Chiral Cd(II) coordination polymers based on amino acid derivatives: The effect of side chain on structure

Article abstract of DOI:10.1021/acs.cgd.0c00468

Homochiral coordination polymers have emerged as promising candidates for a range of chirotechnological applications, including asymmetric catalysis and enantioselective separation. The use of ligands derived from naturally occurring l-amino acids is an inexpensive and effective approach for generating a range of homochiral coordination polymers. To investigate the structure-directing effect of the amino acid side chain, seven homochiral Cd(II) frameworks were synthesized using semirigid dicarboxylates composed of l-amino acids appended to terephthalic acid (H2TMXxx, where Xxx = Ala, Val, Phe, Trp, Tyr, and His) and bis(4-pyridyl)ethylene coligands. When Xxx = Val, Tyr, Phe, or Trp, a series of 2D (4,4)-networks were obtained, in which the different intermolecular interactions of the side chains result in subtle changes in crystal packing. Employing Xxx = Ala or Tyr led to 3D frameworks with a {65·8} topology, in which the varying steric bulk of the side chains results in significant differences in framework geometry as well as the shape and volume of the solvent-accessible channels. When Xxx = His, the imidazole side chains coordinate to the metal center to direct the formation of a 3D pillared structure that undergoes 2-fold interpenetration.

Full text of DOI:10.1021/acs.cgd.0c00468

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Article
Chiral Cd(II) coordination polymers based on amino
acid derivatives: the effect of side chain on structure
Hui Min Tay, and Carol Hua
Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.0c00468 • Publication Date (Web): 21 Jul 2020
Downloaded from pubs.acs.org on August 3, 2020
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Chiral Cd(II) coordination polymers based on amino
acid derivatives: the effect of side chain on structure
Hui Min Tay and Carol Hua*
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School of Chemistry, The University of Melbourne, Parkville, Victoria, 3010, Australia. *E-mail:
carol.hua@unimelb.edu.au
Abstract
Homochiral coordination polymers have emerged as promising candidates for a range of
chirotechnological applications, including asymmetric catalysis and enantioselective separation.
The use of ligands derived from naturally occurring L-amino acids is an inexpensive and effective
approach to generate a range of homochiral coordination polymers. To investigate the structure-
directing effect of the amino acid side chain, seven homochiral Cd(II) frameworks were
synthesised using semi-rigid dicarboxylates composed of L-amino acids appended to terephthalic
acid (H2TMXxx, where Xxx = Ala, Val, Phe, Trp, Tyr and His) and bis(4-pyridyl)ethylene co-
ligands. When Xxx = Val, Tyr, Phe or Trp, a series of 2D (4,4)-networks were obtained, in which
the different intermolecular interactions of the side chains result in subtle changes in crystal
packing. Employing Xxx = Ala or Tyr led to 3D frameworks with a {65·8} topology, in which the
varying steric bulk of the side chains results in significant differences in framework geometry as
well as the shape and volume of the solvent-accessible channels. When Xxx = His, the imidazole
side chains coordinate to the metal centre to direct the formation of a 3D pillared structure that
undergoes two-fold interpenetration.
Introduction
Chirality is prevalent throughout nature, with most biologically important molecules, including
amino acids, nucleotides and sugars, occurring predominantly as a single enantiomer. The
enantiomers of a chiral molecule may interact differently with enzymes, receptors and other chiral
biomolecules, giving rise to different biological effects.1, 2 This behavior is exemplified in the two
enantiomers of dopamine; L-dopamine is used to treat Parkinson’s disease while D-dopamine
elicits neurotoxic side effects.3 Obtaining enantiomerically pure chiral molecules is therefore of
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great importance in the pharmaceutical industry, with nearly 50% of drugs on the market being
chiral molecules.4, 5 Motivated by the high demand for enantiopure drugs, significant research
effort has been devoted to developing methods for the preparation of chiral molecules.4, 6, 7
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Homochiral coordination polymers have emerged as a promising class of materials with various
applications in chirotechnology, including as asymmetric catalysts8-12 or chiral stationary phases
for the chromatographic separation of racemic mixtures.13-16 Frameworks containing large solvent-
accessible chiral pores are particularly promising as the environment in the pores can be altered
by changing the inorganic ions and chiral organic ligands, thereby tailoring the framework towards
specific chiral substrates.17 However, the large-scale preparation of homochiral frameworks in an
inexpensive and reproducible manner remains a considerable challenge.18 The use of enantiopure
organic linkers is currently the most direct and reliable method of introducing chirality into
frameworks, but this approach is synthetically demanding as the organic linkers used often require
multi-step syntheses with prohibitively low overall yields.19-22 Another approach involves
combining metal ions and achiral ligands in the presence of a chiral template in order to direct the
formation of a homochiral network.23-25 A major limitation of this approach, however, is the
difficulty of systematically predicting and controlling the enantiomeric excess of the reaction
products.
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A reliable and inexpensive strategy for preparing homochiral coordination polymers is to use
ligands derived from commercially available chiral molecules.26-28 The family of naturally-
occurring α-amino acids are promising candidates for chiral precursors as they are non-toxic,
inexpensive and can be readily obtained in high enantiopurity.29 The structural flexibility of α-
amino acids, which may hinder the formation of robust porous frameworks, can be reduced by
functionalisation with suitable rigid aromatic units.30-32 A straightforward implementation of this
strategy involves appending a benzoate group to the N-terminus of the amino acid, which can be
achieved in two synthetic steps to obtain semi-rigid terephthaloyl mono amino acid linkers
(H2TMXxx, Xxx = amino acid). Five homochiral frameworks, some of which contain significant
pore space (up to 2968 Å3 per unit cell or 36.2% of the crystal volume), have been constructed
using the alanine-derived ligand (H2TMAla),30 demonstrating the propensity of H2TMXxx linkers
to promote the formation of porous homochiral coordination polymers. The inclusion of rigid N-
donor co-ligands was used to further increase the dimensionality and porosity of the frameworks.
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The side chain of alanine consists of a single methyl group, making it the simplest of the 19 chiral
naturally-occurring α-amino acids. The other α-amino acids contain a variety of side chains
capable of participating in different intermolecular interactions, including hydrophobic
interactions, π-stacking, electrostatic interactions and metal coordination. The diversity of
functional groups available within the family of α-amino acids therefore offers opportunities for
tuning the structure and properties of the homochiral coordination polymers simply by changing
the amino acid precursor.
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To investigate the effect of varying the amino acid side chain on the structure of the resulting
coordination polymers, H2TMAla and five novel H2TMXxx ligands were synthesised using the
amino acid precursors: valine (Val), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp) and
histidine (His). Combining the H2TMXxx ligands with Cd(II) and the rigid dipyridyl bis(4-
pyridyl)ethylene (bpee) co-ligand yielded seven 2D and 3D homochiral coordination polymers.
Single-crystal X-ray diffraction studies on the coordination polymers revealed the important
structure-directing role of the amino acid side chains, which ranged from exerting a subtle
influence on the crystal packing to dramatically altering the dimensionality of the framework.
Experimental section
General Considerations
All chemicals and solvents were used as obtained and without further purification. Distilled
dichloromethane (dried over CaH2) was used in all experiments requiring anhydrous
dichloromethane.
NMR spectra (1H and 13C{1H}) were recorded on a Varian MR400 spectrometer operating at 400
MHz for 1H and 100 MHz for 13C. 1H and 13C chemical shifts were referenced internally to residual
solvent resonances. High resolution electrospray ionisation (ESI) mass spectra were acquired as
solution samples in a methanol/formic acid mixture or in acetonitrile (~1 ppm) on an Agilent 6520
Accurate-Mass Q-TOF spectrometer. Fourier Transform Infrared spectra were measured on a
Bruker Alpha spectrometer between 4000 – 400 cm−1 with 4 cm−1 resolution and 32 scans and
normalised as absorbance spectra. Thermal gravimetric analysis was conducted on a Mettler
Toledo TGA/SDTA851 instrument using aluminum crucibles as sample holders under high purity
nitrogen. Typical analysis involved heating the sample up to 450 °C with a temperature increment
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of 4 °C min−1. Microanalysis was carried out at the Chemical Analysis Facility – Elemental
Analysis Service in the Department of Chemistry and Biomolecular Science at Macquarie
University, Australia.
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Single crystal X-ray diffraction data was collected on a Rigaku Oxford Diffraction Synergy-S
diffractometer equipped with CuKα radiation or on the MX1 or MX2 beamline at the Australian
Synchrotron.33, 34 In general, single crystals were transferred directly from the mother liquor into
immersion oil and placed under a stream of nitrogen at 100 K or 240 K. Crystal structures were
solved by direct methods using the program SHELXT35 and refined using a full matrix least-
squares procedure based on F2 (SHEXL),36 within the Olex237 GUI program. In structures
containing disordered solvent molecules that could not be satisfactorily modelled, the solvent mask
routine in Olex2 was used.38
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Framework Synthesis
[Cd2(TMVal)2(bpee)2]·0.8DMF·3.9H2O (1). A solution of H2TMVal (8.0 mg, 0.03 mmol), bis(4-
pyridyl)ethylene (5.5 mg, 0.03 mmol) and Cd(NO3)2·4H2O (27.8 mg, 0.09 mmol) in DMF/H2O (3
mL, 1:1 v/v) was heated at 80 °C for 2 days. The reaction mixture was cooled to room temperature,
filtered and washed with 1:1 DMF/H2O (5 mL) to obtain colourless needles (12.9 mg, 64%). IR
(ATR): 3055, 2960, 2873, 1669, 1635, 1604, 1545, 1399, 1302, 1094, 1014, 985, 874, 832, 777,
661, 551, 472 cm−1. Elemental analysis (%): calcd for C52.8H59.4Cd2N6.8O14.7: C 50.76, H 4.79, N
7.62; found: C 50.58, H 4.77, N 7.66.
[Cd2(TMTyr)2(bpee)2]·1.6DMF·2.3H2O (2). A solution of H2TMTyr (9.9 mg, 0.03 mmol), bpee
(5.5 mg, 0.03 mmol) and Cd(NO3)2·4H2O (9.3 mg, 0.03 mmol) in DMF/H2O (3 mL, 1:2 v/v) was
heated at 80 °C for 7 days. The reaction mixture was cooled to room temperature, filtered and
washed with 1:1 DMF/H2O (5 mL) to obtain colourless needles (9.1 mg, 44%). IR (ATR): 3060,
2918, 1670, 1642, 1605, 1583, 1516, 1392, 1267, 1066, 1016, 979, 833, 736, 658, 550, 497 cm−1.
Elemental analysis (%): calcd for C62.8H58.8Cd2N7.6O15.9: C 53.91, H 4.24, N 7.61; found: C 53.92,
H 4.27, N 7.64.
[Cd4(TMPhe)4(bpee)4]·2.3DMF·6.4H2O (3). A solution of H2TMPhe (9.4 mg, 0.03 mmol), bpee
(5.5 mg, 0.03 mmol) and Cd(NO3)2·4H2O (9.3 mg, 0.03 mmol) in DMF/H2O (3 mL, 1:1 v/v) was
heated at 80 °C for 5 days. The reaction mixture was cooled to room temperature, filtered and
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washed with 1:1 DMF/H2O (5 mL) to obtain colourless needles (13.4 mg, 68%). IR (ATR): 3057,
2919, 1665, 1605, 1585, 1542, 1387, 1096, 1017, 832, 737, 700, 549, 499 cm−1. Elemental analysis
(%): calcd for C122.9H118.9Cd4N14.3O28.7: C 54.56, H 4.43, N 7.41; found: C 54.57, H 4.35, N 7.41.
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[Cd3(TMTrp)2(bpee)3(formate)2]·2.6DMF·7H2O (4). A solution of H2TMTrp (10.6 mg, 0.03
mmol), bis(4-pyridyl)ethylene (5.5 mg, 0.03 mmol), sodium formate (1.0 mg, 0.015 mmol) and
Cd(NO3)2·4H2O (9.3 mg, 0.03 mmol) in DMF/H2O (3 mL, 5:1 v/v) was heated at 80 °C for 5 days.
The reaction mixture was cooled to room temperature, filtered and washed with DMF (5 mL) to
obtain fine colourless needles (16.7 mg, 64%). IR (ATR): 3372, 3053, 2929, 1656, 1605, 1584,
1517, 1487, 1402, 1252, 1067, 1014, 972, 827, 741, 549 cm−1. Elemental analysis (%): calcd for
C83.9H88.3Cd3N12.6O23.6: C 50.69, H 4.48, N 8.88; found: C 50.65, H 4.61, N 8.89.
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[Cd4(TMAla)4(bpee)4]·2DMF·12.2H2O (5). A solution of H2TMAla (7.1 mg, 0.03 mmol), bis(4-
pyridyl)ethylene (5.5 mg, 0.03 mmol) and Cd(NO3)2·4H2O (9.3 mg, 0.03 mmol) in DMF/H2O (3
mL, 1:1 v/v) was heated at 80 °C for 5 days. The reaction mixture was cooled to room temperature,
filtered and washed with 1:1 DMF/H2O (5 mL) to obtain colourless octahedral blocks (7.1 mg,
38%). IR (ATR): 3360, 2923, 1649, 1603, 1585, 1534, 1390, 1284, 1067, 1012, 830, 806, 551
cm−1. Elemental analysis (%): calcd for C98H114.4Cd4N14O34.2: C 47.36, H 4.64, N 7.89; found: C
47.36, H 4.46, N 7.47.
[Cd2(TMTyr)2(bpee)2]·2DMF·7.7MeOH (6). A solution of H2TMTyr (9.9 mg, 0.03 mmol),
bis(4-pyridyl)ethylene (5.5 mg, 0.03 mmol) and Cd(NO3)2·4H2O (9.3 mg, 0.03 mmol) in
DMF/MeOH (3 mL, 2:1 v/v) was heated at 80 °C for 24 hours. The reaction mixture was cooled
to room temperature and washed with 1:1 DMF/H2O (3 × 4 mL) to remove the white amorphous
powder. The remaining solid was filtered and washed with 1:1 DMF/H2O (5 mL) to obtain
colourless cube-like crystals (10.2 mg, 37%). IR (ATR): 3291, 2926, 2916, 1658, 1605, 1582,
1535, 1512, 1386, 1294, 1246, 1092, 973, 877, 805, 739, 665, 512 cm−1. Elemental analysis (%):
calcd for C72.7H89.8Cd2N8O21.7: C 52.99; H 5.49; N 6.80; found: C 53.01, H 4.31, N 6.80.
[Cd(TMHis)(bpee)]·DMF·3H2O (7). A solution of H2TMHis (9.1 mg, 0.03 mmol), bis(4-
pyridyl)ethylene (5.5 mg, 0.03 mmol) and Cd(NO3)2·4H2O (9.3 mg, 0.03 mmol) in DMF/H2O (3
mL, 1:1 v/v) was heated at 80 °C for 2 days. The reaction mixture was cooled to room temperature
and washed with 1:1 DMF/H2O (3 × 4 mL) to remove the white amorphous powder. The remaining
solid was filtered and washed with 1:1 DMF/H2O (5 mL) to obtain colourless block crystals (11.1
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mg, 51%). IR (ATR): 3536, 3413, 3132, 3058, 2997, 2868, 1664, 1638, 1605, 1579, 1494, 1385,
1332, 1283, 1104, 1013, 989, 955, 841, 839, 745, 657, 550, 467, 445 cm−1. Elemental analysis
(%): calcd for C29H34CdN6O9: C 48.18; H 4.74; N 11.62; found: C 48.05, H 4.74, N 11.43.
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Results and Discussion
Synthesis of H2TMXxx
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A two-step synthetic route was employed to synthesise the H2TMXxx ligands. This involves an
amide coupling between monomethyl terephthaloyl acid chloride and the appropriate L-amino acid
methyl ester, followed by hydrolysis of the two methyl ester groups (Scheme 1). When Xxx = Ala,
Val, Phe or Trp, the desired product was obtained in 73-81% overall yield (Table 1). However,
when Xxx = His or Tyr, the nucleophilic side chains also reacted with monomethyl terephthaloyl
acid chloride to give disubstituted intermediates. The terephthaloyl group appended to the side
chain was hydrolysed in the subsequent step to yield the desired product. This generated
terephthalic acid as a by-product, which was removed by column chromatography (Xxx = Tyr,
81%) or by exploiting the greater water solubility of the ligand under acidic conditions (Xxx =
His, 25%).
O
O
H
H
O
Cl
O
N
O
N
OMe
OH
O
Et3N
NaOH
R1
R
-Cl+H3N
+
OMe
CH2Cl2
H2O/EtOH
R
O
OMe
O
OMe
O
OH
1a-f
2a-f
Scheme 1. Synthetic scheme for the preparation of H2TMXxx ligands
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Table 1. Synthetic yield (%) of compounds 1a-f and 2a-f with structures of side chains
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6
R1
Yield of 1 (%)
R
Yield of 2
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9
(%)
95
90
a
b
c
-CH3
-iPr
-Bn
82
84
90
-CH3
-iPr
-Bn
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90
N
N
d
e
f
99
77
87
74
33
93
H
H
O
O
MeO2C
HO
MeO2C
N
N
N
HN
O
Framework Synthesis
Seven homochiral coordination polymers (1-7) were synthesised via the solvothermal reaction of
H2TMXxx with Cd(NO3)2·4H2O and bpee in solvent mixtures of DMF/water or DMF/methanol at
80 °C. A stoichiometric ratio of 1:1:1 Cd(NO3)2: H2TMXxx: bpee was consistently used for the
initial syntheses. However, for some compounds, increasing the concentration of Cd(NO3)2·4H2O
enabled higher yields to be obtained. Powder XRD experiments were used to verify that the
structure of the coordination polymer was unchanged.
2D Networks with Xxx = Val, Phe, Tyr and Trp (1-4).
The reactions of H2TMXxx, where Xxx = Val, Phe and Tyr, with bpee in a mixture of DMF and
water yielded colourless needle crystals which were found to be 2D rectangular sheet structures of
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composition [Cd(TMXxx)(bpee)]·xDMF·yH2O (Xxx = Val (1), Tyr (2), Phe (3)). The structures
of 1-2 were solved in the monoclinic space group P21 while 3 was solved in the triclinic space
group P1. The inorganic node in 1-3 is a Cd2(COO)4N4 cluster connecting four TMXxx2− ligands
and four bpee ligands (Figure 1).
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In 1, the two crystallographically distinct Cd(II) atoms are both six-coordinate with a distorted
octahedral coordination environment, as determined using the SHAPE39 program. The four
equatorial sites of each Cd(II) are occupied by oxygen atoms from the carboxylate groups of three
TMXxx2− ligands, one of which binds in a chelating mode while the other two serve as a three-
atom bridge that connects the two Cd(II) centres. The axial positions of the Cd(II) ion are occupied
by pyridyl nitrogen atoms from two bpee ligands (Figure 1a). The Cd(II)-O bond lengths vary
from 2.250(6) Å to 2.412(6) Å and the Cd(II)-N bond lengths fall in the range of 2.280(8) Å to
2.33(1) Å. These bond lengths are consistent with reported structures containing six-coordinate
Cd(II) centres.40
In contrast, the Cd2(COO)4N4 clusters in 2 contain a six-coordinate Cd1 and a seven-coordinate
Cd2, which were calculated using SHAPE39 to possess a distorted octahedral and pentagonal
bipyramidal coordination geometry respectively. The Cd(II)-O bond lengths for Cd1 range from
2.249(4) Å to 2.470(6) Å, typical of six-coordinate Cd(II), while the corresponding distances for
Cd2 are increased, ranging from 2.329(7) Å to 2.528(6) Å, consistent with the presence of a seven-
coordinate Cd(II) centre.40 The oxygen atoms O43 and O19, which are coordinated to Cd1 and
belong to the bridging carboxylate groups, form an O-Cd-O angle of 124.5°. The corresponding
oxygen atoms bound to Cd2 (O42 and O18) form a significantly larger O-Cd-O angle of 137.4°.
The large difference in the two O-Cd-O angles positions O43 at a distance of 2.311(5) Å from Cd1
and 2.454(6) Å from Cd2, sufficiently close to coordinate to both Cd(II) centres and act as a μ2
bridge. This increases the coordination number of Cd2 from six to seven (Figure 1b). In contrast,
the corresponding O-Cd-O angles in 1 are similar (128.4° for Cd1 and 125.8° for Cd2), giving rise
to two six-coordinate Cd(II) centres with no μ2-O bridge.
Compound 3 contains two types of Cd2(COO)4N4 clusters, one of which contains two six-
coordinate Cd(II) centres, similar to 1, while the other contains a six-coordinate and a seven-
coordinate Cd(II) centre, similar to 2. As before, the coordination geometries for the six- and
seven-coordinate Cd(II) centres were calculated to be distorted octahedral and pentagonal
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bipyramidal respectively. 39 The Cd(II)-O bond lengths fall in the range 2.233(8)-2.558(7) Å for
the six-coordinate Cd(II) centres (Cd1, Cd2 and Cd3) and 2.318(9)-2.611(8) Å for the seven-
coordinate Cd(II) centre (Cd4). Equivalent clusters are connected by TMPhe2− ligand pairs while
inequivalent clusters are linked via bpee ligands.
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(a)
(b)
Figure 1. The Cd2(COO)4N4 cluster in (a) 1, in which both Cd1 and Cd2 are six-coordinate; (b) 2, in which Cd1 is
six-coordinate while Cd2 is seven-coordinate. The Cd2-O43 bond is highlighted in green. Atoms are depicted as
follows in parts a-b: cadmium (purple), oxygen (red), nitrogen (blue) and carbon (black).
In 1-3, adjacent clusters are linked by pairs of TMXxx2− ligands to form a double chain in which
the TMXxx2− ligands on each side of the chain are arranged in a head-to-tail manner and run anti-
parallel to the ligands on the opposite side of the chain (Figure 2a). These anti-parallel double
chains are bridged by pairs of bpee ligands to form sheets with an sql topology and Schläfli symbol
{44·62}41 (Figure 2b). The sheets are stacked in a staggered manner to give narrow channels,
which are occupied by solvent molecules (Figure 2c). In 2 and 3, some of these solvent molecules
were disordered and could not be satisfactorily modelled, hence the solvent mask routine within
Olex2 was employed.38 The asymmetric unit of 2 was estimated to contain 91 residual electrons,
which is in good agreement with the proposed solvent content of 1.6 DMF and 2.3 H2O. The
structure of 3 contains 2 DMF and 4 H2O molecules that were well-ordered, as well as 41 residual
electrons from disordered solvent. This corresponds well to the proposed solvent content of 2.3
DMF and 6.4 H2O molecules.
Evacuation of the channels would give a total void space of 22% in 1 and 14% in 2 and 3. The
lower potential void space in 2 and 3 can be attributed to the bulkier aromatic side chains in
phenylalanine and tyrosine compared to the isopropyl side chain of valine. The thermal
gravimetric analysis (TGA) of 1 (Figure S8) indicates a mass loss of 4.5% between 30 and 105 °C,
which corresponds to the loss of 3.3 H2O molecules per asymmetric unit, followed by a further
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mass loss of 4.5% between 110-195 °C, corresponding to 0.8 DMF molecules. There is a plateau
in the TGA trace from 195 – 290 °C, indicating framework stability, before the framework
decomposes about 290 °C. The TGA trace of 2 contains a gradual mass decrease of 3.6% between
70 and 226 °C, which may correspond to 2.3 H2O and 0.1 DMF molecules. In 3, there is a gradual
mass loss of 8.3% from 60-260 °C, which may correspond to the loss of 6.4 H2O molecules and
1.5 DMF molecules per asymmetric unit. Framework decomposition occurs at 295 °C in 2 and 330
°C in 3.
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(a)__________________________________________________
(b)
(c)
Figure 2. Structure of [Cd(TMVal)(bpee)]·xDMF·yH2O (1) showing (a) the double chain formed by linking adjacent
Cd(II) clusters with anti-parallel pairs of TMVal2− ligands; (b) a single sheet viewed along the c axis; (c) a view of the
framework down the c axis, showing the staggered packing of the sheets. Atoms are depicted as follows in parts a-b:
cadmium (purple), oxygen (red), nitrogen (blue) and carbon (black). Hydrogens have been omitted for clarity.
Despite the similar bonding and connectivity within each (4,4)-sheet in 1-3, there are subtle
differences in the packing of the sheets, resulting from conformational differences in the amino
acid side chains. In 3, there are four crystallographically distinct TMPhe2− ligands which differ
markedly in the position and orientation of the benzyl side chain, as seen from a comparison of the
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torsion angles in the four types of TMPhe2− ligands (Table 2). In particular, there are large
variations in the torsion angles defined by C0-N-Cα-Cβ, which range from +75.41° to +144.67°,
and N-Cα-Cβ-Cγ, which range from −58.98° to +56.53°. In contrast, 1 and 2 crystallise in the higher
symmetry space group P21 and contain two crystallographically inequivalent TMXxx2− ligands.
Within each structure, the two types of TMXxx2− ligands have similar C0-N-Cα-Cβ and N-Cα-Cβ-
Cγ torsion angles, differing by a maximum of 22.38° and 2.81° respectively (Table 2).
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Table 2. Torsion angles of TMXxx2− ligands in the crystal structures of 1-3
Structure Ligand Colour1
Carom-C0-N-Cα
(°)
C0-N-Cα-Cβ (°)
N-Cα-Cβ-Cγ (°)
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2
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Red
Blue
Red
Blue
Red
Blue
Green
Purple
+175.98
-179.60
−176.47
−173.96
−165.78
−165.96
+176.77
−173.03
+92.57
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+114.20
+136.58
+102.16
+144.67
+75.41
−59.22, +66.33
−58.35, +65.66
−67.47
−64.66
−58.98
−56.95
+48.03
+91.99
+56.53
1Corresponds to the colour displayed in Figure 3a.
The large differences in the orientation of the benzyl side chains in 3 can be attributed to the large
number of possible non-covalent interactions that can be formed between the benzyl groups of
TMPhe2− and neighbouring components of the framework (Figure 3a). This includes various π-π
stacking and CH-π interactions at distances of 3.5-4.0 Å. In contrast, there are fewer variations in
the intermolecular interactions involving the TMVal2− and TMTyr2− side chains in 1 and 2. The
isopropyl side chains of the TMVal2− ligands in 1 form CH-π interactions with the pyridyl rings of
adjacent bpee ligands with distances of 3.609 Å and 3.851 Å. Although the phenol side chains of
the TMTyr2− ligands in 2 also have the propensity to form π-π stacking and CH-π interactions, the
predominant interaction appears to be hydrogen bonding between the phenol hydroxyl group and
the amide oxygen of a neighbouring sheet, with H-bond distances of 2.64(1) Å and 2.85(2) Å.
These directional interactions restrict the conformations adopted by the side chains in the
TMXxx2− ligands of 1 and 2 (Figure 3b).
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(b)
1 (Xxx = Val2−)
2 (Xxx = Tyr2−)
3 (Xxx = Phe2−)
Figure 3. (a) An overlay of the crystallographically inequivalent ligands in 1-3, showing the different arrangement of
groups about the N-Cα bond (highlighted in black); (b) The crystal packing in 1, 2 and 3, with individual sheets
represented in purple, blue, green and red. Intermolecular interactions involving the side chains, including hydrogen
bonding interactions (in 2) and short contacts in the range of 3.5-4.0 Å (in 1 and 3) are represented by grey and black
bands.
The reaction of H2TMTrp with Cd(NO3)2·4H2O and bpee under similar reaction conditions
resulted in an inhomogeneous mixture formed after seven days, which contained pale orange
needles suitable for analysis by X-ray diffraction. This unexpectedly revealed a 2D coordination
polymer of composition [Cd3(TMTrp)2(bpee)3(formate)2] (4), which crystallised in the space
group P21. The formate ions have likely formed from the hydrolysis of DMF at high
temperatures.42 Upon the addition of sodium formate to the reaction mixture, homogenous
microcrystalline needles separated after two days, which were confirmed by PXRD to be the same
compound. Remarkably, although 4 differs significantly in composition from 1-3 due to the
inclusion of formate ions, SCXRD studies of 4 revealed a 2D (4,4)-sheet41 structure topologically
identical to that of 1-3 (Figure 4).
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The structure of 4 differs from 1-3 predominantly in the inorganic node, with 4 containing a linear
Cd3(COO)6N6 cluster (0a). The central Cd(II) atom (Cd1) is located on the site of a pseudo-
inversion centre and was found to possess an octahedral coordination environment.39 Two of its
four equatorial sites, which are situated trans to each other, are occupied by oxygen atoms from
the carboxylate groups of two TMTrp2− ligands. Each of the TMTrp2− carboxylate groups serve as
a three-atom bridge connecting Cd1 to either Cd2 or Cd3. The other two equatorial sites, which
also have a trans relation to each other, are coordinated by oxygen atoms from two formate ions.
Each of these oxygen atoms serves as a μ2-bridge that links Cd1 to either Cd2 or Cd3. The Cd(II)-O
bond distances fall in the range 2.270(6) Å to 2.308(8) Å.
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Cd2 and Cd3 are both seven-coordinate with a distorted pentagonal bipyramidal coordination
geometry.39 The five equatorial sites are occupied by carboxylate oxygen atoms from a chelating
TMTrp2−, a chelating formate ion and a bridging TMTrp2−. Most of the Cd(II)-O bond lengths fall
in the range 2.298(6)-2.410(7) Å, with the exception of the non-bridging formate oxygen atoms
(O32 and O72), which have unusually long Cd(II)-O distances of 2.601(8) Å (Cd2-O32) and
2.574(7) Å (Cd3-O72). Bond distances in this range have been observed in structures containing
carboxylate groups chelated to Cd(II)40 and may indicate a weak Cd(II)-O bonding interaction.
The four TMTrp2− ligands within each cluster bridge adjacent clusters along the a-direction to
form an antiparallel double chain similar to that in 1-3. The two axial sites of each cadmium centre
are occupied by pyridyl nitrogen atoms from bpee co-ligands, which link double chains in the b-
direction to form a rectangular grid (Figure 4b). Similar to that observed in 1-3, the sheets in 4
stack in a staggered manner to form channels running parallel to the c axis. Despite the large size
of the indole side chains in TMTrp2−, the side chains do not obstruct the channels; this is due to
theformation of extensive CH-π interactions between the indole groups and a triad of bpee ligands
on a neighbouring sheet, which forces the indole groups to rotate towards the bpee pillars and away
from the rectangular channels, as seen in Figure 4b. Due to the conformation of TMTrp2− in 4, the
bulky indole side chains force adjacent sheets further apart, increasing the sheet-to-sheet mean
plane separation from approximately 7.5 Å in 1-3 to 9.9 Å in 4 (Figure 4c). As a result, 4 has a
higher calculated void volume of 34%. The TGA trace of 4 contains stepwise mass losses of 6.1%
from 30-85 °C (6.7 H2O molecules) and 9.9% from 90-210 °C (2.7 DMF molecules), before the
framework decomposes above 230 °C.
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Figure 4. Structure of [Cd3(TMTrp)2(bpee)3(formate)2] (4) showing (a) the trinuclear Cd(II) cluster in 4, with the
bridging formate ligands represented with green bonds, (b) the rectangular grid present in a single sheet and (c) a view
along the a axis, showing the staggered packing of the sheets with separate sheets represented in red, green and blue.
Atoms are depicted as follows in parts a and b: cadmium (purple), oxygen (red), nitrogen (blue) and carbon (black).
Hydrogens have been omitted for clarity.
3D Networks with Xxx = Ala and Tyr (5-6).
Combining H2TMAla or H2TMTyr with bpee and Cd(NO3)2·4H2O in DMF/H2O or
DMF/methanol respectively gives rise to 3D frameworks of composition [Cd(TMXxx)(bpee)]
(Xxx = Ala (5), Tyr (6)) (Figure 5). Interestingly, although H2TMTyr formed a 2D network when
combined with Cd(II) and bpee in DMF/H2O, changing the co-solvent from water to methanol,
which has a lower propensity for hydrogen bonding, induced the formation of a different
crystalline phase with a rectangular block-like morphology.
The structure of 5 was solved in the monoclinic space group P21 while 6 was solved in the higher
symmetry tetragonal space group P43212. Despite the marked differences in space group and unit
cell parameters (5: a = 14.2809, b = 15.0250, c = 23.6927, β = 101.573°; 6: a = b = 19.4835, c =
50.6104), both frameworks have the topology of a sqc5 net with the Schläfli symbol of {65·8}.41
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However, the crystal packing in the two structures differ significantly, which arises from the
different sizes of the alanine and tyrosine side chains.
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The inorganic nodes in 5-6 are Cd2(COO)4N4 clusters seen previously in 1-3. As before, the
clusters are linked by pairs of TMXxx2− ligands to form 1D double chains, with bpee ligands
extending from the axial positions of each cluster. However, unlike in 1-3 where the bpee ligands
on every cluster are oriented parallel to each other, the double chains in 5-6 adopt a twisted
conformation, causing the orientation of the bpee co-ligands of adjacent clusters to alternate along
the length of the chain (Figure 5a). Consequently, each chain is linked to four neighbouring chains
to form a 3D framework.
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In 6, the bpee ligands bonded to adjacent clusters are oriented at approximately 90° to each other,
whereas in 5, there is a distortion from orthogonality, with the corresponding angle being
approximately 53°. This has a significant effect on the packing of the framework. In 6, the
orthogonal arrangement of the bpee ligands results in the formation of undulating channels with a
solvent-accessible volume of 51%. In contrast, 5 contains compressed rhombic channels, with a
significantly reduced void volume of 18% (Figure 5b). These differences may arise from the
sterically bulky phenol side chain of tyrosine compared to the smaller methyl side chain of alanine,
which prevents the TMTyr2− ligands from adopting the close packed arrangement obtained with
TMAla2− ligands. Due to the disordered nature of the solvent molecules in the channels, the solvent
mask routine38 was used in the refinement of 5 and 6. The structure of 5 was calculated to contain
207 residual electrons per asymmetric unit, corresponding to 2 DMF and 12.2 H2O molecules. 6
contained 303 residual electrons, which is significantly higher than the 212 electrons calculated
based on the proposed solvent content of 1.8 DMF and 7.8 methanol molecules. This could be due
to the large channel size, which may facilitate loss of volatile solvent molecules in the samples
prior to elemental analysis.
The TGA traces of 5 and 6 both contain a series of stepwise mass losses. In 5, the first mass loss
of 6.9% occurs gradually between 30 and 150 °C, corresponding to 9.5 H2O molecules, followed
by a second sharper mass loss of 3% from 170-245 °C, corresponding to 1 DMF molecule, before
framework decomposition occurs above 265 °C. In 6, the mass losses occur at 30-90 °C (4.0%, 2
MeOH molecules), 95-225 °C (6.2%, 3.1 MeOH molecules) and 280-335 °C (13.1%, 1.8 DMF
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and 2.5 MeOH molecules). There is a short plateau in the TGA trace from 335-350 °C before
framework decomposition occurs.
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5 (Xxx = Ala)
6 (Xxx = Tyr)
(b)
5 (Xxx = Ala)
6 (Xxx = Tyr)
Figure 5. (a) A view of the twisted double chains in 5 (top) and 6 (bottom) with the Cd-N bonds (shown in blue)
alternating in direction between adjacent clusters. The green and yellow bonds each depict one of the two chains
present. For clarity, only the nitrogen centres of the bpee ligands are shown. (b) A simplified representation of the 3D
frameworks in 5 (top) and 6 (bottom), with the TMXxx ligands shown as green and yellow rods and the bpee ligands
as blue rods.
A 3D network obtained with H2TMHis (7).
Despite the structural diversity of 1-6, several recurring motifs were apparent; all six compounds
contain di- or trinuclear Cd(II) clusters linked by anti-parallel pairs of TMXxx2− ligands into
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double chains. The double chains were bridged by bpee co-ligands to obtain either 2D or 3D
networks. When H2TMHis was used as the chiral ligand, a completely different 3D framework
formed. This is due to the presence of the imidazole side chain, where the N-donors readily
coordinates to metal centres.
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Combining H2TMHis with bpee and Cd(NO3)2·4H2O in DMF/H2O at 80 °C resulted in the
formation of colourless rectangular block crystals of composition [Cd(TMHis)(bpee)] (7), which
crystallised in the orthorhombic space group P212121 (Figure 6). In the structure of 7, the TMHis2−
ligands act as three-connecting linkers through the two carboxylate groups and one imidazole side
chain (Figure 6a). In further contrast to compounds 1-6, the inorganic node of 7 is a single six-
coordinate Cd(II) ion with a highly distorted octahedral coordination geometry (Figure 6b).39 One
of the four equatorial sites is occupied by an imidazole nitrogen atom from a TMHis2− ligand with
a Cd(II)-N distance of 2.280(7) Å. The other three equatorial sites are occupied by oxygen atoms
from the carboxylate groups of two other TMHis2− ligands. One of the carboxylate groups binds
in a chelating mode with Cd(II)-O bond distances of 2.365(5) Å and 2.571(5) Å. In the second
carboxylate, one of the oxygen atoms is tightly coordinated to the Cd(II) centre with a Cd(II)-O
distance of 2.280(4) Å, while the second oxygen atom is situated 2.722(5) Å from the Cd(II) centre
and is likely to be involved in a long-ranged Cd(II)-O interaction. These TMHis2− ligands connect
each cadmium atom to three other Cd(II) centres to form a corrugated 2D sheet with a (6,3)-
network topology in the ac plane (Figure 6c).
The two apical sites of each Cd(II) are coordinated by bpee ligands (Cd(II)-N distances of
2.356(6) Å and 2.338(6) Å), which act as pillars that connect adjacent (6,3)-sheets to form a 3D
framework with hms topology (Figure 6d).41 Due to the large intraframework space, the
framework undergoes two-fold interpenetration to generate a dense structure with no solvent-
accessible voids (Figure 6e). The TGA trace of 7 indicates at mass loss of 7.4% from 30-100 °C,
corresponding to 3 H2O molecules. Above 100 °C, the TGA trace decreases continuously,
indicating gradual decomposition of the framework. The formation of this two-fold interpenetrated
3D framework when TMHis2− ligands are used, elegantly demonstrates that the choice of the
amino acid precursor can drastically alter the structure of the resulting framework.
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(c)
(b)
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(d)
(e)
Figure 6. Structure of [Cd(TMHis)(bpee)] (7) showing (a) TMHis2− acting as a three-connecting linker, with the
imidazole side chain shown in green, (b) the seven-coordinate Cd(II) centre in 7, (c) a view of a corrugated 2D sheet
containing Cd(II) centres linked by TMHis2− ligands (d) A single 3D framework of 7 with the bpee pillars shown in
blue, (e) A stick representation of the two-fold interpenetrating frameworks in 7, with the two independent frameworks
shown in blue and green. Atoms are depicted as follows for a-d: cadmium (purple), oxygen (red), nitrogen (blue) and
carbon (black). Hydrogens have been omitted for clarity.
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In this work, a systematic study was conducted to investigate the effect of the amino acid side
chain on the structure of the homochiral coordination polymers containing semi-rigid amino acid
derivatives. The amino acids selected possess side chains containing aliphatic groups (alanine and
valine), aromatic groups (tryptophan, tyrosine and phenylalanine) and coordinating groups
(histidine). Using Cd(II) as the metal ion and bpee as a co-ligand, a series of 2D and 3D homochiral
coordination polymers were obtained. When ligands derived from valine, tyrosine and tyrosine
were used, three isostructural (4,4)-networks (1-3) were obtained. Despite the identical
connectivity within the networks, the different intermolecular interactions formed by the side
chains exerted a subtle influence on crystal packing and symmetry. The use of tryptophan led to a
topologically identical framework constructed from trinuclear Cd(II) clusters and possessing a
larger void space, possibly due to the greater steric bulk of the indole side chain. The use of alanine-
and tyrosine-derived ligands surprisingly led to a pair of topologically identical 3D frameworks
(5-6). The large different in steric bulk of the side chains significantly altered the framework
geometry, resulting in channels of different shape and volume. The most dramatic structure-
directing effect of the side chain was observed in the histidine-containing framework (7), in which
the chiral ligand and metal centre both act as three-connecting nodes to form a pillared 3D structure
stabilized by interpenetration.
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Acknowledgements
We thank A/Prof. Brendan Abrahams for guidance, helpful discussions and feedback during this
work. C.H. gratefully acknowledges the University of Melbourne for a McKenzie Fellowship.
H.M.T. gratefully acknowledges the Australian Commonwealth Government and the University
of Melbourne for a Research Training Programme Scholarship as well as the University of
Melbourne for a Rowden White Scholarship and an Elizabeth and Vernon Puzey Scholarship. This
research was undertaken on the MX1 beamline at the Australian Synchrotron, part of ANSTO.
Electronic Supplementary Information
Crystallographic and structural details, powder XRD, thermal gravimetric analysis and ATR-FTIR
spectra. The crystallographic information files can be obtained from the Cambridge Structural
Database: CCDC 1994309-1994315, 1994343.
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Conflict of Interest Disclosure
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The authors declare no competing financial interest.
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References
1.
2.
Lin, G.; You, Q. D.; Cheng, J. F., Overview of Chirality and Chiral Drugs. In Chiral
Drugs, Sons, J. W., Ed. Somerset, United States, 2011; pp 3-28.
Eichelbaum, M.; Gross, A. S., Stereochemical aspects of drug action and disposition. In
Advances in Drug Research, Testa, B.; Meyer, U. A., Eds. Academic Press: 1996; Vol. 28,
pp 1-64.
3.
4.
5.
Zhang, X.; Yin, J.; Yoon, J., Recent Advances in Development of Chiral Fluorescent and
Colorimetric Sensors. Chem. Rev. 2014, 114, 4918-4959.
Sholl, D. S.; Gellman, A. J., Developing chiral surfaces for enantioselective chemical
processing. AIChE J. 2009, 55, 2484-2490.
Singh, N.; Sharma, L., Enantioseparation of D- and L- isomers of chiral drugs for
improving their bioavailability: some techniques including micellization with gemini
surfactants. Indian J. Pharm. Educ. Res. 2018, 52, 334-341.
6.
7.
8.
Rekoske, J. E., Chiral separations. AIChE J. 2001, 47, 2-5.
Baiker, A., Chiral catalysis on solids. Curr. Opin. Solid State Mater. Sci. 1998, 3, 86-93.
Falkowski, J. M.; Sawano, T.; Zhang, T.; Tsun, G.; Chen, Y.; Lockard, J. V.; Lin, W.,
Privileged Phosphine-Based Metal-Organic Frameworks for Broad-Scope Asymmetric
Catalysis. J. Am. Chem. Soc. 2014, 136, 5213-5216.
9.
Ma, L.; Falkowski, J. M.; Abney, C.; Lin, W., A series of isoreticular chiral metal–organic
frameworks as a tunable platform for asymmetric catalysis. Nat. Chem. 2010, 2, 838.
Nguyen, K. D.; Kutzscher, C.; Drache, F.; Senkovska, I.; Kaskel, S., Chiral
Functionalization of a Zirconium Metal-Organic Framework (DUT-67) as a
Heterogeneous Catalyst in Asymmetric Michael Addition Reaction. Inorg. Chem. 2018,
57, 1483-1489.
10.
11.
12.
Xi, W.; Liu, Y.; Xia, Q.; Li, Z.; Cui, Y., Direct and Post-Synthesis Incorporation of Chiral
Metallosalen Catalysts into Metal-Organic Frameworks for Asymmetric Organic
Transformations. Chem. Eur. J. 2015, 21, 12581-12585.
Dong, X. W.; Yang, Y.; Che, J. X.; Zuo, J.; Li, X. H.; Gao, L.; Hu, Y. Z.; Liu, X. Y.,
Heterogenization of homogeneous chiral polymers in metal-organic frameworks with
enhanced catalytic performance for asymmetric catalysis. Green Chem. 2018, 20, 4085-
4093.
13.
14.
15.
Xiong, R. G.; You, X. Z.; Abrahams, B. F.; Xue, Z.; Che, C. M., Enantioseparation of
Racemic Organic Molecules by a Zeolite Analogue. Angew. Chem. Int. Ed. 2001, 40, 4422-
4425.
Tanaka, K.; Muraoka, T.; Otubo, Y.; Takahashi, H.; Ohnishi, A., HPLC enantioseparation
on a homochiral MOF–silica composite as a novel chiral stationary phase. RSC Adv. 2016,
6, 21293-21301.
Zhuo, C.; Wen, Y.; Hu, S.; Sheng, T.; Fu, R.; Xue, Z.; Zhang, H.; Li, H.; Yuan, J.;
Chen, X.; Wu, X., Homochiral Metal–Organic Frameworks with Tunable Nanoscale
ACS Paragon Plus Environment

Page 21 of 23
Crystal Growth & Design
1
2
3
4
5
6
7
8
9
Channel Array and Their Enantioseparation Performance against Chiral Diols. Inorg.
Chem. 2017, 56, 6275-6280.
Padmanaban, M.; Müller, P.; Lieder, C.; Gedrich, K.; Grünker, R.; Bon, V.; Senkovska,
I.; Baumgärtner, S.; Opelt, S.; Paasch, S.; Brunner, E.; Glorius, F.; Klemm, E.; Kaskel,
S., Application of a chiral metal–organic framework in enantioselective separation. Chem.
Commun. 2011, 47, 12089-12091.
16.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
17.
18.
19.
Zhou, H. C.; Long, J. R.; Yaghi, O. M., Introduction to Metal–Organic Frameworks.
Chem. Rev. 2012, 112, 673-674.
Han, Z.; Shi, W.; Cheng, P., Synthetic strategies for chiral metal-organic frameworks.
Chin. Chem. Lett. 2018, 29, 819-822.
Liu, Y.; Xuan, W.; Cui, Y., Engineering Homochiral Metal-Organic Frameworks for
Heterogeneous Asymmetric Catalysis and Enantioselective Separation. Adv. Mater. 2010,
22, 4112-4135.
Wu, C. D.; Hu, A.; Zhang, L.; Lin, W., A Homochiral Porous Metal−Organic Framework
for Highly Enantioselective Heterogeneous Asymmetric Catalysis. J. Am. Chem. Soc.
2005, 127, 8940-8941.
Grosshans, P.; Jouaiti, A.; Bulach, V.; Planeix, J. M.; Hosseini, M. W.; Nicoud, J. F.,
Molecular tectonics: from enantiomerically pure sugars to enantiomerically pure triple
stranded helical coordination network. Chem. Commun. 2003, 1336-1337.
Barron, J. A.; Glazier, S.; Bernhard, S.; Takada, K.; Houston, P. L.; Abruña, H. D.,
Photophysics and redox behavior of chiral transition metal polymers. Inorg. Chem. 2003,
42, 1448-1455.
Gruselle, M.; Thouvenot, R.; Malézieux, B.; Train, C.; Gredin, P.; Demeschik, T. V.;
Troitskaya, L. L.; Sokolov, V. I., Enantioselective Self-Assembly of Bimetallic [MnII(Δ)-
CrIII(C2O4)3]− and [MnII(Λ)-CrIII(C2O4)3]− Layered Anionic Networks Templated by the
Optically Active (Rp)- and (Sp)-[1-CH2N(n-C3H7)3-2-CH3C5H3FeC5H5]+ Ions. Chem. Eur.
J. 2004, 10, 4763-4769.
20.
21.
22.
23.
24.
Train, C.; Gheorghe, R.; Krstic, V.; Chamoreau, L. M.; Ovanesyan, N. S.; Rikken, G.
L. J. A.; Gruselle, M.; Verdaguer, M., Strong magneto-chiral dichroism in enantiopure
chiral ferromagnets. Nat. Mater. 2008, 7, 729-734.
25.
26.
Lin, Z.; Slawin, A. M. Z.; Morris, R. E., Chiral Induction in the Ionothermal Synthesis of
a 3-D Coordination Polymer. J. Am. Chem. Soc. 2007, 129, 4880-4881.
Hailili, R.; Wang, L.; Qv, J.; Yao, R.; Zhang, X. M.; Liu, H., Planar Mn4O Cluster
Homochiral Metal–Organic Framework for HPLC Separation of Pharmaceutically
Important (±)-Ibuprofen Racemate. Inorg. Chem. 2015, 54, 3713-3715.
Liang, X. Q.; Li, D. P.; Zhou, X. H.; Sui, Y.; Li, Y. Z.; Zuo, J. L.; You, X. Z.,
Metal−Organic Coordination Polymers Generated from Chiral Camphoric Acid and
Flexible Ligands with Different Spacer Lengths: Syntheses, Structures, and Properties.
Cryst. Growth Des. 2009, 9, 4872-4883.
Gu, Z. G.; Zhan, C.; Zhang, J.; Bu, X., Chiral chemistry of metal–camphorate frameworks.
Chem. Soc. Rev. 2016, 45, 3122-3144.
Pu, F.; Liu, X.; Xu, B.; Ren, J.; Qu, X., Miniaturization of Metal–Biomolecule
Frameworks Based on Stereoselective Self-Assembly and Potential Application in Water
Treatment and as Antibacterial Agents. Chem. Eur. J. 2012, 18, 4322-4328.
27.
28.
29.
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Crystal Growth & Design
Page 22 of 23
1
2
3
4
5
6
7
8
9
30.
31.
32.
33.
Guan, G. X.; Liu, X.; Yue, Q.; Gao, E. Q., Homochiral Metal–Organic Frameworks
Embedding Helicity Based on a Semirigid Alanine Derivative. Cryst. Growth Des. 2018,
18, 364-372.
Xu, Z. X.; Tan, Y. X.; Fu, H. R.; Liu, J.; Zhang, J., Homochiral Metal–Organic
Frameworks with Enantiopure Proline Units for the Catalytic Synthesis of β-Lactams.
Inorg. Chem. 2014, 53, 12199-12204.
Rebilly, J. N.; Bacsa, J.; Rosseinsky, M. J., 1ꢀD Tubular and 2ꢀD Metal–Organic
Frameworks Based on a Flexible Amino Acid Derived Organic Spacer. Chem. Asian J.
2009, 4, 892-903.
McPhillips, T. M.; McPhillips, S. E.; Chiu, H. J.; Cohen, A. E.; Deacon, A. M.; Ellis,
P. J.; Garman, E.; Gonzalez, A.; Sauter, N. K.; Phizackerley, R. P.; Soltis, S. M.; Kuhn,
P., Blu-Ice and the Distributed Control System: software for data acquisition and
instrument control at macromolecular crystallography beamlines. J. Synchrotron Radiat.
2002, 9, 401-406.
Aragao, D.; Aishima, J.; Cherukuvada, H.; Clarken, R.; Clift, M.; Cowieson, N. P.;
Ericsson, D. J.; Gee, C. L.; Macedo, S.; Mudie, N.; Panjikar, S.; Price, J. R.; Riboldi-
Tunnicliffe, A.; Rostan, R.; Williamson, R.; Caradoc-Davies, T. T., MX2: a high-flux
undulator microfocus beamline serving both the chemical and macromolecular
crystallography communities at the Australian Synchrotron. J. Synchrotron Radiat. 2018,
25, 885-891.
Sheldrick, G., SHELXT - Integrated space-group and crystal-structure determination. Acta
Cryst. A 2015, 71, 3-8.
Sheldrick, G., Crystal structure refinement with SHELXL. Acta Cryst. C 2015, 71, 3-8.
Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H.,
OLEX2: a complete structure solution, refinement and analysis program. J. Appl.
Crystallogr. 2009, 42, 339-341.
Van Der Sluis, P.; Spek, A. L., BYPASS: an effective method for the refinement of crystal
structures containing disordered solvent regions. Acta Cryst. A 1990, 46 (3), 194-201.
Llunell, M.; Casanova, D.; Cicera, J.; Alemany, P.; Alvarez, S. SHAPE, 2.1; Barcelona,
Spain, 2013.
Groom, C. R.; Bruno, I. J.; Lightfoot, M. P.; Ward, S. C., The Cambridge Structural
Database. Acta Cryst. B 2016, 72, 171-179.
Blatov, V. A.; Shevchenko, A. P.; Proserpio, D. M., Applied Topological Analysis of
Crystal Structures with the Program Package ToposPro. Cryst. Growth Des. 2014, 14,
3576-3586.
Burrows, A. D.; Cassar, K.; Friend, R. M. W.; Mahon, M. F.; Rigby, S. P.; Warren, J.
E., Solvent hydrolysis and templating effects in the synthesis of metal–organic
frameworks. CrystEngComm 2005, 7, 548-550.
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For Table of Contents Use Only:
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Chiral Cd(II) coordination polymers based on amino acid derivatives: the effect of side chain on
structure
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Hui Min Tay and Carol Hua*
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School of Chemistry, The University of Melbourne, Parkville, Victoria, 3010, Australia. *E-mail:
carol.hua@unimelb.edu.au
Seven homochiral Cd(II) coordination polymers were generated using dicarboxylates composed
of L-amino acids appended to terephthalic acid. 2D networks were obtained using ligands derived
from valine, tyrosine, phenylalanine and tryptophan while 3D frameworks were generated from
alanine, tyrosine and histidine. The side chain influenced both network connectivity and crystal
packing.
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