Missing Linker Defects in a Homochiral Metal-Organic Framework: Tuning the Chiral Separation Capacity

Article abstract of DOI:10.1021/jacs.7b10112

Efficient chiral separation remains a very challenging task due to the identical physical and chemical properties of the enantiomers of a molecule. Enantiomers only behave differently from each other in the presence of other chiral species. Homochiral metal-organic frameworks (MOFs) have received much attention for their promising enantioseparation properties. However, there are still challenges to overcome in this field such as high enantiomeric separation. Structural defects play an important role in the properties of MOFs and can significantly change the pore architecture. In this work, we introduced missing linker defects into a homochiral metal-organic framework [Zn₂(bdc)(l-lac)(dmf)] (ZnBLD; bdc = 1,4-benzenedicarboxylic acid, l-lac = l-lactic acid, dmf = N,N′-dimethylformamide) and observed an increase in enantiomeric excess for 1-phenylethanol of 35% with the defective frameworks. We adjusted the concentration of monocarboxylic acid ligand l-lactic acid by varying the ratio of Zn²⁺ to ligand from 0.5 to 0.85 mmol. Additionally, a defective framework was synthesized with propanoic acid as modulator. In order to elucidate the correlation between defects and enantiomeric excess, five characterization techniques (FTIR, TGA, ¹H NMR, ICP, and PXRD) were employed. Full width at half-maximum analysis (fwhm) was performed on the powder X-ray diffraction traces and showed that the higher concentration of monocarboxylic acid MOFs were isostructural but suffered from increased fwhm values.

Full text of DOI:10.1021/jacs.7b10112

Subscriber access provided by UniSA Library
Article
Missing Linker Defects in a Homochiral Metal Organic
Framework: Tuning the Chiral Separation Capacity
Benjamin Slater, Zeru Wang, Shanxue Jiang, Matthew R Hill, and Bradley P Ladewig
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b10112 • Publication Date (Web): 27 Nov 2017
Downloaded from http://pubs.acs.org on November 28, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 8
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Missing Linker Defects in a Homochiral Metal Organic Framework:
Tuning the Chiral Separation Capacity
,†,§ ‡
†,§
†
‡
†
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Benjamin Slater
Zeru Wang, Shanxue Jiang, Matthew R. Hill, Bradley P. Ladewig*, .
†Barrer Centre, Department of Chemical Engineering, Imperial College London, United Kingdom
CSIRO, Private Bag 10, Clayton South MDC, Victoria 3169, Australia
‡
KEYWORDS: chiral separation, homochiral metal organic framework, missing linker defects, ZnBLD
ABSTRACT: Efficient chiral separation remains a very challenging task due to the identical physical and chemical prop-
erties of the enantiomers of a molecule. Enantiomers only behave differently from each other in the presence of other
chiral species. Homochiral metal organic frameworks have received much attention for their promising enantioseparation
properties. However, there are still challenges to overcome in this field such as high enantiomeric separation. Structural
defects play an important role in the properties of MOFs and can significantly change the pore architecture. In this work,
we introduced missing linker defects into a homochiral metal organic framework [Zn2(bdc)(L-lac)(dmf)] (ZnBLD) and
observed an increase in enantiomeric excess for 1-phenylethanol of 35% with the defective frameworks. We adjusted the
2+
concentration of monocarboxylic acid ligand L-lactic acid by varying the ratio of Zn to ligand from 0.5 to 0.85mmol. Ad-
ditionally, a defective framework was synthesized with propanoic acid as modulator. In order to elucidate the correlation
1
between defects and enantiomeric excess, five characterization techniques (FTIR, TGA, H NMR, ICP and PXRD) were
employed. Full width at half maximum analysis (FWHM) was performed on the powder x-ray diffraction traces and
showed that the higher concentration of monocarboxylic acid MOFs were isostructural but suffered from increased
FWHM values.
A promising homochiral MOF, ZnBLD [Zn (bdc)(L-
2
.
lac)(dmf)] (DMF) (bdc = 1,4-benzenedicarboxylic acid, L-
lac = L-lactic acid, dmf=N,N’-dimethylformamide) has
INTRODUCTION
drawn much attention for enantioselective separation of
8
racemic mixtures, such as chiral alcohols, and alkyl aryl
Separation of racemic chemicals plays a significant role
in pharmaceutical development, as a result of different
pharmacological and toxicological properties of enantio-
mers. Because of some shortcomings such as high price
and low efficiency of conventional methods (e.g., chroma-
3d
sulfoxides, observing enantiomeric excess (ee%) values
of up to 21% and 27%, respectively. ZnBLD is synthesized
from zinc nitrate, 1,4-benzenedicarboxylate and L-lactic
2
d
acid in a 1:0.5:0.5 ratio.
1
tography) for chiral resolution. Metal organic frameworks
Recent research has focused on defect engineering of
MOFs and readers are directed to two thorough reviews
(
MOFs), a class of crystalline porous material have proven
9
to be an excellent candidate for enantiomeric separa-
on this subject. Fang et al. defined defects as “sites that
2
tions, amongst other promising applications like cataly-
locally break the regular periodic arrangement of atoms
or ions of the static crystalline parent framework because
of missing or dislocated atoms or ions”. Similarly, Sholl
and Lively very broadly defined defects as “any deviations
from an ideally ordered crystal structure”. An interesting
class of defects contain missing linkers which have been
3
4
5
sis, drug delivery, and gas separation, due to their high
porosity and highly tunable structure. Host-guest interac-
tions between the framework and guest molecules can
vary dramatically with the changing size of guest mole-
cules, having profound implications on the observed en-
antiomeric excesses. This was demonstrated with the sep-
aration of racemic methyl and ethyl lactate, where the
extra carbon caused the enantiomeric excess to drop from
1
0
appropriately named as missing linker defects. Modulat-
ed synthesis is the intentional addition of missing linker
defects into MOFs and allows researchers to tune a MOF’s
properties by partially substituting multi-coordinating
bridging linker ligands such as 1,4-benzenedicarboxylate
6
65.8% to 14.9%. Similarly a homochiral hydrogen bonded
framework showed dramatic decreases in enantiomeric
excess from 2-butanol (77%ee) to 2-heptanol (<4%ee).
7
11
with non-bridging ligands such as acetic acid. This tech-
nique can significantly change the pore architecture and
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 8
properties. Defective UiO-66 has been thoroughly inves-
tigated and defective frameworks have benefitted from
without further purification and purchased from com-
mercial sources as follows: terephthalic acid (H2bdc, Al-
drich, 98%), zinc nitrate hexahydrate (Zn(NO3)2·6H2O,
Alfa Aesar, 98%), L-(+)-lactic acid (L-lac, C3H6O3, Al-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
1a, 12
higher porosity and BET surface areas,
increased cata-
thermomechanical
1
3
lytic
activity,
and
tunable
1
4
properties.
drich,
98%),
1-phenylethanol
(1PhEtOH,
C6H5CH(OH)CH3, Aldrich, 98%), propanoic acid
(CH3CH3COOH, VWR), DL-α-Hydroxy-β,β-dimethyl-γ-
butyrolactone (pantolactone, C6H10O3, Aldrich, 98%),
dimethylformamide (DMF, VWR), diethyl ether
((CH3CH2)2O, VWR), dichloromethane (DCM, VWR),
acetonitrile (H3CCN, VWR), dimethyl sulfoxide-d6
Inspired by recent work on defect engineering of metal
organic frameworks, we investigated the influence miss-
ing linker defects have on the enantioseparation proper-
ties of ZnBLD. By synthesizing a series of ZnBLD MOFs
with varying concentrations of monocarboxylic acid (see
Scheme 1). L-lactic acid and propanoic acid were used as
modulators. We correlate defect concentration with en-
antioselective capacity. All frameworks were character-
ized by Fourier-transform infrared spectroscopy (FTIR),
powder x-ray diffraction (PXRD), Zn analysis by induc-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
%
DMSO-D6, Merck, 99.8%), conc HCl (HCl, VWR, 37 wt.
).
Synthesis of ZnBLD with a range of lactate con-
centration. ZnBLD was synthesized by adapting the pre-
1
2d
tively coupled plasma (ICP), H nuclear magnetic reso-
viously reported procedure. Briefly, zinc nitrate hexahy-
1
nance (after MOF digestion) ( H NMR) and thermogravi-
drate, terephthalic acid and L-lactic acid in varying molar
quantities (Scheme 1) was dissolved in 10 mL DMF per 1
mmol zinc nitrate hexahydrate. This solution was heated
in a Teflon lined stainless steel reaction vessel at 110 °C for
48 hours. After cooling to room temperature, the crystals
were filtered under reduced pressure, washed with DMF
metric analysis (TGA) (unless otherwise stated). The sep-
aration capacity for three chiral molecules 1-
phenylethanol, pantolactone and 2-butanol were deter-
mined by chiral gas chromatography (GC). Additionally,
two different crystal washing methods were compared,
DMF washing or DMF and Et O washing respectively (See
and for the Et O washed MOFs, an additional diethyl
2
2
Scheme S1). Samples were used without prior activation
as is common with gas applications, taking advantage of
ether wash was completed before the crystals were dried
under reduced pressure.
1
5
the dynamic process of chiral recognition. There was a
significant difference in the chiral separation capacity
between the two washing techniques for the separation of
Synthesis of ZnBLD-Propanoic acid. ZnBLD-
Propanoic acid modulated MOF was prepared similarly to
0
.5Lac except 0.35 mmol of propanoic acid was added to
1
-phenylethanol. By tailoring the pore architecture, our
the reaction mixture before transferring to the high-
pressure reactor. After adding propanoic acid, identical
conditions were used for heating and crystal treat-
ment/washing procedure. Rod-like crystals were obtained
which are characteristic of the ZnBLD phase.
separation performance is significantly higher than the
8
2
1ee% previously reported for 1-phenylethanol. Frame-
works were named based on the molar ratio of L-lactic
acid or propanoic acid followed by an abbreviation de-
picting the monocarboxylic acid used (Lac=L-lactic acid,
Prop=propanoic acid) followed by a suffix indicating
which washing technique was used (not included in
Scheme 1 sample names) DMF (only DMF washed) or
Et O (DMF and Et O washed).
Characterization. FTIR spectra were recorded on a
Perkin-Elmer, model Spectrum-100 a, 1H NMR spectra
were recorded on a Bruker Av500MHz solution state
2
2
EXPERIMENTAL SECTION
Material and Synthesis. All chemicals were used
Scheme 1. Compositions of the ZnBLD Synthesis.
ACS Paragon Plus Environment

Page 3 of 8
Journal of the American Chemical Society
spectrometer, integrals were calculated in Mestrenova
see Figure S33 for peak characterization). PXRD traces
50 °C for 5 minutes, ramp at 5°C/min to 200 °C, FID at 210
°C, carrier gas helium 60 cm/sec.
1
2
3
4
5
6
7
8
9
(
were recorded on a PANalytical X-Pert Pro MPD X-ray
diffractometer. TGA analyses were recorded on a TA In-
struments TGA Q500 whilst thermogravimetric analysis-
mass spectrometry (TGA-MS) traces were recorded on a
Metler Toledo TGA coupled with a Hiden Analytical
HPR20-QIC evolved gas mass spectrometer, both TGA
and TGA-MS samples were heated in a nitrogen atmos-
phere at 10°C/min from 30°C to 900°C. GC chromato-
graphs were recorded on a Shimadzu 2010plus gas chro-
matograph fitted with an autosampler and a flame ioniza-
tion detector (FID). Inductively coupled plasma meas-
urements were recorded on a Perkin Elmer Optima 2000
DV.
Enantiomeric Excess (ee%). Each sample was injected
three times and the standard deviation was used to calcu-
late error bars. The separation capacity was evaluated by
calculating the ee% value, comparing peak areas of each
enantiomer according to Eq. (1). Where, S is the fraction
of S isomer and R is the fraction of R isomer. When ap-
plied to gas chromatography, the area of each peak is
used.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ꢃ ꢄ ꢅ
ꢀꢀ% ꢁ ꢂ
ꢇ ꢈ 100%ꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢊ1ꢋ
ꢃ ꢆ ꢅ
RESULTS AND DISCUSSION
1
H NMR spectra were recorded and used to determine
1
1
H NMR digestion sample preparation. H NMR pro-
the relative concentration of L-lactic acid, terephthalic
acid and DMF in the frameworks by integration of select-
ed peaks (see S5 for further details). The expected ratio of
0.85:0.5 of L-lactic acid: terephthalic acid was not ob-
served for 0.85Lac. Instead there was a slight increase
from 0.5Lac to 0.85Lac (Figure 1a). We attributed this to
missing terephthalate linkers in the framework and calcu-
lated that there were 1 in 20 missing terephthalate linkers
cedure: DMSO-D6 (0.6 mL) was added as a deuterated
digestion medium to 30mg of MOF crystals, subsequently
concentrated HCL was added dropwise until all the mate-
rial dissolved.
Powder X-ray Diffraction measurements. MOF ma-
terial (around 30 mg) was ground to a homogeneous
powder in a ceramic mortar and pestle. Powder traces
were recorded with 40 kV generator voltage, 20mA tube
current, with Cu Kα radiation at 293K. A scan step size of
1
1a
in 0.85Lac. 0.35Prop did not contain a higher concentra-
tion of lactic acid, as expected, instead a small amount of
propanoic acid was detected for 0.35Prop, there was some
0
.00835 2θ degree with a scan range from 4 to 50 2θ de-
gree was used. Further, the FWHM was calculated in
Origin Pro using the Peaks and Baseline function (See
S6).
Procedure for chiral adsorption. 0.010 g of ZnBLD
was placed in a glass vial and either 0.1 mL of racemic 1-
phenylethanol or 2-butanol was added or 1ml of 100mg/ml
racemic pantolactone in acetonitrile. Samples were left
for 24 hours at room temperature. Each sample was pre-
pared in triplicate.
Procedure for chiral desorption. ZnBLD and the 1-
phenylethanol/2-butanol/pantolactone solution was fil-
tered under reduced pressure and lightly washed with
DCM to remove residue on the surface of the crystal. Af-
ter drying for a few minutes, the crystals were collected
and transferred to a glass vial, 0.8 mL of DCM was added
to desorb guest molecules. After 24 hours at room tem-
perature, 0.4 mL of supernatant was taken from each vial
and analyzed by chiral gas chromatography.
Chiral Gas Chromatography. All analytes were sepa-
rated on a Supelco Beta Dex 120 capillary column. The
conditions for 1-phenylethanol were as follows: Injection;
1
µL split ratio of 100:1, injection port temperature: 200 °C,
column isothermal at 120 °C for 28 minutes, ramped at 10
C/min to 170 °C holding for 6 minutes (post elution of
°
both enantiomers), FID at 210 °C, carrier gas of helium 20
cm/sec. 2-butanol; Injection; 1 µL split ratio: 100:1, injec-
tion port temperature: 200 °C, column temperature iso-
thermal at 30°C for 44 minutes, ramp at 10 °C/min to 170
°
C holding for 6 minutes (post elution of both enantio-
mers), FID at 210 °C, helium carrier gas 15 cm/sec. Panto-
lactone, : Injection; 1 µL split ratio: 50:1, injection port
temperature: 250 °C, column temperature isothermal at
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 8
1
Figure 1. H NMR integral data: (a) comparing peak area ratio
of L-lactic acid: terephthalic acid with molar concentration of
monocarboxylic acid, (b) comparing peak area ratio of DMF:
terephthalic acid and molar ratio of monocarboxylic acid.
Gaussian shape profile fitted for 0.5-0.85LacDMF and
0.35PropDMF.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
PXRD traces (Figure 2a) were highly crystalline and the
increase in defect concentration did not have an effect in
peak positions or relative intensities. A secondary phase
could be assigned to Zn(bdc)·xH2O (8.6 2θ degree) from
partial hydrolysis of the framework. This has been previ-
overlap with other peaks and therefore the propanoic acid
concentration could not be determined accurately. ICP
analysis also confirmed higher Zn content for the defec-
tive frameworks, (see S8 and table S1 for details). Addi-
tionally, an increase in DMF concentration was observed
from 0.5Lac to 0.85Lac frameworks. As there is no differ-
ence in the MOF structure we can describe this increase
in DMF as an increase in porosity of the framework as
solvated guest molecules. The DMF: terephthalic acid
ratio of 0.35Prop and 0.85Lac were very similar and over-
lap in Figure 1b indicating that the enhanced porosity was
present in 0.35Prop MOFs. An increase in porosity can be
expected with increasing missing linker defect concentra-
tion as the total void space increases with monocarboxylic
acid replacement. Increased porosity has been correlated
16
ously reported in MOF-5 PXRD traces. Unfortunately
this peak overlapped with the 011 peak from the ZnBLD
phase. In order to confirm higher defect concentrations
with increasing monocarboxylic acid concentration, we
compared full width at half maxima (FWHM) values.
FWHM is inversely proportional to crystallite size which
can be described by the Scherrer Eq. (2). Crystallite size is
inversely proportional to the defect concentration in crys-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
7
talline solids, therefore the FWHM is proportional to the
defect concentration for a PXRD trace.
ꢐꢑ
ꢌꢍꢎꢏ ꢁ
ꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢉꢊ2ꢋ
ꢒ cos ꢓ
1
0a, 11a
with missing linker defects in several studies.
Frame-
Where:
works also contained varying amounts of formate, gener-
ated by DMF hydrolysis, however there was no correla-
tion between formate concentration and ee% or defect
concentration (See Figure S33) therefore we discounted
FWHM is in radians, K is the Scherrer constant (a di-
mensionless number near 0.9), is the wavelength of the
radiation (in this case, ), is the grain size (nm) and pre-
sents Bragg angle (in degrees).
this
as
insignificant.
Diffraction peaks were selected to calculate the FWHM
using a Gaussian function fit profile (Peak Analyzer,
OriginPro 2016) (See S6). Figure 2b shows how FWHM for
the 004 peak varies with increasing molar ratio of L-lactic
acid, 0.35PropDMF and 0.85LacDMF overlap for the 004
peak (see Figure S48 for all peak FWHM values). For all
diffraction peaks, there was an increase in FWHM with
increasing molar ratio of L-lactic acid. The increase in
FWHM contributes to our overall hypothesis that the
frameworks synthesized with higher concentrations of
monocarboxylic acid are more defective.
TGA traces were recorded for 0.5LacDMF, 0.5LacEt O,
2
0
0
.85LacDMF,
0.85LacEt O,
0.35PropDMF
and
2
.35PropEt O to investigate the thermal stability and
2
weight losses of the various frameworks. Figure 3 shows
TGA traces for 0.5LacEt O and 0.85LacEt O (See S7 for all
2
2
other TGA traces recorded). The weight loss below 200°C
was attributed to guest molecule removal of DMF, this
confirmed higher proportions of DMF were present in the
more defective MOFs. No difference in stability was ob-
served for the defective and non-defective frameworks.
Through TGA-MS experiments we did not observe mono-
carboxylic acid removal of lactic acid between 200 and
1
1a
1
3
50°C. As expected from H NMR digestion experiments,
the more defective MOFs have higher weight losses below
200°C.
For the 1-phenylethanol separation (Figure 4a), our re-
sults show a steady increase in ee% from 0.5Lac to 0.85Lac
where we observed a plateau in ee%. For 1Lac, the charac-
teristic needle like crystals of ZnBLD (See Image S1) were
not obtained and there was poor adsorption of 1-
phenylethanol and no enantioseparation. The largest ee%
increase of over 35% was observed from 0.5LacDMF to
0.85LacDMF. DMF washing proved to be superior to DMF
Figure 2. Powder diffraction patterns of (a) as-synthesized
MOFs in this study. (b) the FWHM of (004) peak with a
ACS Paragon Plus Environment

Page 5 of 8
Journal of the American Chemical Society
and Et O washing for the separation of 1-phenylethanol.
2
1
2
3
4
5
6
7
8
9
The solvation of the framework plays an essential role in
the success of the separation. DMF has also been shown
to play a critical role for enantioseparation in two other
homochiral MOF studies where the coordinated DMF
8
,
carbons interact with the OH groups of 1-phenylethano.
1
8
Our results indicate that solvated DMF molecules can
enhance the enantioseparation. For 2-butanol and panto-
lactone (Figure 4b, 4c) there was little to no change in
ee% between the different washing techniques indicating
that partial removal of solvated DMF did not have nega-
tive consequences for all separation processes although it
appears to be a redundant step in the synthesis.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 3. TGA traces (solid lines, left axis) of 0.5LacEt O and
2
0.85LacEt O. TGA-MS trace of 0.5LacEt O, dashed line, right
2
2
axis.
Additionally, there was no change in the separation ca-
pacity for 2-butanol and pantolactone between the non-
defective and defective frameworks. We rationalise that
the selectivity increases for 1-phenylethanol, the largest
molecule we separated because the introduction of miss-
ing linker defects increases the pore size for some pores
and allows for enhanced separation capacities due to a
subtle change in host-guest interactions (See S9 for calcu-
lated area of all test molecules).
Figure 5 shows the correlation between DMF concen-
tration and ee% for 1-phenylethanol. There is a clear trend
between DMF concentration and ee% for both DMF and
Et O washed frameworks. The 0.35Prop MOFs also follow
2
the trend for both washing techniques. This highlights
the correlation between framework porosity and separa-
tion capacity.
Figure 4. Enantioselective capacity: (a) 1-phenylethanol sorp-
tion for 0.5Lac to 0.95Lac and 0.35Prop: enhancement in ee%
value as a function of increasing monocarboxylic acid con-
centration with different washing techniques. (b) 2-butanol
sorption experiment for the 0.5Lac, 0.85Lac and 0.35Prop
series. (c) pantolactone sorption experiment for the 0.5Lac,
0.85Lac and 0.35Prop series.
ACS Paragon Plus Environment

Journal of the American Chemical Society
ACKNOWLEDGMENT
Page 6 of 8
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
BS
acknowledges The Commonwealth Scientific
and Industrial Research Organization and Imperial College
London for financial support. ZW acknowledges the China
Scholarship Council for financial support. Dr Lisa Haigh and
Peter Haycock are acknowledged for their assistance with
mass spectrometry and NMR spectroscopy respectively. Ad-
ditionally,
we would like to thank Diamond Light Source for
access to B23 (CM16778) and Prof Giuliano Siligardi and Dr
Rohanah Hussain for their time and effort measuring and
analysing circular dichroism spectra.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
REFERENCES
(
1) Chankvetadze, B.; Chankvetadze, L.; Sidamonidze, S.;
Yashima, E.; Okamoto, Y. J. Pharm. Biomed. Anal. 1996, 14, 1295.
2) (a) Zhang, J.; Li, Z.; Gong, W.; Han, X.; Liu, Y.; Cui, Y.
(
Figure 5. An overlay of Figures 1b and 4a, showing the corre-
lation between DMF concentration (from H NMR digestion
data) of the monocarboxylic acid modulated frameworks and
enantiomeric excess for 1-phenylethanol.
1
Inorg. Chem. 2016, 55, 7229 (b) Zhang, S.-Y.; Wojtas, L.;
Zaworotko, M. J. J. Am. Chem. Soc. 2015, 137, 12045 (c) Chang, C.
L.; Qi, X. Y.; Zhang, J. W.; Qiu, Y. M.; Li, X. J.; Wang, X.; Bai, Y.;
Sun, J. L.; Liu, H. W. Chem. Commun. 2015, 51, 3566 (d) Dybtsev,
D. N.; Nuzhdin, A. L.; Chun, H.; Bryliakov, K. P.; Talsi, E. P.;
Fedin, V. P.; Kim, K. Angew. Chem. Int. Ed. 2006, 45, 916 (e) Gu,
Z. G.; Grosjean, S.; Bräse, S.; Wöll, C.; Heinke, L. Chem.
Commun. 2015, 51, 8998.
(3) (a) Lee, J.; Farha, O. K.; Roberts, J.; Scheidt, K. A.; Nguyen,
S. T.; Hupp, J. T. Chem. Soc. Rev. 2009, 38, 1450 (b) Gole, B.;
Sanyal, U.; Banerjee, R.; Mukherjee, P. S. Inorg. Chem. 2016, 55,
2345 (c) Luque, R.; Li, Y. Chemical Science 2014, 5, 3708 (d)
Nuzhdin, A. L.; Dybtsev, D. N.; Bryliakov, K. P.; Talsi, E. P.;
Fedin, V. P. J. Am. Chem. Soc. 2007, 129, 12958.
CONCLUSIONS
In summary, we have shown for the first time how the
enantioselective properties of a MOF can be enhanced by
introducing missing linker defects. An increase in enanti-
omeric separation was observed with increasing defect
concentration for 1-phenylethanol. No increase in separa-
1
tion was observed for 2-butanol or pantolactone. H NMR
digestion data supports missing terephthalate linker de-
fects and as expected this gives a slightly higher porosity
(higher DMF: terephthalic acid ratio), a higher proportion
of DMF is also observed in TGA traces for the more defec-
tive MOFs. We cannot conclude that a higher porosity is
responsible for an increase in enantiomeric excess. In-
stead we describe the increased enantioselectivity as be-
ing caused by a larger pore size which provides a better fit
for the guest molecules of 1-phenylethanol, the smaller
guest molecules of 2-butanol and pantolactone do not
benefit from the enhanced separation due to the smaller
molecular area of these molecules. We hope that implica-
tions of our results significantly decrease the costs in-
volved for industrial applications of these materials, by
partially replacing expensive enantiopure ligands with
cheap alternatives such as propanoic acid.
(4) (a) Zheng, H.; Zhang, Y.; Liu, L.; Wan, W.; Guo, P.;
Nyström, A. M.; Zou, X. J. Am. Chem. Soc. 2016, 138, 962 (b) Ray
Chowdhuri, A.; Bhattacharya, D.; Sahu, S. K. Dalton Trans 2016,
45, 2963.
(5) (a) Spanopoulos, I.; Tsangarakis, C.; Klontzas, E.;
Tylianakis, E.; Froudakis, G.; Adil, K.; Belmabkhout, Y.;
Eddaoudi, M.; Trikalitis, P. N. J. Am. Chem. Soc. 2016, 138, 1568
(b) Zhang, M.; Li, B.; Li, Y.; Wang, Q.; Zhang, W.; Chen, B.; Li, S.;
Pan, Y.; You, X.; Bai, J. Chem. Commun. 2016, 52, 7241.
(6) Xu, Z. X.; Fu, H. R.; Wu, X.; Kang, Y.; Zhang, J. Chem. Eur.
J. 2015, 21, 10236.
(7) Li, P.; He, Y.; Guang, J.; Weng, L.; Zhao, J. C. G.; Xiang, S.;
Chen, B. J. Am. Chem. Soc. 2014, 136, 547.
(
8) Suh, K.; Yutkin, M. P.; Dybtsev, D. N.; Fedin, V. P.; Kim, K.
Chem. Commun. 2012, 48, 513.
9) (a) Fang, Z.; Bueken, B.; De Vos, D. E.; Fischer, R. A.
(
Angew. Chem. Int. Ed. 2015, 54, 7234 (b) Sholl, D. S.; Lively, R. P.
J. Phys. Chem. Lett. 2015, 6, 3437.
ASSOCIATED CONTENT
(10) (a) Wu, H.; Chua, Y. S.; Krungleviciute, V.; Tyagi, M.;
Supporting Information. Additional method details, mi-
croscope crystal image, GC chromatograms, FTIR spectra,
Calculation details for NMR spectra, methods for the calcula-
tion of FWHM from PXRD, TGA traces, ICP analysis details
and molecular area of test molecules are available in the sup-
porting information. This material is available free of charge
via the Internet at http://pubs.acs.org.
Chen, P.; Yildirim, T.; Zhou, W. J. Am. Chem. Soc. 2013, 135, 10525
(b) Gutov, O. V.; Hevia, M. G.; Escudero-Adán, E. C.; Shafir, A.
Inorg. Chem. 2015, 54, 8396 (c) Van de Voorde, B.; Stassen, I.;
Bueken, B.; Vermoortele, F.; De Vos, D.; Ameloot, R.; Tan, J.-C.;
Bennett, T. D. J. Mater. Chem. A 2015, 3, 1737.
(11) (a) Shearer, G. C.; Chavan, S.; Bordiga, S.; Svelle, S.;
Olsbye, U.; Lillerud, K. P. Chem. Mater. 2016, 28, 3749 (b)
Schaate, A.; Roy, P.; Godt, A.; Lippke, J.; Waltz, F.; Wiebcke, M.;
Behrens, P. Chem. Eur. J. 2011, 17, 6643 (c) Tsuruoka, T.;
Furukawa, S.; Takashima, Y.; Yoshida, K.; Isoda, S.; Kitagawa, S.
Angew. Chem. Int. Ed. 2009, 48, 4739 (d) Cliffe, M. J.; Castillo-
Martínez, E.; Wu, Y.; Lee, J.; Forse, A. C.; Firth, F. C. N.;
Moghadam, P. Z.; Fairen-Jimenez, D.; Gaultois, M. W.; Hill, J. A.;
Magdysyuk, O. V.; Slater, B.; Goodwin, A. L.; Grey, C. P. J. Am.
Chem. Soc. 2017, 139, 5397.
AUTHOR INFORMATION
Corresponding Author
*Bradley P. Ladewig b.ladewig@imperial.ac.uk
Author Contributions
§
BS and ZW contributed equally to this work
ACS Paragon Plus Environment

Page 7 of 8
Journal of the American Chemical Society
(
12) Hu, Z.; Peng, Y.; Kang, Z.; Qian, Y.; Zhao, D. Inorg. Chem.
2015, 54, 4862.
13) Vermoortele, F.; Bueken, B.; Le Bars, G.; Van de Voorde,
(16) Ravon, U.; Savonnet, M.; Aguado, S.; Domine, M. E.;
Janneau, E.; Farrusseng, D. Microporous Mesoporous Mater.
2010, 129, 319.
1
2
3
4
5
6
7
8
9
(
B.; Vandichel, M.; Houthoofd, K.; Vimont, A.; Daturi, M.;
Waroquier, M.; Van Speybroeck, V.; Kirschhock, C.; De Vos, D.
E. J. Am. Chem. Soc. 2013, 135, 11465.
(17) Baig, A. A.; Fox, J. L.; Young, R. A.; Wang, Z.; Hsu, J.;
Higuchi, W. I.; Chhettry, A.; Zhuang, H.; Otsuka, M. Calcif.
Tissue Int. 1999, 64, 437.
(18) Dybtsev, D. N.; Yutkin, M. P.; Samsonenko, D. G.; Fedin,
V. P.; Nuzhdin, A. L.; Bezrukov, A. A.; Bryliakov, K. P.; Talsi, E.
P.; Belosludov, R. V.; Mizuseki, H.; Kawazoe, Y.; Subbotin, O. S.;
Belosludov, V. R. Chem. Eur. J. 2010, 16, 10348.
(14) Cliffe, M. J.; Hill, J. A.; Murray, C. A.; Coudert, F.-X.;
Goodwin, A. L. Phys. Chem. Chem. Phys. 2015, 17, 11586.
(15) Navarro-Sánchez, J.; Argente-García, A. I.; Moliner-
Martínez, Y.; Roca-Sanjuán, D.; Antypov, D.; Campíns-Falcó, P.;
Rosseinsky, M. J.; Martí-Gastaldo, C. J. Am. Chem. Soc. 2017, 139,
4
294.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 8
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
8
ACS Paragon Plus Environment