Homochiral D4-symmetric metal–organic cages from stereogenic Ru(II) metalloligands for effective enantioseparation of atropisomeric molecules

Absolute chiral environments are rare in regular polyhedral and prismatic architectures, but are achievable from self-assembly of metal–organic cages/containers (MOCs), which endow us with a promising ability to imitate natural organization systems to accomplish stereochemical recognition, catalysis and separation. Here we report a general assembly approach to homochiral MOCs with robust chemical viability suitable for various practical applications. A stepwise process for assembly of enantiopure ΔΔΔΔΔΔΔΔ- and ΛΛΛΛΛΛΛΛ-Pd6(RuL3)8 MOCs is accomplished by pre-resolution of the Δ/Λ-Ru-metalloligand precursors. The obtained Pd–Ru bimetallic MOCs feature in large D4-symmetric chiral space imposed by the predetermined Ru(II)-octahedral stereoconfigurations, which are substitutionally inert, stable, water-soluble and are capable of encapsulating a dozen guests per cage. Chiral resolution tests reveal diverse host–guest stereoselectivity towards different chiral molecules, which demonstrate enantioseparation ability for atropisomeric compounds with C2 symmetry. NMR studies indicate a distinctive resolution process depending on guest exchange dynamics, which is differentiable between host–guest diastereomers.

Supplementary Figure

General methods
Unless otherwise stated, all commercial reagents and solvents were used as commercially purchased without additional purification. The 1 H NMR、COSY spectra were recorded on Bruker AVANCE III 400 (400 MHz). Circular dichroism spectra and UV-vis absorption spectra were measured with a JASCO J-810 spectropolarimeter. Specific rotations were measured on ADP440+B+S. HR-ESI-TOF mass spectra were tested on Bruker Maxis 4G and data analyses were processed on Bruker Data Analysis software. HPLC spectra were measured on Agilent-2000.
The structures were solved by direct methods and refined by full-matrix least squares against F 2 of all data using the SHELXTL-2014 program package.
Δ-1-PF 6 crystallizes in the chiral space groups P4(1) with a chemical composition of [Ru(Phen) 3 ] 2 (PF 6 ) 4 (C 6 H 5 CH 3 )(CH 3 CN) 2 in the asymmetric unit. Two [Ru(Phen) 3 ] 2+ motifs have the same absolute Δ-configuration. The Flack parameter was refined as 0.00(4) by classical fit to all intensities, conforming the correct chirality in agreement with the experimental synthesis. The solvated toluene molecules are disordered over two positions and treated isotropically with the free-variable occupancy. The benzene ring was modelled by AFIX 66 and the methyl group was fixed by SADI. FLAT was used to constrain all toluene atoms as planar. SAME is used to simulate the PART 2 as those in PART 1. Totally 21 restraints were introduced. were fixed by DFIX. FLAT was used to constrain all toluene atoms being planar. ISOR was applied to all the disordered toluene atoms. Totally 99 restraints were resulted.
The water molecule is disordered over two positions and treated as fractional occupancy with (

Synthesis of K 2 [Sb 2 {(+)-tartrate} 2 ]· 3H 2 O
In a 100 mL round-bottom flask, L-(+)-tartaric acid (0.76 g, 5.1 mmol), KOH (0.28 g, 5.0 mmol), and deionized water (50 mL) were added. After being stirred for 20 min at 70 o C, the supernatant solution was obtained. To this solution was added Sb 2 O 3 (0.73 g, 5.0 mmol) powder and the reaction mixture was stirred at 100 o C for 3 days. After filtration, the water was rotary evaporated to give the concentrate which was standing for three days to afford crystal product. Yield: 1.20 g (71 %).

(5) (±)-2-(6-Methoxynaphthalen-2-yl)propanoic acid (Naproxen)
Upon combination and vigorous stirring of an aqueous solution of Δ-or Λ-MOC-16 (1 mM, 1 mL) and an ethereal layer of racemic Naproxen (15 mM, 2 mL) at room temperature for 0.5 h, S51 the bottom layer was taken out of the solution and extracted with CHCl 3 (3 × 4 mL). The extract was combined and the solvent was removed by rotary evaporator to afford white solid as resolved guest by chiral host. The solid was redissolved with 0.4 mL isopropanol. The enantiomeric excess of Naproxen was determined by HPLC (Chiralcel AS-H column, isopropanol/hexane/TFA = 8:92:0.1; flow rate 1.0 mL/min).
The extract was combined and removed by rotary evaporator to afford white solid as resolved guest by chiral host. The solid was redissolved with 0.5 mL isopropanol. The enantiomeric excess of 1-(1-Naphthyl)ethanol was determined by HPLC (Chiralcel OD-H column, isopropanol/hexane=10:90; flow rate 1.0 mL/min).