Felix Vitor, Drew Michael G B, Webber Philip R A, Beer Paul D
School of Chemistry, University of Reading, Whiteknights, Reading, Berks RG6 6AD, UK.
Phys Chem Chem Phys. 2006 Jan 28;8(4):521-32. doi: 10.1039/b510412b. Epub 2005 Nov 23.
Molecular modelling studies have been carried out on two bis(calix[4]diquinone) ionophores, each created from two (calix[4]diquinone)arenes bridged at their bottom rims via alkyl chains (CH(2))(n), 1: n = 3, 2; n = 4, in order to understand the reported selectivity of these ligands towards different sized metal ions such as Na(+), K(+), Rb(+), and Cs(+) in dmso solution. Conformational analyses have been carried out which show that in the lowest energy conformations of the two macrocycles, the individual calix[4]diquinones exhibit a combination of partial cone, 1,3-alternate and cone conformations. The interactions of these alkali metals with the macrocycles have been studied in the gas phase and in a periodic box of solvent dmso by molecular mechanics and molecular dynamics calculations. Molecular mechanics calculations have been carried out on the mode of entry of the ions into the macrocycles and suggest that this is likely to occur from the side of the central cavity, rather than through the main axis of the calix[4]diquinones. There are energy barriers of ca. 19 kcal mol(-1) for this entry path in the gas phase, but in solution no energy barrier is found. Molecular dynamics simulations show that in both 1 and 2, though particularly in the latter macrocycle, one or two solvent molecules are bonded to the metal throughout the course of the simulation, often to the exclusion of one or more of the ether oxygen atoms. By contrast the carbonyl oxygen atoms remain bonded to the metal atoms throughout with bond lengths that remain significantly less than those to the ether oxygen atoms. Free energy perturbation studies have been carried out in dmso and indicate that for 1, the selectivity follows the order Rb(+) approximately K(+) > Cs(+) >> Na(+), which is partially in agreement with the experimental results. The energy differences are small and indeed the ratio between stability constants found for Cs(+) and K(+) complexes is only 0.60, showing that has only a slight preference for K(+). For the larger receptor , which is better suited to metal complexation, the binding affinity follows the pattern Cs(+) >> Rb(+) >> K(+) >> Na(+), with energy differences of 5.75, 2.61, 2.78 kcal mol(-1) which is perfectly consistent with experimental results.
已对两种双（杯[4]二醌）离子载体进行了分子建模研究，每种离子载体均由两个在其底部边缘通过烷基链（CH(2)）(n)桥连的（杯[4]二醌）芳烃构成，1：n = 3，2；n = 4，目的是了解这些配体在二甲基亚砜（dmso）溶液中对不同大小金属离子（如Na(+)、K(+)、Rb(+)和Cs(+)）的报道选择性。已进行构象分析，结果表明在这两个大环的最低能量构象中，各个杯[4]二醌呈现出部分锥式、1,3 - 交替式和锥式构象的组合。通过分子力学和分子动力学计算，研究了这些碱金属与大环在气相和溶剂二甲基亚砜的周期性盒子中的相互作用。已对离子进入大环环腔的模式进行分子力学计算，结果表明这可能发生在中心腔的侧面，而非通过杯[4]二醌的主轴。在气相中，此进入路径存在约19千卡/摩尔(-1)的能垒，但在溶液中未发现能垒。分子动力学模拟表明，在1和2中，尤其是在后者的大环中，在整个模拟过程中，一个或两个溶剂分子与金属结合，常常排斥一个或多个醚氧原子。相比之下，羰基氧原子在整个过程中始终与金属原子结合，其键长明显小于与醚氧原子的键长。已在二甲基亚砜中进行自由能微扰研究，结果表明对于1，选择性顺序为Rb(+) ≈ K(+) > Cs(+) >> Na(+)，这与实验结果部分一致。能量差异较小，实际上Cs(+)和K(+)配合物的稳定常数之比仅为0.60，表明其对K(+)仅有轻微偏好。对于更适合金属络合的较大受体，结合亲和力遵循Cs(+) >> Rb(+) >> K(+) >> Na(+)的模式，能量差异分别为5.75、2.61、2.78千卡/摩尔(-1)，这与实验结果完全一致。
