Breyer E D, Strasters J K, Khaledi M G
North Carolina State University, Department of Chemistry, Raleigh 27695.
Anal Chem. 1991 Apr 15;63(8):828-33. doi: 10.1021/ac00008a019.
In a previous paper, the usefulness of micellar liquid chromatography (MLC) in predicting octanol-water partition coefficients of organic compounds was reported. This paper is the first successful report of a quantitative retention-activity relationship study using the retention factor in MLC for predicting the biological activity of a group of phenolic compounds. Excellent correlation was obtained between the capacity factor in MLC and the bioactivity (measured as log 1/C, where C is the 50% inhibitory growth concentration) of 26 para-substituted phenols. A single MLC retention parameter is capable of describing the bioactivity of phenols, while three conventional molecular descriptors (log P(ow), pKa, and R) are needed to achieve a similar correlation. This indicates that both hydrophobic and electronic interactions are incorporated in a single MLC retention parameter, which is due to the amphiphilic nature of surfactants in the system. In situations like this, QRAR is a suitable alternative to QSAR since measuring MLC retention is much easier than measuring different molecular descriptors needed to build the QSAR model. Addition of 10% 2-propanol to a micellar system (hybrid system) proved to be the best chromatographic system for the best estimation of the phenols bioactivity. Other chromatographic factors such as pH and stationary phase also showed significant effect on the correlation between capacity factor k' and log 1/C.
在之前的一篇论文中，报道了胶束液相色谱法（MLC）在预测有机化合物正辛醇 - 水分配系数方面的实用性。本文首次成功报道了一项定量保留 - 活性关系研究，该研究使用MLC中的保留因子来预测一组酚类化合物的生物活性。在MLC中的容量因子与26种对位取代酚的生物活性（以log 1/C衡量，其中C是50%抑制生长浓度）之间获得了良好的相关性。单个MLC保留参数能够描述酚类的生物活性，而需要三个传统的分子描述符（log P(ow)、pKa和R）才能实现类似的相关性。这表明疏水相互作用和电子相互作用都包含在单个MLC保留参数中，这是由于体系中表面活性剂的两亲性质所致。在这种情况下，定量保留活性关系（QRAR）是定量构效关系（QSAR）的合适替代方法，因为测量MLC保留比测量构建QSAR模型所需的不同分子描述符要容易得多。向胶束体系（混合体系）中添加10%的2 - 丙醇被证明是用于最佳估计酚类生物活性的最佳色谱系统。其他色谱因素，如pH和固定相，也对容量因子k'与log 1/C之间的相关性有显著影响。
