Zheng Meng

Iptycene-Derived Crown Ether Hosts for Molecular Recognition and Self-Assembly

CONSPECTUS: Synthetic macrocyclic hosts have played key roles in the development of host-guest chemistry. Crown ethers are a class of macrocyclic molecules with unique flexible structures. They have served as the first generation of synthetic hosts, and researchers have extensively studied them in molecular recognition. However, the flexible structures of simple crown ethers and their relatively limited modes of complexation with guests have limited the further applications of these molecules. In recent years, researchers have moved toward fabricating interlocking molecules, supramolecular polymers, and other assemblies with specific structures and properties. Therefore, researchers have developed more complex crown ether-based macrocyclic hosts with multicavity structures and multicomplexation modes that provide more diverse and sophisticated host-guest systems. In this Account, we summarize our research on the synthesis and characterization of iptycene-derived crown ether hosts, their use as host molecules, and their applications in self-assembled complexes. Iptycenes including triptycenes and pentiptycenes are a class of aromatic compounds with unique rigid three-dimensional structures. As a result, they are promising building blocks for the synthesis of novel macrocyclic hosts and the construction of novel self-assembled complexes with specific structures and properties. During the last several years, we have designed and synthesized a new class of iptycene-derived crown ether hosts including macrotricyclic polyethers, molecular tweezer-like hosts, and tritopic tris(crown ether) hosts, which are all composed of rigid iptycene building blocks linked by flexible crown ether chains. We have examined the complexation behavior of these hosts with different types of organic guest molecules. Unlike with conventional crown ethers, the combination of iptycene moieties and crown ether chains provides the iptycene-derived crown ether hosts with complexation properties that differ based on the structure of the guests. The rigid iptycene moieties within these synthetic host molecules both maintain their inherent three-dimensional cavities and generate multicavity structures. The flexible crown ether chains allow the iptycene-derived hosts to adjust their conformations as they encapsulate guest molecules. Moreover, the expanded complexation properties also allow the host-guest systems based on the iptycene-derived crown ethers to respond to multiple external stimuli, resulting in a variety of supramolecular assemblies. Finally, we also describe the construction of mechanically interlocked self-assemblies, molecular switches/molecular machines, and supramolecular polymers using these new host molecules. We expect that the unique structural features and diverse complexation properties of these iptycene-derived crown ether hosts will lead to increasing interest in this field and in supramolecular chemistry overall.

Stepwise Motion in a Multivalent [2](3)Catenane.

The motions of biomolecular machines are usually multistep processes, and are involved in a series of conformational changes. In this paper, a novel triply interlocked [2](3)catenane composed of a tris(crown ether) host eTC and a circular ditopic guest with three dibenzyl ammonium (DBA) sites and three N-methyltriazolium (MTA) sites was reported. Due to the multivalency nature of the catenane, the acid-base triggered motion was performed by a stepwise manner. The coconformations of the four related stable states have been directly identified and quantified which confirmed the multistep process. In order to quantify the dynamics with environmental acidity changes, the values of the three levels of dissociation constant pKa have been determined. The special interlocked topology of the [2](3)catenane also endows the motion of each crown ether ring in the host with unexpected selectivity for the MTA sites. This study provides clues to comprehend the underlying motion mechanism of intricate biological molecular machines, and further design artificial molecular machine with excellent mechanochemistry properties.

Tristable [n]rotaxanes: from molecular shuttle to molecular cable car

New tristable [n]rotaxanes (n = 2, 3, 4) were developed based on host–guest interactions, featuring pyromellitic diimide (PmI), anthraquinone (AQ) and N-methyltriazolium (MtA) units as the three kinds of recognition sites and triptycene-derived macrocycle(s) as the moveable part. In the [2]rotaxane molecular shuttle, the states of the macrocycle on different sites can be reversibly and controllably switched using chemical stimuli. The controllable motion mode of the [2]rotaxane molecular shuttle can be extended to its analogous oligorotaxanes, thus creating synchronous behavior for the macrocycles and producing an original visual prototype of artificial molecular machines (AMMs)—molecular cable car.

Triptycene‐Based Chiral Macrocyclic Hosts for Highly Enantioselective Recognition of Chiral Guests Containing a Trimethylamino Group

A new class of chiral macrocyclic arene composed of three chiral 2,6-dihydroxyltriptycene subunits bridged by methylene groups was designed and synthesized. Structural studies showed that the macrocyclic molecule adopts a hex-nut-like structure with a helical chiral cavity and highly fixed conformation. Efficient resolution was achieved through the introduction of chiral auxiliaries to give a couple of enantiopure macrocycles, which exhibited high enantioselectivity towards three pairs of chiral compounds containing a trimethylamino group.

Directional Molecular Transportation Based on a Catalytic Stopper-Leaving Rotaxane System

Ratchet mechanism has proved to be a key principle in designing molecular motors and machines that exploit random thermal fluctuations for directional motion with energy input. To integrate ratchet mechanism into artificial systems, precise molecular design is a prerequisite to control the pathway of relative motion between their subcomponents, which is still a formidable challenge. Herein, we report a straightforward method to control the transportation barrier of a macrocycle by selectively detaching one of the two stoppers using a novel DBU-catalyzed stopper-leaving reaction in a rotaxane system. The macrocycle was first allowed to thread onto a semidumbbell axle from the open end and subsequently thermodynamically captured into a nonsymmetrical rotaxane. Then, it was driven energetically uphill until it reached a kinetically trapped state by destroying its interaction with ammonium site, and was finally quantitatively released from the other end when the corresponding stopper barrier was removed. Although the directional transportation at the present system was achieved by discrete chemical reactions for the sake of higher transportation efficiency, it represents a new molecular transportation model by the strategy of using stopper-leavable rotaxane.

Self‐Assembly of a [2]Pseudorotaxane by an Inchworm‐Motion Mechanism

The threading of biomolecules through pores or channels in membranes is important to validate the physiological activities of cells. To aid understanding of the controlling factors required for the translocation in space with confined size and distorted conformation, it is desirable to identify experimental systems with minimized complexity. We demonstrate the mechanism of a linear guest L1 threading into a tris(crown ether) host TC with a combinational distorted cavity to form a triply interlocked [2]pseudorotaxane 3in-[L1⊂TC]. An inchworm-motion mechanism is proposed for the process. For the forward-threading steps that lead to the formation of higher-order interlocked species, guest L1 must adopt a bent conformation to find the next crown ether cavity. Two simplified models are applied to investigate the self-assembly dynamic of 3in-[L1⊂TC]. Kinetic NMR spectroscopic and molecular dynamics (MD) studies show that formation of the singly penetrated species is fast, whereas formation of the doubly and triply threaded species is several orders of magnitude slower. During threading the freedom of both the guest L1 and host TC gradually decrease due to their interactions. This results in a significant entropy effect for the threading dynamic, which is also observed for the threading of a biomolecular chain through a channel.

Synthesis and Structures of Triptycene-Derived Oxacalixarenes with Expanded Cavities: Tunable and Switchable Complexation Towards Bipyridinium Salts

New triptycene-derived oxacalixarene H1 was efficiently synthesized by a template cyclization step, and anilino-substituted macrocycle H2 was subsequently afforded through straightforward nucleophilic displacement of the active chlorine atom in H1. Oxacalixarene H1 adopts a fixed boat-like 1,3-alternate conformation and shows moderate complexation abilities towards various bipyridinium salts. However, the affinities of H2 towards the guests were found to be substantially stronger, which could be tentatively attributed to the additional hydrogen-bonding site, π-π stacking site, and especially the increased electron richness of the host. Furthermore, the acid-base switchable complexation process between H1 and the bipyridinium salt was also realized, which could potentially facilitate the construction of high-level stimuli-responsive supramolecular structures based on the newly synthesized oxacalixarene.

Efficient control of movement in non-photoresponsive molecular machines by a photo-induced proton-transfer strategy

The movement of three pairs of different non-photoresponsive rotaxanes can be efficiently controlled by visible light through a photo-induced proton-transfer (PIPT) strategy in the presence of the photoacid 1-MEH. Moreover, the PIPT strategy also provides systems with a good fatigue resistance after more than 50 cycles.