Stereoselective degradation of chiral drugs during wastewater treatment

药理学活性化合物（PACs）构成了一个庞大而多样的化学物质群体。尽管这些化合物在环境基质中的ppt浓度很低，但由于其中许多在极低浓度下仍具有活性，因此pac引起了相当大的环境问题。此外，pac在环境中以多残留物混合物的形式存在，因此还应考虑pac的协同效应。由于大多数pac的非挥发性，以及它们不断进入环境，它们对环境的影响不容低估。饮用水中也检测到pac，这对人类构成直接风险，并引发水源污染问题，特别是水的再利用问题。在不断增长的全球经济和人口中，水是一种有限的资源。未来气候变化将显著影响其可及性。因此，将水回收用于非饮用（灌溉、城市、工业）或饮用目的被认为是可持续水资源管理的一个重要组成部分。然而，与水再利用有关的某些风险包括微生物和化学风险（例如，再生水中存在pac）。在更大规模地实施水再利用之前，必须对它们进行核实。几组pac，如-受体阻滞剂、抗生素或止痛药，之前已经在环境中进行了研究，但令人惊讶的是，尽管它们在制药工业中非常重要，但它们的手性特征却被环境研究人员所忽视。目前使用的药物中有一半以上是手性化合物，其中许多是由两种对映异构体的等摩尔混合物组成的外消旋体。同一药物的对映体具有相同的化学式和物理化学性质，但它们与手性环境（如酶）的相互作用不同。因此，在生物系统中，它们必须被视为两种不同的物质，引起不同的反应：同一药物的一种对映体可能产生所需的治疗活性，而另一种对映体可能无效甚至有毒。手性药物在给药、体内代谢和排出体外后，其活性/非活性对映体的比例会发生显著变化。随后，在废水处理过程中以及当药物已经存在于环境中时，它可以被改变。这是因为对映体的降解可能具有立体特异性，并且在某些情况下可能导致药物毒性的增加。因此，手性PACs可能表现出不同的环境持久性、命运和毒性。目前，手性药物的环境命运和毒性评估没有考虑其对映体形式。这可能导致严重低估或高估手性药物的毒性和不准确的环境风险评估。因此，迫切需要确定手性药物，这些药物对目前使用的废水处理技术具有抗性，其特点是在废水处理过程中具有立体选择性降解，因此可以以非消旋混合物的形式释放到环境中或留在再生水中。该项目将解决这一问题，因为它旨在测试手性药物在废水处理和接收水中的降解是立体选择性的假设，并将在实验室规模上使用微观方案和全规模的废水处理厂进行。该研究项目有可能在了解手性药物在废水处理和接收水中的分布和命运机制方面取得重大进展，并开辟一个新的研究领域，指导药物在环境中的立体选择行为。它对核查与水回收有关的危险也至关重要

Pharmacologically active compounds (PACs) constitute a vast and diverse group of chemicals. Despite low ppt concentrations of these compounds in environmental matrices, PACs pose considerable environmental concern as many of them are active at very low concentrations. Additionally, PACs are present in the environment as multi-residue mixtures, and therefore synergistic effects of PACs should also be considered. Due to the non-volatile nature of the majority of PACs, and their continuous introduction into the environment, their environmental impact cannot be underestimated. PACs have also been detected in drinking water, which poses a direct risk to humans and raises the issue of contaminated water sources and especially water reuse.Water is a limited resource in an expanding global economy and population. In the future its accessibility will be significantly impacted by changing climate. Reclaiming water for non-potable (irrigation, urban, industrial) or potable purposes is therefore considered to be an important element of sustainable water resource management. There are, however, certain risks associated with water reuse including microbiological and chemical risks (e.g. the presence of PACs in reclaimed water). They have to be verified before water reuse is to be implemented on a wider scale.Several groups of PACs such as beta-blockers, antibiotics or analgesics have been studied before in the environment but surprisingly their chiral character, despite its great importance in the pharmaceutical industry, 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. Enantiomers of the same drug have the same chemical formula and physicochemical properties but they differ in interactions with chiral environments such as enzymes. Therefore in biological systems they have to 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 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. As a result chiral PACs might reveal different environmental persistence, fate and toxicity. Currently, the environmental fate and toxicity of chiral drugs are assessed without taking into consideration their enantiomeric form. This might lead to a significant under or overestimation of toxicity of chiral drugs and to inaccurate environmental risk assessment.As a consequence there is an urgent need to identify chiral drugs, which are resistant to currently used wastewater treatment technologies, are characterised by stereoselective degradation during wastewater treatment and can as a result be released into the environment or remain in reclaimed water in the form of non-racemic mixtures. This project will tackle this issue as it aims to test the hypothesis that degradation of chiral drugs during wastewater treatment and in receiving waters is stereoselective and will be undertaken at the laboratory scale with the usage of microcosm protocol and in a full scale wastewater treatment plant. This research project has the potential to provide significant advances in understanding of the mechanisms of the distribution and fate of chiral drugs during wastewater treatment and in receiving waters and open up a new area of research directed at the stereoselective behaviour of drugs in the environment. It will also be of vital importance for the verification of risks associated with water reclamation