Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio, United States.
J Phys Chem B. 2013 Mar 21;117(11):3240-9. doi: 10.1021/jp401841w. Epub 2013 Mar 12.
We designed, prepared, and characterized three cup-shaped cavitands 1-3 for trapping organophosphonates (O═PR(OR')2, 118-197 Å(3)) whose shape and size correspond to G-type chemical warfare agents (132-186 Å(3)). With the assistance of computational (molecular dynamics) and experimental ((1)H NMR spectroscopy) methods, we found that host 1-H3 orients its protonated histamine residues at the rim outside the cavity, in bulk water. In this unfolded form, the cavitand traps a series of organophosphonates 5-13 (K(app) = 87 ± 1 to 321 ± 6 M(-1) at 298.0 K), thereby placing the P-CH3 functional group in the inner space of the host. A comparison of experimental and computed (1)H NMR chemical shifts of both hosts and guests allowed us to derive structure-activity relationships and deduce that, upon the complexation, the more sizable P-OR functional groups in guests drive organophosphonates to the northern portion of the basket 1-H3. This, in turn, causes a displacement of the guest's P-CH3 group and a contraction of the cup-shaped scaffold. The proposed induced-fit model of the recognition is important for turning these modular hosts into useful receptors capable of a selective detection/degradation of organophosphorus nerve agents.
我们设计、制备并表征了三种杯状主体 1-3，用于捕获与 G 型化学战剂（132-186Å(3)）形状和尺寸相对应的有机膦酸盐（O═PR(OR')2，118-197Å(3)）。借助计算（分子动力学）和实验（（1）H NMR 光谱）方法，我们发现主体 1-H3 在其外部边缘处将质子化的组氨酸残基定向在空腔外，处于本体水中。在这种未折叠的形式中，主体可以捕获一系列有机膦酸盐 5-13（在 298.0 K 时，K(app) = 87 ± 1 至 321 ± 6 M(-1)），从而将 P-CH3 官能团置于主体的内部空间中。对主体和客体的实验和计算（1）H NMR 化学位移的比较使我们能够得出结构-活性关系，并推断出，在配合物形成时，客体中较大的 P-OR 官能团会将有机膦酸盐驱动到主体 1-H3 的北部。这反过来又会导致客体的 P-CH3 基团的位移和杯状支架的收缩。所提出的识别诱导契合模型对于将这些模块化主体转化为具有选择性检测/降解有机磷神经毒剂的有用受体非常重要。
