Sulfonatocalixarene Counterion Exchange Binding Model in Action: Metal-Ion Catalysis Through Host-Guest Complexation

Article abstract of DOI:10.1002/cctc.201901254

p-Sulfonatocalixarene water soluble macrocyclic host receptors are known to form cooperative ternary complexes with complementary organic guest and metal cations. This property may be explored to enhance the interaction of weak nitrogen ligands with metal cations in a confined space showing some resemblance to metal-containing enzymes. However, the best of our knowledge, catalytic potential of this property remains unexplored. In this work the Ni²⁺ catalyzed hydrolysis of a picolinate ester (2,4-dinitrophenyl picolinate, 1) was used as a model reaction to evaluate the effect of sulfonatocalixarene macrocycles in the kinetics of this reaction. The results show that the host molecules promote the reaction through simultaneous complexation of the metal cation and the substrate and, in the case of the larger calixarenes containing more basic phenol groups, substantially higher rate enhancements are observed owing to additional assistance provided by base/nucleophilic catalysis. However, due the ionic nature of these receptors auto-inhibition of the reaction is observed at higher concentrations due counterion (Na⁺) binding that competes with the catalytically active Ni²⁺ -complexes.

Full text of DOI:10.1002/cctc.201901254

DOI: 10.1002/cctc.201901254
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Sulfonatocalixarene Counterion Exchange Binding Model in
Action: Metal-Ion Catalysis Through Host-Guest
Complexation
[a]
[a]
[b]
[b]
Nuno Basílio,* Márcia Pessêgo, Angel Acuña, and Luis García-Río*
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p-Sulfonatocalixarene water soluble macrocyclic host receptors
are known to form cooperative ternary complexes with
complementary organic guest and metal cations. This property
may be explored to enhance the interaction of weak nitrogen
ligands with metal cations in a confined space showing some
resemblance to metal-containing enzymes. However, the best
of our knowledge, catalytic potential of this property remains
unexplored. In this work the Ni catalyzed hydrolysis of a
picolinate ester (2,4-dinitrophenyl picolinate, 1) was used as a
model reaction to evaluate the effect of sulfonatocalixarene
macrocycles in the kinetics of this reaction. The results show
that the host molecules promote the reaction through simulta-
neous complexation of the metal cation and the substrate and,
in the case of the larger calixarenes containing more basic
phenol groups, substantially higher rate enhancements are
observed owing to additional assistance provided by base/
nucleophilic catalysis. However, due the ionic nature of these
receptors auto-inhibition of the reaction is observed at higher
2+
+
concentrations due counterion (Na ) binding that competes
2+
with the catalytically active Ni -complexes.
1
. Introduction
dinations cages are well-documented to provide extra stabiliza-
tion to their positively charged guests through electrostatic
interactions (ion-dipole, Coulombic, cation-π, etc) which often
leads to higher selectivity towards positively charged species
and consequently to complexation-induced upward pKa
Catalysis through encapsulation of reactants in the nanosized
cavities of synthetic host molecules is a topic that draw
inspiration from Nature’s enzymatic catalysts. The microscopic
environment offered by the cavities of synthetic macrocyclic
receptors displays several characteristics that are reminiscent of
enzyme active sites and, therefore, can be exploited to
accelerate and/or catalyze organic reactions. Substrate recog-
nition, pre-orientation of reactants into reactive conformations,
stabilization of intermediates/ transition states through non-
covalent interactions or increase of effective concentrations are
some of the features shared by enzymatic and supramolecular
[12–18]
shifts.
In fact, both the activation of substrates and/or the
stabilization of intermediates through selective binding of the
positively charged protonated species has been demonstrated
to be an effective strategy for rate acceleration and catalysis of
organic reactions through the formation of host-guest
[19–24]
complexes.
Conceptually equivalent to complexation-induced pK shifts,
a
the amplification of metal ligand interactions between an
organic guest/substrate and a metal cation brought together in
close proximity through simultaneous encapsulation in a
synthetic receptors holds great potential for catalytic
[1–11]
catalysts.
builds on complexation-induced shifts of protolytic equilibria
i.e. pK shifts) to stabilize protonated/unprotonated reactive
Another important strategy applied by enzymes
(
a
[11]
species under pH conditions where they usually are not
observed. Similarly, both neutral and anionic synthetic receptors
such cucurbiturils, p-sulfonatocalixarenes or metal-ligand coor-
applications. This approach can be addressed through the
functionalization of synthetic macrocyclic receptors with poly-
[
11]
dentate (often nitrogen-based) ligands for metal ion-binding
or by using macrocyclic receptors such as p-sulfonatocalix[n]
arenes (SCn) or cucurbiturils which comprise binding pockets
decorated with negatively charged or electronegative carbonyl
groups, respectively, that in favorable conditions may accom-
modate the organic substrate and the metal cation in close
proximity through the cooperative formation of heteroternary
[a] Dr. N. Basílio, Dr. M. Pessêgo
LAQV-REQUIMTE
Departamento de Química
Faculdade de Ciências e Tecnologia
Universidade NOVA de Lisboa
Caparica 2829-516 (Portugal)
E-mail: nuno.basilio@fct.unl.pt
[25–29]
metal cation:substrate:receptor complexes.
In addition to
[
b] Dr. A. Acuña, Prof. L. García-Río
their ability to form heteroternary complexes comprising a
metal cation and an organic guests, SCn comprise phenols
groups that offer the possibility of general base or nucleophilic
participation in the catalyzed reaction. To test this hypothesis
and evaluate for the first time the formation of heteroternary
Centro Singular de Investigación en Química Biolóxica
Moleculares (CIQUS) and Departamento de Química Física
Universidad de Santiago, Santiago,
e Materiais
1
5782 (Spain)
E-mail: luis.garcia@fct.unl.pt
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cctc.201901254
2
+
SCn complexes for catalysis, we selected the Ni catalyzed
hydrolysis of 2,4-dinitrophenyl picolinate (1) as model reaction
(Scheme 1). The mechanism of this reaction was established by
This manuscript is part of the Special Issue on New Concepts in Homo-
geneous Catalysis.
ChemCatChem 2019, 11, 1–9
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2+
Scheme 1. Proposed mechanism for the Ni catalyzed hydrolysis of 2,4-dinitrophenyl picolinate.
2
+
2+
Fife and Przystas who found that both Ni and Cu activate
the substrate, through a fast chelation equilibrium, followed by
the rate-limiting attack of H O, OH or acetate and formate
acidic phenol with pK values below 10, being the less acidic
a
1
1
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those with pK =4.9 and pK =7.8 for SC6 and SC8, respectively.
This agrees with the higher rate enhancement observed for the
larger calixarene.
a
a
À
2
[30]
buffers.
Calixarenes, including SCn, may exist in different conforma-
tion owing to the rotation of the phenol units through the
[32]
2. Results and Discussion
macrocyclic ring.
exist in a flexible cone conformation in solution, SC6 and SC8
are more flexible and their preferential conformation in
While SC4 is suggested to preferentially
The hydrolysis of 1 can be conveniently monitored by UV-Vis
absorption spectroscopy at ca. 405 nm (maximum absorption of
the 2,4-dinitrophenolate ion). At neutral pH and in the absence
of buffers, the reaction proceeds slowly with a t1/2 �16 hours.
Firstly, the effect of different SCn (Scheme 2) and as well of the
[33–35]
aqueous solution cannot be elucidated.
The larger size and
flexibility of these last receptors may also play a role in the
observed catalytic effects enabling the approach of the
hydroxyl groups to the substrate while for SC4 in the cone
conformation these type of interactions are not feasible. Never-
theless, the structures of the complexes could not be exper-
imentally investigated in the present work owing to the
reactivity and low solubility of 1 in aqueous solution.
The kinetic data shown in Figure 1 for SC6 and SC8 can be
fitted to a model [Eq. (1)] that considers the hydrolysis of free
and complexed 1 with the respective rate constants being k0
and k . Besides of the kinetic parameters, from data fitting to
1
Equation (1) the apparent binding constant (Kapp) for the
formation of a host-guest complex between 1 and the SCn can
also be obtained. However, it must be stressed that for the
concentrations of SCn used here, SC6 and SC8 exist in solution
as 1:1 and 1:2 sodium complexes and that different stoichio-
+
metric complexes containing 1, SCn and Na are likely to
Scheme 2. Structures of the SCn used in this work along with their
respective monomer HBS. Some hydroxyl protons are ionized at neutral pH.
parent monomer 4-hydroxybenzenesulfonate (HBS) on the
observed rate constant (kobs) for the hydrolysis of 1 was
investigated at 25°C. As can be observed both SC4 and SC6HM
(
see the Supporting Information) hardly affect the k while on
obs
the other hand SC6, SC8 and HBS increase the rate of the 2,4-
dinitrophenolate ion formation. However, while for HBS (see the
Supporting Information) the kobs values shows a linear depend-
ence with its concentration, for the macrocyclic hosts SC6 and
SC8 the plots show saturation profiles compatible with the
formation of reactive host-guest complexes. The observed
behavior can be assigned to the nucleophilic or base catalysis
operated by the ionized phenol groups of these receptors. This
agrees with the fact that both SC6HM that lacks ionizable
Figure 1. Observed rate constants (kobs) for the hydrolysis of 1 in the
presence of increasing concentrations SC4 (open squares), SC6 (open circles)
and SC8 (closed circles). All experiments were carried out at 25°C and at
phenol groups and SC4 for which the pK of the ionized phenol
is very low (pK =3.3) do not show appreciable catalytic
effects. On the other hand, SC6 and SC8 have more than one
a
a
[31]
neutral pH conditions in the absence of buffers.
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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[28,36–39]
occur.
Therefore k must be considered as an apparent
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rate constant that results from the sum of the rate constants of
the different complexes averaged by their relative mole
fraction.
k þ k K ½SCnꢀ
0
1
app
kobs
¼
(1)
1
þ K ½SCnꢀ
app
As can be observed from Table 1, reliable k and Kapp cannot
1
be accurately obtained for SC4 either due to a very small
catalytic effect or/and poor binding affinity of 1 towards this
host. On the other hand, both SC6 and SC8 form host-guest
1
1
1
1
1
1
1
1
1
1
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À 1
complexes of moderate affinity with 1 (10 M range), which is
expected based on the lower affinity of these receptors for
[28,40,41]
neutral aromatic species.
As already discussed above, the
k1 values seems to correlate with the pK of the ionizable
a
phenols group of the SCn and thus the rate acceleration affect
is higher for SC8.
Table 1. Rate and equilibrium constants for the hydrolysis of 1 in the
presence of SCn at 25
°
C.
À 1
À 1
À 1
k
0
[s
]
k
1
[s
]
K
app [M ]
[
a]
À 5
À 5
À 5
SC4
SC6
SC8
(1.2ꢁ0.2)×10
(1.3ꢁ0.2)×10
(1.4ꢁ0.2)×10
–
–
À 5
À 4
(5.8ꢁ1.0)×10
237ꢁ30
(2.0ꢁ0.2)×10
165ꢁ20
[
a] The small variation of the rate constants with the SC4 concentrations
precluded a reliable fitting of data to Equation (1).
As previously mentioned, the hydrolysis of 1 is catalyzed by
2
+
Lewis acids such as Ni offering suitable conditions to test the
catalytic potential of SCn through the formation of ternary
complexes. When the kobs for the hydrolysis of 1 is measured for
2
+
different concentrations of Ni
(in the absence of SCn) a
straight line is obtained in agreement with a low association
2
+
constant (K1
) for the formation of the 1: Ni complex.
:Ni2þ
According to the mechanism of Scheme 1 and assuming that
the equilibrium reaction for the formation of the complex is
much faster than the hydrolysis, it is straightforward to show
that the kobs is given by Equation (2) similar to Equation (1):
2
þ
k þ k K
½Ni ꢀ
0
2
1:Ni2þ
kobs
¼
(2)
2þ
1
þ K1
½Ni ꢀ
:Ni2þ
2
þ
When K1
½Ni ꢀ!1 (i.e. for small K
), then Equation (2) is
1:Ni2þ
:Ni2þ
Figure 2. (a) Observed rate constants (kobs) for the hydrolysis of 1 in the
reduced to Equation (3) which can be experimentally confirmed
by the straight line observed for kobs vs [Ni ] plot. The slope of
2+
presence of increasing concentrations of SC4 in the presence of [Ni
]
2
+
=0.01 M. (b) Influence of NaNO3 on the kobs for the hydrolysis of 1 in the
2+
À 1
À 1
presence of [Ni ]=0.01 M and [SC4]=0.01 M. (c) Mole fraction of SC4
this plot gives a value for k2K
1:Ni2þ
=0.019 s .M (see the
2+
species as a function of the SC4 concentration in the presence of [Ni
0.01 M. (d) Mole fraction of 1 species as a function of the SC4
]
Supporting Information).
=
2
+
concentration in the presence of [Ni ]=0.01 M. All experiments were
2
þ
carried out at 25°C and at neutral pH conditions in the absence of buffers.
kobs ¼ k þ k K
½Ni ꢀ
(3)
0
2
1:Ni2þ
Figure 2a shows the influence of SC4 on k obtained at
obs
2
+
constant concentration of Ni (0.01 M). As can be observed,
the kobs increases up to maximum at circa 0.01 M of SC4 and
then the rate of the reaction starts to decrease as the
concentration of the macrocycle is further increased. The rate
acceleration can be ascribed to the higher affinity of SC4
2
+
2+
towards the 1: Ni
adduct forming a 1: Ni :SC4 ternary
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+
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Scheme 3. Proposed mechanism for the complexation and hydrolysis of 1 with SC4 in the presence of Na an Ni
.
À 1
2+
Table 2. Rate and equilibrium constants (M ) for the hydrolysis of 1 in the presence of SCn and Ni at 25°C.
À 1
K
1
K
NiNa
K
T1
K
2T1
K
T2
K
2T2
K
T3
3
k [s ]
À 3
À 3
À 2
SC4
SC6
SC8
–3 20ꢁ60
–
150
<500
–
–
<10
180
612
<1000
<1000
–
–
(2.4ꢁ0.4)×10
(3.8ꢁ0.3)×10
(2.8ꢁ0.2)×10
315ꢁ60
500ꢁ100
400ꢁ80
1000ꢁ200
350ꢁ75
350ꢁ70
À 1
complex which increases the effective concentration of the
reactive species in solution and consequently its decomposi-
tion. At higher concentration the formation of the ternary
(K =610 M ) is almost two times higher than K while the
T2 1
opposite effect is observed for the ternary complex with sodium
À 1
cations (K =150 M ) in agreement with positive and negative
T2
+
complex between 1, SC4, Na counterions starts to predom-
cooperativity phenomena already documented for the SC4
binding with other pyridine and azoalkanes guests in the
presence of transitions and alkaline metal cations,
The cooperative formation of the ternary 1:
Ni :SC4 complex can be proposed to be main responsible for
inate leading to a decrease in the observed rate constant. The
proposed mechanism is presented in Scheme 3. As an approx-
[25,28]
imation the rate constant (k ) for the hydrolysis of the 1: SC4
respectively.
1
+
2+
binary complex and for 1: Na :SC4 ternary complex is
considered to be the same. Based on the proposed mechanism,
Equation (4) can be deduced to account for the observed rate
constant for formation of 2,4-dinitrophenolate product. It is
worth noting that the equilibrium concentrations of Na , Ni ,
SC4 must be obtained through the resolution of the system of
equations based on the mass balance and equilibrium
expressions (see the Supporting Information).
the observed rate acceleration in the hydrolysis of 1. Although
the k cannot be obtained independently, the observation of a
2
2
+
linear dependence in the k vs [Ni ] plot implies that K1:Ni ꢂ1
obs
À 1
+
2+
and therefore k ꢃ0.019 s . This observation implies that the
2
2
+
rate constant for the hydrolysis of 1: Ni is lower for the
2
+
À 3 À 1
ternary 1: Ni :SC4 complex (k =2.5×10 s ) and therefore
3
the SC4-induced rate enhancement must be attributed to an
increase in the concentration of the metal-ligand complex
promoted by the calixarene through the formation of the
ternary complex. As a control experiment, the effect of NaNO3
on the observed rate constants for the SC4 concentration where
maximum rate acceleration was observed (0.01 M) was inves-
tigated (Figure 2b). As can be observed the kobs decreases to the
value observed in the absence of macrocycle in agreement with
the displacement of Ni from SC4 by Na competitive binding.
With the binding constants determined, the speciation plots
for SC4 and 1 species can be constructed (Figure 2c and 2d)
showing that the mole fraction of the complex SC4: Ni
disappears to give SC4: Na due counterion binding and the
As can be observed, the kinetic data in Figure 2a can be
satisfactorily fitted with Equation (4) thus supporting the
proposed mechanism. Owing to the high number of optimiz-
able parameters, k and k K obtained above in independent
0
2 1:Ni
À 1
experiments were fixed. Similarly, the values for K =180 M
and K =5560 M were known from previous works and also
Na
À 1
Ni
[42]
kept constant. k and K that could not be obtained for SC4
1
1
2
+
2+
+
from the kinetic experiments in the absence of Ni , were
À 5 À 1
À 1
estimated to be k �2×10
s
and K =320 M . The remain-
1
1
ing kinetic and thermodynamic parameters were obtained from
the fitting and are presented in Table 2. Noteworthy, the
2
+
2
+
+
association constant for the binding of 1 towards SC4:Ni
ChemCatChem 2019, 11, 1–9
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+
preferential formation of the 1: Ni :SC4 at lower concen-
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trations of SC4 and its disappearance at higher concentrations
+
to give the 1: Na :SC4 complex due to the increasing
concentration of sodium counterions in solution.
2
þ
þ
k þ k K ½Ni ꢀ þ ðK þ K K ½Na ꢀÞk ½SC4ꢀþ
0
2
1:Ni
1:1
T1 Na
1
2þ
(4)
k K K ½Ni ꢀ½SC4ꢀ
3
T2 Ni
kobs ¼ 1
þ
2þ
þ K ½SC4ꢀ þ K K ½Na ꢀ½SC4ꢀ þ K K ½Ni ꢀ½SC4ꢀ
1:1
T1 Na
T2 Ni
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
2
+
The Ni -catalyzed hydrolysis of 1 was also investigated in
presence of larger hosts SC6 and SC8. Figure 3 shows results
obtained in these cases. Comparatively with SC4, the rate
enhancement, at the maximum, is ca. 2-fold higher for SC6 and
ca. 10-fold for SC8 demonstrating that the last one is much
2
+
more efficient at promoting the Ni -catalyzed hydrolysis of 1.
When compared with the results obtained in the absence of
SC8, the rate is enhanced 85-fold with 10 mM of SC8. A similar
mechanism to that proposed for SC4 in Scheme 3, can be
proposed for SC6 and SC8 (see Scheme 4) but for these
receptors the formation of 1:1 and 1:2 host:guest complexes
with the metal cations and respective heteroternary complexes
must be accounted for. Before analyzing the kinetic data
2
+
presented in Figure 3, the binding constants for Ni towards
SC6 and SC8 were determined using the lucigenin displacement
assay protocol previously stablished for other metal cations (see
[38]
the Supporting Information). This allowed the determination
5
À 1
of the following binding constants K =1.6x10 M , K = 2.4×
Ni
2Ni
3
3
À 1
6
À 1
À 1
1
0 M for SC6 and K =1.5×10 M , K =8.5×10 M for
Ni
2Ni
SC8. The values are in agreement with an increase in the
stability of the complexes as the charge of the host and guest
increase, as expected for the formation of non-covalent species
dominated by attractive coulombic interactions. In the same
2
+
manner, the stability of the 1:2 SCn:Ni
complex shows
negative cooperativity due to partial charge neutralization
[38]
during the formation of the binary species.
As can be observed from Scheme 4, the number of species
that can be formed for SC6 and SC8 increase substantially with
respect to SC4. This complex dynamic multistate system arises
from the fact that these hosts can form 1:1, 1:2 and
[38]
heteroternary complexes with the cations present in solution.
Then, the calixarene-metal complexes may bind 1 to form the
respective ternary and quaternary complexes. In order to
simplify the analysis of the kinetic data we neglected the
potential formation of 1:2 host:guest complexes between SC6/
8
and 1. This approximation is based on the fact that in the
experimental conditions the concentration of calixarene is
usually higher than that of 1 and the binding constants for the
formation these complexes are relatively small (see Table 1)
which precludes the formation of 1:2 species at lower
concentrations of host (unless their formation is highly cooper-
ative but this is not expected on the basis of the stablished SCn
binding properties). In a second approximation, it can be
Figure 3. Observed rate constants (kobs) for the hydrolysis of 1 in the
2
+
presence [Ni ]=0.01 M and increasing concentrations of (a) SC6 and (b)
SC8. Mole fraction of SC6 (c) and SC8 (d) species as a function of the
2
+
calixarene concentration in the presence of [Ni ]=0.01 M. All experiments
were carried out at 25 C and at neutral pH conditions in the absence of
buffers.
°
2
+
assumed that rate constants for the Ni containing host-guest
complexes are similar independently of their stoichiometry (k3)
and on the other hand, it is also assumed that SCn:1 and as well
this way, the unknown parameters are k , K , K , K , K , K2T2,
3
1
T1
2T1
T2
KT3 and KNiNa. The remaining parameters are introduced as
constants using the values from Table 1 and Table S1 (see the
+
+
the SCn:Na :1/SCn:2Na :1 also show similar reactivity (k ). In
1
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+
2+
Scheme 4. Proposed mechanism for the complexation and hydrolysis of 1 with SC6 (or SC8) in the presence of Na an Ni
.
2
+
+
Supporting Information). The observed rate constant is given by
Equation (5) which is analogous to Equation (4) for SC4 where
the equilibrium constants are related to the equilibria of
Scheme 4. This Equation is then coupled the respective mass
balance expressions and the systems can be numerically solver
using the Newton-Raphson algorithm and the constants
optimized. As can be observed from Figure 3 the theoretical
heteroternary complex SCn:Ni :Na was assumed to be equal
to K2Na/2. The constant is correlated with k and therefore an
underestimation of the first will lead to an overestimation of
the last and vice versa. Based on these assumptions, the kinetic
data of Figure 3 was successfully fitted using the combination
of parameters shown in Table 2.
3
2þ
model describes very well the experimental data. K can be
k
0
þ k
2
K
1:Ni½Ni ꢀþ
1
neglected as it does not contribute significantly to kobs because
the concentration of free SC6 or SC8 is very small under the
experimental conditions, i.e., their complexes with metal
À
�
þ
þ 2
K þ K K ½Na ꢀ þ K K K ½Na ꢀ k ½SCnꢀ
1
T1 Na
2T1 Na 2Na
1
kobs
¼
þ
D
0
1
2þ
(5)
2þ
2
[38]
K K ½Ni ꢀ þ K K K ½Ni ꢀ þ
T2 Ni
2T2 Ni 2Ni
cations predominate. However, due to the large number of
correlated parameters the binding and kinetics constants
cannot be all accurately determined from the fitting. Never-
theless, some parameters can be estimated and the ones that
included errors can be determined assuming the described
approximations. As can be observed from speciation plots
shown in figures 3c and 3d, the most abundant species are
@
A
k3½SCnꢀ
2þ
þ
K K K ½Ni ꢀ½Na ꢀ
T3 Ni NiNa
D
With
þ
D ¼ 1 þ K ½SCnꢀ þ K K ½Na ꢀ½SCnꢀþ
1
T1 Na
+
2+
those for which the calixarene is occupied with 2 Na , 2 Ni or
þ 2
K2T1K K ½Na ꢀ ½SCnꢀþ
Na 2Na
+
2+
1
Na and 1 Ni and thus the binding constants for the
(
6)
2
þ
2þ 2
K K ½Ni ꢀ½SCnꢀ þ K K K ½Ni ꢀ ½SCnꢀþ
T2 Ni
2T2 Ni 2Ni
association of 1 with these species can be determined and for
the remaining ones only the upper limits can be estimated
2þ
þ
K
K
T3 Ni
K
NiNa½Ni ꢀ½Na ꢀ½SCnꢀ
(
Table 2). Owing to the more efficient charge neutralization of
2
+
Ni , KNiNa, i.e., the binding constant for the formation of
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6
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In the cases of SC6 and SC8 the rate acceleration is mainly
(FCT/MCTES fund UID/QUI/50006/2019) and the Portuguese
Fundação para a Ciência e Tecnologia (grant CEECIND/00466/
2017 to N.B.). Financial support from Ministerio de Economia y
Competitividad of Spain (project CTQ2017-84354-P), Xunta de
Galicia (GR 2007/085; IN607 C 2016/03 and Centro singular de
investigación de Galicia accreditation 2016-2019, ED431G/09) and
the European Union (European Regional Development Fund-
ERDF), is gratefully acknowledged.
1
2
3
4
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9
0
1
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0
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0
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8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
2
+
2+
+
due to the binding of 1 to SCn:2Ni
and SCn:Ni :Na
species which leads to an increase in the mole fraction of more
2
+
reactive 1: Ni . Then, as for SC4, at concentrations above ca.
.01 M of SC6 or SC8 the rate starts to decrease due to
0
+
competitive binding of Na cations to the calixarene species.
This is especially relevant in the cases of SC8 (and SC4) but for
SC6 the decrease in kobs is smoother due to inefficient binding
+
À 1
of 1 to the SC6: SCn:2Na species (K <10 M ). As for the
2
T1
2
+
hydrolysis of 1 in the absence of Ni , the rate constant for the
hydrolysis of 1 associated with Ni and SCn (k ) the values Conflict of Interest
increase with more basic character of the ionizable phenol
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
2
+
3
groups suggesting the participation of the phenolate in
promoting the hydrolysis.
The authors declare no conflict of interest.
Keywords: Binding Models · Calixarenes · Host-Guest Systems ·
Kinetics and Supramolecular Catalysis
3
. Conclusions
2
+
SCn were demonstrated to promote the Ni
catalyzed
hydrolysis of 1 through higher-order complexes that promote
2
+
the formation of reactive 1- Ni metal-ligands complexes in
the confined environment provided by the macrocyclic recep-
tor. The rate enhancement is mainly attributed to a thermody-
namic effect, i.e. increase in the effective metal-ligand associa-
tion constant for smaller hosts SC4 and SC6 while SC8 acts a
multifunctional enzyme-mimetic catalyst that by one hand
provide a microenvironment that brings together the substrate
and the metal cation and on the other hand further promotes
the reactions through participation of the weakly basic
phenolate groups that assist the hydrolysis through base or
nucleophilic catalysis. This reaction also served to test and
demonstrate the SCn counterion exchange model and its
application in the mechanistic interpretation of binding and
catalysis involving multicomponent host-guest systems.
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[
Manuscript received: September 25, 2019
Revised manuscript received: September 5, 2019
Accepted manuscript online: September 19, 2019
Version of record online: ■■■, ■■■■
2
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Host-guest systems: Simultaneous
Dr. N. Basílio*, Dr. M. Pessêgo, Dr. A.
Acuña, Prof. L. García-Río*
2
+
binding of a Ni cation and an ester
substrate with sulfonatocalixarenes
was found to accelerate the hydroly-
sis of the organic guest owing to the
cooperation of two main factors:
promoted formation of reactive
1 – 9
Sulfonatocalixarene Counterion
Exchange Binding Model in Action:
Metal-Ion Catalysis Through Host-
Guest Complexation
1
1
1
1
1
1
1
1
1
1
2
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2
2
2
2
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metal-ligand species and catalytic as-
sistance of phenolate groups present
in the structure of the receptor.