Anion Binding versus Intramolecular Hydrogen Bonding in Neutral Macrocyclic Amides

Abstract

Although amide groups are important hydrogen-bond donors in natural and synthetic anion receptors, studies on structure-affinity relationships of amide-based macrocyclic receptors are still very limited. Therefore, we synthesized a series of macrocyclic tetraamides 5-8 derived from 1,3-benzenedicarboxylic (isophthalic) acid and aliphatic alpha,omega-diamines of different lengths. (1)H NMR titrations in DMSO solution show that the anion affinity of these receptors decreases with increasing size of the macrocycle irrespective of the anion, and this suggests a minor role of geometric complementarity. Comparison with their previously studied pyridine congeners reveals that the isophthalic acid based macrocycles are less potent, in contrast to what was found for simple model diamides. Combined theoretical and experimental structural studies were carried out to determine the reasons behind this behaviour. The results show that the unexpectedly low anion binding ability of the isophthalic acid-based receptors is due to the self-complementary nature of the isophthalic bis-amide fragments: when two such moieties are present within a sufficiently flexible macrocycle, they adopt syn-anti conformations and bind each other by two strong intramolecular hydrogen bonds that close the macrocyclic cavity. Nevertheless, anion binding is able to break these hydrogen bonds and switch a macrocycle into a convergent all-syn conformation. Despite the ill-preorganized conformation, 20-membered receptor 6 is better than either its open-chain analogue (macrocyclic effect) and/or its isomer having differently placed carbonyl groups. The crystal structures of four anion complexes of the macrocyclic receptors are reported. X-ray studies and solution NMR data confirmed the inclusive nature of the complexes and pointed to strong involvement of aromatic CH hydrogen atoms in anion binding.

Anion binding induced conformational changes exploited for recognition, sensing and pseudorotaxane disassembly

“…1 (X = N). In solution the former motif preferentially adopts a syn-anti amide conformation to minimise its overall dipole moment, 18,19 which results in the receptor being in an 'open' conformation. However upon anion binding, cooperative hydrogen bonding and electrostatic interactions between the bis-amide-pyridine and imidazolium groups would require a substantial conformational change to a more 'closed' receptor geometry, as illustrated in Fig.…”

Synthesis, structure, and complexing properties of macrocyclic receptors for anions

“…Thus, the size match between an anion and the cavity of the receptor does not solely determine the observed selectivity. Extensive structural analysis of macrocycles 7-14 and their complexes allowed us to understand these results [26,29]. In all complexes observed, anions are not encapsulated but perch on ligands, hence there is no reason for the size correlation.…”

“…We continued our studies of macrocyclic receptors with a family of ligands based on 5-tert-butylisophthalic acid [29,30]. Owing to the low reactivity of isophthalic esters, we could not employ aminolysis for macrocyclization, so instead we used isophthalic acid chloride and a high-dilution technique.…”

“…This question is especially interesting in the case of dipicolinic acid derivatives which consist of two rigid fragments that are already well preorganized for anion binding, and therefore should not suffer very much from the lack of macrocyclic topology. To investigate this question, we prepared two model acyclic tetraamides 16 and 17 based on building blocks previously studied [26,29]. Their binding properties were examined in DMSO-d 6 , and the stability constants are shown in Table 4.…”

Theoretical investigation on the structural and electronic properties of complexes formed by thymine and 2′-deoxythymidine with different anions

“…Excess amounts of anionic pollutants such as phosphate and nitrate lead to eutrophication and consequent disruption of aquatic life cycles. Noncovalent interactions with negatively charged species play an important role in many essential chemical and biological processes [5]. Anion coordination chemistry during the last two decades has evolved as a field and become established mainly due to interest in biological reactions and the need for more efficient catalysts.…”