Chirality sensing of choline derivatives by a triple anion helicate cage through induced circular dichroism

Article abstract of DOI:10.1039/c8cc03883j

Chirality sensing of choline derivatives is achieved by a self-assembled, racemic triple anion helicate cage which exhibits induced circular dichroism (ICD) upon encapsulation of a chiral guest. The host-guest interactions were illustrated by NMR, crystal

Full text of DOI:10.1039/c8cc03883j

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: W. Zuo, Z. Huang,
Y. Zhao, W. Xu, Z. Liu, X. Yang, C. Jia and B. Wu, Chem. Commun., 2018, DOI: 10.1039/C8CC03883J.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
Page 1 of 5
ChemComm
View Article Online
DOI: 10.1039/C8CC03883J
Journal Name
COMMUNICATION
Chirality sensing of choline derivatives by a triple anion helicate
cage through induced circular dichroism
Received 00th January 20xx,
Accepted 00th January 20xx
Wei Zuo, Zhe Huang, Yanxia Zhao, Wenhua Xu, Zhihua Liu, Xiao-Juan Yang, Chuandong Jia,* and
Biao Wu*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Chirality sensing of choline derivatives is achieved by a self-
assembled, racemic triple anion helicate cage which exhibits
induced circular dichroism (ICD) upon encapsulation of a
chiral guest. The host-guest interactions were illustrated by
NMR, crystal structure, CD and DFT calculations. The absolute
configurations and ee values were determined by ICD.
Choline and its derivatives, such as acetylcholine,
methylcholine and carnitine, play important roles in biological
systems.1 When the molecule is chiral, the biological activity is
closely related to its chirality. For examples, R(+)-α-
Scheme 1. (a) Structures of chiral quaternary ammonium ions G1−G7 (cations were
−
used as PF6 salts) (b) The proposed host-guest system for chiroptical sensing of
quaternary ammonium ions with the triple anion helicate host, [(PO4)2L3]6- (H).
methylcholine and S(+)-β-methylcholine (Scheme 1a, (R)-G1
,
(S)-G2) are significantly better inhibitors of the high-affinity
choline transport system than their enantiomers.2 L-carnitine
(Scheme 1a, (R)-G3) has important pharmacological and
nutritional functions and is used as a drug for the therapy of
dislipoproteinemia, anorexia, and dyspepsia, while D-carnitine
is harmful to human health.3,4 Therefore, it is essential to
determine the enantiomeric purity of these biomolecules.
Chirality sensing is commonly realized by chiral
chromatography, NMR spectroscopy and various optical
methods.5 The circular dichroism (CD) is especially attractive
because of such advantages as simultaneous determination of
both of the absolute configuration and enantiomeric excess
(ee) values, and concentration-independent spectral
response.6 However, since many chiral species lack a strong
chromophoric group, direct chirality sensing by CD is not
applicable. Alternatively, these CD-silent analytes, such as
amines, alcohols, amino alcohols, amino acids, carboxylic acids
and epoxides are generally sensed by induced circular
dichroism (ICD) of reporter molecules which are held nearby
via a dynamic covalent (derivation system)7 or noncovalent
binding event (host-guest system), such as metal
coordination,8 hydrogen bonding,9 hydrophobic effect,10 and
••• stacking.11
Determination of the enantiomeric purity of some chiral
quaternary ammonium ions (including G3, G4 and G6) was
achieved by NMR spectroscopy using chiral macrocycles or
counter anions as the chiral shift agents.12 The ICD method
was employed to detect the absolute configuration G4 and G6
by achiral hosts such as p-sulfonatocalix[n]arenes10c or a single
helical resorcinol oligomer.11b However, chirality sensing of α-
/β-methylcholine (G1
, G2) and carnitine (G3) through ICD has
not been reported yet. We recently reported a triple anion
6−
helicate cage, [(PO4)2L3
biomimetic aromatic box capable of binding choline and
acetylcholine through cation-
and electrostatic interactions.13
Considering the inherent chirality and guest encapsulation
ability of , we set to exploit its possible use for sensing chiral
]
(H, host), which features a

H
choline analogues.
Though there is no chiral ligand in the triple helicate
structure of
nonsymmetric arrangement of the ligands. In the absence of
guests, the host exists as a racemic mixture of P and M
conformers and is thus CD silent. When encapsulating a chiral
(non-racemic) guest, due to the different binding affinities, the
balance between P and M conformers will be broken and the
H
, supramolecular chirality14 is encoded through
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the
Ministry of Education, College of Chemistry and Materials Science, Northwest
University, Xi’an 710069 (China).
E-mail: jcd2015@nwu.edu.cn (C.J.); wubiao@nwu.edu.cn (B.W.)
† Electronic Supplementary Information (ESI) available: Synthetic procedures,
characterization and computations (PDF), and corresponding CIF files (CIF). CCDC
1815936. For ESI and crystallographic data in CIF or other electronic format see
DOI:10.1039/x0xx00000x
H
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 5
COMMUNICATION
Journal Name
supramolecular chirality is expressed as either P or M (ICD
signals), thus enabling the chirality detection. Herein we report
View Article Online
DOI: 10.1039/C8CC03883J
the ICD-based studies on host
H with choline derivatives,
including determination of the absolute configuration,
association constants, and ee values. Without the requirement
of guest-derivation, this host-guest system enables real-time
monitor of guest chirality. To elucidate the influence of
substituents on the chirality sensing, seven pairs of analytes
were examined, including
methylcholine (G2), D,L-carnitine (G3) and analogues with
phenyl-, naphthyl-, and cyclohexyl groups (G4 G7) (Scheme 1).
-methylcholine
(G1),
-
–
1H NMR spectra (400 MHz, MeCN-d3) reveal the binding of
H
toward the guests ±G1−±G7 by upfield shifts of the ‘Me3N+’
signals (H = −0.4 to −2.5 ppm compared with free guests),

which is
trimethylammonium head of the guest in the aromatic box of
(Figs. 1a and S21−26).13 As estimated by the upfield shifts,
G2 H = −2.5 ppm) and ±G1 H = −2.3 ppm) showed the
strongest binding, followed by ±G5 H = −1.4 ppm), ±G4
H = −1.2 ppm), ±G7 H = −0.9 ppm), ±G6
a clear indication of encapsulation of the
H
±
(
(
(

(
(
(H = −0.7



ppm) and ±G3 (H = −0.4 ppm).
In the case of ±G1, guest encapsulation was further
supported by the crystal structure of the complex
(TBA)5[(±G1
which is composed of equal amounts of (R)-G1
G1 (P)- , indicating the enantioselective binding of (R)-G1
and (S)-G1 by (M)- and (P)- , respectively (Fig. 1b). The
trimethylammonium head of G1 is included in the ‘aromatic
box’ of through electrostatic and cation–
interactions15
(blue dashed lines, N•••centroid distances: 4.467−5.573 Å,
average 4.810 Å, Fig. S27). The methyl group (H , Fig. 1a) of
G1 forms CH••• interaction with one phenyl group of
(C•••centroid distance: 3.686 Å, Fig. S27). Notably, the hydroxyl
tail of G1 is also located inside the cage and donates a
hydrogen bond to one oxygen atom of a phosphate ion (O•••
)

(PO4)2L3] (±G1

H
; TBA = tetrabutylammonium),

(M)- and (S)-
H

H
H
H
Fig. 1 (a) 1H NMR spectra (400 MHz, MeCN-d3) of
proton signals). (b) X-ray single-crystal structures of
(R)-G1(M)-H and (S)-G1(P)-H (counter cations, solvent molecules, and non-acidic
protons are omitted for clarity). (c) UV−vis spectrum (dotted line) and CD spectra of H
(10 M, MeCN) before and after addition of one equiv. of enantiomers of G1 and G4.
±
G1,
±
±
G1H and H (Insets: enlarged

H

G1H, showing enantiomers of


H
reconsider the proposed binding mode of choline (Ch) in our
previous studies.13 Based on the DFT optimized structure of

O
ChH
, it was assumed that the Me3N+ head was encapsulated
= 2.887 Å,

OHO = 170o).
The H NMR results of ±G1
1
H
(TBA+ as the countercation,
in the aromatic box of
H while the hydroxyl tail was bound in

the outside by two urea oxygen atoms (instead of by PO43− ion
Fig. 1a) match well with the crystal structure. Upon
encapsulation by , the signals of H  = −2.3 ppm), H 
= −3.2 ppm) and H  = −2.3 ppm) of ±G1 all display
significant upfield shifts (that of the methylene H could not
1
as observed for ±G1). A comparison of the H NMR spectra of
complexes ChH and ±G1H reveals almost same features
H

(
 (

(
(except that the OH signal of Ch could not be assigned due to

severe broadening, Fig. S35). Large upfield shift of Me3N-+ of
be assigned due to signals overlap), demonstrating the
shielding effect imposed by the aromatic cage. The OH signal
shows a large downfield shift ( = 2.8 ppm), while the urea
Ch ( = −2.4 ppm) and downfield shift of NHa of
H ( = 1.0
ppm) were observed, implying that the hydroxyl tail of Ch is
possibly bound by the phosphate ion rather than by urea
oxygen atoms. To further elucidate this issue, DFT
NHa signal of host
H shifts back to upfield by −1.0 ppm (see
Scheme 1a for proton numbering). These changes are
consistent with the hydrogen bonding interaction between OH
computations were carried out on ChH. Both binding modes
3−
for OH group (Model I, with phosphate ion; Model II, with two
urea oxygen atoms; Fig. S36) were optimized, with the mode I
being more energetically favored by 9.72 kcal mol−1 (Table S2).
Since the crystal structure of
enantioselective binding of (R)-G1 and (S)-G1 by (M)-
(±G1) and one coordinated PO4 (the interaction with
hydroxyl weakens the binding of PO43− with NHa). The 2D NMR
spectra of ±G1
(±G1)/NHa-c (
Additionally, HRMS studies confirmed the formation of a

H
H
show strong NOE correlations between OH
) and Me3N+ (±G1)/H2 (
H
) (Fig. S28−S32).
±G1
H
reveals
H
and (P)-
H
, respectively, it is resonable to assume that the binding of a
chiral (non-racemic) guest would induce enhanced population
of (M)- or (P)- , and thus allows detection of the ICD signals
of , which is correlated with the guest chirality. With this in
mind, chirality sensing of guests G1−±G7 by was
complex
with
the
stoichiometry
[(PO4)2L3(±G1)]
([(PO4)2L3(±G1)(TBA)3]2−, obsd. 1709.8159 vs cald. 1709.8288,
Fig. S34).
H
H
H
It should be mentioned that the dual-site binding mode of
±
H
±G1 (-methylcholine) presented herein prompts us to
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 5
ChemComm
Please do not adjust margins
Journal Name
investigated by CD measurements. Either
COMMUNICATION
H
or enantiomers of
View Article Online
DOI: 10.1039/C8CC03883J
±G1−±G7 do not show obvious signals throughout the tested
wavelength range (230−500 nm, Fig. 1c, S38) in MeCN.
However, with addition of 1.0 equiv of an enantiomer of guest
to the solution of
positive, three negative) were observed in the region where
absorbs (230−450 nm, Fig. 1c, see UV-Vis spectrum of ). All
H (10 M), strong Cotton effects (three
H
H
guests induced similarly shaped CD spectra and each pair of
enantiomers induced perfectly mirror imaged spectra (Fig. 1c,
S39). Noticeably, ±G1−±G3 and ±G4−±G7 induced contrary
chirality correlation between the guest’s chirality (R or S) and
the host’s helicity (P or M). For example, the CD spectrum of
and (R)-G1 shows a maximum positive Cotton effect at max
H
=
261 nm, while addition of (R)-G4 caused one negative Cotton
effect at max = 262 nm (Fig. 1c). According to the crystal
structure of G1
and the induced helicity was assigned as M. In contrast, the
helicity induced by (R)-G4 was P. Consistently, DFT caclutions
H (Fig. 1b), (R)-G1 prefers to be bound by (M)-
H
indicated that the optimized structure of (R)-G4

(P)-
H is 10.7
kcal mol−1 lower in energy than (R)-G4
(M)-H (Fig. S37 and
Table S3).
The association constants between
G1 G7 were determined by CD titrations. Following
incremental addition of a chiral guest to , the CD signals
H and enantiomers of
−
H
gradually increased till reaching saturation (Fig. S40, Table 1).
The appearance of clear isodichroic points at 252, 270, 284,
304, 377 nm suggests that the equilibrium involves a single
Fig. 2 (a) CD spectra of H (10 M, MeCN) in the presence of 2 equiv. of G1 with various
ee values, and (b) the corresponding ee calibration plots at 246, 261, 292 and 350 nm.
stoichiometric relationship between
determined as 1:1 by the Job’s plot (Fig. S41). The intensity of
the strongest CD signal ( ) for G1 G7 at max = 259−262 nm
(Table 1) was plotted against the concentration of a guest
enantiomer, and the titration profiles were subjected to least-
squares nonlinear fiting to a 1:1 binding model by Dynafit
program.16 As shown in Table 1, each pair of enantiomers
shows almost the same association constant and the
H and G, which was
underestimated. Upon formation of the host-guest complex,
±
±
G1 and ±G2 show larger changes of the chemical shifts than

−
G4−±G7 due to the dual-site binding of both of the Me3N+
head and OH tail. The charge neutral zwitterion ±G3 displays
the smallest Ka which is reasoned by the lack of electrostatic
interactions with the host
H. The stronger binding of ±G6 than
±G4 may be attributed to the stronger ••• interactions of the
aryl tail of the guest with the host, which is indicated by the
selectivity of
G5 > ±G6 > ±G4 > ±G7 > ±G3. This tendency is consistent with
the NMR results except that the binidng affinity of ±G6 was
H for the tested guests is in the order ±G2 > ±G1 >
upfield shifts of the guest’s phenyl protons in the 1H NMR
±
spectra of ±GH (Fig. S23-24 and S26). Finally, the weaker
binding of the cyclohexyl-functionalized ±G7 can be attributed
to both the larger steric effect and the lack of an aromatic tail.
To evaluate the possibility of fast ee determination, CD
Table 1 Guest encapsulation induced host helicities,
association constants (Ka, M−1) of
to G1 G7.
max (mDeg)/ (nm), and
H
−
Guest
Induced
max(mDeg)/(nm)
Ka/M−1
spectra of
H were collected in the presence of G1−G7 with
varying enantiomeric compositions (Figs. 2a and S42).
Saturated equivalents of the analytes were used to ensure
concentration-independent spectral responses. For a typical
helicity
(R)-G1
(S)-G1
(R)-G2
(S)-G2
(R)-G3
(S)-G3
(R)-G4
(S)-G4
(R)-G5
(S)-G5
(R)-G6
(S)-G6
(R)-G7
(S)-G7
M
P
M
P
M
P
P
M
P
M
P
M
P
M
+36/261
-37/261
+39/261
-40/261
+42/259
-43/259
-52/262
+53/262
-59/262
+57/262
-20/261
+20/261
-22/259
+23/259
1.18 × 106
1.16 × 106
1.88 × 106
1.78 × 106
1.57 × 104
1.50 × 104
1.75 × 105
1.86 × 105
3.31 × 105
3.29 × 105
2.11 × 105
2.21 × 105
4.82 × 104
4.91 × 104
instance, the CD intensity of
H was plotted against the %ee
value of G1 at 246, 261, 292, 350 nm, which consistently
showed linear relationship (R2 = 0.9995−0.9970, Fig. 2b). CD
spectra of five “unknown” solutions of G1 were recorded and
the average errors were calculated. The lowest value,
1%,
was obtained at 261 nm (Fig 2b). Accordingly, the strongest CD
signal at max = 259−262 nm (Table 1) was selected to
determinate the ee values of
G2−G7, with acceptable
average errors of 1.0%~


1.8% (Fig. S42 and Table S4).8c
In conclusion, a self-assembled triple anion helicate cage is
capable of encapsulating chiral choline analogues to generate
strong ICD signals, which enables a real-time CD screening
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 5
COMMUNICATION
Journal Name
8
(a) K. W. Bentley, P. Zhang and C. Wolf, Sci. Adv., 2016, 2,
View Article Online
system for determination of the absolute configurations, ee
values and association constants. The presented example
combines the advantage of self-assembly of a complex host
(triple helicate cage) from simple, inexpensive starting
materials, and that of noncovalent host-guest interactions for
instant chirality sensing without the requirement of
derivatization. Further exploration of the application of such
anion-based cages in chirality recognition is underway.
e1501162; (b) X. Li, C. E. Burrell, R. J. SDtaOpI:le10s.1a0n3d9/BC.8BCoCr0h3a8n8,3JJ.
Am. Chem. Soc., 2012, 134, 9026–9029; (c) L. A. Joyce, M. S.
Maynor, J. M. Dragna, G. M. da Cruz, V. M. Lynch, J. W.
Canary and E. V. Anslyn, J. Am. Chem. Soc., 2011, 133
,
13746–13752; (d) S. J. Wezenberg, G. Salassa, E. C. Escudero-
Adán, J. Benet-Buchholz and A. W. Kleij, Angew. Chem. Int.
Ed., 2011, 50, 713–716; (e) G. Proni, G. Pescitelli, X. Huang, K.
Nakanishi and N. Berova, J. Am. Chem. Soc., 2003, 125
,
12914–12927; (f) H. Tsukube and S. Shinoda, Chem. Rev.,
2002, 102, 2389–2403; (g) X. Huang, B. H. Rickman, B.
Borhan, N. Berova and K. Nakanishi, J. Am. Chem. Soc., 1998,
120, 6185–6186; (h) X. Huang, B. H. Rickman, B. Borhan, N.
Berova and K. Nakanishi, J. Am. Chem. Soc., 1995, 117, 7021–
7022; (i) J. Am. Chem. SOC., 1995, 117, 7021-7022.
Acknowledgements
We are grateful to the financial supports of National Natural
Science Foundation of China (21701132, 21772154 and
21325102), Education Department of Shaanxi (16JS113),
Northwest University (2018212) and China Postdoctoral
Science Foundation (2016M602849).
9
(a) M. Hasan, V. N. Khose, A. D. Pandey, V. Borovkov and A. V.
Karnik, Org. Lett., 2016, 18, 440-443; (b) Y. Ishii, Y. Onda and
Y. Kubo, Tetrahedron Lett., 2006, 47, 8221–8225; (c) M.
Inouye, M. Waki and H. Abe, J. Am. Chem. Soc., 2004, 126
,
2022–2027; (d) T. Mizutani, H. Takagi, O. Hara, T. Horiguchi
and H. Ogoshi, Tetrahedron Lett., 1997, 38, 1991–1994; (e)
M. Anyika, H. Gholami, K. D. Ashtekar, R. Acho and B. Borhan,
J. Am. Chem. Soc., 2014, 136, 550–553; (f) H. Gholami, M.
Anyika, J. Zhang, C. Vasileiou and B. Borhan, Chem. Eur. J.,
2016, 22, 9235–9239; (g) M. J. Kim, Y. R. Choi, H.-G. Jeon, P.
Kang, M.-G. Choi and K.-S. Jeong, Chem. Commun., 2013, 49
11412–11414.
Conflicts of interest
There are no conflicts to declare.
Notes and references
10 (a) L.-L. Wang, Z. Chen, W.-E. Liu, H. Ke, S.-H. Wang and W.
Jiang, J. Am. Chem. Soc., 2017, 139, 8436–8439; (b) R. B.
Prince, S. A. Barnes and J. S. Moore, J. Am. Chem. Soc., 2000,
122, 2758–2762; (c) T. Morozumi and S. Shinkai, J. Chem.
Soc., Chem. Commun., 1994, 1219–1220.
1
(a) D. D. Allen and P. R. Lockman, Life Sci., 2003, 73, 1609–
1615; (b) P. H. N. Celie, S. E. v. Rossum-Fikkert, W. J. v. Dijk, K.
Brejc, A. B. Smit and T. K. Sixma, Neuron, 2004, 41, 907–914;
(c) G. Jogl and L. Tong, Cell, 2003, 112, 113-122; (d) A. Karlin,
11 (a) Y. Tsunoda, K. Fukuta, T. Imamura, R. Sekiya, T. Furuyama,
Nat. Rev. Neurosci., 2002, 3, 102–114.
N. Kobayashi and T. Haino, Angew. Chem., Int. Ed., 2014, 53
7243–7247; (b) H. Goto, Y. Furusho and E. Yashima, Chem.
Commun., 2009, 1650–1652; (c) F. Biedermann and W. M.
Nau, Angew. Chem. Int. Ed., 2014, 53, 5694–5699.
,
2
3
4
S. S. G. Ferguson, M. Diksic and B. Collier, J. Neurochem.,
1991, 57, 915–921.
J. D. McGarry and N. F. Brown, Eur. J. Biochem., 1997, 244
1–14.
,
12 (a) G.-W. Zhang, P.-F. Li, Z. Meng, H.-X. Wang, Y. Han and C.-F.
Chen, Angew. Chem. Int. Ed., 2016, 55, 5304–5308; (b) J. R.
Cochrane, A. Schmitt, U. Wille and C. A. Hutton, Chem.
Commun., 2013, 49, 8504–8506; (c) M. A. Petti, T. J. Shepodd,
J. Richard E. Barrans and D. A. Dougherty, J. Am. Chem. Soc.,
1988, 110, 6825–6840; (d) M. E. Amato, F. P. Ballistreri, S.
Gentile, A. Pappalardo, G. A. Tomaselli and R. M. Toscano, J.
Org. Chem., 2010, 75, 1437–1443; (e) K. Ito, M. Noike, A.
Kida and Y. Ohba, J. Org. Chem., 2002, 67, 7519–7522; (f) J.
(a) L. Sánchez-Hernández, M. Castro-Puyana, C. García-Ruiz,
A. L. Crego and M. L. Marina, Food Chem., 2010, 120, 921–
928; (b) L. Sánchez-Hernández, C. García-Ruiz, A. L. Crego
and M. L. Marina, J. Pharm. Biomed. Anal., 2010, 53, 1217–
1223.
5
(a) L. You, D. Zha and E. V. Anslyn, Chem. Rev., 2015, 115,
7840–7892; (b) D. Leung, S. O. Kang and E. V. Anslyn, Chem.
Soc. Rev., 2012, 41, 448–479; (c) J. Dong, C. Tan, K. Zhang, Y.
Liu, P. J. Low, J. Jiang and Y. Cui, J. Am. Chem. Soc., 2017, 139
1554–1564; (d) W. Xuan, M. Zhang, Y. Liu, Z. Chen and Y. Cui,
J. Am. Chem. Soc., 2012, 134, 6904–6907.
,
Lacour, L. Vial and C. Herse, Org. Lett., 2002, 4, 1351–1354.
13 C. Jia, W. Zuo, X.-J. Yang, Y. Chen, D. Yang, L. Cao, R.
Custelcean, J. Hostaš, P. Hobza, R. Glaser and B. Wu, Nat.
Commun., 2017, 8, 938.
6
7
(a) L. Pu, Acc. Chem. Res., 2017, 50, 1032-1040; (b) L. Pu,
Chem. Rev., 2004, 104, 1687–1171; (c) X. Zhang, J. Yin and J.
Yoon, Chem. Rev., 2014, 114, 4918–4959; (d) H. H. Jo, C.-Y.
Lin and E. V. Anslyn, Acc. Chem. Res., 2014, 47, 2212–2221.
(a) Z. Chen, Q. Wang, X. Wu, Z. Li and Y.-B. Jiang, Chem. Soc.
Rev., 2015, 44, 4249–4263; (b) C. Wolf and K. W. Bentley,
Chem. Soc. Rev., 2013, 42, 5408–5424; (c) C. Ni, D. Zha, H. Ye,
Y. Hai, Y. Zhou, E. Anslyn and L. You, Angew Chem. Int. Ed.,
2018, 1300 –1305; (d) F. Y. Thanzeel and C. Wolf, Angew.
Chem. Int. Ed., 2017, 56, 7276–7281; (e) S. L. Pilicer, P. R.
Bakhshi, K. W. Bentley and C. Wolf, J. Am. Chem. Soc., 2017,
139, 1758–1761; (f) S. L. Pilicer, P. R. Bakhshi, K. W. Bentley
and C. Wolf, J Am Chem Soc, 2017, 139, 1758–1761; (g) C.-Y.
Lin, M. W. Giuliano, B. D. Ellis, S. J. Miller and E. V. Anslyn,
14 (a) E. Yashima, N. Ousaka, D. Taura, K. Shimomura, T. Ikai
and K. Maeda, Chem. Rev., 2016, 116, 13752–13990; (b) M.
Liu, L. Zhang and T. Wang, Chem. Rev., 2015, 115, 7304–7397;
(c) M. A. Mateos-Timoneda, M. Crego-Calama and D. N.
Reinhoudt, Chem. Soc. Rev., 2004, 33, 363–372.
15 (a) D. A. Dougherty, Acc. Chem. Res., 2013, 46, 885–893; (b)
A. S. Mahadevi and G. N. Sastry, Chem. Rev., 2013, 113
2100−2138.
,
16 P. Kuzmič, Anal. Biochem., 1996, 237, 260–273.
Chem. Sci., 2016, 7, 4085–4090; (h) Z. A. De los Santos and C.
Wolf, J. Am. Chem. Soc., 2016, 138, 13517–13520; (i) X.-X.
Chen, Y.-B. Jiang and E. V. Anslyn, Chem. Commun., 2016, 52
12669–12671; (j) J.-B. Xiong, H.-T. Feng, J.-P. Sun, W.-Z. Xie,
D. Yang, M. Liu and Y.-S. Zheng, J. Am. Chem. Soc., 2016, 138
11469–11472.
,
,
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C8CC03883J
TOC
A racemic A2L3 triple anion helicate cage is able to sense chiral choline derivatives by
induced circular dichroism.