York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York, United Kingdom.
J Phys Chem B. 2012 Dec 27;116(51):14915-21. doi: 10.1021/jp309819r. Epub 2012 Dec 13.
Drugs that are poorly soluble in water can be solubilized by the addition of hydrotropes. Albeit known for almost a century, how they work at a molecular basis is still controversial due to the lack of a rigorous theoretical basis. To clear up this situation, a combination of experimental data and Fluctuation Theory of Solutions (FTS) has been employed; information on the interactions between all the molecular species present in the solution has been evaluated directly. FTS has identified two major factors of hydrotrope-induced solubilization: preferential hydrotrope-solute interaction and water activity depression. The former is dominated by hydrotrope-solute association, and the latter is enhanced by ionic dissociation and hindered by the self-aggregation of the hydrotropes. Moreover, in stark contrast to previous hypotheses, neither the change of solute hydration nor the water structure accounts for hydrotropy. Indeed, the rigorous FTS poses serious doubts over the other common hypothesis: self-aggregation of the hydrotrope hinders, rather than promotes, solubilization.
水溶性差的药物可以通过加入增溶剂来增溶。尽管增溶剂已经为人所知近一个世纪，但由于缺乏严格的理论基础，其在分子基础上的作用仍存在争议。为了澄清这种情况，已经结合了实验数据和溶液涨落理论（FTS）；直接评估了溶液中所有分子物种之间相互作用的信息。FTS 确定了增溶剂诱导增溶的两个主要因素：优先增溶剂-溶质相互作用和水活度降低。前者主要由增溶剂-溶质缔合决定，后者则通过离子离解增强，同时受到增溶剂自聚集的阻碍。此外，与先前的假设形成鲜明对比的是，溶质水合的变化或水结构都不能解释增溶现象。事实上，严格的 FTS 对其他常见的假设提出了严重的质疑：增溶剂的自聚集阻碍了增溶，而不是促进了增溶。
