Ionic Liquids as Pharmaceutically Active Molecules

本项目拟开展离子液体（ILs）和深度共晶溶剂（DESs）与活性药物成分（APIs）的化学基础研究。药物产品通常作为晶体材料分离，这导致了关键问题，包括溶解度差，热稳定性低和多态性，从而通过降低生物利用度而降低治疗效率。第二个挑战是抗菌素耐药性的上升，对全球健康构成最大威胁之一（世卫组织）细菌中的生物膜引起抗生素耐药性，治疗基于皮肤的细菌生物膜是一项重大挑战。ILs/DESs可以创建独特的电荷分布环境，为api提供增强和优化的溶解度。最近最令人兴奋的进展是，ILs/DESs既能增强原料药的经皮递送，又具有广谱抗菌活性，这在日益耐药的感染时代至关重要。到目前为止，还没有对IL/DES-API相互作用的基本分子理解。具体来说，本项目将使用量子化学（QC）方法来研究分子间的短程相互作用。该项目将采用最先进的分析技术，并专注于QC擅长的领域；成键相互作用，电荷分布和氢键。

This project proposes to conduct a fundamental study of the chemistry of ionic liquids (ILs) and deep eutectic solvents (DESs) in relation to active pharmaceutical ingredients (APIs). Pharmaceutical products are typically isolated as crystalline materials which this leads to key problems, including poor solubility, low thermal stability and polymorphism which in turn diminish therapeutic efficiency by reducing bioavailability. A second challenge is the rise of antimicrobial resistance, creating one of the biggest threats to global health (WHO) The biofilms in bacteria give rise to antibiotic resistance and the treatment of skin based bacterial biofilms is a significant challenge. ILs/DESs can create unique charge distributed environments that deliver enhanced and optimised solubility for APIs. The most exciting recent advances are that ILs/DESs provide both enhanced transdermal delivery of APIs as well as having broad spectrum antimicrobial activity, key in a time of increasingly resistant infections. As yet there is no fundamental molecular understanding of IL/DES-API interactions. Specifically this project will use quantum chemical (QC) methods to examine the short range molecule to molecule interactions. The project will employ state-of-the-art analysis techniques and focus on area where QC excels; bonding interactions, charge distribution and H-bonding.