Effect of Extra-Framework Anion Substitution on the Properties of a Chiral Crystalline Sponge

Chiral metal–organic materials, CMOMs, are of interest as they can offer selective binding sites for chiral guests. Such binding sites can enable CMOMs to serve as chiral crystalline sponges (CCSs) to determine molecular structure and/or purify enantiomers. We recently reported on the chiral recognition properties of a homochiral cationic diamondoid, dia, network {[Ni(S-IDEC)(bipy)(H2O)][NO3]}n (S-IDEC = S-indoline-2-carboxylicate, bipy = 4,4′-bipyridine), CMOM-5[NO3]. The modularity of CMOM-5[NO3] means there are five feasible approaches to fine-tune structures and properties via substitution of one or more of the following components: metal cation (Ni2+); bridging ligand (S-IDEC); linker (bipy); extra-framework anion (NO3–); and terminal ligand (H2O). Herein, we report the effect of anion substitution on the CCS properties of CMOM-5[NO3] by preparing and characterizing {[Ni(S-IDEC)(bipy)(H2O)][BF4]}n, CMOM-5[BF4]. The chiral channels in CMOM-5[BF4] enabled it to function as a CCS for determination of the absolute crystal structures of both enantiomers of three chiral compounds: 1-phenyl-1-butanol (1P1B); methyl mandelate (MM); ethyl mandelate (EM). Chiral resolution experiments revealed CMOM-5[BF4] to be highly selective toward the S-isomers of MM and EM with enantiomeric excess, ee, values of 82.6 and 78.4%, respectively. The ee measured for S-EM surpasses the 64.3% exhibited by [DyNaL(H2O)4] 6H2O and far exceeds that of CMOM-5[NO3] (6.0%). Structural studies of the binding sites in CMOM-5[BF4] provide insight into their high enantioselectivity.


■ INTRODUCTION
The pharmaceutical and pesticide industries have developed products based upon enantiomerically pure active ingredients (AIs) 1−3 because, whereas enantiomers have the same physicochemical properties, their biological properties can be distinctly different.For example, one enantiomer can be therapeutically effective and the other ineffective (e.g., verapamil) or toxic (e.g., thalidomide). 4,5Between 2018 and 2022, the US Food and Drug Administration approved 167 new drug products based upon small molecule AI(s); 101 of these are homochiral AIs and 9 are racemates. 6Access to homochiral compounds is therefore critical but challenging because enantiomers exhibit the same physicochemical properties. 7,8−10 For example, whereas singlecrystal X-ray diffraction (SCXRD) provides determination of absolute structures, it cannot be readily applied to ambient liquids or compounds only available in minute quantities, such as some natural products. 11,12In terms of separation, derivatives of organic oligomers (e.g., cyclodextrin) and polymers (e.g., cellulose) have been utilized as chiral materials for separation of racemates.−15 New chiral materials that can enable absolute structure determination and chiral separation and provide insights into binding mechanisms are therefore of topical interest. 16,17−23 In addition, the crystalline sponge method 24−26 can harness the crystallinity of MOFs to enable adsorption and ordered packing of guests within their pores, in turn facilitating structure determination by SCXRD. 2 7 − 2 9 The prototypal crystalline sponge, [(ZnI 2 ) 3 (tpt) 2 ] n (tpt = tris(4-pyridyl)-1,3,5-triazine), exemplifies their potential utility, as in effect, it mimics enzymatic binding sites for a range of guest molecules. 27,30,31hiral MOMs (CMOMs) can be generated using homochiral ligands 32−35 and offer opportunities for chiral separation, detection, and catalysis.−38 Low-cost homochiral ligands such as camphorates have also been studied. 39−43 For mandelate CMOMs, four modular components can be readily substituted: metal cation (Co 2+ / Zn 2+ ); bridging ligand (mandelate or their derivates); linker (4,4′-bipyridine, bipy); extra-framework counteranion (NO 3 − / OTf − /BF 4 − ).The stoichiometry of metal cation/mandelate/ bipy/counteranion is 1:1:1.5:1,−43  − anions as extra-framework anions. 6The Ni 2+ cations in the S-IDEC RBBs are linked by two bipy linkers, and the other coordination site is occupied by an aqua ligand.This means that CMOM-5[NO 3 ] has five modular components in a 1:1:1:1:1 ratio.−42 Phenylalcohols and mandelate esters are well-known precursors for the synthesis of a wide range of pharmaceutical drug products. 44−49 Our group has reported the structures of R-1P1B, S-1P1B, and S-MM based on CMOM-3S and CMOM-5[NO 3 ], 6,41

■ EXPERIMENTAL SECTION
All reagents and solvents are commercially available and were used without further purification.Details of the experimental procedures are provided in the Supporting Information.Characterization.SCXRD data were collected at 150 K using a Bruker D8 Quest diffractometer equipped with a Cu Kα IμS microfocus source (λ = 1.54178Å) and a Photon II detector.Temperature was controlled by an Oxford Cryosystem with liquid nitrogen flow.Data were indexed by APEX4 (v2021.10−0);integrations were conducted by SAINT V8.40A in APEX4; absorption corrections were performed by SADABS in APEX4; space groups were determined by XPREP in APEX4.−52 Electron density corresponding to highly disordered guest molecules was addressed by PLATON SQUEEZE. 53ccupancies for chiral guest molecules were determined by considering MASK-calculated electrons and analyzing 1 H nuclear magnetic resonance (NMR) data after sample digestion.NMR data were recorded using a JEOL ECX400 NMR spectrometer. 54,55hiral Resolution Studies. 100 mg of CMOM-5[BF 4 ]•EtOH crystals was soaked in 0.5 mL of ethanol containing 400 mg (or μL) of racemate.The screw cap was loosened to enable slow evaporation of ethanol over 5 days.Crystals were then filtered and washed with ethyl acetate (3 × 1 mL) and n-hexane (3 × 10 mL) to remove chiral molecules adhering to the surface of the crystals.Guest molecules in CMOM-5[BF 4 ] were extracted by soaking the crystals in 10 mL of methanol for 3 days, after which the crystals were filtered and washed with methanol.The filtrates were combined, and the solvent was removed by using a rotary evaporator.The dried fractions were dissolved in 1 mL of isopropanol for ee analysis.
Crystalline Sponge Studies.Crystals of CMOM-5[BF 4 ]•EtOH were soaked in 0.5 mL of ethanol containing 40 mg (or μL) of an enantiomer of 1P1B, MM, or EM.The screw cap was loosened to enable slow evaporation of ethanol over 3 days; single crystals were isolated for SCXRD experiments.

■ RESULTS AND DISCUSSION
Blue single crystals of {[Ni(S-IDEC)(bipy)(DMF)](BF 4 )-(DMF)} n were obtained through solvothermal reaction of Ni(BF 4 ) 2 , S-IDECH and bipy in DMF/methanol at 85 °C for 1 day (Figure S1a).SCXRD analysis revealed that the crystals had adopted the orthorhombic space group P2 1 2 1 2 1 (Table S2).The crystal structure revealed that RBBs had formed via coordination of Ni 2+ cations to S-IDEC bridging ligands in a manner similar to that for CMOM-5[NO 3 ].The terminally coordinated aqua ligand present in CMOM-5[NO 3 ] was replaced by DMF (Figure 1a).RBBs were linked by bipy to form the expected dia net with BF 4 − counteranions in channels (Figures 1d,e and S6).The remaining void space was occupied by DMF (Figure S10 and Table S10).TGA (thermogravi-metric analysis) weight loss of 13.5 wt % at 145 °C (Figure S20) was consistent with the loss of DMF molecules.
For the fully open phase of CMOM-5[BF 4 ], the Langmuir surface area was determined to be 613 m 2 g −1 (Figure S33).Four continuous cycles of 195 K CO 2 sorption isotherms revealed that the phase change pressure and uptake are consistent over multiple cycles (Figure S31).The N 2 adsorption isotherm for CMOM-5[BF 4 ] registered a negligible uptake (Figure S30).The high-pressure CO 2 adsorption isotherm at 298 K was also F−II isotherm type (Figure S32).The first step occurred at 8 bar with an uptake of 2.6 mmol g −1 and the second at 40 bar with an uptake of 5.1 mmol g −1 .
In the guest-loaded structures, non-hydrogen atoms of the enantiomers were refined anisotropically (Figure 3).The unit cells of the phases accommodating chiral guests are similar to those of the as-synthesized solvate (Figures S7−S9, Tables S4−S6).However, there are differences after guest loading as seen from diagonal distances between Ni(II) cations across the channel (Figures 3 and S7).The linker ligand coordination geometries for bipy (Table S8) and S-IDEC (Table S9) indicate that the host framework had adapted itself to bind with the chiral guest molecules.PXRD patterns are consistent with the SCXRD data (Figures S27−S29).These subtle structural changes suggest that CMOM-5[BF 4 ] is, in effect, a self-adaptive skeleton that adapts to guest molecules.
In the structures associated with CCS studies, S-MM and S-EM engage in guest−guest H-bonding to form chains in the channels (Figure 4g,h).This was not observed in the structures of their enantiomers or in the isomers of 1P1B.The guest− guest H-bonding interactions could facilitate higher loading, and in turn, enable the observed enatioselectivity. 59  ] can serve as an enantioselective physisorbent, exhibiting higher affinity for S-MM and S-EM than their R-enantiomers.The ee value for the EM is much higher than that seen for CMOM-5[NO 3 ].The adaptive nature of CMOM-5 [BF 4 ] enabled it to serve as a CCS for X-ray crystallographic analysis of both the R-and Sisomers of 1P1B, MM, and EM.These results suggest that crystal engineering approaches can fine-tune the composition of CMOMs in order to control the enantioselectivity of chiral porous materials.
Experimental details, supplementary characterization results, additional figures, data analysis, and computational calculations (PDF) In the prototypal S-IDEC CMOM, {[Ni(S-IDEC)(bipy)(H 2 O)]-[NO 3 ]} n , CMOM-5[NO 3 ], Ni 2+ cations are bridged by S-IDEC anions to form RBBs cross-linked by bipy linkers to generate dia topology with NO 3 but the crystal structures of the enantiomers of EM have not been reported in the CSD (Cambridge Structural Database) (Figures S3−S5 ,

Figure 4 .
Figure 4. H-bonding interactions involving the chiral guest molecules in their binding sites.(a) to (f) correspond to R-1P1B, R-MM, R-EM, S-1P1B, S-MM, and S-EM.H-bonded chains of S-MM (g) and S-EM (h) lie in the channels of CMOM-5[BF 4 ].The non-hydrogen atoms of the chiral guest molecules are drawn in thermal ellipsoids at a 50% probability.The distances between donors and acceptors in the H-bonds marked by red dashed lines are given.Guest−guest H-bonds are highlighted by light blue dashed lines.
CCDC 2266468−2266477 contain the supplementary crystallographic data for this paper.These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.