Stereoselective degradation of chiral drugs during wastewater treatment

废水处理过程中手性药物的立体选择性降解

• 批准号: EP/I038608/1
• 负责人: Barbara Kasprzyk-Hordern
• 金额: $ 9.6万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI038608%2F1
• 关键词: Stereoselective; degradation; chiral; drugs; during

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

药理活性化合物(PAC)构成了一大类不同的化学物质。尽管这些化合物在环境基质中的ppt浓度很低，但PAC引起了相当大的环境问题，因为它们中的许多在非常低的浓度下都是活性的。此外，PAC在环境中以多残留混合物的形式存在，因此也应考虑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中，它们对环境的影响不能被低估。在饮用水中也发现了PAC，这对人类构成了直接风险，并引发了受污染的水源问题，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。在未来，它的可及性将受到气候变化的严重影响。因此，将水回收用于非饮用水(灌溉、城市、工业)或饮用水目的被认为是可持续水资源管理的一个重要因素。然而，与水再利用相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)。在更大范围内实施水回用之前，必须对它们进行验证。几类PAC，如β-受体阻滞剂、抗生素或止痛剂，以前曾在环境中进行过研究，但令人惊讶的是，尽管它们在制药工业中非常重要，但它们的手性被环境研究人员忽视了。目前使用的药物中有一半以上是手性化合物，其中许多是由两个对映体组成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，但它们与酶等手性环境的相互作用不同。因此，在生物系统中，它们必须被识别为两种不同的物质，引起不同的反应：同一药物的一个对映体可能产生预期的治疗活性，而另一个可能是无效的，甚至是有毒的。手性药物给药、体内代谢和排泄后，其活性/非活性对映体的比例会发生显著变化。随后可以在废水处理过程中以及当药物已经存在于环境中时改变它。这是因为对映体的降解可能是立体专一性的，在某些情况下可能会导致药物毒性的增加。因此，手性PAC可能表现出不同的环境持久性、归宿和毒性。目前，评估手性药物的环境命运和毒性时没有考虑它们的对映体形式。这可能会导致对手性药物毒性的严重低估或高估，并导致不准确的环境风险评估。因此，迫切需要识别手性药物，这些药物对当前使用的废水处理技术具有抵抗力，其特点是在废水处理过程中具有立体选择性降解，因此可以释放到环境中或以非外消旋混合物的形式留在再生水中。该项目将解决这一问题，因为它旨在验证这样一种假设，即在废水处理期间和在接收水中手性药物的降解是立体选择性的，并将在实验室规模上使用Microesm方案进行，并在全面的废水处理厂中进行。这一研究项目有可能在了解手性药物在废水处理和接受水中的分布和去向的机理方面取得重大进展，并开辟一个针对药物在环境中的立体选择性行为的新的研究领域。它对于核实与水回收有关的风险也将至关重要。

项目成果

Study of stereoselective degradation of pharmaceuticals and illicit drugs in wastewater and receiving water bodies

废水和受纳水体中药品和违禁药物的立体选择性降解研究

• 发表时间: 2013
• 期刊: 14th EuCheMS International Conference on Chemistry and the Environment, 2013-06-25 - 2013-06-28, Barcelona
• 作者: Evans, S.;Kasprzyk-Hordern, B.,
• 通讯作者: Kasprzyk-Hordern, B.,

Chiral pharmaceuticals and illicit drugs stereoselective degradation in activated sludge: Methodology and results of quantification in microcosm study. In: , 2014-05-11 - 2014-05-15

活性污泥中手性药物和违禁药物的立体选择性降解：微观研究中的定量方法和结果。

• 发表时间: 2014
• 期刊: SETAC Europe 24th Annual Meeting
• 作者: Evans, S

Chiral illicit drugs and pharmaceuticals - stereoselective degradation, and its implications for analysis, toxicology and regulatory frameworks

手性非法药物和药品 - 立体选择性降解及其对分析、毒理学和监管框架的影响

• 发表时间: 2013
• 期刊: Joint Annual Meeting of the Ecotoxicology Research and Innovation Centre Plymouth University, and the Society of Environmental Toxicology and Chemistry UK Branch, 2013-09-09 - 2013-09-10, Plymouth
• 作者: Evans, S., Bagnall, J.;Kasprzyk-Hordern, B.,
• 通讯作者: Kasprzyk-Hordern, B.,