Application of a chiral metal-organic framework in enantioselective separation

Article abstract of DOI:10.1039/c1cc14893a

A modular approach for the synthesis of highly ordered porous and chiral auxiliary (Evans auxiliary) decorated metal-organic frameworks is developed. Our synthesis strategy, which uses known porous structures as model materials for incorporation of chirality via linker modification, can provide access to a wide range of porous materials suitable for enantioselective separation and catalysis. Chiral analogues of UMCM-1 have been synthesized and investigated for the enantioseparation of chiral compounds in the liquid phase and first promising results are reported. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1cc14893a

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COMMUNICATION
Application of a chiral metal–organic framework in enantioselective
separationw
Mohan Padmanaban,a Philipp Mu
¨
ller,b Christian Lieder,c Kristina Gedrich,b Ronny Gru
¨
nker,b
b
b
c
c
d
¨
Volodymyr Bon, Irena Senkovska, Sandra Baumgartner, Sabine Opelt, Silvia Paasch,
Eike Brunner,d Frank Glorius,*a Elias Klemm*c and Stefan Kaskel*b
Received 8th August 2011, Accepted 16th September 2011
DOI: 10.1039/c1cc14893a
A modular approach for the synthesis of highly ordered porous and
chiral auxiliary (Evans auxiliary) decorated metal–organic frame-
works is developed. Our synthesis strategy, which uses known
porous structures as model materials for incorporation of chirality
via linker modification, can provide access to a wide range of
porous materials suitable for enantioselective separation and cata-
lysis. Chiral analogues of UMCM-1 have been synthesized and
investigated for the enantioseparation of chiral compounds in the
liquid phase and first promising results are reported.
Whereas various porous materials including zeolites,
activated carbon, silica gel and various polymer resins have been
shown to be useful stationary phases in gas chromatography,4
liquid chromatography5 and electrochromatography, MOFs
are far less explored. Recently, it has been shown that MOFs
are able to separate mixtures of compounds in small volumes.6
Because of their defined architectures, accessible volumes,
pore size etc., these porous solids can be used as a promising
stationary phase for the separation of organic compounds.
Moreover, examples of in situ incorporation of chiral auxili-
aries into MOF building blocks followed by their subsequent
utilization in the enantioseparation are rare and to the best of
our knowledge no high performance liquid chromatography
(HPLC) enantioseparation by chiral porous MOFs has been
reported so far.
Metal–organic frameworks (MOFs) are highly porous, crystalline
coordination polymers generated from metal atoms or clusters
as ‘‘nodes’’ and organic linkers as nodal ‘‘connectors’’.1
Following their recent development, MOFs have found several
attractive applications, including gas separation, gas storage
and selective catalysis.2 Among others, the properties and
utilities of the MOFs depend on their pore size and shape,
the interior and exterior surfaces, and the functional groups
employed. Intriguingly, the properties of the MOFs can be
easily modified, but minor changes in the synthetic process,
linker or the metal often lead to the dramatic changes in their
structure and properties.3
One possible way to form chiral materials is utilizing privileged
chiral ligands like BINOL or BINAP in the construction of
MOFs.7 Thereby, amorphous solids are generally obtained and
control of the resulting topology and porosity is difficult.7,8 An
alternative strategy is the attachment of chiral auxiliaries to well-
known linkers, either by postsynthetic modification9 or by starting
from auxiliary substituted linkers in the first place. In the latter
case, the synthesis of MOFs with desired chemical inter-
actions, topology, and pore sizes seems to be within reach.3a
Herein we report the synthesis, structural characterization,
and separation performance of chiral modified UMCM-1
structure (Chir-UMCM-1). UMCM-1 (Zn4O(BTB)4/3(BDC))
was discovered by Matzger et al. and is a high surface area
mesoporous MOF which consists of 1,4-benzenedicarboxylate
(BDC) and benzene-1,3,5-tribenzoate (BTB) linkers.10 In the
Chir-UMCM-1 reported here, the BDC linker was replaced
with chiral auxiliary substituted BDC (ChirBDC).
a Westfalische Wilhelms-Universitat, NRW Graduate School of
Chemistry, Organisch-Chemisches Institut, Corrensstr. 40,
¨
¨
48149 Munster, Germany. E-mail: glorius@uni-muenster.de;
¨
Fax: +49 251 8333202; Tel: +49 251 8333248
b Department of Inorganic Chemistry, Dresden University of
Technology, Bergstr. 66, 01062 Dresden, Germany.
E-mail: Stefan.Kaskel@chemie.tu-dresden.de;
Fax: +49 351 46337287; Tel: +49 711 685 65590
c Institute of Chemical Technology, University of Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany.
For the ChirBDC linker synthesis, 2-bromoterephthalic acid
was converted into dimethyl 2-bromoterephthalate. This was
coupled with enantiopure chiral (S)-oxazolidinone (Evans
auxiliary)11 in the presence of CuI, K2CO3 and dimethylethylene
diamine in toluene. Chiral auxiliary substituted BDCs
were obtained by basic hydrolysis of the corresponding esters
(Scheme S1, ESIw). The linkers were used for the synthesis of
ChirMOFs.
E-mail: elias.klemm@itc.uni-stuttgart.de; Fax: +49 711 68564065;
Tel: +49 351 46334885
d Department of Bioanalytical Chemistry, Dresden University of
Technology, Bergstr. 66, 01062 Dresden, Germany.
E-mail: eike.brunner@tu-dresden.de; Fax: +49 351 463 37188;
Tel: +49 351 46332631
w Electronic supplementary information (ESI) available: Details of the
synthesis of Chir-BDC derivatives and MOFs, packing procedure and
details of HPLC measurements, details of crystallographic measurements;
1H and 13C NMR spectra, XRD patterns, N2 and H2 physisorption
isotherms. CCDC 831931 and 831930. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c1cc14893a
We modified the ratio of reagents and reaction conditions of
the original UMCM-1 synthesis procedure in order to prevent
c
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Chem. Commun., 2011, 47, 12089–12091 12089

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the formation of chiral MOF-5 analogue or MOF-177
(for more details see ESIw).
framework and/or minor temperature-induced structural
changes. Thermal motions lead to decreasing signal intensities
in CP spectra. The aforementioned signals due to the chiral
side groups are weak at room temperature but become more
intense at ꢀ26 1C. This behavior indicates the presence of
thermal motions especially for the side groups.
Thus, Zn4O(BTB)4/3(iPr-ChirBDC)(DEF)19(H2O)6 (iPr-Chir-
UMCM-1, 1) and Zn4O(BTB)4/3(Bn-ChirBDC)(DEF)20(H2O)8
(Bn-ChirUMCM-1, 2) were obtained as single phase materials
(the composition was derived from TGA and elemental analysis).
The powder (Fig. S1, ESIw) and single crystal X-ray diffraction
experiments revealed that the compounds are isotypic to
UMCM-1. The structures of 1 and 2 were refined in chiral
space group P63 with similar cell parameters.z This led to the
absence of an inversion center, which is present in UMCM-1
at the center of gravity of the BDC linker. The structures of
both compounds consist of Zn4O6+ clusters interconnected
into the 3D-network by 4 BTB and 2 substituted BDC linkers.
As expected, the framework structure, topology and pore
shape of Chir-UMCMs are similar to UMCM-1.10 Compound
1 exhibits positional disorder of the BDC oxazolidinone
substituent over two equally occupied positions, arranged on
the same side of the phenyl ring. Refinement of structure 2
shows disorder of the nitrogen atom of the oxazolidinone over
four positions. Unfortunately, only the nitrogen atom and not
the chiral substituent itself could be located crystallographically.
Hence, they were modelled separately for each position using
Forcite geometry optimization tool of Material Studio 5.0
(Accelrys Software, Inc., San Diego, CA, USA). It has been
shown that in both cases chiral substituents occupy the positions
in the trigonal microporous cages (Fig. 1). The successful
incorporation of the substituted BDC linker was proven via
IR, liquid and solid state NMR experiments (see ESIw).
The 13C{1H} cross-polarization (CP) MAS NMR spectra of
compounds 1 (iPr-ChirUMCM-1) and 2 (Bn-ChirUMCM-1)
were measured at ꢀ26 1C (Fig. S19, ESIw). At this temperature,
the signals due to the chiral side groups are clearly detectable
in contrast to the room temperature spectra (Fig. S19, ESIw).
It should be noted that the spectra in general exhibit a
pronounced temperature dependence which may be caused
by the presence of thermal motions within the relatively flexible
Solvent accessible voids, calculated using PLATON,12 are
79.4 and 78.2% for compounds 1 and 2, respectively, which
are slightly lower than for non-substituted UMCM-1 (82.8%).
The porous chiral framework could be also obtained after
solvent removal. The porosity of the activated compounds was
verified via nitrogen and hydrogen (Fig. S3, ESIw) physisorption
experiments. The multipoint BET surface areas calculated
from nitrogen physisorption measurements at ꢀ196 1C are
3310 m2gꢀ1 for 2 and 3770 m2gꢀ1 for 1. The pore volumes are
1.78 cm3 gꢀ1 and 2.03 cm3 ꢀ1, respectively. The hydrogen
g
adsorption capacities are 1.48 wt% for 1 and 1.21 wt% for 2 at
1 bar and ꢀ196 1C.
The Bn-ChirUMCM-1 was tested as the stationary phase
for the HPLC column. Particles with spherical shape of less
than 100 mm and a narrow particle size distribution are
important requirements for a good stationary phase of high
performance liquid chromatography. Since the as-synthesized
particles are much too large and needle-shaped, they were
manually pestled (Fig. S20, ESIw). Fractionation could not be
performed, because of the limited amount of the samples.
Unfortunately, the crushing process gives a broad particle size
and shape distribution (estimated from the SEM image,
Fig. S20, ESIw), which seems not to be easily reproducible.
Nevertheless, to control the packing quality, the pressure drop
of the columns was measured after the packing procedure with
a flow of 0.5 ml minꢀ1 n-heptane at 30 1C. Tests for the
stability of the MOF were made by dispersing the Bn-Chir-
UMCM-1 in isopropanol. From the XRD (Fig. S2, ESIw) it
can be seen that the crystal structure of the material retains. To
guarantee the same packing quality, only Bn-ChirUMCM-1
columns are used which have pressure drops between 25 and
30 bar. All other columns have been rejected. For the comparison
between the UMCM-1 column and the Bn-ChirUMCM-1
column, a more densely packed unmodified UMCM-1 column
with a pressure drop of 70 bar was used.
Thus, shorter retention times on the unmodified UMCM-1
column cannot be caused by an inferior packing quality but
must be caused by the linker modification with the chiral
auxiliary.
Since the chiral auxiliary group of the Bn-ChirUMCM-1 is
a (4S)-benzyl-2-oxazolidinone, oxazolidinones were chosen as
appropriate analytes in the first attempt. Indeed one can
clearly see a selective interaction with the selector, because
on the unmodified UMCM-1 column no retention was observed,
whereas on the chirally modified UMCM-1 a significant
retention occurs. Unfortunately, we could not find an enantio-
selective interaction on the chirally modified UMCM-1
(see Table S2, ESIw). Probably, the difference in the free
adsorption enthalpies of the enantiomers is too small to
observe enantioseparation on that short column. Thus, we
decided to choose analytes expecting a stronger interaction
with the chiral selector by hydrogen bonding. Therefore,
2-butanol, as a representative of a chiral aliphatic alcohol,
Fig. 1 (a) Structure of iPr-ChirUMCM-1 (1). (b) Structure of
Bn-ChirUMCM-1 (2). Left: view along the c axis; Right: micropore
containing the chiral fragment (only one position is shown for
disordered oxazolidinone groups). Hydrogen atoms are omitted for
clarity.
c
12090 Chem. Commun., 2011, 47, 12089–12091
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measurements and the HZB for financing the travel costs to
BESSY II.
Notes and references
z Crystal data for 1: C50H32NO15Zn4, M = 1148.25, hexagonal, a =
41.459(6), c = 17.561(4) A, V = 26140(7) A3, T = 293 K, space group
P63, Z = 6, 80 884 reflections measured, 28 147 unique (Rint =
0.0501). The final R1 was 0.0532 and wR2 was 0.1181 (all data). 2:
C54H30NO15Zn4, M = 1194.27, hexagonal, a = 41.414(6), c =
17.637(3) A, V = 26197(7) A3, T = 293 K, space group P63, Z =
6, 83 244 reflections measured, 28 628 unique (Rint = 0.0354). The final
R1 was 0.0533 and wR2 was 0.1115 (all data).
CCDC 831931 and CCDC 831930 contain the supplementary
crystallographic data for 1 and 2, respectively.
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Fig. 2 Chromatogram of 1-phenylethanol enantiomers using Bn-
ChirUMCM-1.
and 1-phenylethanol, as a representative of a chiral aromatic
alcohol, were tested. Both showed a significant selective
interaction with the chiral column compared to the non-
modified column (see Table S2, ESIw).
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selective interactions with the chiral selector can be found
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modified Bn-ChirUMCM-1 column (for results on the unmodified
UMCM-1 see Fig. S21, ESIw). The selectivity a and the
resolution RS for the enantiomer separation can be calculated
as 1.6 and 0.65, respectively. The resolution of less than 1
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efficiency, the length of the column must be adapted and/or a
gradient elution is necessary.
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The use of 1-phenylethylamine as a 1-phenylethanol analogue
with an amino-function instead of the hydroxyl-function was
not successful, because the interactions were too strong
already even with the unmodified UMCM-1. The same holds
true for the amino acid D,L-alanine.
After around 200 injections the column material was
characterized by nitrogen adsorption and PXRD. No significant
changes were detected.
In summary, we have prepared and characterized two
porous chiral metal–organic frameworks (iPr-ChirUMCM-1
and Bn-ChirUMCM-1). Bn-ChirUMCM-1 was successfully
used as the stationary phase for HPLC applications. Namely,
1-phenylethanol as analyte showed both selective and enantio-
selective interactions with the MOF. The potential for enantio-
separation can be clearly seen from the selectivity, which is
high enough to reach enantiomer separation. However, the
resolution was too low to reach peak separation under the
chosen conditions. The results presented herein are promising
for the proof of principle and in the future these valuable chiral
materials should be useful for the separation of enantiomers in
the liquid phase.
The authors thank the German Research Foundation with-
in the priority program ‘‘Porous MOFs’’ (SPP 1362) for
financial support. The authors are grateful to the BESSY staff
(Dr U. Mueller, Dr M. S. Weiss) for support during the
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 12089–12091 12091