Diamond Annual Review 2019/20

90 91 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 1 9 / 2 0 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 1 9 / 2 0 Designingmetal-organic frameworks to detect chiral molecules Related publication: Han Z.,Wang K., Guo Y., ChenW., Zhang J., Zhang X., Siligardi G., Yang S., Zhou Z., Sun P., ShiW. & Cheng P. Cation- induced chirality in a bifunctional metal-organic framework for quantitative enantioselective recognition. Nat. Commun. 10 , 5117 (2019). DOI: 10.1038/s41467-019-13090-9 Publication keywords: Chiral metal-organic frameworks; Ions exchange; Enantioselective recognition; Enantiomeric excess A molecule that cannot be superimposed on its mirror image is called chiral. Chirality can be crucial in chemical processes, as pairs of chiral molecules (known as enantiomers) can have different properties. This is particularly important in pharmaceuticals, where one of the molecules can be a valuable drug while its mirror image is toxic. Identifying unwanted enantiomers is there for a vital task, but it is challenging. State-of-the-art methods to recognise chiral molecules (such as high-performance liquid chromatography, capillary electrophoresis and gas chromatography) can be slow and expensive. Luminescent sensors are an attractive alternative due to their low-cost, high efficiency and ease of operation. Integrating luminescence and chirality into metal-organic frameworks (MOFs) allows the development of advanced luminescent sensors. A team of researchers were able to introduce chirality into a zinc-based MOF via simple cation exchange. The material they created has dual luminescent centres and a chiral centre in the pores, and they were able to characterise its chiral binding properties using the Circular Dichroismbeamline (B23) at Diamond Light Source. The researchers showed that this MOF has excellent sensitivity and effectively selects enantiomers. It is notably cheaper to synthesise than current state-of-the-art systems based upon complex, chiral organic linkers. Their methods could potentially be used to detect other chiral molecules. This study paves a pathway for the design of multifunctional metal-organic framework systems as a useful method for rapid sensing of chiral molecules. Chirality is crucial to many chemical processes in pharmacy, agriculture and biology.Enantiomersoftendisplaydifferentproperties intheseprocessesand, in particular cases, certain isomers can cause fatal effect on living cells 1 .Therefore, the recognition of enantiomer is a vital but challenging task. State-of-the-art methods to recognise chiral molecules usually require capital instrument, such as high-performance liquid chromatography, capillary electrophoresis or gas chromatography with high running cost and delays in response. By contrast, luminescent sensors have attracted great attention for their easy-operation, low-cost, high efficiency and ideal portability 2 .To construct a chiral luminescent sensor, chiral materials that show selective binding to certain chiral enantiomers are required. Small organic chiral molecules, especially the binaphthyl and its derivatives, andmacrocyclic rigid scaffolds have been studied attentively 3 .These materials, however, have limited recyclability and are often subject to high cost and synthetic challenges. The theory and applications of coordination chemistry have been greatly promoted by the research on metal-organic frameworks (MOFs) over the last two decades with their tunable chemical composition and tailored-to-property crystal structures. Due to the designable functionality and porosity of MOFs, a wide range of applications, such as chemical recognition, gas storage and separation, and catalysis, have been studied 4 . Small molecules such as volatile organic compounds, persistent organic pollutants and large molecules such as biomakers and, in exceptional cases, chiral molecules can be recognised by designed MOFs via luminescence sensing which is facile for operation. Compared with other luminescence materials, porous materials have the ability of adsorbing molecules into the pores achieving local enrichment. However, the recognition of chiral molecules remains a highly challenging task due to the similar interactions of the enantiomers with the MOF host. To exhibit the function of chiral recognition and discrimination, MOFs have to be chiralised. Currently, there are three main approaches to construct chiral MOFs: (i) direct synthesis using chiral ligands, (ii) chiral-template synthesis and (iii) post-synthetic chiralisation. All these methods introduce the chirality to the frameworks of MOFs and usually rely on the use of complex chiral ligands that require multi-step synthesis and purification. As a promising alternative, the introduction of chirality to the pores of MOFs could be easily conducted Soft CondensedMatter Group Beamline B23 via exchanging the guest molecules or counter ions with chiral molecules or ions, which to our knowledge has remained unexplored to date. On the other hand, although numerous chiral MOFs containing luminescent centers have been reported, very few of them can be used as sensors for enantioselective recognition because of the very small difference of host-guest interactions between the enantiomer and theMOF host.The introduction of additional chiral binding sites could effectively overcome this problem. Here, we report the introduction of a commercial optically pure compound, N-benzylquininium chloride, with five chiral sites into a luminescent Zn-MOF ([(CH 3 ) 2 NH 2 ] 1/2 [Zn 2 (adenine)(TATAB)O 1/4 ]·6DMF·4H 2 O, H 3 TATAB=4,4’,4’’-s-triazine-1,3,5-triyltri-p-aminobenzoic acid) that contains dimethylamine cations in the one-dimensional hexagonal channels 5 , to generate Zn-MOF-C, which exhibits targeted chirality. We then introduced Tb 3+ as the second luminescent center into the channels of Zn-MOF-C to produce Zn-MOF-C-Tb. Importantly, this chiral and luminescent bi-functional MOF with dual luminescent centers has enabled the quantitative enantioselective recognitionofchiralmoleculesforthefirsttime,demonstratedbytheepimersof CinchonineandCinchonidine,whicharepotentantimalarialdrugswithdifferent half lethal dose and also used as asymmetric catalytic agents.Thanks to the dual luminescence fromboth the ligand andTb 3+ , the enantiomeric excess (ee) value of the epimers can be determined based upon the ratio of luminescence from two centers. Zn-MOF-C-Tb has shown general applicability towards a range of epimers and enantiomers with excellent stability and reusability. Although the lead-in of the chiral cation is easy and controllable, it is a challenge to characterise the success of the introduction directly by single crystal X-ray diffraction because of the unambiguous determination of the location and orientation. In this case, we attempted to use solid-state circular dichroism, 1 H nuclear magnetic resonance, elemental analyses and thermal gravimetric analyses to confirm the existence of this cation in the pores. Unfortunately, also because of the low contents of the chiral cations compared with the framework, we could not detect the obvious Cotton effects on JASCO J-715 circular dichroism. Thanks to the forceful beamline at Diamond, we found the obvious negative Cotton effects of our cation-exchanged MOF. This further certificated the chiral cation in the pores. In summary, we report a novel strategy to construct bifunctional (chiral and luminescent) MOFs for enantioselective fluorescence recognition and quantitative determination of ee values for enantiomers.The competition for the absorption of the enantiomers to the post-modified pore chirality is responsible for the recognition property. Based upon the methods developed here, anionic MOFs can be generally modified to be used for enantioselective fluorescence recognition, paving a new pathway for the design and development of new functional sensors of organic chiral molecules. References: 1. WangY. et al. Emerging chirality in nanoscience. Chem. Soc. Rev. 42 , 2930 (2013). DOI: 10.1039/c2cs35332f 2. Jung H. S. et al. Recent progress in luminescent and colorimetric chemosensors for detection of thiols. Chem. Soc. Rev. 42 , 6019 (2013). DOI: 10.1039/c3cs60024f 3. Zhang X. et al. Recent advances in development of chiral fluorescent and colorimetric sensors. Chem. Rev. 114 , 4918 (2014). DOI: 10.1021/cr400568b 4. Zhou H. -C. et al. Introduction to metal-organic frameworks. Chem. Rev. 112 , 673 (2012). DOI: 10.1021/cr300014x 5. Du M. et al. Ligand symmetry modulation for designing a mesoporous metal-organic framework: dual reactivity to transition and lanthanide metals for enhanced functionalization. C hem. Eur. J. 21, 9713 (2015). DOI: 10.1002/chem.201500457 Funding acknowledgement: This work was supported by the National Natural Science Foundation of China (grant numbers 21622105, 21861130354, and 21931004), the Natural Science Foundation ofTianjin (grant number 18JCJQJC47200), and the Ministry of Education of China (grant number B12015). S.Y. andW.S. acknowledge the receipt of a Royal Society Newton Advanced Fellowship.We thank Prof. Shou- Fei Zhu from Nankai University for his helpful discussion on chiral recognition. We thank Diamond Light Source for access to Beamlines B23 and I19. Corresponding author: DrWei Shi, Key Laboratory of Advanced Energy Materials Chemistry (MOE), Nankai University, shiwei@nankai.edu.cn Figure 1: Ions exchange of Zn-MOF. First step: the replacement of (CH 3 ) 2 NH 2 + with N-benzylquininium cations. Second step: the lead-in of minute quantities of Tb 3+ . The inserted photos were taken under 254 nm irradiation with Xe ultraviolet lamp. Green ball stands for Tb, blue for N, gray for C, white for H and turquoise for Zn. e f a, b Emission spectra of Zn-MOF-C-Tb dispersed in DMF upon incremental addition of Cinchonidine and Cinchonine. c, d Fluorescence intensity changes at 544nm and lower concentrations (the solid lines are fitting results). e, CD spectra of Cinchonidine (pink) and Cinchonine (violet) in DMF. f, CD spectra the of the equal proportion of the Cinchonidine and Cinchonine mixt re with the additi of Zn-MOF-C-Tb showing in solution the increased fracti of the unbound Ci chonidine as a function of time as Cinchonine is sequestered by Zn-MOF-C-Tb. Figure 2: a, b Emission spectra of Zn-MOF-C-Tb dispersed in DMF upon incremental addition of Cinchonidine and Cinchonine. c, d Fluorescence intensity changes at 544nm and lower concentrations (the solid line are fitting results). e, CD spectra of Cinchonidine (pink) and Cinchonine (violet) in DMF. f, CD spectra the of the equal proportion of the Cinchonidin and Cinchonine mixture with the addition of Zn-MOF-C-Tb showing in solution the increased fraction of the unbound Cinchonidine as a function of time as Cinchonine is sequestered by Zn-MOF-C-Tb.