Host-guest complexes of cucurbit[8]uril with some pentaerythritol derivative guests

Article abstract of DOI:10.1039/c0nj00752h

A series of first generation dendritic guests from pentaerythritol derivatives have been designed and synthesized. Investigation of the complex structures of cucurbit[8]uril (Q[8]) and the guests based on the ¹H NMR technique have revealed that the host Q[8] selectively included different branch(es) of the first generation dendritic guests and formed inclusion complexes with different structural conformations. The experimental results obtained from electronic absorption spectroscopy showed that the 1:1 ratio of Q[8]-based host-guest inclusion complexes have moderate stability with an average formation constants of 10⁴ L mol^-1. The single crystal structures of some of the guests (g5 and g6) and Q[8]-guest complexes (Q[8]-g4 and Q[8]-g6) further confirm but in some cases contradict the research results of the ¹H NMR technique and electronic absorption spectroscopy in aqueous solution. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011.

Full text of DOI:10.1039/c0nj00752h

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PAPER
Host–guest complexes of cucurbit[8]uril with some pentaerythritol
derivative guestsw
Xian-Mei Li,a Fan Fan,a Jing-Song Lu,a Sai-Feng Xue,a Yun-Qian Zhang,a
Qian-Jiang Zhu,a Zhu Tao,*a Geofferey A. Lawrance*b and Gang Wei*c
Received (in Montpellier, France) 1st October 2010, Accepted 7th February 2011
DOI: 10.1039/c0nj00752h
A series of first generation dendritic guests from pentaerythritol derivatives have been designed
and synthesized. Investigation of the complex structures of cucurbit[8]uril (Q[8]) and the guests
1
based on the H NMR technique have revealed that the host Q[8] selectively included different
branch(es) of the first generation dendritic guests and formed inclusion complexes with different
structural conformations. The experimental results obtained from electronic absorption
spectroscopy showed that the 1 : 1 ratio of Q[8]-based host–guest inclusion complexes have
moderate stability with an average formation constants of 104 L molꢀ1. The single crystal
structures of some of the guests (g5 and g6) and Q[8]–guest complexes (Q[8]-g4 and Q[8]-g6)
1
further confirm but in some cases contradict the research results of the H NMR technique and
electronic absorption spectroscopy in aqueous solution.
has been reviewed during different periods in the development
of cucurbit[n]uril chemistry.20–26 However, little research on
Introduction
Derivatives of pentaerythritol, with an initial core from which
the binding interactions between Q[n] hosts and dendrimers
has been reported27–31 although this was summarized recently
reactive or functional branch units can be introduced at the
by Kaifer.15
periphery, can be used as starting materials for the synthesis of
dendrimers1–3 or organic ligands for synthesis of metal–organic
In this work, we selected pentaerythritol as a starting
frameworks (MOFs).4–9 These show potential for applications in
material, designed and synthesized several of its first-generation
the nanoscale molecular devices and new material areas.10–14 In
or partial first-generation dendritic guests (referring to
particular, water soluble dendrimer guests can be used to study in
Scheme 1), and Q[8] as the host with a larger cavity. The
host–guest chemistry or supramolecular self-assembly.15
guests are 1,10-(2-phenyl-1,3-dioxane-5,5-diyl)bis(methylene)-
dipyridinium(g1), 1,10-(2-(thiophen-2-yl)-1,3-dioxane-5,5-diyl)-
bis(methylene)dipyridinium(g2), 1,10-(2-admintanyl-1,3-dioxane-
A hydrophobic cavity and polar carbonyl groups surrounding
the opening portals are common features of a relatively
new host or receptor family—the cucurbit[n]uril (Q[n])
5,5-diyl)bis(methylene)dipyridinium(g3), 1,10-(2,2-dimethyl-
compounds. Of known examples, the structure of cucurbit-
1,3-dioxane-5,5-diyl)bis(methylene)dipyridinium(g4), 1,10-(2,2-
[6]uril (Q[6]) was first determined and reported by Mock and
co-workers in 1981.16 About two decades later, the homologous
bis(hydroxymethyl)propane-1,3-diyl)dipyridinium(g5) and 1-(3-
bromo-2,2-bis(bromomethyl)propyl)pyridinium bromide(g6),
cucurbit[n = 5,7,8]urils (Q[5], Q[7], Q[8]) were synthesized and
reported by two groups,17,18 while cucurbit[10]uril (Q[10]),
as shown in Scheme 1.
Generally, Q[8] can accommodate two molecules to form a
formed along with Q[5], was reported in 2002.19 Since the
1 : 2 or 1 : 1 : 1 host–guest complex.21 The capability of Q[8]
structures of the Q[n]s were well known, the binding properties
provides a unique microenvironment or molecular container
of Q[n]s have been extensively studied, and the related research
to study new forms of stereoisomerism,32–39 molecular
recognition,40–45 and novel supramolecular assemblies.46–49
a Key Laboratory of Macrocyclic and Supramolecular Chemistry of
Guizhou Province, Guizhou University, Guiyang 550025,
On the other hand, the dendritic guests contain different short
branches, which offer an opportunity to investigate the selective
inclusion of Q[8] for these different branches. The investigation
of the interaction between Q[8] and these water soluble
dendritic guests has revealed that the inclusion complexes of
Q[8]-gn (n = 1–6) have different conformations but with a
fixed host : guest ratio of 1 : 1. The stability of the complexes
has been estimated by using electronic absorption spectro-
scopy and the results of this study reported in this work.
P. R. China. E-mail: gzutao@263.net; Fax: (086) 851-362-0906;
Tel: (086) 851-362-3903
b Discipline of Chemistry, School of Environment and Life Science,
The University of Newcastle, Callaghan, NSW 2308, Australia.
E-mail: geoffrey.lawrance@newcastle.edu.au
c CSIRO Materials Science and Engineering, P.O. Box 218,
Lindfield NSW 2070, Australia. E-mail: gang.wei@csiro.au;
Fax: (061) 294137044; Tel: (061)294137704
w CCDC reference numbers 791487–791490. For crystallographic data
in CIF or other electronic format see DOI: 10.1039/c0nj00752h
c
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5.00, 4.75 (4H, s, Py–CH2), 4.44, 4.16 (4H, d, dioxane CH2,
J = 12.8 Hz). MS (m/z): calcd., 514.3; found, 514.2(M+Br)+.
1,10-(2-Adamantanyl-1,3-dioxane-5,5-diyl)bis(methylene)-
dipyridinium (g3). A solution of compound (1) in Scheme 1
(1.2 g, 4.6 mmol), 2-adamantanone (0.69 g, 4.6 mmol), and a
catalytic amount of p-toluenesulfonic acid in toluene (100 mL)
was heated to reflux with a Dean–Stark trap for 8 h. The
mixture was filtered and the filtrate was evaporated under
vacuum, to leave a brown solid. The resulting solid was
washed with cold water (2 ꢁ 100 mL) and then recrystallized
from EtOH to give a white solid (4), for use in the next
reaction. The solid (4) was reacted by using procedure (g) as
shown in Scheme 1 to give a gray solid g3 (1.2 g, 55%).
1H NMR (400 MHz, H2O), d (ppm): 8.77 (4H, d, Py–H, J =
5.6 Hz), 8.54 (2H, t, Py–H, J = 8.0 Hz), 8.00 (4H, t, Py–H,
J = 6.8 Hz), 4.79 (4H, s, Py–CH2), 3.98 (4H, s, dioxane CH2),
1.39–1.63 (15H, m, adamantane). MS (m/z): calcd., 552.3;
found, 552.1(M+Br)+.
Scheme 1 Synthesis of guests g1, g2, g3, g4, g5, g6: Reagents and
conditions: (a) (CH3CO)2O, gas HBr, EtOH/HCl; (b) toluene,
p-toluenesulfonic acid, reflux; (c) DMF, pyridine, 120 1C; (d) toluene,
p-toluenesulfonic acid, reflux; (e) DMF, pyridine, 120 1C; (f)
toluene, p-toluenesulfonic acid, reflux; (g) DMF, pyridine, 120 1C;
(h) acetone, p-toluenesulfonic acid, 30 1C; (i) DMF, pyridine, 120 1C;
(j) pyridine, reflux, 48 h; (k) pyridine, TsCl, NaBr, PEG600; (l)
dioxane, pyridine, reflux.
1,10-(2,2-Dimethyl-1,3-dioxane-5,5-diyl)bis(methylene)dipyri-
dinium (g4). A solution of 2,2-bis(bromomethyl) propane-1,3-
diol, 1 in Scheme 1, (0.80 g, 3.1 mmol), and a catalytic amount
of p-toluenesulfonic acid in 100 mL acetone was heated to
30 1C for 4 h, then concentrated to 10 mL. After cooling, the
mixture was poured into saturated NaHCO3 (100 mL). The
resulting precipitate was filtered and washed with cold water
(3 ꢁ 100 mL) then dried at 40 1C to give a white solid (5) in
Scheme 1, to be used for the next reaction. To a stirred
solution of pyridine (0.38 mL, 4.6 mmol) in DMF (50 mL)
was added a solution of compound (5) (0.70 g, 2.3 mmol) in
DMF (20 mL) at 120 1C and the resulting reaction mixture
was refluxed for 48 h, then concentrated to 5 mL. Acetone
(100 mL) was added to precipitate the product. The
resulting gray precipitate was filtered and washed with acetone
(3 ꢁ 100 mL) then dried at 80 1C to give g4 (0.43 g, 40%)
as a white solid. 1H NMR (400 MHz, H2O), d (ppm): 8.81
(4H, d, Py–H, J = 6.0 Hz), 8.57 (2H, t, Py–H, J = 15.6 Hz),
8.05 (4H, t, Py–H, J = 14.0 Hz), 4.82 (4H, s, Py–CH2), 4.51
(4H, s, dioxane CH2), 1.00 (6H, s, –CH3). MS (m/z): calcd.,
460.2; found, 460.2(M+Br)+.
Experimental
Materials
Unless otherwise indicated, all commercially available starting
materials were used directly without further purification.
DMF was dried by CaH2. Silica gel Sorbent Technologies
200–300 mm were used for flash column chromatography.
Syntheses
1,10-(2-Phenyl-1,3-dioxane-5,5-diyl)bis(methylene)dipyri-
dinium (g1). Benzaldehyde (1.0 g, 9.4 mmol) was reacted by
using procedures (b) and (c) as shown in Scheme 1 to give a
yellow solid, which was recrystallized from ethanol–
chloroform(4 : 1), and a white solid g1 (1.1 g, 56%) was
1
obtained. H NMR (400 MHz, H2O), d (ppm): 8.85 (2H, d,
Py–H, J = 11.2 Hz), 8.75 (2H, d, Py–H, J = 5.2 Hz), 8.62
(1H, t, Py–H, J = 15.6 Hz), 8.42 (1H, t, Py–H, J = 16.0 Hz),
8.11 (2H, t, Py–H, J = 14.8 Hz), 7.94 (2H, t, Py–H, J =
14.4 Hz), 7.25 (3H, m, Ar–H, J = 26.4 Hz), 6.89 (2H, d, Ar–H,
J = 7.2 Hz), 5.379 (1H, s, Ar–CH), 5.04, 4.76 (4H, s,
Py–CH2), 4.42, 4.13 (4H, d, dioxane CH2, J = 12.4 Hz). MS
(m/z): calcd., 508.2; found, 508.2(M+Br)+.
1,10-(2,2-Bis(hydroxymethyl)propane-1,3-diyl)dipyridinium (g5).
A solution of 1 (1.0 g, 3.8 mmol) in pyridine (100 mL) was
heated to reflux for 48 h, then cooled. A white solid
which precipitated out was filtered off, washed with acetone
(3 ꢁ 100 mL), and dried at 80 1C to give g5 (0.67 g, 48%) as a
1
white product. H NMR (400MHz, H2O), d (ppm): 8.78 (4H,
d, Py–H, J = 6.8 Hz), 8.50 (2H, t, Py–H, J = 14.4 Hz),
8.00 (4H, t, Py–H, J = 14.4 Hz), 4.75 (4H, s, Py–CH2),
3.10 (4H, s, CH2OH). MS (m/z): calcd., 420.1; found,
420.2(M+Br)+.
1,10-(2-(Thiophen-2-yl)-1,3-dioxane-5,5-diyl)bis(methylene)-
dipyridinium (g2). Thiophene-2-carbaldehyde (1.5 g, 13.4 mmol)
was reacted by using procedures (d) and (e) as shown in Scheme 1
to give a brown solid which was recrystallized from methanol, a
1-(3-Bromo-2,2-bis(bromomethyl)propyl)pyridinium bromide
(g6). A solution of pentaerythritol tetrabromide (6) (2.0 g,
5.2 mmol) and pyridine (0.41 mL, 5.2 mmol) in dioxane
(100 mL) was refluxed for 24 h, then concentrated until the
mass solid precipitated. The brown solid was filtered and
washed with ether (3 ꢁ 60 mL). The needle product g6
(0.48 g, 20%)was obtained after recrystallization from methanol.
1
gray solid g2 (2.5 g, 37%) was obtained. H NMR (400 MHz,
H2O), d (ppm): 8.84 (2H, d, Py–H, J = 5.6 Hz), 8.76 (2H, d,
Py–H, J = 6.4 Hz), 8.62 (1H, t, Py–H, J = 15.6 Hz), 8.47 (1H, t,
Py–H, J = 8.0 Hz), 8.10 (2H, t, Py–H, J = 8.0 Hz), 7.95 (2H, t,
Py–H, J = 8.0 Hz), 7.29 (1H, d, thiophene-H, J = 6.4 Hz), 6.89
(2H, m, thiophene-H, J = 16.4 Hz), 5.65 (1H, s, thiophene–CH),
c
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Table 1 Crystallographic data for the compounds g5, g6, Q[8]-g4, Q[8]-g6
Compounds
g5
g6
Q[8]-g4
Q[8]-g6
Empirical formula
Formula weight
C15H23N2O3.5Br2
447.17
C10H13NBr4
466.85
C66H104N34O34Br2
2077.67
C58H110.5N33O40.5Br3.5Cl
2233.43
Crystal system
Space group
a/A
b/A
c/A
a (1)
b (1)
g (1)
V/A3
Z
Orthorhombic
P b c n
9.339(8)
15.689(14)
12.461(11)
90.00
Monoclinic
P 21/c
13.284(3)
9.1181(18)
11.576(2)
90.00
Monoclinic
P 21
18.139(5)
21.311(5)
22.340(6)
90.00
Orthorhombic
P 21 21 2
25.514(4)
27.351(4)
12.6917(18)
90.00
90.00
90.00
90.00
97.245(7)
90.00
90.915(3)
90.00
90.00
1826(3)
4
1390.9(5)
4
8635(4)
4
8857(2)
4
l/A
0.71073
1.629
900
0.71073
2.229
880
0.71073
1.601
4336
0.71073
1.675
4612
D calcd., g cmꢀ3
F 000
T/K
293
293
223
223
m(Mo-Ka)/mmꢀ1
Unique reflns
Obsd reflns
Params
4.456
1620
1128
97
11.544
2719
1999
1.047
27095
21096
2199
1.733
15516
9360
136
987
Rint
0.0557
0.0327
0.0772
0.0772
0.0478
0.1155
0.0401
0.0599
0.1571
0.034(2)
0.0923
0.0697
0.1692
0.340(10)
R[I > 2s(I)]a
wR[I > 2s(I)]b
Flack value
a
b
Conventional R on Fhkl: SJFo| ꢀ |FcJ/S|Fo|. Weighted R on |Fhkl|2: S[w(Fo2 ꢀ Fc2)2]/S[w(Fo2)2]1/2
.
1H NMR (400 MHz, H2O), d (ppm): 8.78 (2H, d, Py–H, J =
6.8 Hz), 8.50 (H, t, Py–H, J = 14.4 Hz), 8.00 (2H, t, Py–H,
J = 14.4 Hz), 4.75 (2H, s, Py–CH2), 3.43 (6H, s, Br–CH2).
6.67. Found: C, 42.76; H, 4.92; N, 6.58, and for C10H13NBr4
(g6): C, 25.73; H, 2.81; N, 3.00. Found: C, 25.57; H, 2.87;
N, 2.89.
Preparation of single crystal of compound {Q[8]-g4}
Instrumentation and measurements
A solution containing Q[8] (0.15 g, 0.10 mmol) and g4 (0.09 g,
0.20 mmol) in water (10 mL) was heated at 70 1C for 10 min,
then filtered and the filtrate was allowed to stand at room
temperature. Rock X-ray quality crystal formed after two
weeks with a yield of 25%.
ESI MS spectra for the pentaerythritol derivatives were obtained
on an HPLC-MSD-Trap-VL spectrometer without using the
LC part. For the study of host–guest complexation of Q[8] and
the title guests, samples of 1.0–2.0 mg of one of the guests in
B0.5 mL D2O were prepared containing enough of the host
Q[8] (note: the excess Q[8] is insoluble and precipitates in
NMR tubes). The 1H NMR spectra were recorded at 20 1C on
a Varian INOVA-400 spectrometer. Absorption spectra of the
host (Q[8])–guest (pentaerythritol derivatives) complexes were
recorded on an Agilent 8453 spectrophotometer at room
temperature. Aqueous solutions of the bromide salts of the
pentaerythritol derivatives were prepared with a concentration
of 1.0 ꢁ 10ꢀ3 mol Lꢀ1. These stock solutions were combined
to give solutions containing a fixed guest concentration of
6.0 ꢁ 10ꢀ5 mol Lꢀ1 in each solution with a Q[8] : guest ratio of 0,
0.2 : 1, 0.4 : 1, 0.6 : 1, 0.8 : 1, 1 : 1 etc., and each solution was
characterized by absorption spectroscopy. Determination of K
values was performed and error analyses carried out as
described by us elsewhere.50
Preparation of single crystal of compound {Q[8]-g6}
A solution containing Q[8] (0.15 g, 0.10 mmol) and g6 (0.09 g,
0.20 mmol) in water (10 mL) was heated at 70 1C for 10 min,
then filtered and the filtrate was allowed to stand at room
temperature. Rock X-ray quality crystal formed after two
weeks with a yield of 23%.
X-Ray crystal structure determination of the related compounds
A suitable corresponding single crystal (B0.2 ꢁ 0.2 ꢁ 0.1 mm3)
was picked up with paratone oil and mounted on a Bruker
Apex2 CCD diffractometer equipped with
a graphite-
monochromated Mo-Ka (l = 0.71073 A) radiation source
and a nitrogen cold stream (ꢀ50 1C). The data were corrected
for Lorentz and polarization effects (SAINT),51 and semi-
empirical absorption corrections based on equivalent reflections
were applied (SADABS).51 The structure was elucidated by
direct methods and refined by the full-matrix least-squares
method on F2 (SHELXTL).52 All the non-hydrogen atoms
were refined anisotropically, and hydrogen atoms were added
to their geometrically ideal positions. Water molecules in the
compounds were omitted using the SQUEEZE option of the
PLATON program. 33 and 24 water molecules were removed
from the asymmetric units in Q[8]-g4 and Q[8]-g6 system
Preparation of single crystals of compound g5 and g6
Single crystals of both compounds g5 and g6 can be obtained
from an ethanol aqueous solution. The compound g5 or g6
(0.40 g) in ethanol aqueous solution (15 mL Vethanol/Vwater
=
1 : 1) was heated with stirring at 50 1C for 2 h. The solution
was filtered and the filtrate was allowed to stand at room
temperature for several days. Colorless X-ray quality crystals
of the compound g5 and g6 were obtained from the solution.
Anal. Calcd for C15H23N2O3.5Br2 (g5): C, 42.88; H, 4.80; N,
c
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respectively. Details of the crystal parameters, data collection,
and refinements for the guest g5, g6 and the complexes Q[8]-g4
and Q[8]-g6 are summarized in Table 1. In addition, the
crystallographic data for the reported structures were recorded
in the Cambridge Crystallographic Data Centre as no. CCDC
791487 (g5), 791488 (g6), 791489 (Q[8]-g4) and 791490
(Q[8]-g6) seeing ESIw for details.
It should be noted that the compound g5 has crystallo-
graphically imposed twofold symmetry on b axis. In the
asymmetric unit of the compound Q[8]-g4, there are two
independent Q[8]-g4 complexes. In addition, the counter anion
Br4 (Br4A, Br4B, Br4C, Br4D) is disordered over four
positions with occupancies of 0.42495, 0.04718, 0.49496.
0.03556 (SHELXL SUMP) respectively, in particular, Br4C
and Br4D are treated with EADP to ensure that these two
atoms have common anisotropic displacement parameters. In
the compound Q[8]-g6, The atoms C12, C31 and C40 of Q[8]
are treated with commands EADP, DELU to modify
anisotropic displacement parameters.
methylene resonances near the portal of the Q[8] molecule are
magnetically not equivalent to those near the opposite portal.
This is clearly evident from the split of the doublet of the
methylene protons of the Q[8] host. A comparison of the
integrals of the protons of the bound g1 with the protons of
Q[8] revealed the complex to be a 1 : 1 host : guest species.
By comparison, the relative chemical shifts observed for the
proton resonances of the guest g2 bound in Q[8] (Fig. 2) are
similar in direction and vary only slightly in magnitude. One of
two pyridyl protons (positions 6, 7, 8), the thiophene protons
(position 10, 11, 12), and the methyl and methylene protons
(positions 40, 5, 50 and 9) of the guest g2 are shifted upfield by
0.2–1.4 ppm, while the resonances of the remaining pyridyl
protons (position 1, 2, 3) and the methyl protons (position 4)
of the guest g2 are shifted downfield by 0.1–0.4 ppm. The
largest difference (0.3 ppm further upfield) is found for the
thiophene ring protons (position 11) when the guest g2 is
bound in the cavity of Q[8], compared to the guest g1. The
reason for this difference could be the size of the aromatic ring.
Obviously, the phenyl ring is larger than the thiophene ring, so
the proton at position 11 on the guest g2 is deeper than that at
position 11 on the guest g1 in the cavity of the host Q[8]. The
integrals of the protons of the bound g2 and Q[8] revealed the
complex also to be a 1 : 1 host : guest species.
Results and discussion
Interaction of Q[8] with g1 and g2
It was surprising to discover that the guests g1 and g2
synthesized from aldehydes exhibit special stereo-rigidity so
that the two methylenepyridyl branches and the 1,3-dioxane
moiety in the molecules show different chemical shifts in the
1H NMR spectra (Fig. 1a and 2a), and the guests g1 and g2
seem to be unsymmetrical.53
Thus, it became clear from the 1H NMR spectra of Q[8] and
the guest g1 or g2 interactions that the host Q[8] includes all
branches of the guest g1 or g2 except one of the methyl-pyridyl
branches due to the limit of cavity capacity. Although Q[8]
proved to have a strong preference for inclusion of two
aromatic rings,40–45,54 the repulsion of the two positively
charged pyridyl rings on the guest would prevent the existence
of two pyridyl rings in the same cavity of the host Q[8]. Thus,
the 1H NMR study implies that the host Q[8] exhibits a
preference towards including one of the methyl-pyridyl
branches and the 1,3-dioxane with an aromatic tail, and
excluding the rest of the methyl-pyridyl branch for the
host–guest complexes of Q[8]-g1 and Q[8]-g2.
Fig. 1 shows the 1H NMR spectra of the guests g1 recorded
in the absence and in the presence of enough equivalents of
Q[8] (the excess Q[8] is insoluble and precipitates in the NMR
tube). Compared to the free guest g1, the most noticeable
effect observed upon Q[8] addition is the significant upfield
displacement of one of the two pyridyls protons of the guest
g1. The resonances of the pyridyl protons (positions 6, 7, 8) of
the bound g1 are shifted upfield by 1.0–1.4 ppm respectively in
the presence of excess Q[8], and moreover, the resonances of
the phenyl protons (position 10, 11, 12), methyl and methylene
protons (positions 40, 5, 50 and 9) are also shifted upfield by
0.2–1.0 ppm, indicating a cavity inclusion. However, the
resonances of another pyridyl protons (position 1, 2, 3) and
the methyl protons (position 4) of the guest g1 are shifted
downfield by 0.1–0.4 ppm, indicating that these parts of the
guest g1 are near or just outside a portal of the host Q[8], and
the consequent effect on the Q[8] proton resonances is that the
To quantify the interaction between Q[8] and g1 or g2, a
ratio-dependent study was pursued by electronic absorption
spectroscopy. Usually, the free host Q[8] shows no absorbance
at l > 210 nm. Fig. 3(a) and (b) show the variation in the UV
spectra obtained from aqueous solutions containing a fixed
concentration of the guest g1 or g2 (6.0 ꢁ 10ꢀ5 mol Lꢀ1) and
variable concentrations of Q[8]. Both absorption bands of the
guests g1 and g2 exhibit a progressively lower absorbance as
the ratio of NQ[8]/Ng1 or g2 is increased, and the sharp isosbestic
points at 244 and 269 nm for the Q[8]-g1 system and at 270 nm
for the Q[8]-g2 system are consistent with a simple interaction
between Q[8] and the guest g1 or g2. The absorbance (A) vs.
ratio of moles of the host Q[8] and the guest g1 or g2
(NQ[8]/Ng1 or g2) data can be fitted to a 1 : 1 binding model for
both of the Q[8]-g1 and Q[8]-g2 systems at lmax 260 nm
[the insert in the Fig. 3(a) and (b)]. This behavior is consistent
1
with the results from the H NMR study.
The data from the absorption spectra for both host–guest
systems fitted to a simple 1 : 1 host : guest complexation,50 and
yielded a calculated binding constant (K) of 2.88 ꢁ 103 L molꢀ1
for the Q[8]-g1 system and 1.24 ꢁ 104 L molꢀ1 for the Q[8]-g2
system.
Fig. 1 1H NMR spectra of g1 recorded in the absence (a) and in the
presence of excess of Q[8] (b).
c
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of the host Q[8]. That is, the whole guest molecule is included
in the cavity of the host Q[8] [Fig. 4(d) and (f)]. The integrals of
the protons of the three bound guests and Q[8] revealed the
inclusion complexes to be also 1 : 1 host : guest species.
Fig. 5 shows the variation in the UV spectra obtained from
aqueous solutions containing a fixed concentration of the
guest g3 or g4 or g5 (6.0 ꢁ 10ꢀ5 mol Lꢀ1) and variable
concentrations of Q[8]. The absorption bands of the guest g3
exhibit a progressively higher absorbance, with a blue shift, as
the ratio of NQ[8]/Ng3 is increased. While the absorption
bands of the guests g4 and g5 exhibit a progressively lower
absorbance as the ratio of NQ[8]/Ng4 or g5 is increased. One can
also see the sharp isosbestic points at 245 and 268 nm for the
Q[8]-g4 system and at 225, 246 and 268 nm for Q[8]-g5. The
absorbance (A) vs. mole ratio of the host Q[8] and the guest g3
or g4 or g5 (NQ[8]/Ng3 or g4 or g5) data can be fitted to a 1 : 1
binding model for these three host–guest inclusion systems at
Fig. 2 1H NMR spectra of g2 recorded in the absence (a) and in the
presence of excess of Q[8] (b).
lmax 258 nm for the Q[8]-g3 system [the insert in Fig. 5(a)] and
lmax 260 nm for both Q[8]-g4 and Q[8]-g5 systems [the inserts
in Fig. 5(b) and (c)], respectively.
The data from the absorption spectra of these three
host–guest systems, fitted to
a simple 1 : 1 host : guest
complexation, yielded a calculated binding constant (K) of
2.43 ꢁ 104 L molꢀ1 for the Q[8]-g3 system, 1.00 ꢁ 104 L molꢀ1
for the Q[8]-g4 system and 2.68 ꢁ 104 L molꢀ1 for the Q[8]-g5
system, respectively.
Based on the results from spectrophotometric analysis, one
can see the absorption bands of all guests exhibiting similar
trends and showing sharp isosbestic points, except those of the
guest g3, which gives progressively higher absorbance bands
without an obvious isosbestic point. A comparison of the
absorption bands of the mentioned five guests with the
Fig. 3 Electronic absorption spectra of g1 (a) and g2 (b) in the
presence of increasing concentrations of Q[8] and corresponding
absorbance vs. N[Q8]/Ng1 curve [insert in (a)] and N[Q8]/Ng2 curve
[insert in (b)] at lmax = 260 nm.
1
corresponding H NMR spectra, in the presence of the host
Q[8], indicates that all five host–guest complexes are with a
1 : 1 host : guest ratio and the preference for inclusion of the
host Q[8] for the different branches of the guests can lead
to different absorbance properties. For example, the guest(s),
for which the methylpyridyl branch is included in the
Interaction of Q[8] with g3–5
Unlike the guests g1 and g2, the guests g3 and g4 which are
synthesized from ketones exhibit a symmetrical configuration,
and the two methylenepyridyl moieties and the 1,3-dioxane
ring in the guest molecules show the same chemical shifts in
the 1H NMR spectra [Fig. 4(a, c, e)]. Fig. 4 shows the
1H NMR spectra of the three guests g3–5 recorded in the
absence and in the presence of enough equivalents of Q[8]
(the excess Q[8] is insoluble and precipitates in the NMR tube).
Compared to the first two Q[8]-g1 and Q[8]-g2 host–guest
interaction systems, there are no significant upfield displacement
for any protons in these three guests g3–5 upon Q[8] addition.
For the guest g3, one can see the obvious upfield displacement
for the protons of the 1,3-dioxane branch and the adamantanyl
tail, indicating a cavity inclusion. However, the protons of the
two methylenepyridyl branches in the guest molecule are
shifted slightly upfield by 0–0.4 ppm in the presence of excess
Q[8] indicating that the two methylpyridyl branches of the
guest molecule are included at a portal zone of the host Q[8].
The split of the doublet resonances of the methylene proton of
the host further supports this conclusion [Fig. 4(b)]. For the
guests g4 and g5, all proton resonances in the molecule are
shifted upfield by 0.15–0.8 ppm in the presence of excess Q[8],
indicating that the whole guest molecule is in the shielding area
cavity of the host Q[8] exhibit
a progressively lower
absorbance and sharp isosbestic points as the ratio of NQ[8]/Ng
is increased. In contrast, Q[8]-g3 system, in which the branches
other than the methylpyridyl branch(es) are included in the
cavity of Q[8], exhibit a progressively higher absorbance
and no obvious isosbestic point as the ratio of NQ[8]/Ng is
increased.
Interaction of Q[8] with g6
In this work, the guest g6 is the only one containing one
substituted pyridyl. Unexpectedly, the 1H NMR spectra of the
guest g6 recorded in the absence and presence of sufficient
Q[8] reveal that the host Q[8] prefer to include the three
brominemethyl branches but the aromatic ring54 (Fig. 6).
Compared to the free guest g6, the proton resonances of the
brominemethyl branches of the bound guest g6 are shifted
upfield by 0.5 ppm indicating a cavity inclusion. However, the
proton resonances of the aromatic ring in the guest g6 are
partially shifted upfield (for the protons at positions 3 by
0.4 ppm) and partially shifted downfield (for the protons at
c
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Fig. 6 1H NMR spectra of g6 recorded in the absence (a) and in the
presence of excess of Q[8] (b).
position 1, 2 by B0.1 ppm) suggesting that the pyridyl moiety
is at the portal zone of the Q[8] cavity. This is confirmed by the
crystal structure of Q[8]-g6, which we will describe later.
Unfortunately, the guest g6 shows no obvious absorption
property, so we cannot use spectrophotometric analysis to
quantify the interaction between Q[8] and g6. However, we can
obtain some structural information from other methods, such
as crystal structure determination.
Although we have not obtained crystal structures of all
species, the crystal structures obtained can provide additional
information for related species, and further confirm or contradict
the structural information obtained under aqueous conditions.
Fig. 7 shows the structure of the guest g5, in which the two
methylpyridyl branches are located far apart so the molecule
has a B6.0 A width and B11.8 A length. Compared to the
portal size of the host Q[8] (showing a variation from B8.6 to
B11.8 A in the crystal structures in this work), the guest
g5 can easily thread through the cavity of the host Q[8]
lengthways with a fast exchange. It should be noted that the
cavity of Q[8] can not contain the whole guest g5, and the
formation of a symmetrical inclusion host–guest complex just
results in the fast exchange of the guest g5 in the cavity of Q[8].
This explains well why the doublet methylene resonances
of the host Q[8] do not split in the 1H NMR spectra
[Fig. 4(f)]. Similarly, the guest g4 can thread through the
cavity of the host Q[8] lengthways, and seems to form a
symmetrical inclusion host–guest complex in aqueous
solution, One can also see that the doublet methylene
resonances of the host Q[8] do not split in the 1H NMR
spectra [Fig. 4(d)].
Fig. 4 1H NMR spectra (400 MHz, D2O, rt) recorded for the free
guest (a) g3, (c) g4, (e) g5 and in the presence of excess of Q[8] (b) Q[8]-g3,
(d) Q[8]-g4, (f) Q[8]-g5.
It is interesting that the observation of an asymmetrical
structural conformation of Q[8]-g4 in the solid state seems to
present a controversy in that the crystal structure is not
consistent with the solution structure. The single crystal
structure of Q[8]-g4 reveals that a pyridylmethylene branch
and the 1,3-dioxane branch are included in the cavity of the
Fig. 5 Electronic absorption spectra of g3 (a), g4 (b) and g5
(c) in the presence of increasing concentrations of Q[8] and absorbance
vs. N[Q8]/Ng3 curve [insert in (a)] at lmax = 258 nm, and absorbance
vs. N[Q8]/Ng4 or g5 curves [insert in (b) and (c)] at lmax = 260 nm.
Fig. 7 Crystal structure of the free guest g5.
c
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vertical to other two C–Br bonds in three brominemethylene
branches in both cases.The pyridyl is trans to this C–Br bond
in the free guest, while the pyridyl is cis to the this C–Br bond
in the bound guest, and the orientation of the pyridyl in the
bound guest facilitates the guest entering the cavity of the host
Q[8]. Although the size of the guest g6 could be entirely
included in the cavity of Q[8], the ion–dipole interaction of
the positive nitrogen in the pyridyl moiety with the carbonyl
oxygens lead the pyridyl to stay at the portal [Fig. 9(c)
and (d)]. Thus, the brominemethylene branches in the
cavity will undergo a shielding effect, and the corresponding
proton resonances will experience an upfield shift (as
observed in the 1H NMR spectra discussed above). Whereas
the methylene-pyridyl branch at the portal zone will undergo a
deshielding effect, and most proton resonances will experience
a downfield shift, as observed in the 1H NMR spectra of
Fig. 6.
Fig. 8 Crystal structures of the inclusion complex Q[8]-g4 top view
(a), side view (b) and the bound guest g4 (c).
host Q[8], while the remaining pyridylmethylene branch is
included in a portal zone of the host Q[8] as shown in
Fig. 8(a) and (b), the bound guest presents an unsymmetrical
conformation as shown in Fig. 8(c). The formation of an
asymmetrical host–guest complex is a direct consequence of
inclusion of the asymmetrical guest. However, based on the
solution studies, we suggest that the host Q[8] prefers to
include the whole guest molecule in a symmetrical arrangement
to form a symmetrical inclusion host–guest complex. To
explain this contradiction, it should be noted that the broadening
of the guest proton resonances indicates host–guest binding
with fast exchange in the solution, the two identical pyridyl
can go alternately into the cavity of Q[8] so that the signals
for pyridyl (7.7–8.5 ppm) might be the average signals
for two pyridyl due to fast exchange. Moreover, if the
guest rearranges itself into the conformation as shown in
Fig. 8(c), the size of the two branches of pyridylmethylene
and the 1,3-dioxane with two methyl tails can be as large as
B6.8 A which is more suitable for the stable inclusion in
the cavity of the host Q[8]. This could be the reason for the
formation of an asymmetrical host–guest complex in the
solid state.
Conclusions
We present a discussion of six Q[8]-based host–guest inclusion
complexes. Based on information obtained from 1H NMR,
electronic absorption spectroscopy and single crystal X-ray
diffraction determinations, the possible interaction models
1
are summarised in Fig. 10. The H NMR spectral analysis of
the interaction between Q[8] and the named six pentaerythritol
derivative guests has established the basic interaction models
in aqueous solution. The host Q[8] selectively binds the
different branch(es) of the first generation dendritic guests
forming different inclusion complexes with a host : guest ratio
of 1 : 1. The formation constants in aqueous solution are
B104 L molꢀ1 and are determined through electronic absorption
spectroscopic analysis. The single crystal structures of two
guests and the two Q[8]-gn complexes are useful for under-
standing the solution structures of the Q[8]-gn complexes
analyzed using the 1H NMR technique and electronic absorption
spectroscopy. In particular, a contradiction in that the crystal
structure shows an asymmetrical structural conformation of
Q[8]-g4, while 1H NMR spectra seem to present a symmetrical
solution structure is explained by using fast exchange of the
guest in the solution.
Fig. 9 shows the crystal structures of the free guest g6 and
the inclusion complex of Q[8]-g6. Compared with the crystal
structure of the free guest g6 to that of the bound guest g6
[Fig. 9(a), (b)], one can see that one C–Br bond is almost
Fig. 9 Crystal structures of the free guest g6 (a), the bound guest g6
(b), the inclusion complex Q[8]-g6, top view (c), side view (d).
Fig. 10 Possible host–guest complex structures of Q[8]-gn (n = 1–6).
c
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27 Y. Zeng, Y.-Y. Li, M. Li, G.-Q. Yang and Y. Li, J. Am. Chem.
Soc., 2009, 131, 9100.
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c
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