Naphthotubes: Macrocyclic Hosts with a Biomimetic Cavity Feature

Abstract

CONSPECTUS: Macrocyclic hosts are the principal tools used in supramolecular chemistry because they can recognize other small molecules through non-covalent interactions. However, in terms of recognition ability, known macrocyclic hosts are often not comparable to bioreceptors. This may be due to the lack of functional groups inside the deep cavity, which is a common feature of bioreceptors. Most of the known macrocyclic hosts contain either a hydrophobic cavity or polar binding sites only. Macrocyclic hosts with functional groups inside a hydrophobic cavity are rare. In 2004, Glass and co-workers reported a pair of water-soluble naphthalene-based molecular tubes with amide protons in the well-defined deep cavity. The cavity feature is very similar to that of bioreceptors. However, the amide protons were not used in molecular recognition and were replaced in 2012 with allyl groups in order to improve the hydrophobic effect. We started our work on the basis of the Glass molecular tubes but paid close attention to the functional groups in the deep cavity. In this Account, we summarize our results on these biomimetic receptors, which we call naphthotubes. The inward-directed functional groups endow the corresponding naphthotubes with unique recognition abilities. Naphthotubes with hydrogen-bond acceptors (ether, ester, and imine) prefer to bind organic cations; naphthotubes with hydrogen-bond donors (urea, thiourea, and amide) can bind neutral molecules; amine naphthotubes are stimuli-responsive to acid/base. In particular, the water-soluble amide naphthotubes are able to selectively recognize highly hydrophilic molecules in watera generally accepted challenge in supramolecular chemistry. The unique recognition ability of these naphthotubes provides the basis for their applications in sensing, self-assembly, and molecular machines. Fluorescent sensing of environmental contaminants in water, chiroptical sensing of small chiral molecules, allosteric cooperative self-assembly, dissipative selfassembly, and directional molecular shuttles have been demonstrated with these naphthotubes. Overall, we hope to convey the message that these naphthotubes have unique recognition properties and promising applications in diverse fields. We believe that further exploration of this class of macrocycles may lead to practical applications in, for example, biomedical science, environmental science, and other related fields.

Enantioselective Recognition of Neutral Molecules in Water by a Pair of Chiral Biomimetic Macrocyclic Receptors

“…We recently reported a pair of water-soluble biomimetic macrocycles with inward-directed hydrogen bonding sites in their hydrophobic cavity, amide naphthotubes 1 and 2 (Scheme 1a). [48][49][50][51][52][53][54][55][56] This cavity is analogous to those found in bioreceptors. The hydrogen bonding sites are shielded from bulk water in the hydrophobic cavity and experience low polarity.…”

“…In order to understand the difference in binding behaviors of 1 and rac 3, the hydrophilic molecule 1,4-dioxane, which is a good guest for 1, 48 was selected as a test case. Both 1 (with the new assignment, 55 show that the hydrogen bonding of 1,4-dioxane in 1 and rac-3 is different. These differences in cavity size and hydrogen bonding behavior obviously do not affect their binding affinity but change their thermodynamic signature, causing different entropy-enthalpy compensations.…”

Design, synthesis and application of carbazole macrocycles in anion sensors

“…By using a cyclic structure, it is possible to accommodate a solvophobic environment alongside polar functional groups. The benefits of this protein-inspired architecture have recently been praised in the use of naphthotubes [3]. Association between the receptor and the analyte may change considerably when the receptor is attached to an electrode surface or embedded in a sensor membrane.…”

Prismarene: An Emerging Naphthol‐Based Macrocyclic Arene

“…Instead of phenols and their derivatives,naphthols may be reacted with paraformaldehyde to afford amacrocyclic arene, presumably with an electron-rich and sizable cavity.However, earlier explorations of calixnaphthalenes [7,8] were not very successful. These macrocycles often suffer from difficulties in isolating the multiple isomers formed and show poor or limited guest-binding ability.This is presumably caused by the low symmetry of the naphthols used for calixnaphthalanes.In contrast, 2,6-dihydroxynaphthalene-based macrocyclic hosts, such as oxatub[n]arenes, [9] naphthocages, [10] and naphthotubes, [11] possess well-defined cavities and generally show excellent host-guest chemistry.In2013, we already proposed that the condensation of 2,6-dialkoxynaphthalene with paraformaldehyde may give new macrocyclic arenes.H owever, in our hands,reacting 2,6-dibutoxynaphthalene (80 mm)with paraformaldehyde under optimized conditions (catalyst: p-TsOH, solvent:C H 2 Cl 2 ,2 5 8 8C, 2h)o nly gave as eries of methylene-bridged naphthalene oligomers. [12] To our surprise and delight, Gaeta and co-workers [13] recently reported the successful synthesis of such macrocyclic arenes (named prism[n]arenes) by reacting 2,6-dimethoxynaphthalene with paraformaldehyde under appropriate conditions.…”

“…Another feature of these macrocycles is that they are fluorescent and may be used as fluorescent sensors. [11] In view of the successes achieved with phenol-based macrocyclic arenes, [2,3,14] it can be anticipated that there will be ab right future for prism-[n]arenes.…”