The smallest cucurbituril analogue with high affinity for Ag+

Article abstract of DOI:10.1039/c7cc01729d

A new host, Me₈TD[4], was prepared for the first time from propanediurea-formaldehyde condensation in the presence of CaCl₂ as the template and it is the smallest cucurbituril analogue reported so far. Measurements of the thermodynamic quantities (log K, ΔH, and ΔS values) of the interactions of Me₈TD[4] with a series of cations by isothermal titration calorimetry indicated that Me₈TD[4] binds selectively towards Ag⁺ with a high binding constant, K ～ 1.3 × 10⁶ M^-1.

Full text of DOI:10.1039/c7cc01729d

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
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The smallest cucurbituril analogue with high affinity for Ag+
Yufan Wua, Lixi Xua, Yenan Shena, Yang Wanga, Lei Zoua, Qiaochun Wang*a, Xiaoqing Jianga,
Jiansen Liua, He Tian*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A new host Me8TD[4] was prepared for the first time from
propanediurea-formaldehyde condensation in the presence of
CaCl2 as template and it is the smallest cucurbituril analogues
reported so far. Thermodynamic quantities (logK, ∆H, and ∆S
values) measurements of the interactions of Me8TD[4] with a
series of cations by isothermal titration calorimetry indicated that
Me8TD[4] binds selectively towards Ag+ with a high binding
constant K~1.3×106M-1.
Cucurbit[n]uril (CB[n]) are cyclic oligomers that consist of
n glycoluril units doubly linked by 2n methylene bridges.[1-4]
These hosts display remarkable affinity towards positively
charged species for their polar uredio carbonyl groups on both
portals and the hydrophobic cavities.[5] The interaction of
CB[n] with various metal ions established the CB[n]-based
coordination chemistry as an increasingly important area in
Figure.1 The formation of Me8TD[4] and its single crystal structure in the absence
(a, b) and presence (c) of calcium (H2O are omitted for clarity. Hydrogen: gray,
Carbon: black, nitrogen: blue, oxygen: red, Calcium: purple).
CB[n] chemistry.[6 ] Novel poly-dimensional CB[n]-metal ions
coordination polymers exhibit important application potentials
in areas such as ionic/molecular transport[8], heterogeneous
catalysis[9] and gas absorption/separation[10]. It is easy to
understand that CB[n] are of various portal sizes and
consequently bind selectively towards metal ions[11]. For
example, Me10CB[5], the smallest analogue, shows a high
selectivity for Pb2+.[12] It is obvious that the smaller n value
would result in smaller portal size, and thus might lead to
selectivity towards special ions. Interestingly, the repeated
,
7
of
9,9-Dimethyl-2,4,6,8-tetraazabicyclo[3.3.1]nonane-3,7-
dione (Me2TD in Scheme 1) with formaldehyde (Sindelar’s
group[17] reported independently the same macrocycle nearly
at the same time, and named it as Me10prCB[5]). It is
interesting that only Me10TD[5] was separated during our
previous preparation, unlike CB[5] would form during common
CB[6] synthesis[2b], which led us to think about the possibility
of synthesizing a smaller homologue. Herein we report a new
member of cucurbituril analogue, Me8TD[4] (Figure 1), which
is of smaller cavity than ever and binds selectively to Ag+, and
the value of n in cucurbit family is reduced to 4 for the first
time.
]
number n that a cucurbituril (or an analogue)[13,14 possesses
has not been lower than 5, mainly due to the high strain
energy upon the cyclization of glycoluril with aldehyde (a
calculated value of 23.03 Kal/mol for CB[4][15]).
We[16] have firstly reported the preparation of a CB[5]-like
macrocycle Me10TD[5] using the acid-catalyzed condensation
Numerous attempts for synthesizing Me8TD[4] had been
carried out under template-free conditions (e.g., verifying the
reaction temperature, acid types and concentrations, and
equivalents of formaldehyde), Me10TD[5] had always been the
sole product obtained and no Me8TD[4] was found. Then we
turned to the template-directed synthesis. The use of
templates in the synthesis and purification of cucurbiturils is
an interesting part of cucurbituril chemistry. For example, p-
xylylenediammonium template was used to originate glycoluril
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Table 1 Cavity dimensions of Me8TD[4] and CB[5]
Portal diameter
(Å) (a) [a]
Cavity width (Å)
Height (Å) (h) [a]
(b) [a]
Me8TD[4]•2Ca2+
Me8TD[4]
CB[5]
1.2
1.5
2.4
3.4
8.6
8.8
9.1
3.4
4.4
[a] The values quoted for a, b, and h take into account the van der Waals radii of the
relevant atoms.
Table 2 The solubility and thermostability of Me8TD[4]
SH2O [mM]
48.5
SCH3OH [mM]
11.3
SDMSO [mM]
2.5
Stability[℃]
560
Me8TD[4]•2Ca2+
＜0.1
Me8TD[4]
4.5
1.8
495
Figure 2. The 1H NMR spectra (400 MHz, 25 °C, D2O) of a) Me8TD[4] and b)
Me10TD[5], all in the presence of CaCl2.
Table 3 Log K, ∆G (kJ·mol-1), ∆H (kJ·mol-1), and T∆S (kJ·mol-1) values for interactions of
Me8TD[4] with metal ions determined calorimetrically at 25.0 °C in deionized water.
hexamer and the preparation of monofunctionalized CB[6][18]
,
and the addition of K+ produced a high proportion of CB[5],
which gave a convenient method for isolating CB[5][19]
.
Ionic
radius
cation
Log K
anion
∆G
∆H
T∆S
Positive results were thus expected to be achieved
during the Me8TD[4] forming reaction by using suitable
templates, for their structural similarities to cucurbituril. It was
indeed surprising when calcium chloride was added to the
Li+
Na+
K+
0.59Å
a
Cl-
Cl-
Cl-
0.97Å
1.33Å
1.15Å
1.67Å
0.72Å
0.75Å
0.73Å
0.75Å
0.99Å
1.13Å
1.35Å
1.19Å
3.54±0.05
-17.2±0.8
-18.8±0.1
-43.0±0.2
-4.8±0.8
-1.6±0.1
-62.5±0.2
12.4
17.2
-19.5
3.38±0.05
1
reaction of Me2TD with formaldehyde. The H NMR spectra of
Ag+
6.11±0.03
NO3
-
the precipitated solid (Figure 2a) shows four groups of proton
resonances with 1 : 1 : 1 : 3 intensity, indicating a typical
symmetrical CB[n] analogue. The chemical shifts of the two
ethylene protons move from 6.26 & 4.19ppm to 6.44 &
4.11ppm, respectively, when compared with Me10TD[5]+CaCl2,
possibly indicating the formation of a new homologue. Further
MALDI-TOF measurement (Fig. S4) gave the expected result—
an intense peak at m/z= 855.3736, which corresponds to the
Cs+
a
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-
Mg2+
Co2+
Cu2+
Zn2+
Ca2+
Sr2+
Ba2+
Pb2+
a
a
a
a
4.85±0.04
4.66±0.04
4.88±0.03
4.79±0.04
-27.7±0.2
-25.7±0.2
-34.7±0.4
-27.4±0.2
-21.0±0.2
-19.3±0.2
-27.5±0.4
-11.3±0.2
6.7
6.4
[M+Na]+ (calcd. 855.3739) of Me8TD[4]
.
The X-ray
crystallography (Figure 1) demonstrated the tetrameric
structure of four Me2TD units doubly bridged by 8 methylene
linkers.
7.2
-
16.1
NO3
The products of Me8TD[4] at this stage was the complex
with CaCl2 in a ratio of 1:2, which was confirmed by X-ray
crystallography (Fig. S19) and Atomic Absorption Spectroscopy
(Fig. S20). The calcium ion was finally removed from Me8TD[4]
after several unsuccessful attempts (for example, column
chromatography on ion-exchange resin and repetitive
a No measurable heat during the isothermal titration calorimetry experiments.
CB[5] (a=2.4Å, b=4.4Å, and h=9.1Å). The cavity volume of the
Me8TD[4] is accordingly estimated as 38 Å3, making it the
smallest cucurbituril-like cavity size so far to the best of our
knowledge. It should be noted that the portal size of Me8TD[4]
decreases by 0.3Å and the height decreases by 0.2Å when
binds with calcium cation.
recrystallization
from
dilute
HCl),
using
ethylenediaminetetraacetic acid (EDTA, a calcium chelator)
and (CH3)4N+OH- (the yield of Me8TD[4].2Ca2+ was 5%, and the
final yield of Me8TD[4] was 2%, see supporting information).
The Ca2+-free Me8TD[4] was also characterized by single-
crystal X-ray diffraction, as can be seen in Figure 1. The
structural dimensions of Me8TD[4] and its calcium complex
obtained from the crystallographic computations are listed in
Table 1. The cavity dimensions a, b and h of Me8TD[4] are
greatly reduced to 1.2 Å, 3.4Å and 8.6Å respectively, which are
significantly smaller than those of the smallest cucurbit family
The solubility of Me8TD[4] in common solvents at room
temperature was also determined by 1H NMR spectroscopy
with an internal standard[13a] (see Supporting Information), as
illustrated in Table 2. It can be seen that Me8TD[4] shows
somewhat solubility in water and methanol (4.5mM and
1.8mM, respectively) and almost no solubility in DMSO. In
comparison , the Ca2+-complexed Me8TD[4] show remarkable
increased solubility in these solvents
―48.5mM in water,
11.3mM in methanol and 2.5mM in DMSO.
2 | J. Name., 2012, 00, 1-3
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Thermal gravimetric analysis (TGA) of Me8TD[4] was
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This work was financially supported by the Science Fund
carried out in nitrogen atmosphere to 600
℃
thermal stability. We did not detect mass loss related to the (21572063, 21372076), and the Program of Introducing Talents
to evaluate their for Creative Research Groups (21421004), NSFC/China
decomposition of Me8TD[4] or its calcium complex up to 490 of Discipline to Universities (B16017).
℃ (Table 2 & Fig. S5), indicating that the macrocycle possesses
excellent thermal stability which is comparable with
[20]
Notes and references
cucurbiturils (exceed 370
℃
)
.
The relatively good solubility of free Me8TD[4] allows us
to investigate the host-guest chemistry of Me8TD[4] with
metal ions in neutral water. Log K, ∆G, ∆H, and T∆S values for
the interactions of the metal ions with Me8TD[4] in H2O are
listed in table 3. Those metal ions with small
radius―Li+(0.59Å), Mg2+(0.72Å), Co2+(0.75Å), Cu2+(0.73Å) and
Zn2+(0.75Å)[5b]―show no measurable heat during the titration
1
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4
(see Supporting Information), suggesting
none or tiny
complexation with Me8TD[4], and Cs+, which is of tremendous
radius(1.67Å), also shows no complexation. By contrast, those
metal ions, whether they are one monovalent or bivalent, with
moderate ionic radius―Na+ (0.97Å), Ca2+ (0.99Å), Sr2+(1.13Å),
Ag+(1.15Å), Pb2+ (1.19Å), K+(1.33Å) and Ba2+ (1.35Å)―display
considerable affinities with Me8TD[4]. For those monovalent
ions, it seems that there has an optimal radius during the
combination, because Ag+ has the maximum K value of
5
1.3
×
106M-1, Na+ (smaller radius than Ag+ with smaller
103M-1) and K+ (bigger radius with smaller K 103M-1)
2.4
K~
3.5
×
~
×
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rate final (no combinations). While for those bivalent ions, no
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radius ranging from 0.99Å to 1.35Å are of similar K values
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(Ca2+
Pb2+
~
6.2
7.1
×
104,
Sr2+
~
4.7×
104,
Ba2+
~
7.6×
104,
and
6
7
8
9
~
×
104M-1, respectively). Nevertheless, the none-
combination to Me8TD[4] of the bivalent ions (Mg2+, Co2+, Cu2+
and Zn2+) with small radius is the same situation as that of the
monovalent ion. It should be pointed out that Me8TD[4] bind
selectively to Ag+ with
a
K
value of more than
M. Cao, J. Lin, H. Yang and R. Cao, Chem. Commun., 2010, 46
5088.
,
two orders of magnitude larger than other ions.
The isothermal titration calorimetry results also indicate
that Ag+, Pb2+ and Ba2+ form 1:1 complexes, while the other
cations form 2:1 ones with Me8TD[4]. These phenomenons
should be attributed to the fact that the two cucurbituril
portals, on one hand, could bind respectively with two ions to
form a capsule-like molecule; and on the other hand, could
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,
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pentacyclopentanocucurbit[5]uril binds 1:2 with Ca2+ and Sr2+,
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In conclusion, we have synthesized a new cucurbituril-like
macrocycle, Me8TD[4], by acid-catalyzed condensation of
dimethylpropanediurea and formaldehyde in the presence of
CaCl2 template. Me8TD[4] is the smallest cucurbituril
analogues reported so far with four repeated bi-uredio units,
having smaller portal diameter, cavity width, and lower height
when compared with other cucurbituril species, and exhibits
excellent thermal stability. It should be emphasized that
Me8TD[4] shows an outstanding binding selectivity toward
silver ion over a series of other metal ions.
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A smallest cucurbituril analogue with four repeated bi-uredio units was firstly
synthesized and it binds selectively towards Ag+.