Determining sequential micellization steps of bile salts with multi-CMC modeling
Determining sequential micellization steps of bile salts with multi-CMC modeling
复制标题
使用多 CMC 建模确定胆汁盐的连续胶束化步骤
DOI：
10.1016/j.jcis.2023.03.146
复制
发表时间：
2023
影响因子：
9.9
通讯作者：
Strein, Timothy G.
中科院分区：
文献类型：
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作者：
Rovnyak, David;He, Jiayi;Kong, Sophie;Eckenroad, Kyle W.;Manley, Gregory A.;Geffert, Raeanne M.;Krout, Michael R.;Strein, Timothy G.
假设胆盐在水溶液中表现出复杂的浓度依赖的胶束化作用，这源于一个长期存在的假设，即胆汁聚集中的大小增加，历史上专注于通过给定的方法只测量一个CMC，而不分解连续的逐步聚集。胆汁的聚集是连续的还是离散的，第一次聚集形成的浓度是多少，以及聚集步骤发生了多少，这些都是悬而未决的问题。实验用核磁共振化学位移滴定和本文提出的多CMC相分离模拟方法研究了胆盐临界胶束浓度(CMC)。提出的策略是建立相分离和质量作用模型的对应关系来处理第一个CMC；随后的胶束化步骤涉及更大的胶束，然后被视为相分离事件。发现核磁共振数据和所提出的多CMC模型揭示并解析了在碱性(PH 12)溶液中的二羟基和三羟基胆盐体系中多个紧密间隔的顺序的初级、初级和次级离散CMC，以及一个核磁共振数据集的单一模型。该模型能很好地解释复杂的核磁共振数据。在100℃以下(298℃，pH 12)的脱氧胆酸溶液中建立了4个CMC，分别为3.8±0.5 mm、9.1±20.3 mm、27±0.2 mm和57±10.4 mm，同时在多个胆汁系统中观察到3个CMCs，同样是在碱性条件下。全局拟合利用了不同质子对不同聚集阶段的敏感性。在解析这些紧密间隔的CMC时，该方法还获得了不同胶束在光谱上不可接近(也称为暗)状态的化学位移。
HypothesisBile salts exhibit complex concentration-dependent micellization in aqueous solution, rooted in a long-standing hypothesis of increasing size in bile aggregation that has historically focused on the measurement of only one CMC detected by a given method, without resolving successive stepwise aggregates. Whether bile aggregation is continuous or discrete, at what concentration does the first aggregate form, and how many aggregation steps occur, all remain as open questions.ExperimentsBile salt critical micelle concentrations (CMCs) were investigated with NMR chemical shift titrations and a multi-CMC phase separation modeling approach developed herein. The proposed strategy is to establish a correspondence of the phase separation and mass action models to treat the first CMC; subsequent micellization steps, involving larger micelles, are then treated as phase separation events.FindingsThe NMR data and the proposed multi-CMC model reveal and resolve multiple closely spaced sequential preliminary, primary, and secondary discrete CMCs in dihydroxy and trihydroxy bile salt systems in basic (pH 12) solutions with a single model of one NMR data set. Complex NMR data are closely explained by the model. Four CMCs are established in deoxycholate below 100 mM (298 K, pH 12): 3.8 ± 0.5 mM, 9.1 ± 0.3 mM, 27 ± 2 mM, and 57 ± 4 mM, while three CMCs were observed in multiple bile systems, also under basic conditions. Global fitting leverages the sensitivity of different protons to different aggregation stages. In resolving these closely spaced CMCs, the method also obtains chemical shifts of these spectroscopically inaccessible (aka dark) states of the distinct micelles.