首页> 外文OA文献 >PARALLEL POLYMER-BASED MICROEXTRACTION METHODS TO STUDY INTERMOLECULAR ASSOCIATION AND PHYSICOCHEMICAL PROPERTIES
【2h】

PARALLEL POLYMER-BASED MICROEXTRACTION METHODS TO STUDY INTERMOLECULAR ASSOCIATION AND PHYSICOCHEMICAL PROPERTIES

机译:基于平行聚合物的微萃取方法研究分子间缔合和理化性质

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Lipophilicity and acid dissociation constants are important physicochemical properties that in part determine the suitability of an organic molecule as a pharmacological agent. Intermolecular associations are omnipresent in chemical and biochemical systems and particularly important in the efficacy of an excipient for a poorly soluble drug. Current standard methods to determine lipophilicity require large amounts of pure sample and have problems due to emulsion formation. This dissertation describes a method based on distribution of the solutes between a polymer phase and an aqueous phase in a 96-well format, in the presence and absence of a receptor (e.g., candidate excipient) in one of the two phases. This parallel approach uses minimal amounts of organic solvent and only requires small amounts of sample. This approach has been used to determine polymer-water distribution coefficients of solutes. In addition, by measuring polymer-water distribution coefficients at a variety of experimental conditions, such as pH and receptor concentration, acid dissociation constants and solute-receptor binding constants have been successfully determined for several chemical systems. udThis method has been applied to measure binding constants of econazole with six cyclodextrins in aqueous solutions. The acid dissociation constant of econazole was determined by measuring econazole-cyclodextrin binding constants at various pH values. Distribution coefficients and acid dissociation constants of twenty-four novel drug-like compounds have also been determined by this parallel approach and compared to the values calculated by commercially available software. The software packages did not adequately predict experimental results, especially for ionizable compounds. This emphasizes the need for laboratory separations-based measurements of distribution coefficients. The polymeric phase was poly(vinyl chloride) (PVC) plasticized by 67% (w/w) dioctyl sebacate (DOS). Intermolecular association has also been studied in Teflon AF 2400, a fluorous polymer phase, with and without fluorous hydrogen bond donor Krytox 157 FSH in the 96-well approach. In addition, a novel fluorous receptor-doped fiber solid phase microextraction (SPME) was developed to selectively detect quinoline in aqueous solutions.
机译:亲脂性和酸解离常数是重要的理化性质,其部分决定有机分子作为药理剂的适用性。在化学和生化系统中分子间的联系是普遍存在的,并且对于难溶性药物的赋形剂的功效特别重要。当前确定亲脂性的标准方法需要大量的纯样品,并且由于形成乳液而存在问题。本发明描述了一种方法,该方法基于在两相之一中存在和不存在受体(例如候选赋形剂)的情况下以96孔形式在聚合物相和水相之间的溶质分布。这种并行方法使用的有机溶剂量最少,只需要少量样品。该方法已用于确定溶质的聚合物-水分布系数。此外,通过在各种实验条件下(例如pH和受体浓度)测量聚合物-水的分配系数,已成功确定了几种化学体系的酸解离常数和溶质-受体结合常数。该方法已用于测量益康唑与六种环糊精在水溶液中的结合常数。益康唑的酸解离常数通过在各种pH值下测量益康唑-环糊精的结合常数来确定。还通过这种并行方法确定了二十四种新型药物样化合物的分布系数和酸解离常数,并将其与市售软件计算的值进行了比较。软件包不能充分预测实验结果,尤其是对于可电离化合物。这强调了对基于实验室分离的分布系数测量的需求。聚合物相是由67%(w / w)癸二酸二辛酯(DOS)增塑的聚(氯乙烯)(PVC)。分子间缔合也已在Teflon AF 2400(一种含氟聚合物相)中进行了研究,在96孔方法中有或没有氟氢键供体Krytox 157 FSH。此外,开发了一种新型的氟受体掺杂的纤维固相微萃取(SPME)来选择性检测水溶液中的喹啉。

著录项

  • 作者

    Lu Dujuan;

  • 作者单位
  • 年度 2014
  • 总页数
  • 原文格式 PDF
  • 正文语种 en
  • 中图分类

相似文献

  • 外文文献
  • 中文文献
  • 专利

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号