Supporting Information
The Influence of Equatorial Substitution and K+ ion Concentration – An
Encapsulation Study of CH4, CH3Cl, CH3F, CH2F2, CF4, in Q[5], CyP5Q[5] and a
CyP5Q[5]-carboxylate Derivative
Pradeep Kumar C., Wu Feng, Clifford E. Woodward, Anthony I. Day*
Chemistry, School of PEMS, University of New South Wales Canberra, Australian
Defence Force Academy, Canberra, ACT 2600, Australia.
a.day@adfa.edu.au
Table of Contents:
Page
Synthetic Procedures
Determination of Binding Constants Using a Curve fitting Method
1
H of AcidCyP5Q[5] (400 and 800 MHz)
Examples of Gas Encapsulation in Q[5], CyP5Q[5] and Acid CyP5Q[5]
1
H and 19F NMR spectra
S2
S2-S7
S8
S9-S12
Plot S1. Methane binding in CyP5Q[5] in the presence of K+
S12
Plot S2. Methane binding in Q[5] in the presence of K+
S13
Plot S3. An example of methane binding in AcidCyP5Q[5] in the
presence of Cs+ ion.
S1
Synthetic Procedures
Preparation of Q[5]NaCl and AcidCyP5Q[5]
Q[5]NaCl
Q[5]2KCl1 (1.0 g) was dissolved in hot water (10 mL) filtered while still hot. NaCl
(1.0 g) dissolved in hot water (2 mL) was added. Crystals began to form within 5min
but the sample was set aside to cool for several hr and then crystals were collected by
filtration. The crystals were then dissolved in water (25 mL) heated to boiling and
NaCl (1.0 g) in water (2 mL) was added and the solution set aside to cool. The
crystals were collected by filtration washed with a little water and oven dried at 80 °C
then stabilised in air to yield colourless needles 685 mg. Found: C, 32.47; H, 4.02; N,
25.48; Cl, 6.46. C30H30N20O10 Na2Cl2 .9H2O requires C, 32.48; H, 4.36; N, 25.24; Cl,
6.39.
Cyclopentanocarboxylic acid cucurbit[5]uril (AcidCyP5Q[5])
The cyclopentyldiethylester glycoluril1 (1.50g, 4.60 mmol), paraformaldehyde
(300mg, 9.66mmol) and LiCl (5mg ) were combined as solids and 37% HCl (20 mL)
was added to the mixture. Initially this mixture was stirred at RT for 30 min and then
the temperature was raised 50 – 60 °C for a further 90 min and finally the temperature
was raised to 95 – 100 °C for an extended period of 13 h. The HCl was removed from
the dark brown under reduced pressure to yield dark brown solid (1.3 g). The solid
was washed with a minimum quantity of water and the suspension collected by
filtration. This crude material showed characteristic resonances for
cyclopentanocarboxylic acid Q[n]. The predominance of the smallest homologue
Acid5Q[5] was indicated by the bubbling of methane into a D2O solution of the crude
material and by the addition of dioxane which showed that Acid Q[6] was present in <
2%. Purification was achieved by dissolving the crude material in a minimum volume
of 50% aqueous HCO2H and loading this onto Dowex cation exchange resin and
eluted with a mixture of 50% HCO2H/0.5 M HCl to yield pure
cyclopentanocarboxylic acid5 Q[5] (910mg, 79%). Mp > 250°C. IR KBr (cm-1) 3383
s, 3246 w, 3213 w, 2945 s, 2993 s, 1460 s, 1328 s, 1276 m, 1174 s,1136 s, 1062 s,
1047 m, 914 s, 850 s, 761 s. 1H NMR: ( D2O at 25°C) δ 5.73 – 5.54 ( 10 H , d’s , J =
16.4 Hz ) , 4.47 (10H, d, J = 16.4Hz) , 3.21 – 3.07 ( 5H, broad m ) , 2.80 – 2.50 ( 20
H, broad m ). MS (ESI) m/z 653.7 [(M + K++ H+ + H2O) 100], 656.2 [(M + K+ + Na+)
54], 664.2 [(M + 2K+) 53], 682.1 [(M + 2K+ + HCl) 59]. ESMS HR (TOF) calc. for
(C25H25N10O10 +K) 664.1392. Found 664.1397. Anal calc. for C50H50N20O20
.10H2O.HCl Found: C, 41.03; H, 4.44; N, 18.75. Requires C, 40.92; H, 4.88; N,
19.08.
Preparation of chloromethane
A gas generator was prepared by mixing TsCl (10g, 0.05 mol), anhydrous LiCl (1 g)
and pyridine (4.6 mL) in dry DMF (20 mL). The mixture was warmed to 60 – 80 °C
and MeOH was added portion-wise to generate the require quantity of gas for each
experiment. The gas was passed through a small volume of D2O and infused into test
solution via a capillary.
S2
Determination of Binding Constants Using a Curve fitting Method
1:1 Binding Model
The titration data were initially fitted to a simple 1:1 binding model of the general
form,
G + H  C1
(1)
G, H and C1 represents the guest, host and 1:1 complex, respectively. Assuming fast
exchange of the guest on the NMR timescale, the observed chemical shift, , is
obtained as,
 = xff + x11
(2)
where xf and x1 are the mole fractions of the free and singly bound host, with
individual chemical shifts f and 1, respectively. For a given equilibrium binding
constant K1, we have the simple relation:
𝐾1 =
𝑥1
(3)
(1−𝑥1 )(𝑅−𝑥1 )[𝐻]0 𝐷𝑓
and we have used xf =1-x1. The ratio R = [G] 0/[H]0, where [G] 0 and [H] 0 are the total
initial concentrations of the guest and host respectively and Df is the dilution factor,
defined as the ratio of the initial volume of solution, V0, and the volume after dilution
(during the titration) Vt, i.e. Df = V0/ Vt. Eq.(3) is solved as a simple quadratic. In our
fitting procedure, the parameter set {K1,1,f } was varied until the calculated
chemical shift (plotted against the dilution factor) was optimal compared to the
experiments, in a least squares sense [The dilution factor relates to how much the
original solution has been diluted as the ratio of salt to Q remains constant and is only
diluted to decrease the concentration of each component].
Comparison with Benesi-Hildebrand
In all titrations the amount of G was far greater than H, and the ratio R>>1. Thus the
method of Benesi and Hildebrand (BH) was also applicable. Generally, it was found
that excellent fits were obtained over a dilution factor range of between 1 to 20, with
good agreement between the least-squares and the BH approaches, when the fitted,f,
was also used for the latter. However, two observations emerged. Firstly, when it
was possible to obtain a reliable experimental measurement of,f , the experimental
value was significantly different to the fitted one. Secondly, where other estimates
for K1 were available in the literature, they were typically orders of magnitude higher
than those obtained by us. Given that the cucurbituril host is able to bind metal ions
at both portals, we surmised that at large values of R, the dominant equilibrium is:
C1 + H  C2
(4)
The binding free energy for the second ion is likely to be significantly weaker than
that for the first, due to electrostatic repulsion between the ions and the diminished
S3
availability of electrons at the binding sites. Also, the chemical shift of C1 is expected
to be different to that of G.
2:1 Binding Model
To test this hypothesis, we fitted the titration data to a model which allowed
accounted for both 1:1 and 2:1 binding (M+ : Q[5]) , Eqs (1) and (4). The relevant
simultaneous equations are:
𝐾1 =
𝐾2 =
𝑥1
𝐷𝑓 [𝐻]0 (1−𝑥1 −𝑥2 )(𝑅−𝑥1 −2𝑥2 )
𝑥2
𝐷𝑓 [𝐻]0 (1−𝑥1 −𝑥2 )(𝑅−𝑥1 −2𝑥2 )2
 = xff + x11 + x22
(5a)
(5b)
(5c)
The parameter set {K1,1, K22,f } was again optimized using least squares. The
large number of parameters means that a clearly defined best-fit may be difficult to
obtain. Furthermore, as with many algorithms used for non-linear parametric
regression, our approach did not distinguish between local and global minima within
the search space. In any case, given experimental uncertainty, it is not obvious that
the global minimum is the physically relevant one in any case. To guide our search,
we applied a number of criteria that we expected would be satisfied by “physically
acceptable” solutions. Firstly, the binding constants were expected to satisfy K2 < K1.
Secondly, we anticipated that 1< K1 < 104. This range reflects the typical sizes of
reported single ion binding constants to various substituted and non-substituted Q[5]
hosts.3,4 Finally, taking into account expected shielding effects, we anticipated all
chemical shifts to lie within the range 4<i <6. In particular, shielding would
sensibly predict progressive down field shifts upon metal ion binding, so
thatf12. These criteria were implemented by use of “penalty functions”,
added to the usual sum of square residuals. Despite these restrictions it was found
that excellent fits to the experimental data were obtained for a wide range of K2 and
K1, with the other parameters falling within the acceptable ranges. We found that the
quality of the fit was instead sensitive to the ratio, K2/K1, rather than their absolute
values. This is not surprising given that the NMR data was collected in the high salt
regime, where the equilibrium given in Eq.(4) is dominant and the chemical shift
changes are greater. Figures S1 – S4, show the fitted and measured titration data,
with fitting parameters given in Table S1. Note that only the ratios, R, of the binding
constants are shown, as their absolute values are not reliable. However, it is clear,
that both1:1 and 2:1 binding are required to fit the experimental data.
Table S1. Fitted values of first and second order binding constants (given as simple ratios).
R = K2/ K1 mol-1
KCl + Q[5]
KCl + CyPQ[5]
NaCl + Q[5]
NaCl + CyPQ[5]
0.125
0.113
0.161
0.089
S4
The corresponding fits to the titration curves are given in Figures S1 to S4.
Figure S1. Plot of chemical shift vs dilution factor (Df) for the KCl+Q[5] mixture.
Points are experimental and lines are least squares fit.
Figure S2. Plot of chemical shift vs dilution factor (Df) for the KCl+CyPQ[5]
mixture. Points are experimental and lines are least squares fit.
S5
Figure S3. Plot of chemical shift vs dilution factor (Df) for the NaCl+Q[5] mixture.
Points are experimental and lines are least squares fit.
Figure S4. Plot of chemical shift vs dilution factor (Df) for the NaCl+CyPQ[5]
mixture. Points are experimental and lines are least squares fit.
A Physical Binding Model
In order to ascertain an estimate for the individual binding constants we need to use a
physical model. Hence we introduce specific free energy contributions to the binding
of metal ions to the cucurbituril as follows.
The binding free energy of metal ions to the Q[5] portaI, has an associated ion-dipole
like character, coupled with solvation effects. We shall denote this quantity as GB.
When the Q[5] barrel contains of alkyl-like substituents, there will be an additional
binding contribution, due to the electron donating character of the additional moieties.
The extra binding term can be thought of as a type of polarization effect (chargeinduced dipole). We denote this (negative) contribution as GP. The competition
S6
between symmetrically bound metal ions at each portal can be expected to lead to a
substantial weakening of GP. We shall approximate this as a total loss of this term
upon binding of two ions. In addition, binding of two metal ions will contribute a
repulsive electrostatic interaction between the metal ions, which is also subject to
some solvent screening. This is denoted as Gel.
Thus we obtain the following approximate expressions for the binding constants to
substituted Q[5], Kn[S], and non- substituted Q[5], Kn[Q], where n = 1,2.
K1[S] ≈ exp[- (GB +GP )/RT]
K1[Q] ≈ exp[- GB/RT]
and
K2[S] ≈ K2[Q] ≈ exp[- (2GB +Gel )/RT]
Denoting the ratios K2[S]/ K1[S] = R[X], we obtain the following result,
log K1[S] = log K1[Q] + log R[Q]- log R[S]
Using the ratios given in Table S1 and the estimates for 1:1 binding to Q[5] in
reference [Buschmann],4 we obtain the approximate binding constants in Table S2.
Table S2. Estimated values of first and second order binding constants. K2 is assumed the same for
both Q[5] and CyPQ[5].
KCl + Q[5]
KCl + CyPQ[5]
NaCl + Q[5]
NaCl + CyPQ[5]
Log K1
1.31
1.35
1.85
2.10
Log K2
0.4
0.4
1.05
1.05
S7
1
H and 19F NMR Spectra
AcidCyP5Q[5] (400 MHz)
AcidCyP5Q[5] (800 MHz) Inset (5.5 – 5.8 ppm) shows greater separation between the
doublets of the stereo isomers. Splitting at the base of each doublet set is due the
encapsulation of air comparable to other Q[5] samples.
S8
Gas Encapsulation Examples
***hhh*
* *
CyP5Q[5] encapsulation of CH2F2, part of the triplet of the bound CH2F2 is indicated
by *.
19
F NMR of CyP5Q[5] encapsulation of CH2F2 showing bound resonances on the
LHS and the free on the RHS.
S9
19
F NMR of Q[5] encapsulation of CH2F2 showing bound resonances on the LHS and
the free on the RHS.
CyP5Q[5] and an excess of CH3F, showing the encapsulated resonance at 3.23ppm.
AcidCyP5Q[5] and an excess of CH3F, showing the encapsulated resonance at 3.16
ppm.
A mixture of Q[5] and AcidCyP5Q[5] in the presence of an excess of CH3F, showing
the encapsulated resonances at 3.35 and 3.13 ppm for Q[5] and AcidCyP5Q[5]
respectively.
S10
19
F NMR of Q[5] and CyP5Q[5] encapsulation of CH3F showing bound resonances
RHS and the free on LHS.
19
F NMR of Q[5] and AcidCyP5Q[5] encapsulation of CH3F showing bound
resonances RHS and the free on LHS.
S11
A mixture of Q[5] and AcidCyP5Q[5] in the presence of saturated solutions of CH4,
showing the encapsulated CH4 resonances at -0.72 and -0.98 ppm for Q[5] and
AcidCyP5Q[5] respectively.
A mixture of Q[5] and CyP5Q[5] in the presence of saturated solutions of CH4,
showing the encapsulated CH4 resonances at -0.72 and -0.88 ppm for Q[5] and
CyP5Q[5] respectively.
S12
CyP5Q[5] in the presence of saturated solutions of CH4 (0.17 free) and CH3Cl (3.02
free) showing the encapsulated CH3Cl and CH4 resonances at 2.13 and -0.88 ppm.
CH4 binding Ka against salt concentrations
Plot S1. Methane binding in CyP5Q[5] under the condition of no salts and varying K+
ion concentrations.
S13
Plot S2. Methane binding in Q[5] under the condition of K+ ion with initial
concentrations higher than example in the paper.
Plot S3. An example of methane binding under the condition of varying
concentrations of Cs+ ion in AcidCyP5Q[5].
References
1. A. I. Day, A. P. Arnold, R. J. Blanch and A. Coe, “Alkali Metals and the Ratio of
Cucurbit[n]urils in Synthesis” J Incl. Phenom. Macrocyclic Chem. 2002, 43, 247250.
2. Mandadapu, V.; Wu, F.; Day, A. I. Org. Lett. 2014, 16, 1275-1277.
3. Zhang, X. X.; Krakowiak, K.E.; Xue, G.; Bradshaw, J. S.; Izatt, R. M. In. Eng.
Chem. Res. 2000, 39, 3516-3520.
4. Buschmann, H. -J.; Cleve, E.; Jansen, K.; Wego, A.; Schollmeyer, E. J. Incl.
Phenom. Macrocyclic Chem. 2001, 40, 117–120.
S14