Chiral DHIP-Based Metal-Organic Frameworks for Enantioselective Recognition and Separation

Article abstract of DOI:10.1021/acs.inorgchem.6b00894

Two chiral porous 2,3-dihydroimidazo[1,2-a]pyridine (DHIP)-based metal-organic frameworks (MOFs) are assembled from an enantiopure dipyridyl-functionalized DHIP bridging ligand. The Zn-DHIP MOF shows a good enantioseparation performance toward aromatic sulfoxides, and the heterogeneous adsorbent can be readily recovered and reused without significant degradation of the separation performance.

Full text of DOI:10.1021/acs.inorgchem.6b00894

Communication
pubs.acs.org/IC
Chiral DHIP-Based Metal−Organic Frameworks for Enantioselective
Recognition and Separation
Jie Zhang,† Zijian Li,† Wei Gong,† Xing Han,† Yan Liu,*,† and Yong Cui*,†,‡
†School of Chemistry and Chemical Engineering and State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong
University, Shanghai 200240, China
‡Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China
S
* Supporting Information
Scheme 1. Synthesis of the Ligand L and MOFs 1 and 2
ABSTRACT: Two chiral porous 2,3-dihydroimidazo[1,2-
a]pyridine (DHIP)-based metal−organic frameworks
(MOFs) are assembled from an enantiopure dipyridyl-
functionalized DHIP bridging ligand. The Zn-DHIP MOF
shows a good enantioseparation performance toward
aromatic sulfoxides, and the heterogeneous adsorbent
can be readily recovered and reused without significant
degradation of the separation performance.
etal−organic frameworks (MOFs) built from metal nodes
M
and multitopic organic linkers have received considerable
attention because of their myriad potential applications in gas
storage, catalysis, separation, and sensing.1−3 One of the current
efforts focuses on the development of MOF materials for the
recognition and separation of small molecules, especially when
they are chiral.4,5 The judicious incorporation of enantiopure
building blocks into the porous framework can precisely control
the surfaces, internal pore metrics, and functionalities, which are
of significant importance for their highly selective recognition
and separation.4b,5 Two enantiomers of a chiral molecule could
be effectively oriented within the confined space to promote
enantiospecific interactions within the network, thus realizing
stereocontrol and chiral separation. During the past years, chiral
metal−organic assemblies have been used for enantioselective
adsorption/separation, some of which exhibit good to excellent
performance.5c,d Nonetheless, reports on the enantioselective
recognition and separation behavior of chiral MOFs are scarce
because of the difficulty in synthesizing enantioselective selectors
with precise synergistic recognition sites.
5-bromo-2-(4-bromophenyl)-2,3-dihydroimidazo[1,2-a]-
pyridine, which was obtained from (R)-2-amino-2-(4-
bromophenyl)ethanol by N-arylation followed by cyclization in
35% overall yield for two steps. The ligand L was characterized by
1H and 13C NMR spectroscopy and electrospray ionization mass
spectrometry. Heating a mixture of L, 1,4-benzenedicarboxylic
acid (BDC), and Zn(NO3)2·6H2O or CdI2 (in a 1:1:2 molar
ratio) in a MeOH/DMF/MeCN or MeOH/DMF/EtOH mixed
solvent at 80 °C for 5 days afforded single crystals of
[M3L2(BDC)3]·3H2O [M = Zn (1), Cd (2)] in good yield.
The complexes were stable in air and common solvents including
water. They were formulated based on single-crystal X-ray
diffraction (XRD), microanalysis, and thermogravimetric anal-
ysis (TGA).
Single-crystal XRD analysis of 1 reveals that it crystallizes in
the chiral monoclinic space group C2, and the asymmetric unit
contains one whole formula unit. Three crystallographically
distinct Zn atoms all lie in a distorted tetrahedral coordination
sphere, being coordinated by two carboxylate O atoms of two
BDC ligands, one imidazole N atom and one pyridyl N atom for
Zn1 and Zn2, or two pyridyl N atoms for Zn3 of two different
ligands L, respectively. All of the Zn−O and Zn−N bond lengths
and angles are within the normal range. The ligand L employs a
twisted conformation with the dihedral angle between the
imidazole and phenyl ring in the range of 85.96−88.41°.
It has been known that chiral 2,3-dihydroimidazo[1,2-
a]pyridine (DHIP) is a core structure for the design of
asymmetric catalysts owing to their ease of preparation and
structural diversity including multivariate steric and electronic
environments.6 Some examples have been claimed to be active
toward enantioselective acyl transfer, kinetic resolution, and
cycloaddition.6a,b,d However, with the exception of catalytic
assemblies, efficient separation systems derived from DHIP have
not been reported. Herein, we report two chiral MOFs
constructed from a dipyridyl-functionalized DHIP ligand for
the first time, one of which exhibits impressive enantioselective
recognition and separation toward aromatic sulfoxides.
As shown in Scheme 1, the dipyridyl-functionalized DHIP
ligand L was synthesized in 65% yield by a palladium-catalyzed
Suzuki coupling reaction between 4-pyridylboronic acid and (R)-
Received: April 11, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.6b00894
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Communication
Each L acts as a tridentate ligand connecting to three Zn ions,
and each Zn is surrounded by two L to form helical chains
running along the b axis, which could be further linked by the
BDC ligands to form a 3D net (Figure 1a). Three such
three crystallographically independent Cd atoms are all six-
coordinated by binding to two chelated carboxylate groups of
two BDC ligands and two N atoms of two L ligands. Similar to 1,
each twisted L ligand bridges three Cd centers to form a right-
handed 21 helical chain along the c axis, and adjacent helices
associated in parallel are interconnected by BDC to form a 3D
network (Figure 1c). The final 3-fold-interpenetrated network
was generated by the interpenetration of three independent
networks, which displayed a (3,3,4,4,4)-c net with the point
symbol (4.8.93.10)(4.8.9)2(4.82.92.10)(82.93.10). 2 possesses
smaller open channels than 1, with dimensions of ∼4.1 × 5.1
Å2 along the a axis (Figure 1d).
1 and 2 contain ∼36.8 and 23.1% void spaces, respectively,
calculated by PLATON.7 The observed powder XRD patterns
are the same as the simulated ones, demonstrating phase purity of
the bulk samples. The solid-state circular dichroism spectra of 1
and 2 formed from R and S enantiomers of L showed almost
mirror images of each other, indicating their enantiomeric nature.
TGA showed that the frameworks are thermally stable up to
∼400 °C for 1 and 2. After the removal of guest solvents by
solvent exchange followed by thermal activation under vacuum at
80 °C, 1 and 2 still retained their frameworks indicated by
powder XRD. Their permanent porosity was investigated by
CO2 adsorption measurements at 273 K, with Brunauer−
Emmett−Teller (BET) surface areas of 211 m2 g−1 for 1 and 106
m2 g−1 for 2, respectively.
Having the significant importance of chiral sulfoxides as both
highly valuable chiral auxiliaries and pharmaceuticals in mind,8
we examined the enantioselective sorption properties toward
chiral sulfoxides of the chiral DHIP-based MOFs. The evacuated
1 was immersed in different solutions of racemic sulfoxides for 12
h, filtered, and washed thoroughly with Et2O to remove the
sulfoxides on the surface. The adsorbed guest molecules could be
obtained by soaking the inclusion solids in Et2O, and the
contents of the enantiomers were analyzed by chiral high-
performance liquid chromatography (HPLC). The enantiose-
lective separation of 3-methoxyphenyl methyl sulfoxide was
selected as a model to optimize separation conditions. After a
series of solvents were screened, MeOH was proven to be the
most suitable solvent for separation, giving 26% enantiomeric
excess (ee) at room temperature. Decreasing the temperature
from room temperature to −10 °C led to increased
enantioselectivity of 35% ee. The kinetic profile of the adsorption
1
of 3-methoxyphenyl methyl sulfoxide was studied by H NMR
monitoring at different times. Typically, it took 2 h to reach
equilibrium, and the 1H NMR results suggested the formation of
a 1:1 host−guest complex for 3-methoxyphenyl methyl sulfoxide
adsorption. The Fourier transform infrared spectrum also
suggested the complexation of 1 and 3-methoxyphenyl methyl
sulfoxide, as shown by the strong SO stretching vibration band
at 1050 cm−1.
The enantioselective adsorption capability of 1 toward a
variety of aromatic sulfoxides was investigated under optimized
conditions. As shown in Table 1, the sulfoxides with electron-
donating substituents in the aromatic ring gave rise to relatively
higher enantioselectivity, with 37.1%, 31.7%, and 34.8% ee values
for 3-methoxyphenyl methyl sulfoxide, 4-methoxyphenyl methyl
sulfoxide, and 4-methylphenyl methyl sulfoxide, respectively.
However, the introduction of electron-withdrawing substituents
such as −F or −Cl could reduce the enantioselectivities to 17−
25.1%. The highest ee of 46.8% was obtained for methyl phenyl
sulfoxide. Interestingly, when the methyl group of methyl phenyl
sulfoxide was replaced by ethyl and isopropyl groups, the
Figure 1. (a) View of one independent network of 1 along the b axis. (b)
Scheme showing the 3-fold-interpenetrated nets in 1. (c) View of one
independent network of 2 along the c axis. (d) View of the (3,3,4,4,4)-c
topology of 2. Color code: Zn, green; Cd, purple; C, gray; O, red; N,
blue. The metal centers are drawn as polyhedra in parts a and c.
independent nets interpenetrated with each other, furnishing the
final 3D framework with 1D channels of ∼4.7 × 5.4 Å2 along the c
axis. The three-fold-interpenetrated framework can be simplified
as a (3,3,3,4,4)-c net with the point (Schlafli) symbol
̈
(4.72.83)(4.72)3(75.9) if considering the ZnII ions as tetrahedral
nodes and the BDC and L ligands as linkers (Figure 1b).
2 also possesses a 3-fold-interpenetrated framework. It
crystallizes in the chiral orthorhombic space group P212121,
and the asymmetric unit contains one whole formula unit. The
B
DOI: 10.1021/acs.inorgchem.6b00894
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Communication
a
Table 1. Enantiosorption of 1 toward Racemic Sulfoxides
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.6b00894.
■
S
Experimental details and spectral data (PDF)
Crystallographic file in CIF format (CIF)
Crystallographic file in CIF format (CIF)
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: liuy@sjtu.edu.cn.
*E-mail: yongcui@sjtu.edu.cn.
Notes
The authors declare no competing financial interest.
a
ACKNOWLEDGMENTS
For details, see experimental procedure for separation in the SI.
Determined by HPLC (letters in parentheses specify the preferable
■
b
This work was supported by NSFC Grants 21371119, 21431004,
21401128, and 21522104, the “973” Program (Grants
2014CB932102 and 2012CB8217), the Shanghai “Eastern
Scholar” Program, and Grant SSTC-14YF1401300.
isomer).
sulfoxides were resolved with much lower enantioselectivity as
20.9% and 12.4%, probably as a result of larger stereohindrance.
It is worth noting that ligand L alone could not resolve the
sulfoxides under otherwise identical conditions, indicating that
the enantioselective recognition process is controlled by the well-
organized inner sphere of the chiral framework. The separator
could be regenerated and used repeatedly for the next three runs
without significant loss of enantioselectivity, and the third
recycled sample could provide 41.2% ee for the separation of
methyl phenyl sulfoxide. After adsorption, no appreciable
difference between the recovered and pristine samples was
observed in the powder XRD patterns, and the recovered 1
displayed a slightly decreased BET surface area of 162 m2 g−1,
further comfirming the framework robustness. Inductively
coupled plasma spectroscopic analysis of the resolution solution
indicated almost no loss of the Zn ion (0.0216%) from the
structures. Unlike 1, MOF 2 showed almost no enantioselective
adsorption ability toward sulfoxides under similar conditions,
probably as a result of the smaller pore sizes of its more
interpenetrating network. The moderate enantioselectivity of 1
may be due to the lack of efficient chiral host−guest interactions
as a result of the fact that the imidazole N atoms proximal to the
chiral centers as potential supramolecular bonding sites are
coordinated by metal ions. Prior to this work, chiral MOFs built
from L-lactic acid or (R)-mandelic acid have been studied for
enantioseparation toward sulfoxides by diverse techniques
including adsorption, chromatography, and even membrane
separation,4b,9 and the enantioselectivity could reach up to
∼62%.9c
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In conclusion, two novel chiral porous DHIP-based MOFs
were constructed, and the enantioseparation ability of a Zn-
DHIP framework toward racemic sulfoxides was demonstrated.
The DHIP MOFs may promise a new heterogeneous system and
bring new inspiration to chiral separation in terms of the
exploration of advanced adsorbents for varieties of adsorbates.
Further efforts will focus on other DHIP-based framework
adsorbents as well as chiral stationary phases and membranes
with potential actual applications.
C
DOI: 10.1021/acs.inorgchem.6b00894
Inorg. Chem. XXXX, XXX, XXX−XXX