Wolfson Catalysis Centre, Inorganic Chemistry Laboratory, University of Oxford, Oxford, UK.
J Sep Sci. 2011 Sep;34(18):2505-12. doi: 10.1002/jssc.201000839. Epub 2011 Jul 21.
We show that highly porous silica-based nanoparticles prepared via micro-emulsion and sol-gel techniques are stable colloids in aqueous solution. By incorporating a magnetic core into the porous silica nano-composite, it is found that the material can be rapidly separated (precipitated) upon exposure to an external magnetic field. Alternatively, the porous silica nanoparticles without magnetic cores can be equally separated from solution by applying a high-speed centrifugation. Using these silica-based nanostructures a new high-throughput method for the determination of partition coefficient for water/n-octanol is hereby described. First, a tiny quantity of n-octanol phase is pre-absorbed in the porous silica nano-composite colloids, which allows an establishment of interface at nano-scale between the adsorbed n-octanol with the bulk aqueous phase. Organic compounds added to the mixture can therefore undergo a rapid partition between the two phases. The concentration of drug compound in the supernatant in a small vial can be determined by UV-visible absorption spectroscopy. With the adaptation of a robotic liquid handler, a high-throughput technology for the determination of partition coefficients of drug candidates can be employed for drug screening in the industry based on these nano-separation skills. The experimental results clearly suggest that this new method can provide partition coefficient values of potential drug candidates comparable to the conventional shake-flask method but requires much shorter analytical time and lesser quantity of chemicals.
我们证明了通过微乳液和溶胶-凝胶技术制备的高多孔硅基纳米粒子在水溶液中是稳定的胶体。通过将磁性核引入多孔硅纳米复合材料中，发现该材料在暴露于外磁场时可以迅速分离（沉淀）。或者，没有磁性核的多孔硅纳米粒子也可以通过高速离心从溶液中同样分离出来。利用这些基于硅的纳米结构，我们描述了一种用于测定水/正辛醇分配系数的高通量方法。首先，将少量的正辛醇相预吸附在多孔硅纳米复合材料胶体中，这允许在吸附的正辛醇与体相水之间建立纳米尺度的界面。因此，添加到混合物中的有机化合物可以在两相之间迅速分配。小瓶中上清液中药物化合物的浓度可以通过紫外可见吸收光谱来确定。通过适应机器人液体处理机，可以将用于测定候选药物分配系数的高通量技术用于基于这些纳米分离技术的工业药物筛选。实验结果清楚地表明，这种新方法可以提供与传统摇瓶法相当的潜在药物候选物的分配系数值，但需要更短的分析时间和更少的化学物质。
