Santos Miguel M, Marques Igor, Carvalho Sílvia, Moiteiro Cristina, Félix Vítor
Departamento de Química, iBiMED and CICECO, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
Org Biomol Chem. 2015 Mar 14;13(10):3070-85. doi: 10.1039/c4ob02283a.
A new dichloroazacalix[2]arene[2]triazine receptor (1) with two chiral urea binding moieties is reported. The binding affinity of this macrocycle was evaluated by (1)H NMR titrations in CDCl3 for the dicarboxylate anions oxalate (ox(2-)), malonate (mal(2-)), succinate (suc(2-)), glutarate (glu(2-)), diglycolate (dg(2-)), fumarate (fum(2-)), maleate (male(2-)), and (R,R)- and (S,S)-tartarate (tart(2-)) enantiomers. Among the first five linear anions, the higher association constants were calculated for the larger anions glu(2-) and dg(2-) and for the smallest anion ox(2-), with Kass values following the sequence dg(2-) > glu(2-) > ox(2-) > suc(2-) > mal(2-). Despite the high binding affinity 1 of for both tart(2-) enantiomers, no enantioselectivity was observed. By contrast, Kass for fum(2-) is ca. 8.9 times greater than that for male(2-), showing the selectivity of 1 for the trans isomer. These binding preferences were further elucidated by theoretical methods. Molecular dynamics simulations showed that the linear anions are lodged between both pendant arms and that each anion can assume two distinct binding poses, with one or two carboxylate groups establishing intermittent hydrogen bonds with both urea binding units. On the other hand, the recognition of male(2-) ensues in an alternative scenario, characterised by the interaction between a carboxylate group and a single urea binding unit, mirroring the lower experimental binding affinity relatively to fum(2-). A linear increase of the receptor's Nurea···Nurea and the anions' (-)O2C···CO2(-) distances versus experimental Kass was established for mal(2-), suc(2-), glu(2-) and dg(2-) associations, indicating that the match between these two distances determines the anion binding strength. The affinity for ox(2-) was associated with the most negative values of electrostatic potential positioned near carboxylate groups.
报道了一种带有两个手性脲结合基团的新型二氯氮杂杯[2]芳烃[2]三嗪受体（1）。通过在CDCl₃中进行¹H NMR滴定，评估了该大环化合物对草酸盐（ox(2-)）、丙二酸盐（mal(2-)）、琥珀酸盐（suc(2-)）、戊二酸盐（glu(2-)）、二乙醇酸盐（dg(2-)）、富马酸盐（fum(2-)）、马来酸盐（male(2-)）以及（R,R）-和（S,S）-酒石酸盐（tart(2-)）对映体等二羧酸盐阴离子的结合亲和力。在前五个线性阴离子中，对于较大的阴离子glu(2-)和dg(2-)以及最小的阴离子ox(2-)，计算得到的缔合常数较高，Kass值的顺序为dg(2-) > glu(2-) > ox(2-) > suc(2-) > mal(2-)。尽管受体1对两种tart(2-)对映体都具有高结合亲和力，但未观察到对映选择性。相比之下，fum(2-)的Kass约为male(2-)的8.9倍，表明受体1对反式异构体具有选择性。这些结合偏好通过理论方法得到了进一步阐明。分子动力学模拟表明，线性阴离子位于两个悬垂臂之间，并且每个阴离子可以呈现两种不同的结合姿势，其中一个或两个羧基与两个脲结合单元形成间歇性氢键。另一方面，male(2-)的识别则发生在另一种情况下，其特征是一个羧基与单个脲结合单元之间的相互作用，这反映出相对于fum(2-)而言较低的实验结合亲和力。对于mal(2-)、suc(2-)、glu(2-)和dg(2-)的缔合，建立了受体两个脲氮原子之间的距离（Nurea···Nurea）和阴离子的（-）O₂C···CO₂（-）距离相对于实验Kass的线性增加关系，表明这两个距离之间 的匹配决定了阴离子的结合强度。对ox(2-)的亲和力与位于羧基附近的最负静电势值相关。
