Determining PPARγ-ligand binding affinity using fluorescent assay with cis-parinaric acid as a probe

Upon the study of small-molecules binding to proteins, the traditional methods for calculating dissociation constants (Kd and Ki) have shortcomings in dealing with the single binding site models. In this paper, two equations have been derived to solve this problem. These two equations are independent of the total concentration or initial degree of saturation of receptor and the activity of the competitive molecule. Through nonlinear fitting against these two equations, Kd value of a probe can be obtained by binding assay, and Ki value of a ligand can be obtained by competitive assay. Moreover, only the total concentrations of receptor([R]t), ligand([L]t) and probe([P]t) are required for the data fitting. In this work, Ki values of some typical ligands of PPARγ were successfully determined by use of our equations, among which the Ki value of PPARγ-LY171883 was reported for the first time.     

An unusual solvent effect in the cuprate displacement reaction of indolizidin-5-yl-methyl p-toluenesulfonate: stereoselective synthesis of indolizidine alkaloids

An unusual solvent effect in the cuprate displacement reaction of indolizidin-5-yl-methyl p-toluenesulfonate with dialkyl cuprates, derived from an alkyllithium and Grignard reagents, during the synthesis of indolizidine alkaloids 167B and 209D is described.     

An Integrated Theory of Adsorption and Partition Mechanism and Eash Contribution to Solute Retention in Reversed Phase Liquid Chromatography

With the combination of the the stoichiometric displacement model for retention (SDM-R) in reversed phase liquid chromatography (RPLC) and the stoichiometric displacement model for adsorption (SDM-A) in physical chemistry,the total number of moles of the re-solvated methanol of stationary phase side.nr,and that of solute side in the mobile phase,q,corresponding the one mole of the desorbing solute,were separately determined and referred as the characterization parameters of the contributions of the adsorption mechanism and partition mechanism to the solute retention,respectively.A chromatographic system of insulin,using mobile phase consisting of the pseudo-homologue of alcohols(methanol,ethanol and 2-propanol)-water and trifluoroacetic acid was employed.The maximum number of the methanol layers on the stationary phase surface was found to be 10.6,only 3 of which being valid in usual RPLC,traditionally referred as a volume process in partition mechanism.However,it still follows the SDM-R.Both of q and nr of insulin were found not to be zero,indicating that the retention mechanism of insulin is a mixed mode of partition mechanism and adsorption mechanism.When methanol is used as the organic modifier,the ratio of q/nr was 1.13,indicating the contribution to insulin retention due to partition mechanism being a bit greater than that due to adsorption mechanism.A linear relationship between q,or nr and the carbon number of the pseudo-homologue in the mobile phase was also found.As a methodology for investigating the retention mechanism retention and behavior of biopolymers.a homologue of organic solvents as the organic modifier in mobile phase has also been explored.     

致密储层压驱焖井阶段渗吸机理分子模拟研究

针对致密储层开发中存在的天然地层能量衰减快、驱替相有效波及体积不足等难题, 考虑将压驱与焖井相结合的高效开发技术应用于致密储层. 基于分子动力学方法从微观作用力角度分析致密储层压驱渗吸机理, 进行致密储层压驱过程溶质动态迁移表征, 并从分子尺度对渗吸阶段进行划分. 采用分子模拟方法, 构建致密储层壁面-油相-驱替相三相体系, 分别从体系弛豫特征、浓度分布及扩散能力和介质间相互作用能等方面分析常规水力压裂后常压驱替条件和压驱高压条件渗吸过程特征性差异, 从分子尺度阐释致密储层压驱渗吸机理. 研究表明: 相对于常规压裂后驱替而言, 压驱条件下, 驱替相分子扩散系数提高20.06%, 与孔隙壁面的相互作用能提高2.3倍; 驱替相分子吸附层数增加, 油相解吸效果更为明显, 渗吸换油效率提高38.73%. 此外, 渗吸效率随储层温度变化的过程存在峰值, 具有先上升后降低的特征; 且受到壁面润湿性的影响, 壁面亲水性越强渗吸效率越高. 从分子尺度将焖井渗吸过程划分为3个阶段: 水分子优先靠近壁面; 驱替相流体与油相分子竞争吸附, 将吸附态油相剥离为游离态, 使其远离壁面; 压驱液溶质分子进入初始油相范围, 进一步置换油相, 提高渗吸效率. 压驱技术高压注入压驱剂可快速补充地层能量, 扩大驱替相流体波及体积并提高洗油效率, 在二者的协同作用下可大幅度提高渗吸驱油效率. 该项研究可为致密储层高效开发提供理论参考.