Chirality transcription in the anion-coordination-driven assembly of tetrahedral cages

Article abstract of DOI:10.1039/c9cc09752j

Enantiopure A₄L₄ tetrahedral cages (either ΔΔΔΔ or ΛΛΛΛ) were obtained through the anion-coordination-driven assembly (ACDA) of phosphate anions with C₃-symmetric tris-bis(urea) ligands bearing chiral groups.

Full text of DOI:10.1039/c9cc09752j

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Chirality transcription in the anion-coordination-
driven assembly of tetrahedral cages†
Cite this:DOI: 10.1039/c9cc09752j
Jin Fu,‡a Bo Zheng, ‡a Huizheng Zhang,a Yanxia Zhao,a Dan Zhang,a
a
ab
Wenyao Zhang,a Xiao-Juan Yang
and Biao Wu
*
Received 16th December 2019,
Accepted 21st January 2020
DOI: 10.1039/c9cc09752j
rsc.li/chemcomm
Enantiopure A4L4 tetrahedral cages (either DDDD or KKKK) were
obtained through the anion-coordination-driven assembly (ACDA)
of phosphate anions with C3-symmetric tris-bis(urea) ligands bearing
chiral groups.
The importance of chirality is underscored by its omnipresence
in nature and significant practical applications.1 To mimic
biological systems, chemists have been studying the mechanism
of chiral information transfer through the intricate interplay
of non-covalent interactions in dynamic artificial systems.2
In particular, great efforts have been devoted to develop well-
organized, chiral discrete molecular cages or containers (MCs)
through metal coordination, dynamic covalent chemistry (DCC),
hydrogen bonding, etc.3 Tetrahedral cages, the simplest Platonic
solids, are one of the most extensively studied cage structures.
The introduction of chirality into metal-coordination-based
tetrahedral cages, both M4L4 and M4L6 (M = metal, L = ligand) types,
has endowed these assemblies with useful potential in stereo-
Scheme 1 Design of tris-bis(urea) ligands and the targeting A4L4 chiral
aniono-supramolecular tetrahedral cages assembled by L and PO43À in the
presence of tetraalkylammonium cations.
selective recognition and sensing, enantiomer separation, nonlinear tris-bis(urea) ligand with the triphenylbenzene and triphenyl-
optical materials, supramolecular asymmetric catalysis, etc.4
triazine units, respectively, and obtained the A4L4 tetrahedral
The anion-coordination-driven assembly (ACDA) as a new cages with larger cavities for guest inclusion.7 These works
strategy has developed rapidly in recent years and exhibited illustrate a reliable and predictable way to build aniono-cages
high efficiency in the fabrication of organized, metal-free aniono- based on C3-symmetric ligands. Although each individual
supramolecular assemblies with fascinating properties.5 In 2013, aniono-tetrahedral cage is intrinsically chiral with either a
we reported the first tetrahedral anion A4L4 cage (A = anion, DDDD or LLLL configuration at the four vertices (as octahedral
L = ligand) assembled by a triphenylamine-based o-phenylene- complexes when taking one urea group as a coordinate vector),
bis(urea) ligand (LNO2 in Scheme 1) and a phosphate anion.6 the whole complexes with the achiral ligands are always present
Later, we replaced the triphenylamine core of the C3-symmetric as a racemic mixture.
In general, it is still challenging to control the chirality of the
resultant assemblies by chiral auxiliaries in a predictable
a Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the
manner and without losing any chiral information.3e Recently, we
Ministry of Education, College of Chemistry and Materials Science,
set to explore the chiral resolution in the hydrogen-bonded aniono-
supramolecular assemblies, which might be more unpredictable
than that in the metal-coordination systems. In the triple helicate
system, chiral guests led to enantiopure structures capable of
chirality sensing biomolecules.8 However, by introducing chiral
groups (which is a common way to realize chirality resolution in
the assembled systems) into C2-symmetric bis-bis(urea) ligands
Northwest University, Xi’an 710127, China. E-mail: wubiao@nwu.edu.cn
b State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000, China
† Electronic supplementary information (ESI) available: Synthetic procedures,
characterization data and corresponding CIF files. CCDC 1955042, 1955280 and
1957114. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c9cc09752j
‡ These authors contributed equally to this work.
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to build the A4L6 tetrahedral cage or A2L3 triple helicate, the
expected assemblies were not obtained despite only small changes
in the ligand.9 So, we turned to the C3-symmetric ligands which are
more reliable for tetrahedral cages (A4L4-type). Two sets of ligands
(L1R/L1S and L2R/L2S; Scheme 1) were synthesized, which bear a
similar point chirality on different positions (see details in the
ESI†).6 Notably, chirality transfer only occurred when the chiral
carbon centers were directly attached to the urea groups (L1R/L1S),
while achiral cages were obtained when the chiral sites were one
carbon away from the urea groups (L2R/L2S). For comparison,
ligand LBn (benzyl) without any chiral center was also prepared,
as an achiral analogue of L1R/1S
.
Treatment of ligand L1R or L1S (which as a free ligand is
3À
insoluble in acetone or acetonitrile) with an equimolar PO4
anion (as tetraalkylammonium salts) in acetonitrile eventually
gave a clear solution. X-ray-quality crystals of two anion complexes
(1 and 2) were successfully obtained by slow vapor diffusion of
diethyl ether into their acetonitrile solutions. As expected, ligands
L
1R and L1S self-assemble with phosphate to form A4L4-type aniono
tetrahedral cages, (TPA)12[(PO4)4(L1R)4] (1) and (TPA)12[(PO4)4(L1S)4]
(2), respectively, with phosphate ions as four vertices and ligands
as the faces (Fig. 1). Besides, the single crystals of the tetrahedral
cage (TEA)12[(PO4)4(LBn)4] (5) (TEA = tetraethylammonium) were
isolated in the same way from the achiral ligand LBn (Fig. S44,
ESI†). The noncovalent interactions in these structures are similar
to previously reported A4L4 aniono-cages6 with twelve N–HÁÁÁO
hydrogen bonds between six urea groups and a phosphate center
at each vertex. The hydrogen bond parameters are very close in the
two enantiomers 1 and 2, with NÁ Á ÁO distances ranging from
2.70 to 3.03 Å and N–HÁ Á ÁO angles from 1351 to 1791 (Tables S1
and S2, ESI†). The cages of both achiral ligands LNO2 and LBn
have quite uniform PO4Á Á ÁPO4 separations,6 at about 15 Å and
the NÁ Á ÁN (triphenylamine) separation between every two
ligands is 7.12 Å. However, the tetrahedral cavity formed by
the chiral ligands L1R/1S is distorted, stretching in one direction
Fig. 1 Crystal structures of the homochiral cages 1 [(PO4)4(L1R)4]12À
(DDDD) and 2 [(PO4)4(L1S)4]12À (LLLL). (a) View from the triangular face;
(b) space-filling representation; and (c) hydrogen bonds formed between a
PO43À ion and six urea (three bis-urea) units. TPA+ cations are omitted for
clarity.
L
2R/L2S with an equimolar PO43À anion (as tetraalkylammonium
(Fig. 1a), where the PO4Á Á ÁPO4 separations range from about salts) afforded complexes 3 and 4. Unfortunately, despite many
13.6 to 15.3 Å, and NÁ Á ÁN separations from 5.84 to 6.56 Å. attempts with different crystallization methods, we were unable
Besides, the distribution of the three bis(urea) groups around a to get X-ray-quality single crystals of them. Therefore, several
phosphate ion in the enantiopure chiral cages is less symmetric characterization methods were employed to investigate the two
than that from the achiral ligands, displaying a twisted fashion complexes in solution, which indicate that complexes 3 and 4 in
due to the steric hindrance. Two of them lie horizontally and the solution exist as diastereomers (vide infra).
1
remaining one reaches out, on top of the phosphate (Fig. 1c). TPA
The H NMR spectrum of complex 1 (in acetone-d6) reveals
cations in the crystal structure are found outside the cage and all of significant downfield shifts (Dd from 1.10 to 3.16 ppm) of the
them are located very close to the tetrahedron, either in the grooves urea NH hydrogen signals compared to those of L1R (NMR
formed by adjacent ligands or around the vertices (Fig. S45, ESI†). spectra of ligands used here were measured in DMSO-d6 for
Complexes 1 and 2 are present as mirror images, both in the solubility reasons) (Fig. 2 and Fig. S26 and S27, ESI†). According to
chiral space group C2. Cage 1 (with L1R) contains solely a DDDD previous studies, these shifts are caused by the typical coordination
configuration for all four vertices, while cage 2 (with L1S) shows between phosphate anions and urea moieties and are in line with
a single LLLL configuration. In contrast, the tetrahedral cages the results of the previously reported aniono-cages.6,7 The protons in
constructed from the achiral ligands LNO2 and LBn (Fig. S44, the aromatic region, H4, H5, H9 and H11, shift to upfield due to the
%
ESI†) crystallize in the space group P42c, with both DDDD and shielding effect of the closely packed anion complex, while H2, H3
LLLL tetrahedra in the same unit cell as a racemic mixture. and H6 suffer downfield shifts caused by the anion–urea bonding.
Thus, it appears that the chiral auxiliaries in the individual Besides, it should be noted that the NH hydrogens on urea groups
ligand have defined the consequent chiral structure.
split into two sets of peaks, indicating the formation of a low-
To further investigate the impact of the chiral auxiliary, we symmetrical structure, which is consistent with the twisting
studied the assembly of the ligand pair L2R/L2S. Treatment of distribution of the ligands at each vertex in the crystal structure.
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and 2074.5349 for [(PO4)4(L1R)4(TPA)7H2]3À (Fig. S38, ESI†),
which are consistent with the simulated patterns. Similar results
referring to the A4L4 cage could also be observed in complexes 2–5
(Fig. S39–S42, ESI†).
As mentioned above, it is noted that ligands with predisposed
chirality exhibited profound influence on the ultimate chirality
of the self-assembled tetrahedral cage. To probe the chirality
transfer from an individual ligand molecule to the consequent
supramolecular architecture, circular dichroism (CD) measure-
ments were employed. For ligands L1R and L1S, wherein the
chiral carbons are directly attached to the urea groups, the CD
intensities of the formed complexes are almost the same as that
of each other with opposite signals; five peaks at 364, 307, 271,
245, and 231 nm with strong Cotton effects are found in the
spectra (Fig. 3, blue and magenta). The crystal structures of the
cages provide unambiguous assignment of their stereochemical
Fig. 2 1H NMR spectra (400 MHz, 298 K) of (a) (TPA)12[(PO4)4(L1R)4] in
acetone-d6 and (b) ligand L1R in DMSO-d6. Signals of TPA+ are labelled by
and solvent residues by
.
In contrast, the peaks of NH hydrogens in the NMR spectrum of configuration. The L1R ligand leads to the DDDD enantiomer,
the achiral (LBn) complex 5 show only one set of signals, while L1S forms the LLLL cage. However, for the ligands (L2R/2S
)
indicating the formation of a more symmetric coordinate geo- with one more carbon between the chiral center and anion
metry in solution (Fig. S31, ESI†) compared with the distorted binding site, distinct attenuation of the CD signals (Fig. 3, black
distribution in L1R/L1S. This is probably ascribed to the removal and red) can be found at the following wavelengths: 364 (by
of the chiral centre (a methyl substituent) to release steric 99%), 307 (94%), 271 (87%), 245 (89%), and 231 nm (85%). The
hindrance for LBn compared with L1R. The same complexation weak Cotton effects imply that the resulting supramolecular
behavior between the phosphate ion and the urea moieties was complexes 3 and 4 in solution may be a mixture of diastereo-
also observed in complex 2, which means that both L1R and L1S mers, with only a slight chirality bias. However, their NMR
ligands self-assembled with the anions into a similar structure. spectra do not show well-resolved signals of the diastereomers
1H NMR experiments were also performed to characterize although some peaks are broadened (Fig. S28 and S29, ESI†).
the assemblies formed by L2R and L2S (Fig. S28 and S29, ESI†). Based on the CD results, it could be concluded that the position
Similarly, urea hydrogens of L2S suffer significant downfield of the introduced chiral site in the ligand is crucial for the
shifts as those of L1R and L1S (Fig. S30, ESI†). Differently, there chirality transfer. Even a slight difference in the chiral ligands
is only one set of NMR signals in the spectrum and the urea can lead to dramatic differences in the chiral transcription from the
peaks do not split, because the chiral centre is shifted one individual component to the final supramolecular structures.
carbon away from the binding site and the three ligand arms at
To further test the chirality transcription in anion-coordination
the vertices can adopt a symmetric geometry in a less crowded tetrahedral cages, we introduced the achiral ligand LCN (R = para-
environment. Both ligands form the same assembly in solution, cyanophenyl for LCN in Scheme 1, see details in the ESI†) into the
sharing almost identical spectra for complexes 3 and 4. Although cage formed by L1S (or L1R). Ligand LCN, which was chosen because
it failed to obtain the crystal structures of 3 and 4, the comparable the most closely related ligand LBn has a poor solubility, was
1H NMR spectra of complexes 1–4 in solution imply that ligands
L
1R/L1S and L2R/L2S coordinate with phosphate anions to form
similar well-defined structures, which cause the similar peak
shifts of urea moieties in these ligands. Furthermore, the diffu-
sion coefficients measured by diffusion-ordered NMR spectro-
scopy (DOSY) experiments for complexes 1 and 3 demonstrated
comparable outcomes (Fig. S37, ESI†), where a single diffusion
coefficient corresponding to the only or dominant species was
observed for each complex. The calculated dynamic radii of
tetrahedral structures through the Stokes–Einstein equation
(12 Å) are in good agreement with the sizes derived from the
crystal structures of 1 and 2. Combining the 1H NMR and DOSY
analysis reveals that similar A4L4 type aniono-tetrahedral cages
are formed between ligands L2R/L2S and (TPA)3PO4 in solution.
The corresponding mass spectra of complexes 1–5 show the
formation of tetrahedrons by ligands and PO43À. Taking ligand
L
1R for example, when sprayed from acetonitrile or acetone, a set
Fig. 3 Circular dichroism spectra of (TPA)12[(PO4)4(L1R/1S)4] (complexes 1
and 2) and (TPA)12[(PO4)4(L2R/2S)4] (complexes 3 and 4) in CH3CN, c = 4 Â
10À5 mol LÀ1 based on ligands.
of mass peaks are found in the spectrum at m/z = 1950.7165 for
[(PO4)4(L1R)4(TPA)5H4]3À, 2012.7938 for [(PO4)4(L1R)4(TPA)6H3]3À
,
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proved to form the A4L4 tetrahedral complex (TMA)12[(PO4)4(LCN)4]
(6) by NMR and HR-MS (Fig. S32 and S43, ESI†). Complex 2
bearing the chiral ligand L1S was thus mixed with complex 6
in different proportions, 4 : 0, 3 : 1, 2 : 2, 1 : 3 and 0 : 4, respectively,
in acetonitrile, keeping the total concentration at c = 4 Â
10À5 mol LÀ1. Concentration-dependent 1H NMR measure-
ments confirmed the stability of tetrahedral cages at tested
concentrations (Fig. S50, ESI†). The much more complicated
NMR spectra of the mixed solution indicate the ligand exchange
process (Fig. S51, ESI†), where chiral and achiral ligands are
mixed together to build cage structures with concomitant
appearance of new peaks in NMR spectra. In the mass spectra,
the mixed cages are also found (Fig. S52 and S53, ESI†). In the
CD spectra (Fig. S49, ESI†), upon formation of the mixed-ligand
cages when L1S was mixed with the achiral LCN, the CD signals
gradually weakened, but can still be observed even in the 1 : 3
(L1S to LCN) system, suggesting the retention of chirality in the
chiral–achiral mixed-ligand systems.
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In summary, tetrahedral cages formed by ligands (L1R/1S
)
with chiral sites directly linked to the coordination center were
enantiopure products, while the chirality of the cages with ligands
shifting the point chiral center one carbon away was attenuated to
form diastereomers. The results clearly demonstrate the profound
influence of prepositioned point chirality in the ligand on the
origin of the consequent chirality of the formed structures. Thus, it
is evident that the chirality of aniono-supramolecular assemblies,
like the metallo-systems, may also be controlled through chiral
transcription by introducing chiral auxiliaries into the ligand.
Further exploration of the chirality issues in the anion-
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We are grateful for the financial support from the National
Natural Science Foundation of China (91856102 and 21772154)
and Shaan’xi Province (334041900005 and 2019JQ-723).
Conflicts of interest
There are no conflicts to declare.
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