Chirality from achiral components: N,N′-bis(4-dimethylaminobenzyl) dodecane-1,12-diammonium in cucurbit[8]uril

Article abstract of DOI:10.1039/b927592d

The long alkyl chain of N,N′-bis(4-dimethylaminobenzyl)dodecane-1,12- diamine (C₁₂DA) adopts different chiral helical conformations, one left-handed and the other right-handed, when bound within the cavities of two distorted cucurbit[8]uril (Q[

Full text of DOI:10.1039/b927592d

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Chirality from achiral components:
N,N0-bis(4-dimethylaminobenzyl)dodecane-1,12-diammonium
in cucurbit[8]urilw
Xin Xiao,a Jing-Xin Liu,b Zhi-Fang Fan,a Kai Chen,a Qian-Jiang Zhu,a Sai-Feng Xuea and
Zhu Tao*a
Received 5th January 2010, Accepted 26th March 2010
First published as an Advance Article on the web 23rd April 2010
DOI: 10.1039/b927592d
The long alkyl chain of N,N0-bis(4-dimethylaminobenzyl)-
dodecane-1,12-diamine (C12DA) adopts different chiral helical
conformations, one left-handed and the other right-handed, when
bound within the cavities of two distorted cucurbit[8]uril (Q[8])
units, as unequivocally established by X-ray crystallography.
report for the first time that the dodecanyl chain of an
N,N0-bis(4-dimethylaminobenzyl)dodecane-1,12-diamine guest
(hereafter abbreviated as C12DA) is coiled in different
directions to produce chiral helical conformations within the
cavity of the host molecule Q[8].
Fig. 2 shows 1H NMR spectra of C12DA, (a) in the absence
of Q[8] and (b) in the presence of 1.0 equiv. of the Q[8] host, in
neutral D2O solution. Compared to the spectrum of the
unbound guest (Fig. 2a), only one set of signals due to the
bound C12DA guest is observed in the corresponding
1H NMR spectrum (Fig. 2b). The resonances of the protons
of the whole dodecanyl chain (e0–j0) are shifted upfield, while
those of the protons of the two terminal 4-dimethylamino-
benzyl moieties (a0–d0) of C12DA exhibit slight downfield
shifts, indicating that the long alkyl chain is entirely encapsulated
within the cavity of the host Q[8] and that the two terminal
4-dimethylaminobenzyl moieties are located at the portals of
Alkanes usually adopt fully extended conformations in solution,
the gas phase and the solid state, that minimizes steric interactions
and maximizes surface area.1 However, alkanes can adopt con-
torted conformations, such as helices or U-shapes, when bound
within some natural and synthetic hydrophobic receptors.
This phenomenon is attracting growing interest in host–guest
chemistry2–5 because folded or bent conformations of alkanes in
cavitands provide unique opportunities to study new types of
stereoisomerism and molecular recognition. More importantly,
the cavitand microenvironments provide ideal vessels for unusual
reactions and unusual conformations.
Q[8]. Thus,
a
symmetric pseudorotaxane shape of
Cucurbit[n]urils (n = 5–8; hereafter abbreviated as Q[n];
Fig. 1), a family of macrocyclic cryptands self-assembled from
acid-catalyzed condensation reactions of glycoluril and
formaldehyde, have a hydrophobic cavity and two identical
carbonyl-laced portals.6 In the past decade, much attention
has been focused on the host–guest chemistry of the Q[n]
family and excellent progress has been made by the research
groups of Mock, Kim, Isaacs, Fedin, etc.7 In particular, Kim
and co-workers reported the formation of an intramolecular
charge-transfer complex induced by inclusion in the cavity of
Q[8], which led to unusual back-folding of the guest molecule.5
More recently, they established unequivocally that alkyl
chains adopt a U-shaped conformation in the cavity of Q[8]
by using NMR spectroscopy, ITC and X-ray crystallography.5
Q[8] offers a special microenvironment in which the conformations
of alkyl chains may be regulated due to the large hydrophobic
cavity. With this background, we set out to see if chirality can
be created from achiral alkyl chains bound to Q[n]. Herein, we
C12DA@Q[8] is formed. Close inspection reveals that the
8.8 ꢀ 9.1 A (equatorial width ꢀ depth) cavity of Q[8] definitely
cannot entirely contain the 17.5 A length of the dodecanyl
chain in extended conformation, but could contain a folded
conformation, such as a helix or U-shape, although it is
impossible to presume the exact dimensional conformation
1
by H NMR spectroscopy.
X-Ray crystal structure analysis provided unequivocal
proof of the helical conformation of the alkyl chains. Slow
vapor diffusion of hydrogen chloride into an aqueous solution
containing the guest and Q[8] host resulted in the formation of
crystals of complex 1, which crystallized in space group P21/n.
The X-ray crystal structure of complex 1 (Fig. 2) clearly reveal
that there are two host–guest inclusion complexes in the unit
cell, and that in each inclusion complex the entire alkyl chain
of the C12DA guest is encapsulated within the Q[8] host by
adopting a folded conformation, while the two terminal
a Key Laboratory of Macrocyclic and Supramolecular Chemistry of
Guizhou Province, Guiyang 550025, P.R. China.
E-mail: gzutao@263.net; Fax: +86-851-3620906
b College of Chemistry and Chemical Engineering, Anhui University of
Technology, Maanshan 243002, China.
E-mail: jxliu411@ahut.edu.cn; Fax: 86-555-2311552;
Tel: 86 851 3623903
w Electronic supplementary information (ESI) available: Details of
experimental procedures for C12DA and cucurbit[8]uril and single-
crystal X-ray crystallographic data. CCDC 751114. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/b927592d
Fig. 1 Molecular structure of cucurbit[n]urils (n = 5–8).
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Obviously, in order to accommodate the helical alkyl guest and to
provide a complementary shape, the Q[8] host has to modulate its
conformation spontaneously during the encapsulation process. As
a result, the empty space of Q[8] is filled with the helical alkyl chain
and a more reciprocal conformational inclusion complex is formed.
There might be several reasons for the formation of the
unusual helical conformation of the host–guest complex. First,
ion–dipole interactions between the quaternized nitrogens on
the guest and the carbonyl oxygens at the portals of the Q[8]
host stabilize the host–guest complex. There are clearly still
strong electrostatic interactions between the host–guest partners.
Second, the hydrophobic effect of the Q[8] cavity drives the
formation of the host–guest inclusion complex. The surfaces of
the extended alkyl chain and the interior of the cavity are
covered with solvent molecules, such as water and hydrochloric
acid, and the release of solvent from these surfaces is favorable
to the entropic and enthalpic changes as the inclusion complex
forms.8 Third, size and shape complementarity of the receptor
and the helical alkyl chain must be taken into account. As has
been mentioned, longer alkane chains are seen to twist into
helical conformations to avoid empty spaces. At the
same time, the Q[8] molecule is ellipsoidally deformed to
accommodate the helical alkyl chain. These reciprocal
conformational changes maximize the host–guest interactions.
To quantify the interaction between Q[8] and C12DA, a
ratio-dependent study was carried out by recording electronic
absorption and fluorescence spectra. The free host Q[8] shows no
absorbance at l > 210 nm. Fig. 4(a) shows the variation in the
UV spectra obtained for aqueous solutions containing a fixed
concentration of C12DA (20 mM) and variable concentrations of
Q[8]. The absorption band of the guest C12DA exhibits a
progressively lower absorbance with a red shift to 267 nm as
the Q[8]/C12DA ratio is increased. The data for absorbance (A)
vs. the ratio of the number of moles (N) of the host Q[8] and
guest C12DA (Q[8]/C12DA) can be fitted by a 1 : 1 binding model
for the Q[8]–C12DA system at lmax 250 nm. This behavior is
Fig. 2 1H NMR spectra of C12DA in the (a) absence of Q[8] and in
the (b) presence of 1.0 equivalent of Q[8] in D2O at 20 1C.
4-dimethylaminobenzyl moieties of the C12DA guest reside at
the respective portals of the Q[8] host. In the crystal structure of
complex 1, each host–guest inclusion complex is surrounded by
six neighbours, stacking into a one-layer hexagonal packing. The
space between the layers is filled with water molecules, chloride
anions and [ZnCl4]2ꢂ anions, and they interact to form a
complicated hydrogen-bonding network.
Most interestingly, both host–guest inclusion complexes of
complex 1 in the unit cell have 1 : 1 stoichiometry between the
host and the guest and the respective aliphatic chains of the
guest adopt the same folded conformation in the Q[8] cavity.
However, the two alkyl chains in the respective host–guest
inclusion complexes have opposite chirality. As shown in
Fig. 3, one helical chain in complex 1 exhibits right-handedness
(a) while the other exhibits left-handedness (b).
Deformation of the Q[8] host during encapsulation was also
observed. The host Q[8] molecule has a certain degree of steric
rigidity and a D8h symmetrical conformation. To accommodate the
helical alkyl chains, both Q[8] hosts in the unit cell undergo severe
ellipsoidal deformation. In complex 1, the OꢃꢃꢃO diameters of the
carbonyl portals of the Q[8] host range from 9.347 to 10.322 A.
1
consistent with the results of the H NMR study.
Similar experiments were performed using fluorescence
spectroscopy. Fig. 5(b) shows emission spectra of the guest
C12DA obtained from aqueous solutions containing a fixed
concentration of C12DA (20 mM) and variable concentrations
of Q[8]. The emission spectra of the guest C12DA exhibit a
progressive change in fluorescence intensity with a blue-shift as
the NQ[8]/NC12DA ratio is increased. The curve of fluorescence
intensity (If) at lmax 369 nm vs. Q[8]/C12DA can also be fitted
by a 1 : 1 binding model for the Q[8]–C12DA system.
Fig. 3 X-Ray crystal structure of the two host–guest inclusion
complexes in complex 1; (a) right-handed helix (b) left-handed helix.
Solvate water molecules and anions are omitted for clarity.
Fig. 4 UV spectra of C12DA with increasing concentrations of Q[8]
and A vs. NQ[8]/NC
curve.
12DA
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Notes and references
1 E. Eliel and S. H. Wilen, in Stereochemistry of Organic Compounds,
Wiley, New York, 1994.
2 G. Zanotti, G. Scapin, P. Spadon, J. H. Veerkamp and
J. C. Sacchettini, J. Biol. Chem., 1992, 267, 18541.
3 G. W. Han, J. Y. Lee, H. K. Song, C. Chang, K. Min, J. Moon,
D. H. Shin, M. L. Kopka, M. R. Sawaya and H. S. Yuan, J. Mol.
Biol., 2001, 308, 263.
4 L. Trembleau and J. Rebek, Jr., Science, 2003, 301, 1219; A. Scarso,
L. Trembleau and J. Rebek, Jr., Angew. Chem., 2003, 115, 5657;
A. Scarso, L. Trembleau and J. Rebek, Jr., J. Am. Chem. Soc., 2004,
126, 13512; M. P. Schramm and J. Rebek, Jr., Chem.–Eur. J., 2006,
12, 5924; B. W. Purse and J. Rebek, Jr., Proc. Natl. Acad. Sci.
U. S. A., 2006, 103, 2530; D. Ajami and J. Rebek, Jr., J. Am. Chem.
Soc., 2006, 128, 5314; J. Rebek, Jr., Chem. Commun., 2007, 2777;
M. R. Ams, D. Ajami, S. L. Craig, J.-S. Yang and J. Rebek, Jr.,
J. Am. Chem. Soc., 2009, 131, 13190.
5 J. W. Lee, K. Kim, S. W. Choi, Y. H. Ko, S. Sakamoto,
K. Yamaguchi and K. Kim, Chem. Commun., 2002, 2692–2693;
Y. H. Ko, H. Kim, Y. Kim and K. Kim, Angew. Chem., 2008, 120,
4174.
6 W. A. Freeman, W. L. Mock and N. Y. Shih, J. Am. Chem. Soc.,
1981, 103, 7367; J. Kim, I. S. Jung, S. Y. Kim, E. Lee, J. K. Kang,
S. Sakamoto, K. Yamaguchi and K. Kim, J. Am. Chem. Soc., 2000,
122, 540; A. I. Day and A. P. Arnold, Int. Pat., WO 0068232, 2000;
A. Day, A. P. Arnold, R. J. Blanch and B. J. Snushall, J. Org.
Chem., 2001, 66, 8094; A. I. Day, R. J. Blanch, A. P. Arnold,
S. Lorenzo, G. R. Lewis and I. Dance, Angew. Chem., Int. Ed., 2002,
41, 275.
7 W. L. Mock, Compr. Supramol. Chem., 1996, 2, 477; O. A. Gerasko,
D. G. Samsonenko and V. P. Fedin, Russ. Chem. Rev., 2002, 71(9),
741; K. Kim, Chem. Soc. Rev., 2002, 31, 96; J. W. Lee, S. Samal,
N. Selvapalam, H.-J. Kim and K. Kim, Acc. Chem. Res., 2003, 36,
621; J. Lagona, P. Mukhopadhyay, S. Chakrabarti and L. Isaacs,
Angew. Chem., Int. Ed., 2005, 44, 4844.
Fig. 5 Fluorescence spectra of C12DA with increasing concentrations
of Q[8] and If vs. NQ[8]/NC curve.
12DA
The absorption spectrophotometric data yielded a calculated
binding constant (K) of 1.7 ꢀ 105 L molꢂ1, while the fluorescence
spectroscopy analysis yielded a value of 2.0 ꢀ 105 L molꢂ1
.
In summary, we have shown that the two identical long
alkyl chains adopt distinct coiled conformations with different
chirality when bound to two distorted Q[8] molecules. Such
different chiral conformations within the same host are rare
and may represent a key advance in understanding the
origin of chirality in life. Control of the ratio of left-handed
to right-handed helical conformations and the preparation of
homochiral complexes remain challenging issues. Work along
these lines is currently ongoing in our laboratory.
This work was supported by the National Natural Science
Foundation of China (NSFC; No. 20961002 and 20971002),
the ‘‘Chun-Hui’’ Fund of the Chinese Ministry of Educa-
tion, the Science and Technology Fund of Guizhou Province,
and the International Collaborative Project Fund of Guizhou
province. All are gratefully acknowledged.
8 E. A. Meyer, R. K. Castellano and F. Diederich, Angew. Chem., Int.
Ed., 2003, 42, 1210; B. R. Peterson, P. Wallimann,
D. R. Carcanague and F. Diederich, Tetrahedron, 1995, 51, 401.
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