Fine-Tuning of Chiral Microenvironments within Triple-Stranded Helicates for Enhanced Enantioselectivity

Article abstract of DOI:10.1002/anie.202104111

Here we report the formation of an unexpected and unique family of chiral helicates. Crystal structures show that these triple-stranded Zn^II₂L₃ complexes are held together by subcomponent assembly of axially chiral diamine

Full text of DOI:10.1002/anie.202104111

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Angewandte
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Accepted Article
Title: Fine-Tuning of Chiral Microenvironments within Triple-Stranded
Helicates for Enhanced Enantioselectivity
Authors: Jingjing Jiao, Jinqiao Dong, Yingguo Li, and Yong Cui
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10.1002/anie.202104111
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RESEARCH ARTICLE
Fine-Tuning of Chiral Microenvironments within Triple-Stranded
Helicates for Enhanced Enantioselectivity
Jingjing Jiao+[a,b], Jinqiao Dong,+[a] Yingguo Li,[a] and Yong Cui*[a]
Abstract: Here we report the formation of an unexpected and
outstanding enantioselective recognition has remained
a
unique family of chiral helicates. Crystal structures show that these
mystery, presumably due to the intrinsic difficulties associated
with the fine-tuning of chiral microenvironments for regulating
enantiomer to helix interactions.[9]
triple-stranded ZnII L3 complexes are held together by
2
subcomponent assembly of axially chiral diamine-functionalized 1,1’-
biphenol ditopic with 2-formylpyridine and Zn(II). Specifically, the
molecular helicity of the complexes can be controlled by the absolute
configurations of the bimetallic vertices, which has been shown to be
homoconfiguration () or mesomeric configuration (), depending
critically on the bulky groups and length of the spacers. Fascinatingly,
in this system we can engineer the space-restricted chiral
microenvironments with varied polar and apolar moieties, which
profoundly influence the binding affinities and chiral discrimination
properties of the helicates, leading to highly enantio- and helix-
sense-selective recognition for chiral amino alcohols (up to 9.35).
This work reveals the transformation of single-molecule chirality to
global supramolecular chirality within well-defined helicates and
demonstrates their chiral discrimination are highly dependent on the
superior microenvironments.
Introduction
Figure 1. (a-b) An example of naturally chiral biomacromolecule with helical
structure – eight-stranded avidin proteins are able to bind chiral biotin (avidin-
biotin complex) with ultrahigh affinities and selectivities (up to 1015 M-1) by
combining hydrogen-bonding with hydrophobic effect (PDB: 2AVI).[8]
The helix is one of the most pervasive structural elements of
biomolecules,[1] such as double-stranded DNA,[2] triple-stranded
collagen,[3] and coiled-coil helix bundle proteins,[4] and is also the
ubiquitous object in nature from microscopic to macroscopic
points of view.[5] Most importantly, the specific twisting of the
helical strands results in inherently chiral (that is, the right- and
left-handed helices are exactly mirror images of each other).[6]
Therefore, the constituent small molecules (e.g., nucleotides,
carbohydrates, and amino acid) can form complex
biomacromolecules with multi-level chiral characteristics[7] – the
system generally contains multiple stereogenic centers. Such
notable feature has led to fascinating chiral environments
capable of exceptionally stereospecific interactions in biological
systems by combining direct hydrogen-bonding with
hydrophobic effect (see an example of avidin-biotin complex in
Figure 1).[8] Inspired by nature, present-day researchers are
Helicates or metallohelices, pioneered by Lehn,[10] are
discrete coordination complexes in which one or more organic
ligands helically wrapped and coordinated to cations (or anions)
by coordination bonds.[11] Typically, the assembly of pre-
designed ligands and metal ions can form various helicates with
structurally well-defined shapes and sizes, including double-
stranded,[12] triple-stranded,[13] quadruple-stranded,[14] six-
stranded,[15] and circular helicates.[16] For example, Nitschke and
co-workers recently reported the assembly of six-stranded
hollow helicates [AgI8L6] and [AgI12L6], where the templating
anion plays an integral structure-defining role.[15b] More
importantly, the length and flexibility of constitutive strands play
a key factor for the helical conformation,[17] which is exemplified
by the structural transformation between coordination cages and
helicates. For instance, Clever and co-workers demonstrated
that the helically twisted complex [PdII L4] can be generated by
[a]
Dr. J. Jiao, Dr. J. Dong, Mr. L. Liu, Prof. Y. Cui
School of Chemistry and Chemical Technology, Frontiers Science
Center for Transformative Molecules and State Key Laboratory of
Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai
200240, P. R. China
2
introducing isoquinoline donors.[14c] Interestingly, some of these
structures are inherently chiral as a consequence of resulting P-
12h, 14b, 18]
configured and M-configured diastereomers.[12f,
However, they are depressed in chiral recognition, probably
E-mail: yongcui@sjtu.edu.cn
Dr. J. Jiao
The Key Laboratory of Resource Chemistry of Ministry of Education,
Shanghai Key Laboratory of Rare Earth Functional Materials,
Shanghai Normal University, Shanghai 200234, China
These authors contributed equally to this work.
19]
arising from the insufficient chiral microenvironments.[9,
[b]
[+]
Nevertheless, the use of enantiomerically pure ligands is able to
drive the formation of chiral helicates that are capable of
recognizing and converting substrates in their interior with
enantioselective ways. We previously reported a quadruple-
stranded helicate consisting of structurally flexible Salan-type
ligands with central chirality,[14b] the resultant chiral
microenvironment within the enclosed cavity has enabled the
Supporting information for this article is given via a link at the end of
the document.
actively pursuing the synthetic analogues. However, chemical
knowledge of how to rationally designed artificial helices with
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10.1002/anie.202104111
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RESEARCH ARTICLE
chiral discriminations towards chiral amino acids. However, in
this case the enantioselectivity is moderate (~3.69) owing to the
difficulties in modifying the microenvironment within the
nanocavity through installation of chiral binding sites and control
of the hydrophobic effect. Thus, rationally designed well-defined
helicates with exceptional chiral recognition performance
remains a formidable challenge.
Scheme 1. Self-assembly of triple-stranded helicates H-1-4 by using axially
chiral 1,1′-biphenyl-type ligands.
In this context, we develop a new system for self-assembly
of well-defined chiral helicates from axially chiral 1,1
′-biphenyl-
type ligands. X-ray crystal structures evidence that the absolute
configurations of the bimetallic vertices of the helicates can
adopt homoconfiguration () or mesomeric configuration (),
critically depending on the bulky groups and length of the
spacers. Fascinatingly, the chiral microenvironments of the
triple-stranded helicates involving molecular helicity, cavity sizes,
chiral recognition sites, and hydrophobic surfaces can be finely
tuned through the deployment of the pre-designed chiral ligands.
It was found that the binding affinities and enantioselectivities of
the helicates are significantly influenced by the hydrophobic
effect and cavity sizes, leading to highly enantio- and helix-
sense-selective recognition for a variety of chiral amino alcohols
(up to 9.35), as unambiguously revealed by extensive
experimental and theoretical results.
Results and Discussion
NH2
NH2
OR
OR
OR
OR
NH2
Figure 2. (a) Partial 1H NMR spectra of L1 (up) and H-1 (down). (b) Partial 1H
NMR spectra of L3 (up) and H-3 (down). 2D DOSY spectra of H-1 (c) and H-3
(d). Experimental (Q-TOF-MS) and calculated isotope patterns of H-1 (e, f), H-
3 (g, h).
L1: OR = OH
L2: OR = OMOM
NH2
L3: OR = OH
L4: OR = OMOM
O
N
ZnII
=
Axially chiral molecules have been extensively used to
develop optically functional materials with excellent
enantioselective processes at the macroscopic scale, such
as metal-organic frameworks (MOFs)[20] and covalent
organic frameworks (COFs).[21] In particular, our previous
N
N
work has shown
a series of 1D helical coordination
N
N
polymers that were formed by the assembly of chiral 1,1′-
biphenyl-type ligands with C2-symmetric coordinated Ag(I)
ions.[22] In this study we employ such axially chiral ligands to
construct discrete chiral helicates at the microscopic level.
OR
OR
OR
OR
The enantiopure ligands L1 L2 L3 and L4 were prepared
, ,
from (R)/(S)-appropriate diiodinated biphenol derivative
through several steps with 42%, 40%, 15% and 12% overall
yields, respectively. Full descriptions of the syntheses and
characterizations for these ligands and intermediates are
provided in Supporting Information (Figure S1-S15).
Notably, it is impressive to observe that the chiral ligands
are able to retain the high optical purity of the starting
biphenol-type molecules after multi-step synthesis. For
N
N
N
N
OR = OH,
OR = OMOM, H-2
H-1
OR = OH,
OR = OMOM, H-4
H-3
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10.1002/anie.202104111
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example, the optical purity of L1 and L2 exceeds 95%
enantiomeric excess (ee) value (Figure S16-S17), which is
beneficial to assemble homochiral helicates with
outstanding enantioselective recognition properties. As
Single-crystal X-ray diffraction study on H-1 evidenced the
formation of helically triple-stranded complex. H-1 crystallizes in
the chiral trigonal R32 space group (Table S1-S2), with one third
formula unit in the asymmetric unit (Figure 3a,b). The complex is
composed of three L1 strands and two Zn2+. The dinuclear Zn2+
locates on the vertices and three bis-bidentate ligands helically
wrap and coordinate to it. Each metal center is approximately
octahedral six-coordinated by bidentate chelating moieties with a
mean average Zn–N bond length of 2.15 Å. The Zn-to-Zn
distance is 13.7 Å and both metal centers are shown to be
homoconfiguration (), thus resulting in homochiral
characteristic that arises from facial (fac) stereochemistry
(Figure 3c-d). By combining the chiral ligands, P-configured
helical conformation, and the same handedness of metal centers,
it has been suggested that H-1 is capable of intriguing chiral
shown in Scheme 1, the reactions between ligand
L (3
equiv.), 2-formylpyridine (6 equiv.), and Zn(OTf)2 or
Zn(BF4)2 (2 equiv.) in acetonitrile at 70 °C produce helicates
H-1-4 with general formula [(Zn2L3)A4]G (L = , ,
L1 L2 L3 and
L4, A = counter anion, G = guest molecule) as the uniquely
observed product. 1H nucleus magnetic resonance (NMR)
spectra of
H-1 displayed one set of ligand resonances
(Figure 2a and Figure S18), suggesting the formation of
discrete and highly symmetric metal-organic assemblies.
1
Similarly, the H NMR signals of
H-3 and H-4 revealed that
they have symmetric structures (Figure 2b and Figure S19-
S22). While showed two sets of equivalent ligand
H-2
resonances (Figure S23-S24), meaning that the structure
was distored which may arise from C2 symmetry missing of
biphenol in the helical complex. In all cases all of the proton
signals are very sharp, implying the formation of discrete
metal complexes rather than oligomeric species,[14b] as
further confirmed via two-dimensional (2D) 1H–1H
correlation spectroscopy (COSY) (Figure S27-S30) and 1H–
1H nuclear Overhauser effect spectroscopy (NOESY)
experiments (Figure S31-S34). Furthermore, 1H NMR
chemical shift on aromatic rings of ligands L1 (Ha,c) and L3
(Ha,b,c,g,f) appeared upfield attributed to the coordination
with Zn2+ (Figure 2a,b). 2D Diffusion-ordered spectroscopy
(DOSY) experiments also confirmed the formation of a
characteristic
that
is
expected
to
mimic
natural
biomacromolecule. Additionally, H-1 has a nanosized cavity
(12.5 Å × 4.8 Å × 4.8 Å) and entrance window (6.3 Å × 5.4 Å)
occupied by guest molecules. Notably, the resultant
microenviroment contains six hydroxyl groups that oriente
toward inside of the pores accessible to guest molecules.
single species with diffusion coefficients of 6.3×10-10
6.6×10-10, 5.1×10-10, and 4.0×10-10 m2 s-1 for
to H-4
,
H-
1
(Figure 2c,d and Figure S35-S36), respectively. Dynamic
diameters of these helicates determined by diffusion
coefficients showed a increased size from
are in good agreements with their molecular structures.
The formation of triple-stranded helicates 1-4 was
H-1 to H-4, which
H-
further identified by Quadrupole time-of-flight mass
spectrometry (Q-TOF-MS), which are well consistent with
the expected Zn2L3 stoichiometry. Each spectrum exhibited
a series of peaks with different charge states derived by the
-
loss of anions (such as BF4 or OTf-) or proton (Figure S37-
S40). For
H-1, the peaks at 675.18, and 978.28 Da can be
assigned to [Zn2(L1)3(BF4)]3+ and [Zn2(L1)3-2H+H2O]2+,
respectively. Furthermore, the experimental isotopic
patterns of two or three charge states of H-1 are in good
agreement with the simulated isotopic distributions (Figure
2e,f). In the case of
H-3 )
, as expected, highly pure Zn2(L3
3
supramolecular structure was also confirmed by the
measured peaks of 1048.34 (simulated data at 1048.32 Da)
and 749.01 Da (simulated data at 749.01 Da for
[Zn2(L3)3(OTf)]3+ and [Zn2(L3)2]4+ (Figure 2g,h), respectively.
As for
H-2 and H-4, clear assigned spectra were observed
with peaks at 905.16, 784.21, and 553.79 Da for
[Zn2(L2)2(OTf)2]2+, [Zn2(L2)3(OTf)]3+, and [Zn2(L2)3+H2O]4+,
as well as 852.75 and 563.17 Da for [Zn2(L4)3+5CH3CN]4+
and [Zn2(L4)2+2H2O]4+ (Figure S38 and S40), respectively.
Taken together, all the above Q-TOF-MS data indicate that
the C2-symmetric chiral ligands are preserved in the Zn2L3
helicates with no existence of other isomers or conformers.
Figure 3. Single-crystal X-ray structure of -H-1 (CCDC: 2047453) (a) and
its space filling model (b). (c-d) The handedness of two Zn(II) centers shows
homoconfiguration ().
Unfortunately, the weak X-ray diffraction limited the crystal
structure determination in H-2. Instead, the high-quality single
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crystal of H-2 (Fe) analogue was obtained, which has
hollow helicates with more flexible strands, wider windows, and
larger cavities relative to H-1/H-2. For example, the distance of
Zn-to-Zn in H-3 is 21.4 Å and cavity size is 19.4 Å × 6.2 Å × 6.2
Å. Impressively, by virtue of anthracene surfaces, the chiral
microenvironment within H-3 is capable of strong hydrophobic
effect that can provide multiple hydrophobic/CH−π interactions
for enhanced binding affinities and chiral discrimination
properties. To the best of our knowledge, H-3 represents a rare
example of chiral helicates with rich chiral binding sites (polar
moiety) and high-density hydrophobic walls (apolar moiety).
1
isomorphic structure with H-2 as confirmed by H and 13C NMR
(Figure S25-S26). Single-crystal X-ray diffraction data reveals
that H-2 (Fe) crystallizes in the chiral orthorhombic P21212 space
group (Table S1 and S3), with one formula unit in the
asymmetric unit (Figure 4a,b). As expected, H-2 (Fe) also
showed a M2L3-type helical structure. However, it has to be
mentioned that that the two Zn(II) centers displyed a mesomeric
configuration () (Figure 4c,d).[23] Such distinct handedness
occurred in H-2 or H-2 (Fe) may result from the relative steric
hindrance of methoxymethoxy groups, and one of the three
biphenol strands changes the twist direction to wrap around the
metal centres. The reduced molecular helicity thus profoundly
affects the chiral features of H-2. Additionally, strong
intermolecular π−π and CH···π interactions direct the packing of
the helicate H-1 and H-2 (Fe) into porous 3D structures (Figure
S41-S45).
Figure 4. Single-crystal X-ray structure of -H-2 (Fe) (CCDC: 2049627) (a)
and its space filling model (b). (c-d) The handedness of two Zn(II) centers
shows mesomeric configuration ().
Figure 5. Energy-minimized molecular structures of -H-3 (a) and -H-4 (c),
and their space filling models -H-3 (b) and -H-4 (d) based on DFT
calculations.
Numerous tries to achieve high-quality single crystals of H-
3 and H-4 are unsuccessful. We thus performed molecular
simulations to construct molecular models for H-3 and H-4 by
DFT calculations (Figure 5). Owing to the decrease of steric
hindrance within the nanocavity, the energy-minimized
structures showed that the two Zn(II) centers adopt the same
handedness with  or  configurations within H-3 and H-4.
The lengthened ligands L3 and L4 thus allow the formation of
The CD spectra of the four helicates made from (R)-
and (S)-enantiomers are mirror images of each other
indicative of their enantiomeric nature (Figure S46-S49).
Surprisingly, the self-assembled helicates accompany chiral
amplification effects. Firstly, Kuhn’s dissymmetry factors
(gabs) can be employed to evaluate the chiral amplification
behaviour.[24] In terms of UV-vis absorption and CD spectra
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of helicates H-1-4 and ligands L1-4, the obtained gabs values
of H-1 (11.0 × 10-3), H-3 (6.3 × 10-3), and H-4 (3.5 × 10-3)
are higher than their corresponding ligands L1 (1.8 × 10-3),
L3 (0.1 × 10-3) and L4 (1.5 × 10-3) (Table S4), respectively,
thus indicating the chiral transfer and amplification in the
assembly process. However, the gabs value of H-2 (5.1 × 10-
3) exhibit smaller than L2 (9.4 × 10-3), which may be
attributed to the reduction of molecular helicity through its
mesomeric configuration (). Secondly, the values of
[Zn2(L1)3+D-leucinol]4+
and
[Zn2(L1)3(BF4)+CH3CN+H2O+D-
leucinol]3+, which is consistent with the 1:1 binding stoichiometry
of fluorescence titration. Notably, control exeprments showed
that the free ligand L1 and mesomeric Δ-H-2 displayed no
obvious enantioselectivities (Figure S70-S71), unambiguously
suggesting that the chiral microenvironments and naked
hydroxyl binding sites are extremely crucial for stereoselective
recognition.
molar optical rotation (ϕ) of -H-1
and (R)-L1 are 8832.5
and 970.1 deg·cm3·dm−1·mol−1, respectively. The helicate
bearing three ligands has an optical rotation per mole that is
>9 times that of (R)-L1, meaning a 3-fold increase in optical
rotation between a set of three free ligands and a set of
three coordinated ligands. This implies that such helical-
shaped suprastructure can indeed generate unexpectedly
strong chirality amplification, which is expected to exhibit
exceptional chiral recognition ability. Similar chiral
amplifications were also observed for the other three
helicates (Table S5). Other information such as
Thermogravimetric analyses (TGA), Scanning electron
microscopy (SEM), and Brunauer−Emmett−Teller (BET)
surface areas are shown in the Supporting Information
(Figure S50-S59).
Chiral 1,2-amino alcohols are imporant compounds due to
their versatility as building blocks in the synthesis of natural
products and commercial drugs.[25] The chiral discrimination of
enantiomers of amino alcohols are therefore significant in the
fields of medicinal and biological chemistry. 19F NMR spectra
showed only one kind of chemical environment of fluorine atom
in all complexes (Figure S60-S63). By combining the crystal
structures of -H-1 and -H-2 (Fe) (Figure S42 and S45), it
has been suggested that the identified counterions reside
outside the cavities of the helicates. Fascinatingly, H-1 and H-3
containing the available recognition sites provide
a good
opportunity to realize the enantioselective recognition of chiral
1,2-amino alcohols. When H-1 and H-3 was treated with D-
leucinol or D-valinol, the UV−vis spectrum remained unchanged,
indicative of the stability of the host structure (Figure S64-
S65).[26] In contrast to the absorption spectrum, however, the
emission was changed. For instance, the fluorescence intensity
of -H-1 was enhanced by both D- and L-leucinol (G1), while
the increase caused by D-leucinol was greater than L-leucinol
(Figure S66). Furthermore, the Job plot result obtained by
fluorescence titration suggested the formation of a 1:1 host-
guest complex in this system (Figure S67). Figure 6b-c showed
Benesi−Hildebrand plots with 1:1 binding model for -H-1 in
the presence of D- and L-leucinol in CH3CN. The association
constants Ka were found to be 4201 M−1 with D-leucinol and
1059 M−1 with L-leucinol, thus giving an enantioselectivity factor
Figure 6. (a) Chemical structures of chiral amino alcohols used in this study.
Benesi−Hildebrand plots of -H-1 (b) and -H-1 (c) titration with D- and L-
leucinol. (c) Benesi−Hildebrand plots of -H-3 and -H-3 titration with L-
threninol. (e) EF values of H-1 and H-3 for chiral amino alcohols. The
concentration of helicates is 1.0
concentration of guests is 1.0 × 10-3 M in CH3CN.
× M in CH3CN (3 mL) and the
10-5
After titration with D-leucinol, the quantum yield of -H-1
increased from 13.21% to 16.98% and the fluorescence lifetimes
changed slightly from 3.46 ns to 3.56 ns (Figure S72-S73).
suggesting that the enantioselective recognition might be a static
enhancement process by the formation of a helicate−amino
alcohol adduct by combining hydrogen-bonding with
hydrophobic effects. To prove our hypotheses, we employed 1H-
1H 2D NOESY and COSY to explore the host-guest binding
(Figure S74-S75). As shown in Figure S75, the crossover
signals at (5.52, 2.05 ppm) and (5.52, 4.19 ppm) in the 2D
NOESY spectrum are assigned to the NH2 group of D-leucinol
with -H-1. Furthermore, 1H NMR titration showed that the
proton signals of -H-1 became broad and have a slight
downfield shift (Figure S76). These results indicate that the host-
guest binding occurs in the cavity of the helicate.
(EF) Ka(-D)/Ka(-L) of 3.97
± 0.04. Furthermore, the
opposite trend in enantioselectivity was observed for the
enhancement -H-1 by leucinol, for which the EF
[Ka(−L)/Ka(−D)] was 4.10 ± 0.06 (Figure 6c and Figure
S68), further confirming
a
chirality-based luminescence-
enhancing selectivity. Additionally, the 1:1 binding stoichiometry
can be further confirmed by ESI-MS, which was performed at
the identical concentration with fluorescence titration (Figure
S69). The peaks at 603.27 and 869.59 are assigned to
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Impressively, we found that the chiral microenvironments of
the helicates involving cavity sizes, chiral binding sites, and
hydrophobic effect significantly influence the binding affinities
and chiral discrimination properties. Particularly, H-3 was found
to have excellent binding affinities towards a varity of chiral
aminol alcohols including both alkyl (G1 to G7) and aryl (G8 to
G10) substrates. For most substrates, H-3 showed higher Ka
values than that of H-1 (Figure S77-S96, Table S6). Such
difference might be attributed to the strong hydrophobic effect
provided by the anthracene surface. For example, Ka values for
H-1 and H-3 upon the same enantiomer of the substrates
showed distinct difference with 1528 M-1 and 10802 M-1 for
valinol (G3), 909 M-1 and 4040 M-1 for threoninol (G7), 253 M-1
and 2816 M-1 for 3-amino-3-phenylpropanol (G8), and 420 M-1
and 4965 M-1 for tryptophanol (G9) (see Table S6), respectively,
demonstrating the higher binding affinities of H-3.
value of H-3 for valinol are obviously larger than the best-
demonstrated chiral MOF (5.37 vs 3.12).[27]
As
expected,
H-3
showed
more
prominent
enantioselectivities than H-1 as a result of the superior chiral
microenvironments. For the alkyl substates G1 to G4, H-1
exhibited a decreased trend in enantioselectivities (3.97, 2.97,
1.67, and 1.40, respectively) with the increase of bulky
resistance. While H-3 showed an increased trend (2.82, 2.02,
5.37, and 4.82, respectively) due to its larger cavity, implying
that the cavity size of the helicate is crucial for binding affinities
and enantioselectivities. For the substates G7 to G10, both H-1
and H-3 displayed decreased EF values (such as H-3: from 9.35,
2.70, 1.67, to 2.30, respectively), indicating the confined effects
(see the molecular sizes of G1-G10 in Figure S97). This
phenomenon might be explained that (1) the steric hindrance of
bulky aromatic groups probably impaired the chiral recognition
ability, as well as (2) the strong π···π and CH···π hydrophobic
interactions occupy the main host-guest interations that weaken
the hydrogen bonding Interactions. To prove our hypothesis, we
empolyed another type of chiral amino alcohols as substrates
that contain three hydrogen bonding groups (see G6 and G7).
Obviously, the enantioselective performance of both H-1 and H-
3 were the highest among all substrates, implying that the
formations of more hydrogen bonds can greatly enhance the
chiral recognition. Moreover, comparing enantioselectivities of
H-1 with H-3 for G6 and G7, the higher EF values for H-3 further
indicate that the hydrophobic effect played a vital role in binding
affinities and chiral discrimination properties. To further reveal
the importance of chiral binding sites within the
microenviroments, we performed the control experiments using
H-4 containing OMOM (methoxymethyl ether) protecting groups
(Figure S98-S99). As expected, the EF values of H-4 titrated by
D/L-leucinol and D/L-valinol are only 1.14 and 1.13, respectively,
which are smaller than H-3 (2.82 for D/L-leucinol and 5.37 for
D/L-valinol, respectively), highlighing the chiral binding sites
Figure 7. The host-guest conformation and binding energies of D-valinol@-
H-1 (a), L-valinol@-H-1 (b), D-valinol@-H-3 (c), L-valinol@-H-3 (d)
based on energy-minimized DFT calculations.
within
the
nanocavity
profoundly
influence
the
enantioselectivities of the helicates. Taken together, H-3
possesses larger hollow cavity, rich chiral binding sites, and
high-density hydrophobic surfaces, leading to an exceptional
enantioselectivity of 9.35 for threoninol. Despite many cavity-
containing chiral materials inlcusing MOFs, COFs, metallacages,
and metallacycles for chiral recognition have been developed,[9]
the present H-3 has been shown to exhibit a superior enantio-
and helix-sense-selective recognition. For example, the EF
In an effort to understand the importance of the chiral
microenviroments for enantioselective recognition, we thus
carried out both experimental studies and theoretical
calculations. On the one hand, it is interesting to note that very
weak enantioselectivity (EF value of 1.51 ± 0.08) was observed
for the luminescence enhancement of -H-1 by D/L-N-Boc-
protected leucinol (Figure S86), which implies the involvement of
NH2 groups in the formation of a ground-state hydrogen-bonded
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10.1002/anie.202104111
Angewandte Chemie International Edition
RESEARCH ARTICLE
complex. On the other hand, energy-minimized DFT calculations
were performed to study the driving forces of host-guest binding
within the chiral microenvironments of H-1 and H-3.[28] We chose
D/L-valinol as guests in terms of the greatest difference on EF
values for H-1 and H-3 (1.67 vs 5.37). The conformation and
binding energies of both enantiomers were evaluated by
inserting -H-1 and -H-3 and performing energy
minimization for the host−guest structures. As shown in Figure 7,
the optimized structures showed that there have several host-
guest interactions including hydrogen bonds (OH···N or OH···O)
(2.2 ~ 2.8 Å) as well as π···π and CH···π interactions (3.0 ~ 4.0
Å). For the host-guest complexes D-valinol@-H-1, L-
valinol@-H-1, D-valinol@-H-3, and L-valinol@-H-3, the
binding energies were calculated to be -19.76, -17.46 -23.68 and
-20.64 kcal mol-1, respectively. The negative values of binding
energies suggest that the hollow helicates are avaliable to
encapsulate the enantiomers. Furthermore, the binding energies
for D-valinol were more negative to that for L-valinol in both
helicates, indicating a stronger host-guest interaction of -H-1
and -H-3 with D-valinol than L-valinol which result in
enantioselective recognition. In particular, the anthracene
groups within -H-3 can provide more hydrophobic surface for
binding guest molecules, thus giving rise to a stronger host-
guest interaction (-23.68 vs -19.76 kcal mol-1) (Figure 7a and 7c).
The theoretical calculations are well consistent with the
experimental results, unambiguously revealing the critical
importance of the chiral microenviroments for chiral recognition.
Acknowledgements
This work was financially supported by the National Science
Foundation of China (Grant Nos. 91956124, 21875136,
21901164, 21620102001 and 91856204), the National KeyBasic
Research Program of China (2016YFA0203400), Key Project of
Basic Research of Shanghai (18JC1413200 and 19JC1412600),
Shanghai Sailing Program (19YF1436100) and Shanghai
Chenguang Project (18CG48).
Conflict of interest
The authors declare no conflict of interest.
Keywords: Helicates • Coordination complexes • Self-assembly
• Chiral microenvironments • Enantioselective recognition
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Entry for the Table of Contents
We report the self-assembly of a new
family of triple-stranded helicates with
fascinating chiral characteristics from
Dr. Jingjing Jiao, Dr. Jinqiao Dong,
Yingguo Li, and Prof. Yong Cui*
Page No. – Page No.
axially
chiral
1,1′-biphenyl-type
ligands. The fine-tuning of chiral
microenvironments within the well-
defined complexes has enabled
Fine-Tuning
Microenvironments
Stranded Helicates for Enhanced
Enantioselectivity
of
Chiral
within Triple-
outstanding
chiral
discrimination
properties, leading to highly enantio-
and helix-sense-selective recognition
for chiral amino alcohols (up to 9.35).
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