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CB[7]·Cat, because it is a truncated system with respect to
MNP-CB[7]·Cat2, lacking the nanoparticle portion. More-
over, the former lies in a completely homogeneous phase, easy
to be reproduced by DFT calculations in solution. Moghaddam
and co-workers characterized the thermodynamics of binding
between CB[7] and adamantanyl guests in water at room
temperature via isothermal titration calorimetry (ITC): for
compete with the catalyst for the occupation of the CB[7]
cavity and expose the unbound catalyst to possible removal
from the reaction media during the organic extractions.
0
Entries a) to h) in Table 3 summarize the enthalpic (ΔH ),
0
0
entropic (À TΔS ) and free energy contributions (ΔG ) in
À 1
kcal·mol to the binding between the macrocycles and the
competitive guests at room temperature. Keq is the binding
constant at equilibrium.
0
instance, adamantanol binds to CB[7] with ΔG =À 14.1�
À 1
0
0.2 kcal·mol
and 1-adamantanylammonium with ΔG =
The results show that β-CD and CB[7] bind the catalytic
À 1 [34]
0
À 19.4�0.1 kcal·mol . Computation has been used also to
species quite strongly: the binding energies, ΔG =
À 1
0
À 1
describe the binding thermodynamics between cucurbit[n]uril
À 18.3 kcal·mol and ΔG =À 16.4 kcal·mol , respectively,
[29]
and guest(s).
Interestingly, cucurbiturils do not obey the
are stronger than the binding energy calculated for 1-
À 1
enthalpy-entropy compensation principle typical of other
adamantanol with CB[7], À 13.9 kcal·mol , but weaker than
[35b,36]
macrocycles in supramolecular chemistry.
Large en-
that for 1-adamantanylammonium iodide with CB[7],
À 1
thalpic gains due to host-guest tight interactions, rigidity and
size-complementarity of the hydrophobic cavity are the
reasons behind the high affinity of the CB[7] with guests,
À 19.0 kcal·mol . The strongest binding in CB[7] has been
reported for the “attomolar” diamantane-4,9-di(NMe I) guest,
3
0
À 1 [38]
being ΔG =À 24.3 kcal·mol .
We considered different
[35c]
particularly adamantanyl species.
binding modes and conformations between CB[7] and the
catalyst, Figure 4. This speciation suggests that the adamantyl
portion of the catalyst is encapsulated into the hydrophobic
pocket. When the triazole portion is encapsulated, concom-
itantly releasing the adamantyl, the free energy rises to
The entropic penalty paid for the reconfiguration of all the
translational, rotational and vibrational degrees of freedom of
the guest when encapsulated into the cavity is somewhat
antagonized by the entropic gain due to the dehydration of the
[35b,c]
À 1
negatively charged portals of CB[7].
Hostaš and co-
+12.3 kcal·mol compared to the most stable structure
À 1
workers employed BLYP-D3/def2-TZVPP//BLYP-D3/def2-
SVP level of theory for accurate calculation of potential
calculated for our catalyst (Figure 4, 0.0), À 4.1 kcal·mol
lower with respect to the separated host and guest. The
cumulative interaction of the tail of the catalyst with the portal
[22c]
energy.
Our computational investigation suggests that DFT
À 1
calculations at the same level of theory, employing aqueous
implicit solvation (SMD) and corrected statistical thermody-
namics, prove to be sufficiently accurate and reliable to
describe the bonding and thermodynamics between CB[7] and
neutral or monocationic adamantanyl guests responsible for
the activation a single portal of the cucurbituril. Our
calculations are in excellent agreement with published exper-
of the cavity is roughly accountable for ~11 kcal·mol of
stabilization energy. The structure at +11.1 kcal·mol in
À 1
Figure 4 shows the destabilization brought to the complex
when the carboxylate group of the proline is set far away from
the outer surface of the CB[7] with concomitant disruption of
***
the intramolecular carboxylic acidÀ OH NÀ proline H-bond.
À 1
This structure lays at À 5.3 kcal·mol from the separated host
0
imental thermodynamics in pure water, with ΔG =
and guest, respectively.
À 1
0
À 1
À 13.9 kcal·mol and ΔG =À 19.0 kcal·mol for adamanta-
Table 3 shows clearly that 4-trifluoromethyl benzaldehyde
is the least interacting (actually non interacting at all) guest
with either CB[7] and β-CD cavities within the subset of
examined competitive species: the interaction is very ender-
nol and 1-adamantanylammonium iodide guests,
respectively. Figure 3 summarizes the conceptual compar-
[37]
ison of our binding study between the macrocyclic host, CB
0
À 1
[7] versus β-CD, and all the potential guests present in the
gonic with β-CD, ΔG = +24.7 kcal·mol , and moderately
0
À 1
reaction vessel at any time of the reaction: the only productive
binding is the encapsulation of the catalytic species while all
the other encapsulations represent unproductive bindings that
endergonic with CB[7], ΔG = +8.6 kcal·mol . Cyclohexa-
none acts as a weak guest towards β-CD, with ΔG =
À 9.2 kcal·mol , and as a very poor guest towards CB[7],
0
À 1
Table 3. Thermodynamics for binding equilibria of competitive guest in CB[7] and β-CD.
0
[a]
0[a],[b]
0[a]
À 1 [c]
Productive and unproductive equilibria
ΔH
À TΔS
ΔG
K (M )
eq
1
2
a) CB[7](aq.) +Catalyst(aq.) < = > CB[7]·Catalyst(aq.)
À 33.8
À 18.4
À 6.9
17.3
14.0
15.5
17.0
15.4
11.2
12.3
14.7
À 16.4
À 4.4
8.6
À 12.1
À 18.3
À 9.2
24.7
1.1·10
1.6·10
4.8·10
3
b) CB[7](aq.) +Cyclohexanone(aq.) < = > CB[7]·Cyclohex.(aq.)
c) CB[7](aq.) +4-CF À Benzaldehyde < = > CB[7]·4-CF À Benz.
À 7
3
(aq.)
3
(aq.)
(aq.)
8
d) CB[7](aq.) +Product < = > CB[7]·Product
À 29.1
À 33.7
À 20.3
12.3
7.4·101
(aq.)
(aq.)
3
e) β-CD(aq.) +Catalyst(aq.) < = > β-CD·Catalyst(aq.)
f) β-CD(aq.) +Cyclohexanone(aq.) < = > β-CD·Cyclohex.(aq.)
2.5·10
5.5·10
6
À 19
g) β-CD(aq.) +4-CF À Benzaldehyde < = > β-CD·4-CF À Benz.
7.9·101
3
(aq.)
3
0
h) β-CD(aq.) +Product < = > β-CD·Product
À 29.0
À 14.3
3.3·10
(aq.)
(aq.)
À 1
À (ΔG0/RT)
[
a] Kcal·mol at 298 K for 1 M reference state. [b] Configurational entropy. [b] K =e
.
eq
Isr. J. Chem. 2020, 60, 1–11
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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