Enantioselective occurrence and fate of chiral drugs in the aqueous environment

药物是具有潜在危险的生物活性的新兴污染物，因为其中许多药物普遍存在且具有持久性，对水生生物具有可疑或已确定的毒性。此外，由于它们不断进入环境，并通过联合平行作用产生协同效应，即使是低持久性的药物也可能在环境中造成不必要的影响。每年有数百吨这些化合物被分配到社区，随后通过废水进入环境。一些药物，如β-受体阻滞剂，抗生素或镇痛剂，已经在环境中进行了研究，但令人惊讶的是，它们的手性特征一直被环境研究人员忽视。目前使用的药物中有一半以上是手性化合物，其中许多是以两种对映体的等摩尔混合物组成的外消旋体形式分布。手性分子具有至少一个手性中心（通常为不对称碳），因此其显示光学活性。它以两种对映异构体的形式存在，彼此是不可重叠的镜像。对映异构体具有相同的化学式和物理化学性质，但它们在光学活性和空间排列方面不同。手性化合物的对映异构体在与体内的手性环境如酶的相互作用方面不同。因此，在生物系统中，它们可以被认为是引起不同反应的两种不同物质：同一药物的一种对映体可能产生所需的治疗活性，而另一种可能是无活性的甚至有毒的。手性药物在体内给药、代谢和排泄后，其活性/非活性对映体的比例会发生显著变化。它可以随后在生物废水处理过程中以及当药物已经存在于环境中时发生改变。这是因为对映异构体的降解可以是立体特异性的，并且在某些情况下可以导致药物毒性的增加。这一领域的研究很重要，因为随着西方国家人口老龄化和发展中世界消费水平的提高，越来越多的药物进入环境，迄今为止，对这些污染物在环境中的流行程度和特点的研究范围有限。此外，现有的报告，由于其非对映体特异性的分析方法，不解决药物的手性问题，所以这些研究不能明确区分生物（对映体选择性）和非生物（非对映体选择性）的过程。因此，该项目旨在确定手性药物在水环境中，并测试的假设，它们在水环境中的分布是立体选择性的，立体选择性机制，其命运是生物学的性质。将通过对西约克郡（考尔德河）的地表水样本进行一系列分析来检验这一假设，重点是人口稠密地区，那里的环境最有可能被毒品污染。污染分析将考虑到当地的废水处理活动，从而更准确地了解与环境中手性药物存在相关的风险。为了实现这一目标，将建立一种多残留分析方法，该方法将允许同时鉴别和定量环境基质中痕量浓度（低ppt水平）的手性滥用药物。在考虑到非立体选择性非生物（光化学过程、水解、吸附）和立体选择性生物（微生物）变量后，还将使用微观方案和模型化合物，在实验室规模上验证手性药物在水环境中降解的立体选择性。

Drugs are potentially hazardous biologically active emerging contaminants as many of them are ubiquitous and persistent with suspected or identified toxicity towards aquatic organisms. Additionally, due to their continuous introduction into the environment and synergistic effects through combined parallel action, even drugs of a low persistence might cause unwanted effects in the environment. Hundreds of tonnes of these compounds are dispensed in communities every year and subsequently enter the environment through wastewater. Several groups of drugs such as beta-blockers, antibiotics or analgesics have been studied before in the environment but surprisingly their chiral character has been overlooked by environmental researchers. More than half of the drugs currently in use are chiral compounds and many of those are distributed as racemates consisting of an equimolar mixture of two enantiomers. A chiral molecule has at least one chiral centre (usually asymmetric carbon) as a result of which it shows optical activity. It exists in the form of two enantiomers, being the non-superimposable mirror images of each other. Enantiomers have the same chemical formula and physicochemical properties but they differ in their optical activity and spatial arrangement. The enantiomers of chiral compounds differ in interactions with chiral environments such as enzymes in the body. Therefore in biological systems they can be recognised as two different substances that elicit different responses: one enantiomer of the same drug may produce the desired therapeutic activity, while the other may be inactive or even toxic. The ratio of active/inactive enantiomer of the chiral drug can change significantly after its administration, metabolism in and excretion from the body. It can be subsequently altered during biological wastewater treatment and when the drug is already present in the environment. This is because degradation of enantiomers can be stereo-specific and can in some cases lead to an increase in the drug's toxicity. Research in this area is important as with the ageing population in western countries and an increase in consumption levels in the developing world increasing quantities of drugs are entering the environment and, to date, studies of the prevalence and characteristics of these contaminants in the environment have been limited in scope. Furthermore, existing reports, due to their non-enantiospecific analytical methodology, do not tackle the problem of chirality of drugs, so these studies cannot unequivocally differentiate between biological (enantioselective) and abiotic (non-enantioselective) processes. Therefore this project aims to identify chiral drugs in the aqueous environment and to test the hypothesis that their distribution in the aqueous environment is stereoselective and that stereoselective mechanisms governing their fate are biological in nature. The hypothesis will be tested through a series of analyses of surface water samples in West Yorkshire (the River Calder), concentrating on densely populated areas where the environment has the greatest potential to be contaminated with drugs. Analysis of contamination will be undertaken taking account of local wastewater treatment activity, thus achieving a more accurate understanding of the risk associated with the presence of chiral drugs in the environment. To achieve this a multi-residue analytical methodology that will allow for simultaneous identification and quantification of trace concentrations (low ppt levels) of chiral drugs of abuse in environmental matrices will be established. Verification of the stereoselectivity of the degradation of chiral drugs in the aqueous environment after taking into consideration non-stereoselective abiotic (photochemical processes, hydrolysis, sorption) and stereoselective biological (microbial) variables will also be undertaken at the laboratory scale with the usage of microcosm protocol and model compounds.