A Systematic Evaluation of Molecular Recognition Phenomena. 4. Selective Binding of Dicarboxylic Acids to Hexaazamacrocyclic Ligands Based on Molecular Flexibility

The host−guest interaction between four hexaaza macrocyclic ligands (3,6,9,17,20,23-hexaazatricyclo[23.3.1.111,15]triaconta-1(29),11,13,15 (30),25(27)-hexaene (Bd), 3,6,9,16,19,22-hexaazatricyclo[22.2.2.211,14]triaconta-1(27),11(30),12,14(29),24(28),25-hexaene (P2), 3,7,11,19,23,27-hexaazatricyclo[27.3.1.113,17]tetratriaconta-1(33),13, 15,17(34),29,31-hexaene (Bn), 3,7,11,18,22,26-hexaazatricyclo[26.2.2.213,16]tetratriaconta-1(31),13(34),14,16(33),28(32),29-hexaene (P3)) and two dicarboxylic acids (oxalic acid, H2Ox; oxydiacetic acid, H2Od) have been investigated using
potentiometric equilibrium methods. Ternary complexes are formed in aqueous solution as a result of hydrogen
bond formation and Coulombic interactions between the host and the guest. In the [(H6P2)(Ox)]4+ complex those
bonding interactions reach a maximum yielding a log KR6 of 6.08. This species has been further characterized by
means of X-ray diffraction analysis showing that the oxalate guest molecule is situated inside the macrocyclic
cavity of the P2 host. X-ray diffraction analysis has also been carried out for the complex [(H6Bn)(Od)2](Br)2·6H2O,
where now the oxydiacetate is bonded to the host but outside the macrocyclic cavity. Competitive distribution
diagrams and total species distribution diagrams are used to graphically illustrate the most salient features of these
systems, which are the following:  (a) The Bd and P2 ligands bind Ox significantly much more stronger than Od.
This is clearly manifested for the P2:Ox:Od competitive system, where a selectivity of 92.5% in favor of the P2−Ox
complexation against P2−Od is obtained at p[H] = 2.8. (b) No isomeric effect is found when comparing binding
capacities of oxalate with two isomeric ligands such as P2 and Bd since their affinity to bind the substrate is
relatively similar. (c) Bn and P3 ligands have a similar behavior as described in (a) for P2 and Bd except that due
to the increase of cavity size the differentiation becomes smaller. (d) Less basic ligands containing two methylenic
units Bd (log βH6 = 40.42) and P2 (40.42) bind stronger to the substrates than those containing three methylenic
units Bn (50.32) and P3 (50.64) even though their relative predominance depends on p[H].

本研究采用电位滴定平衡法（potentiometric equilibrium methods），探究了四种六氮杂大环配体（hexaaza macrocyclic ligands）与两种二元羧酸之间的主客体相互作用（host-guest interaction）。四种六氮杂大环配体分别为：3,6,9,17,20,23-六氮杂三环[23.3.1.111,15]三十碳-1(29),11,13,15(30),25(27)-六烯（Bd）、3,6,9,16,19,22-六氮杂三环[22.2.2.211,14]三十碳-1(27),11(30),12,14(29),24(28),25-六烯（P2）、3,7,11,19,23,27-六氮杂三环[27.3.1.113,17]三十四碳-1(33),13,15,17(34),29,31-六烯（Bn）以及3,7,11,18,22,26-六氮杂三环[26.2.2.213,16]三十四碳-1(31),13(34),14,16(33),28(32),29-六烯（P3）；两种二元羧酸分别为草酸（H2Ox）和氧二乙酸（H2Od）。体系中通过主体与客体之间的氢键形成与库仑相互作用，在水溶液中生成三元配合物。在[(H6P2)(Ox)]4+配合物中，此类键合作用达到最强，其log KR6为6.08。该物种经X射线衍射分析（X-ray diffraction analysis）进一步表征，结果显示草酸根客体分子位于P2主体的大环空腔内部。研究还对配合物[(H6Bn)(Od)2](Br)2·6H2O开展了X射线衍射分析，结果表明氧二乙酸根与主体结合，但位于大环空腔外部。本研究采用竞争分布图（competitive distribution diagrams）与总物种分布图（total species distribution diagrams），对该体系的核心特征进行可视化阐释，具体如下：(a) Bd与P2配体对Ox的结合能力显著强于Od。在P2:Ox:Od竞争体系中，这一差异体现得尤为明显：当p[H]=2.8时，P2与Ox的络合选择性相较于P2与Od的络合高达92.5%。(b) 对比草酸根与两种异构配体P2、Bd的结合能力，未发现异构效应，二者对底物的亲和性较为相近。(c) Bn与P3配体的行为与P2、Bd类似，但由于空腔尺寸增大，二者的结合选择性差异有所缩小。(d) 含两个亚甲基单元的碱性较弱的配体Bd（log βH6=40.42）与P2（log βH6=40.42），对底物的结合能力强于含三个亚甲基单元的Bn（50.32）与P3（50.64），尽管其相对占比取决于p[H]。