光探针的例子仍然很少。文献中描述的化学传感器利用容易观察和测量的荧光和颜色变化，并涉及基于光子诱导电子转移（PET）的过程，[10]含肟酸盐的衍生物，[11]分子印迹聚合物，[12]纳米颗粒，[13]碳纳米管，[14]推拉发色团中的环化反应，[15]置换测定，[16]有机-无机杂化材料。[17]在大多数这些研究中，使用神经气体模拟物，如二乙基氰基磷酸盐（DCNP）和二异丙基氟磷酸盐（DFP）。由于这些化合物含有与真实的神经毒剂沙林、梭曼和塔崩相同的离去基团，它们表现出类似的反应性，但它们缺乏严格的毒性。大多数这些报道的显色荧光探针依赖于神经气体与合适的亲核试剂的亲电反应性，这在许多情况下导致ON-OFF行为。然而，尽管在这种显色荧光探针的设计的内在利益，报告的例子有一定的局限性。特别是，事实上，反应是非特异性的，在一般情况下，报告的染料为基础的探针显示相同的光学响应所有神经毒剂。然而，沙林，梭曼，或塔崩的个人信号的快速方法的发展可能被证明是重要的。例如，尽管所有神经毒气的紧急反应方案都是相似的，但不同的毒性和一些解毒剂对某些神经毒剂无效的实验证据表明，在这一系列致命化学品中区分某些毒剂是重要的。[18]根据我们对神经毒剂的显色荧光探针的开发兴趣，[15，17]我们在此报告了一种简单的比色系统，该系统不仅能够对神经毒剂模拟物做出反应，而且还能够将DFP（沙林和梭曼神经毒气的模拟物）与其他模拟物和有机磷酸盐区分开来。信号方案涉及显色探针1（方案1）。该分子被设计为包含两个显色化学传感部分;即，1）亲核羟基，为亲电子磷原子（例如神经毒剂中的磷原子）提供合适的反应位点，以及2）叔丁基二甲基硅醚（TBDMS）已知与氟化物反应的基团，[19]这是一种专门用于..的特定副产物。
The use of chemical-warfare (CW) agents in terrorism has proven the need for development of reliable and accurate methods to detect these lethal compounds.[1] Among CW, nerve agents are especially dangerous, and the UN classifies them as weapons of mass destruction. Nerve agents are capable of interfering with the action of the nervous system through the inhibition of acetylcholinesterase, resulting in acetylcholine accumulation in the synaptic junctions; this hinders muscles from relaxing.[2] From a chemical viewpoint, nerve agents are organophosphonates with good leaving groups. Current nerve-agents-monitoring methods are mainly based on biosensors,[3] ion mobility spectroscopy,[4] photonic crystals,[5] electrochemistry,[6] microcantilevers,[7] and optical-fiber arrays [8] and show certain limitations, such as low portability and complexity. Recently, as an alternative to these classical methods, the development of fluorogenic and chromogenic probes has proven useful for the recognition of these chemicals in solution and gas phase.[9] Chromogenic systems are especially appealing because of the use of widely available instrumentation and detection with the naked eye. Nevertheless, examples of selective and sensitive chromofluorogenic probes for detection of these derivatives are still rare. The chemosensors described in the literature make use of easily observable and measurable fluorescence and color changes, and involve photon-induced electron transfer (PET)-based processes,[10] oximate-containing derivatives,[11] molecularly imprinted polymers,[12] nanoparticles,[13] carbon nanotubes,[14] cyclization reactions in push–pull chromophores,[15] displacement assays,[16] and organic–inorganic hybrid materials.[17] In most of these studies nerve-gas simulants, such as diethylcyanophosphate (DCNP) and diisopropylfluorophosphate (DFP), are used. Because these compounds contain the same leaving groups as the real nerve agents Sarin, Soman, and Tabun, they display similar reactivity, but they lack the rigorous toxicity. Most of these reported chromofluorogenic probes rely on the electrophilic reactivity of nerve gases with suitable nucleophiles, which, in many cases, result in an ON–OFF behavior. However, despite the intrinsic interest in the design of such chromofluorogenic probes, the reported examples have certain limitations. In particular, the fact that the reactions are nonspecific and, in general, the reported dye-based probes display the same optical response to all nerve agents. However, the development of rapid methods for the individual signaling of Sarin, Soman, or Tabun may prove important. For instance, even though the emergency response protocol is similar for all nerve gases, different toxicities and experimental evidence that some antidotes are ineffective for certain nerve agents indicate the importance of distinguishing certain agents within this family of lethal chemicals.[18] Following our interest in the development of chromofluorogenic probes for nerve agents,[15, 17] we report herein a simple colorimetric system that is not only able to respond to nerveagent mimics, but is also able to distinguish DFP (a mimic of Sarin and Soman nerve gases) from other simulants and organophosphates. The signaling protocol involves chromogenic probe 1 (Scheme 1). This molecule was designed to contain two chromo–chemosensing moieties; that is, 1) a nucleophilic hydroxyl group that provides a suitable reactive site for electrophilic phosphorous atoms, such as those in nerve agents and 2) a tert-butyldimethylsilylether (TBDMS) group that is known to react with fluoride,[19] which is a specific byproduct to be exclusively …