Effector-dependent structural transformation of a crystalline framework with allosteric effects on molecular recognition ability

Abstract

Structurally flexible porous crystals that combine high regularity and stimuli responsiveness have received attracted attention in connection with natural allostery found in regulatory systems of activity and function in biological systems. Porous crystals with molecular recognition sites in the inner pores are particularly promising for achieving elaborate functional control, where the local binding of effectors triggers their distortion to propagate throughout the structure. Here we report that the structure of a porous molecular crystal can be allosterically controlled by local adsorption of effectors within low-symmetry nanochannels with multiple molecular recognition sites. The exchange of effectors at the allosteric site triggers diverse conversion of the framework structure in an effector-dependent manner. In conjunction with the structural conversion, it is also possible to switch the molecular affinity at different recognition sites. These results may provide a guideline for the development of supramolecular materials with flexible and highly-ordered three-dimensional structures for biological applications.

Fig. 1. Concept of this study and crystal structure of MMF.

a Schematic diagram of a flexible crystalline host whose structure and function can be remotely controlled by precise molecular recognition at independent allosteric sites. b Crystal structure and microscopic image of an MMF crystal co-crystallised with four stereoisomers of Pd^II-macrocycle. c Chemical structure of the interstitial binding site at the bottom corner of the channel that serves as an allosteric site to accommodate effectors. The magenta dotted lines indicate non-covalent interactions such as hydrogen bonds, CH–π and π–π interactions. The (P)-syn, (M)-syn, (P)-anti and (M)-anti isomers of the Pd^II-macrocycle are shown in brown, orange, teal and turquoise, respectively.

Fig. 2. Powder X-ray diffraction (PXRD) patterns of MMF soaked in several ethers.

PXRD profiles (rt, CuKα) for MMF crystals packed in a glass capillary with organic solvents: acetonitrile (black), 1,2-dimethoxyethane (red), diethylene glycol dimethyl ether, (rac)−1,2-dimethoxypropane, 1,2-diethoxyethane, methyl n-butyl ether, 1,4-dioxane (blue), 1,3-dioxolane and tetrahydropyran.

Fig. 3. Crystal structures of the unit-space and the allosteric binding sites of the structurally extended MMF with effectors.

a 1,2-Dimethoxyethane (red) and b 1,4-dioxane (blue). The magenta dotted lines show non-covalent interactions (NH···O, CH···O, NH···Cl and CH···Cl) between an effector and a Pd^II-macrocycle or between two Pd^II-macrocycles. In the structures of the allosteric binding site, the (P)-syn, (M)-syn, (P)-anti and (M)-anti isomers of the Pd^II-macrocycle are shown in brown, orange, teal and turquoise, respectively.

Fig. 4. MMF unit-space structure and interaction patterns around its allosteric site accommodating an effector.

a Tetraethylene glycol dimethyl ether (yellow), b 1,1-bis(hydroxymethyl)cyclopropane (pink) and c benzyl alcohol (green, left; metastable crystal structure observed in the first step, right; the most stable crystal structure obtained in the second step). The magenta dotted lines represent non-covalent interactions between an effector and a Pd^II-macrocycle or between two Pd^II-macrocycles. In the structures of the allosteric binding site, the (P)-syn, (M)-syn, (P)-anti and (M)-anti isomers of the Pd^II-macrocycle are shown in brown, orange, teal and turquoise, respectively.

Fig. 5. Characterisation of MMF crystal structures by principal component analysis based on interatomic distances in Pd^II-macrocycles.

a Internuclear distances (d₁–d₆) of six atomic pairs (N/C···Cl) used as variables. b PCA score plot of 50 MMF crystal structures with various effectors (variance; PC1 = 68%, PC2 = 29%). Typical structures are labelled with the accommodated effectors, and all structures are categorised into three clusters I–III. c The characteristics of three structural clusters: the void volume in the unit-cell, interactions around allosteric sites, and effectors accommodated. The pink lines in (c) represent atom pairs that are close enough to interact, while the grey lines represent unbound atom pairs. The pink arrows indicate structural misalignment due to specific interactions with effector molecules in each cluster. All seven effectors in cluster II can also afford cluster III, which is generally the most stable structure. The molecules enclosed by the rectangular dashed box in (c) are solid effectors housed in the solution. For solid effectors, the crystal structures obtained in 1,2,3,4-tetrahydronaphthalene solutions were used for PCA analysis.

Fig. 6. Allosteric effects of structural changes in MMF channels on the molecular recognition ability for trans-azobenzene.

Left; the unit-space structure and channel surface structure of as-crystalised MMF (effector: MeCN) soaked in a DME:MeCN = 95:5 (vol:vol) solution of trans-azobenzene (1.0 M), right; the unit-space structure, channel surface, host-guest interaction patterns and electron density maps of trans-azobenzene adsorbed on a structurally extended MMF (effector: DME) soaked in a DME solution of trans-azobenzene (1.0 M). The contour level of the electron density map is 0.7σ. In the chemical and crystal structures, trans-azobenzene molecules are shown in pink.