Metallacycle-catalyzed SNAr reaction in water: Supramolecular inhibition by means of host-guest complexation

Article abstract of DOI:10.1021/jo402689p

The performance of a Pt^II diazapyrenium-based metallacycle as a reusable substoichiometric catalyst for the S_NAr reaction between halodinitrobenzenes and sodium azide at rt in aqueous media is reported. The results suggest that the c

Full text of DOI:10.1021/jo402689p

Article
pubs.acs.org/joc
Metallacycle-Catalyzed SNAr Reaction in Water: Supramolecular
Inhibition by Means of Host−Guest Complexation
Eva M. Lopez-Vidal,† Antonio Fernandez-Mato,† Marcos D. García,† Moises Perez-Lorenzo,‡
́
́
́
́
Carlos Peinador,*,† and Jose M. Quintela*,†
́
†Departamento de Química Fundamental and Centro de Investigaciones Científicas Avanzadas (CICA), Facultad de Ciencias,
Universidade da Coruna, A Zapateira s/n, 15008 A Coruna, Spain
̃
̃
‡Departamento de Química Física, Universidade de Vigo, 36310 Vigo, Spain
S
* Supporting Information
ABSTRACT: The performance of a PtII diazapyrenium-based metallacycle as a reusable substoichiometric catalyst for the SNAr
reaction between halodinitrobenzenes and sodium azide at rt in aqueous media is reported. The results suggest that the catalytic
effect is promoted by the association of the azide to the diazapyrenium cationic subunits of the catalyst. The findings demonstrate
that the formation of an inclusion complex between pyrene and the metallacycle has a regulatory effect over the system, resulting
in allosteric-like inhibition of the SNAr reaction.
diazapyrenium-based metallacycle 3 on a nucleophilic aromatic
substitution (SNAr) (Scheme 1). A priori, as a result of the
special characteristics of the diazapyrenium-containing metalla-
cycle 3, it can act as catalyst for the SNAr through cation-
induced desolvation of the anionic nucleophile.7 Moreover, its
central cavity would be suitable to accommodate aromatic
substrates,8 a fact that could potentially alter their reactivity in
the SNAr.4c Finally, we anticipated that the cavity of the
metallacycle could also act as a regulation center for the
catalytic system, as appropriate aromatic nonreactive com-
pounds could be complexed by 3, altering in that manner the
catalysis.
In the work presented herein, we demonstrate that
metallacycle 3 efficiently catalyzes the SNAr reaction between
halodinitrobenzenes and sodium azide in aqueous media by
means of nucleophile desolvation, which was found to be
caused by the diazapyrenium ligands within the metallacycle
structure. Furthermore, inclusion of a suitable guest for 3 in the
system results in deactivation of the catalysis as a result of
host−guest interactions.
INTRODUCTION
■
The high diversity of regulation mechanisms found in
enzymatic reactions has become a major source of inspiration
for the design of abiotic systems with efficient and controlled
catalytic activity.1 In this regard, coordination-driven self-
assembly has enabled the rational preparation of a myriad of
2D/3D metallacycles with diverse potential purposes,2
including the development of a substantial amount of cavity-
controlled reactions.3 In most cases, the peculiar chemical
environment created within the inner cavities of these hosts is
exploited to create supramolecular catalytic systems that use
encapsulation of reactants to decrease the entropic penalty of a
given reaction. However, the use of metallacycles as efficient
catalysts has rarely been demonstrated, as in many cases they
bind products as effectively as reactants, thereby inhibiting the
catalytic turnover.4 Moreover, few examples where the catalytic
activity can be controlled by means of regulatory effectors have
been reported.5
Over the past few years, by using N-monoalkyl-2,7-
diazapyrenium salts and square-planar PtII metals, our research
group has developed a coordination-driven self-assembly
approach for the preparation of 2D metallacycles.6 In order
to explore the potential of our designed molecular hosts in the
field of catalysis, we decided to study the effect of the PtII
Received: December 4, 2013
Published: January 20, 2014
© 2014 American Chemical Society
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Scheme 1. Model SNAr Reaction and Species Discussed in This Work
RESULTS AND DISCUSSION
■
As model for the SNAr, we examined the reaction between
halodinitrobenzenes 1a−d and sodium azide (10 equiv) in D2O
at rt in the presence or absence of catalytic amounts of the
water-soluble metallacycle 3·6NO3 (Scheme 1). Control
reactions in the absence of 3·6NO3 showed that 1a was
transformed into the expected azide 2 (100% conversion in 22
h, as determined by 1H NMR analysis of a CDCl3 extract). On
the contrary, no reaction product at all was detected after 24 h
in the CDCl3 extracts for 1b−d. These reactions proceeded
rather slowly, with low conversions achieved only after 8 days
(X = Cl, 33%; X = Br, 44%; X = I, 23%). Remarkably, the use of
3·6NO3 as catalyst dramatically changed the reactivity of 1b−d
in water: after 20 h, no starting material was detected, and azide
2 was the only reaction product.
Kinetic studies of the reaction between 1b (6 mM) and
Figure 1. Kinetic data for the SNAr reaction between 1b (6 mM) and
NaN3 (60 mM) in D2O/CD3CN (4:1) at rt in the presence of 3·6NO3
sodium azide (60 mM) were carried out at rt in D2O/CD3CN
(4:1).9 As expected, the reaction for 1b was much faster in
presence of 3·6NO3 (0.6 mM, 10 mol %) compared with the
control reaction (Figure 1). Unsurprisingly, ligand 4·NO3 (1.2
mM, 20 mol %) was also observed to catalyze the reaction to
the same extent as 3·6NO3, although no catalytic effect was
found for (en)Pt(NO3)2 (1.2 mM, 20 mol %) (see Figure S9 in
the Supporting Information).
■
◆
(0.6 mM, 10 mol %) (red ), 4·NO3 (1.2 mM, 20 mol %) (green ),
▲
or metallacycle 3·6NO3 (0.6 mM, 10 mol %) + pyrene (blue ) or in
●
the absence of catalyst (black ) as a control.
Table 1. Conversions and Yields for the Laboratory-Scale
Reaction of 1b with NaN3 in the Presence or Absence of 3·
a
6NO3
At this point, is important to remark on the similarities and
differences between the reactions catalyzed by metallacycle 3·
6NO3 and ligand 4·NO3. First, the observation of comparable
activities for 3·6NO3 and 4·NO3 suggests a similar catalytic
mechanism involving the diazapyrenium moieties, with the
cavity of 3·6NO3 not playing a key role in it. Nevertheless, in
terms of practical use, metallacycle 3·6NO3 proved to be
superior to ligand 4·NO3 as a catalyst. In this regard, laboratory-
scale experiments using 1b, NaN3, and a catalytic amount of 3·
6NO3 (10 mol %) in D2O at rt showed that when the reaction
was complete (after 10 h), it was possible to obtain the clean
product 2 in 98% yield by a simple extraction with CHCl3. The
resulting aqueous phase containing 3·6NO3 and excess NaN3
could be reutilized four more times in subsequent reactions
upon the addition of 1b (1 equiv) and NaN3 (1 equiv) (Table
1). On the contrary, ligand 4·NO3 was not reusable because of
its slight solubility in organic solvents.
b
cycle
yield (%)
time (days)
1
2
3
4
5
98
92
95
90
91
4
0.42
1.5
3
5
7
c
control
0.42
a
Reaction conditions: 1b (70 mg, 10 mM), NaN3 (100 mM), and 3·
6NO3 (10 mol %) in D2O at rt for the required time to reach a
conversion of 100%. Yields based on isolated product. Reaction
b
c
conditions: 1b (70 mg, 10 mM) and NaN3 (100 mM) in D2O at rt.
In order to quantitatively evaluate the catalytic effect of
metallacycle 3·6NO3 on the model SNAr reaction, a kinetic
model based on the reaction mechanism depicted in Scheme 2
was built. Applying the steady-state approximation to the
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On the basis of eq 1, in the presence of added catalyst at a
given azide concentration, kcoabts can be easily estimated from the
difference between the observed rate constants in the presence
and absence of metallacycle. Figure 2 also displays the fit of our
experimental results to eq 1, with a satisfactory agreement
between the kinetic data and the proposed rate law. Likewise,
from this hyperbolic fit the values kcat = 0.085 0.023 M−1 s−1
Scheme 2. Mechanistic Proposal for the Catalyzed SNAr
Reaction between 1b and NaN3; The Inhibitory Effect
Observed upon Addition of Pyrene (PYR) for Cat = 3·6NO3
Is Also Represented
and K3·N = 38.0 7.6 M−1 were obtained.
3
At first glance, the kinetic experiments shown in Figure 2 for
the catalyzed reaction exhibit a rather marked saturation profile.
Thus, while the uncatalyzed reaction rate increases linearly with
−
[N3 ] (Figure 2), the metallacycle-catalyzed reaction rate
becomes gradually independent of the nucleophile concen-
−
tration, that is, zeroth order in [N3 ]. This leveling off can be
easily justified in terms of the limited availability of azide
associated to the catalyst. As an illustrative example, for a
−
nucleophile concentration [N3 ] = 0.6 M and the measured
value of K3·N , it can be estimated that 96% of the added catalyst
3
−
−
is associated to N3 to afford 3·N3 complexes. Therefore, a
further increase in the azide concentration will not lead to a
−
substantial increase in [3·N3 ] and accordingly will not increase
reaction intermediate and considering that the nucleophile
concentration is in large excess over the aromatic substrate
allows eq 1 for the observed rate constant kobs to be derived:
the rate of the catalyzed reaction.
Most importantly, taking into account the values derived
from Figure 2 yields a kcat/kuncat ratio of ∼1000. Given the
steady-state condition for the Meisenheimer intermediate (T−),
it can be assumed that at no point is the equilibrium for the
formation of T− established, and hence, both steps (step 1:
addition of the azide nucleophile; step 2: elimination of the
halide leaving group) can be virtually treated as irreversible
processes. In other words, kcat = k2 and kuncat = k1.10
Consequently, it can be concluded that the presence of the
metallacycle gives rise to a remarkable 1000-fold increase in the
formation of the Meisenheimer complex. Additional spectro-
scopic experiments on the interaction between 3·6NO3 and 1b
demonstrated the absence of preassociation between the
metallacycle and the uncharged aromatic substrate, which
rules out an unlikely situation where the reaction intermediate
would be formed by the attack of the nucleophile on a 1b·3
complex.
kcatK3·N [3][N3 ]
−
3
uncat
obs
cat
kobs = k
+ k = kuncat[N3−] +
obs
1 + K3·N [N3 ]
−
3
(1)
where kuncat and kcat are the rate constants for the uncatalyzed
and catalyzed SNAr reactions, respectively, and K3·N represents
3
the equilibrium constant for the formation of the azide−
metallacycle complex. Therefore, the overall observed rate
constant is given by the sum of two different contributions: the
uncatalyzed process and the metallacycle-catalyzed reaction.
Figure 2 shows the influence of azide concentration on the
observed rate constant in the absence of added catalyst. As
uncat
obs
expected from eq 1, a linear dependence of k
on the
nucleophile concentration was found, and the linear fit
displayed in this figure gave the value kuncat = (9.04 0.02)
× 10−5 M−1 s−1.
Figure 2. Influence of azide ion concentration on the overall (left), uncatalyzed (middle), and catalyzed (right) observed rate constants for the SNAr
uncat
obs
cat
obs
reaction between 1b and NaN3 in D2O/CD3CN (4:1), where kobs = k
+ k . [1b] = 6 mM; [3·6NO3] = 0.6 mM (10 mol %); T = 25 °C.
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An alternative mechanistic proposal for the reaction between
1b and NaN3 would consist of a rate-limiting decomposition of
the reaction intermediate (step 2 as rate-limiting). However,
this alternative may be ruled out by comparing the results
obtained for 1b with those for halodinitrobenzenes 1a, 1c, and
1d. As previously stated (vide supra), in the absence of catalyst,
1a is fully transformed into the expected azide 2 (100%
conversion in 22 h), while the corresponding substitution
reactions for 1b−d are much slower (33%, 44%, and 23%
conversion, respectively, after 8 days). This sequence of halide
leaving group abilities (F > Cl ≈ Br ≈ I) is often found in
kinetic studies of SNAr reactions involving nitroactivated
aromatic halides. Where found,11 this result establishes an
addition−elimination mechanism for the SNAr reaction in
which the first step consists of rate-limiting nucleophilic attack
to afford the σ adduct. Thus, groups with strong −I effects, such
as fluorine, will likely promote the formation of the reaction
intermediate, justifying the higher reactivity found for 1a.
Accordingly, for a hypothetical rate-limiting second step a much
lower reactivity of 1a compared with 1b−d should be expected,
which allows such a mechanism to be discarded.
In order to gain further insights into the role of the cavity of
3·6NO3 in the catalyzed reaction, substrate 1b (clearly not a
good guest for host 3·6NO3), was replaced by 4-chloroquino-
line (5), a substrate potentially able to react with NaN3 by SNAr
as well as to get complexed by the metallacyclic host. Contrarily
to the case of 1b, changes in the NMR spectra of the system
consistent with the formation of 5⊂3·6NO3 were observed
upon addition of 5 to a solution of 3·6NO3 in D2O/CD3CN
(4:1). For instance, in the 1H NMR spectra, resonances for the
protons of the guest and protons located in the central part of
the phenylene−diazapyrene system of 3·6NO3 were shifted
upfield as a consequence of their mutual shielding. On the
other hand, resonances for the hydrogen nuclei of the pyridine
rings of 3·6NO3 were shifted to higher frequencies upon
complexation, suggesting the occurrence of [C−H···π]
interactions with 5.
Kinetic studies showed significant differences between the
reactions of 5 and NaN3 catalyzed by the metallacycle 3·6NO3
(0.6 mM, 10 mol %) and the ligand 4·NO3 (1.2 mM, 20 mol
%) (Figure 3). Here, the assembly 5⊂3·6NO3 induced a
In light of the kinetic results obtained for the catalytic system,
the mechanistic proposal for the reaction between 1b and NaN3
(Scheme 2) involves the formation of the reaction intermediate
T− as the rate-limiting step. The desolvation experienced by the
azide ion when it is associated to the positively charged
diazapyrenium-based catalyst would make the nucleophile more
reactive, thereby facilitating the formation of T− and speeding
up the overall process. The association of azide ion to 3 is an
exergonic process, meaning that the binding of the nucleophile
to the macrocycle lowers the free energy of the metallacycle−
azide ion complex compared with that of the free nucleophile.
Such a decrease logically must be accompanied by a greater
lowering of the corresponding activation energy, without which
the catalytic effect reported herein would not take place. In fact,
experiments carried out with catalysts 3·6NO3 and 4·NO3 using
an excess of NaNO3 revealed a significant reduction in the
catalytic effect that can be connected with disruption of the
azide−catalyst association complex by the nitrate anions. This
hypothesis is also substantiated by the observation of the
catalytic efficiency of 3·6NO3 in different media [i.e., D2O and
D2O/CD3CN mixtures (4:1 and 1:1)]. The control reaction
was clearly decelerated as the proportion of deuterium oxide
increased (Table 2), which can be ascribed to the less effective
solvation of the corresponding Meisenheimer intermediate T−
in water as well as the reduction of the nucleophilicity of the
azide anion in protic solvents.12 However, in the catalyzed
reactions the reaction rate increases in the opposite direction
with the concentration of D2O because of the worse solvation
of the azide−metallacycle complex by polar protic solvents.
Figure 3. Kinetic data for the SNAr reaction between 5 (6 mM) and
NaN3 (60 mM) in D2O/CD3CN (4:1) at rt in the presence of 3·6NO3
■
(0.6 mM, 10 mol %) (red ) or 4·NO3 (1.2 mM, 20 mol %) (green
◆
●
) or in the absence of catalyst (black ) as a control.
decreased reaction rate in comparison with the SNAr catalyzed
by 4·NO3, giving evidence that the cavity of metallacycle 3·
6NO3 not only is not vital to the catalytic activity but also is
potentially important as an allosteric-like regulatory center.13
With the mechanistic proposal in our hands, and taking into
account the evidence exonerating the cavity of the metallacycle
3·6NO3 from responsibility for the observed catalytic activity,
we decided to test the effect of a suitable nonreactive aromatic
guest for receptor 3·6NO3 on the behavior of the catalytic
system. Pyrene (PYR)8 was chosen for that purpose, and as a
consequence of the host−guest complexation, it was found that
the rate of the reaction catalyzed by 3·6NO3 (10 mol %)
decreased clearly (Figure 1), stressing the potential role of the
cavity not on the observed catalysis but on the modulation of
the catalytic activity.14
Table 2. Conversions for the Reactions of 1b with NaN3 at t
= 10 h in the Presence or Absence of 3·6NO3 in Different
Solvents
conversion (%)
a
b
solvent
with 3·6NO3
control
D2O
100
77
5
17
51
D2O/CD3CN (4:1)
D2O/CD3CN (1:1)
Considering the catalytic effect associated with the metalla-
cycle 3·6NO3 as a result of a specific cation-induced desolvation
effect on the nucleophile, the supramolecular inhibition
observed when a good guest is present in the system can be
59
a
Conditions: 1b (6 mM), NaN3 (60 mM), and 3·6NO3 (0.6 mM, 10
b
mol %) at rt. Conditions: 1b (6 mM) and NaN3 (60 mM) at rt.
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explained by the formation of inclusion complexes. Thus,
complexation would result in the modification of the electronic
characteristics of the catalyst, rendering the diazapyrenium
subunits less π-deficient because of the donation of electron
density from the guest. This would reduce the amount of azide
associated to the cation, reducing in consequence its desolva-
tion and reactivity.15 In other words, reversible host−guest
complexation potentially allows the inhibitory activity to be
modulated by the addition of guests with different binding
strengths.
CONCLUSIONS
■
catalyst 3·6NO3 (0.6 mM) or 4·NO3 (1.2 mM) in D2O/CD3CN (4:1)
were prepared from stock solutions of 1b in CD3CN and 3·6NO3/4·
NO3 in D2O. The sodium azide was added in solid form to initiate the
reaction.
In summary, in the work presented here we have reported the
performance of the PtII diazapyrenium-based metallacycle 3·
6NO3 as a reusable substoichiometric catalyst for the SNAr
reaction between halodinitrobenzenes 1a−d and NaN3 at rt in
aqueous media. The experimental results suggest that the
catalytic effect is promoted by association of the azide to the
diazapyrenium cationic subunits of the catalyst. Moreover,
making use of the internal cavity and π-deficient aromatic
subunits within the metallacycle, we have explored the
inhibitory activity of pyrene in the catalytic system under
study. The findings reported herein demonstrate that the
formation of an inclusion complex has a regulatory effect over
the system that results in allosteric-like inhibition of the SNAr
reaction. Ongoing studies are showing that the results reported
in this work can be applicable to other nucleophiles and
substrates in SNAr reactions in water.
Control Reaction in the Presence of (en)Pt(NO3)2. Samples (1 mL)
suitable for 1H NMR analysis containing 1b (6 mM) and
(en)Pt(NO3)2 (1.2 mM) in D2O/CD3CN (4:1) were prepared from
stock solutions of 1b in CD3CN and (en)Pt(NO3)2 in D2O. The
sodium azide was added in solid form to initiate the reaction.
Control Reaction in the Presence of NaNO3. Samples (1 mL)
suitable for 1H NMR analysis containing 1b (6 mM) and NaNO3 (1.2
mM) in D2O/CD3CN (4:1) were prepared from stock solutions of 1b
in CD3CN and NaNO3 (0.6 mM) in D2O. The sodium azide was
added in solid form to initiate the reaction.
Catalyzed Reaction in the Presence of Pyrene. Samples (1 mL)
1
suitable for H NMR analysis containing 1b (6 mM), and pyrene⊂3·
6NO3 (0.6 mM) in D2O/CD3CN (4:1) were prepared from stock
solutions of 1b in CD3CN and pyrene⊂3·6NO3 (0.6 mM) in D2O/
CD3CN (4:1). The sodium azide was added in solid form to initiate
the reaction.
EXPERIMENTAL SECTION
In all cases, the progress of the reaction was monitored by 1H NMR
spectroscopy at 298 K. The concentrations of 1b and azide 2 were
determined by relative integrations of the peaks at δ = 8.17 ppm (d, J =
9.0 Hz, H1; substrate 1b) and δ = 7.94 ppm (d, J = 9.0 Hz, H1′;
reaction product 2) as functions of time.
■
General Remarks. Compounds 1a−d, sodium azide, and 5 were
obtained from standard commercial vendors and used without any
further purification. Metallacycle 3·6NO3 and ligand 4·NO3 were
obtained according to published procedures.8a Likewise, 4-azidoquino-
line (6) was prepared using the method reported in the literature.16
Proton and carbon NMR spectra were recorded in Fourier mode at
300 or 500 MHz using the deuterated solvent as a lock and the
residual protiated solvent as an internal standard.
Synthesis of 1-Azido-2,4-dinitrobenzene (2). A mixture of 1b
(70 mg, 0.32 mmol), NaN3 (205 mg, 3.2 mmol), and 3·6NO3 (51 mg,
0.032 mmol) in D2O (30 mL) was stirred at room temperature for 10
h. The reaction mixture was extracted with CHCl3 (3 × 10 mL), and
the combined organic layers were dried over magnesium sulfate and
filtered. Finally, the solvent was removed under reduced pressure to
give an amorphous pale-brownish solid (71 mg, 97%). The physical
Kinetic Measurements for the Reaction between 5 and
NaN3. Control Reaction. For kinetic measurements, 1 mL samples
1
suitable for H NMR analysis containing 5 (6 mM) in D2O/CD3CN
1
and spectral data of the obtained compound (FTIR, MS, H and 13C
(4:1) were prepared from a stock solution of 5 in CD3CN. The
sodium azide was added in solid form to initiate the reaction.
Catalyzed Reactions. For kinetic measurements, 1 mL samples
NMR) were found to be in good agreement with those previously
reported for 2.17
1
suitable for H NMR analysis containing 5 (6 mM) and 3·6NO3 (0.6
Characterization of the Inclusion Complex 5⊂3·6NO3. An
NMR tube containing 3·6NO3 (3.5 mM) and 5 (35 mM) in D2O/
CD3CN (4:1) was prepared from stock solutions of 5 in CD3CN and
mM) or 4·NO3 (1.2 mM) in D2O/CD3CN (4:1) were prepared from
stock solutions of 5 in CD3CN and 3·6NO3/4·NO3 in D2O. The
sodium azide was added in solid form to initiate the reaction.
In all cases, the progress of the reaction was monitored by 1H NMR
spectroscopy at 298 K. The concentrations of 5 and 6 were
determined by relative integrations of the peaks at δ = 7.91 ppm (d,
J = 5.0 Hz, H2; substrate 5) and δ = 7.58 ppm (d, J = 5.0 Hz, H2′;
reaction product 6) as functions of time.
1
3·6NO3 in D2O. H NMR (500 MHz, D2O/CD3CN 4:1 (v/v), 298
K): δ = 10.26 (s, Hi), 9.31 (s, Hf), 9.14 (d, J = 6.9 Hz, Ha), 8.76 (d, J =
4.8 Hz, H1), 8.66 (d, J = 9.15 Hz, Hh), 8.30 (d, J = 9.15 Hz, Hg), 8.21
(d, J = 8.35 Hz, H3), 8.04 (d, J = 8.45 Hz, H6), 7.90 (t, J = 7.5 Hz, H5),
7.82 (d, J = 6.9 Hz, Hb), 7.77 (t, J = 7.6 Hz, H4), 7.70 (d, J = 4.8 Hz,
H2), 7.67 (d, J = 8.7 Hz, Hd), 7.47 (d, J = 8.7 Hz, He), 4.37 (s, Hc),
3.11 (s, Hj) ppm.
Kinetic Measurements for the Reaction between 1b and
NaN3. Control Reaction. In order to perform the kinetic measure-
ments for the uncatalyzed reaction, 1 mL samples suitable for 1H
NMR analysis containing 1b (6 mM) in D2O/CD3CN (4:1) were
prepared from a stock solution of 1b in CD3CN. The sodium azide
was added in solid form to initiate the reaction.
Catalyzed Reaction. For catalyzed reactions, 1 mL samples suitable
1
for H NMR analysis containing 1b (6 mM) and the corresponding
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(9) The D2O/CD3CN (4:1) mixture was employed in order to
ensure the solubilization of all the reactants, as it was necessary to do
the kinetic study in a homogeneous medium.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H, 13C, and 2D NMR spectra for the inclusion complex 5⊂3·
6NO3, references, and results of representative kinetic experi-
ments. This material is available free of charge via the Internet
at http://pubs.acs.org.
(10) The rate-limiting step of an SNAr is determined by the relative
rates of the expulsion of the nucleophile and the leaving group from
the Meisenheimer intermediate. If one group leaves faster than the
other, the step involving the poorer leaving group (in this case, the
azide ion) is rate-determining. This means that the reverse direction of
the equilibrium for the formation of the reaction intermediate must be
slower than that of its irreversible collapse, which confirms that kuncat
and kcat can be identified as the rate constants in the forward direction
in the equilibria for the formation of T− (k1 and k2, respectively).
(11) This sequence of reactivity is also known as the “element effect”.
See: Bunnett, J. F.; Garbisch, E. W., Jr.; Pruitt, K. M. J. Am. Chem. Soc.
1957, 79, 385.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: carlos.peinador@udc.es.
*E-mail: jose.maria.quintela@udc.es. Fax: +34 981 167 065.
Tel: +34 981 167 000.
Notes
(12) (a) Miller, J.; Parker, A. J. J. Am. Chem. Soc. 1961, 83, 117.
(b) Alexander, R.; Ko, E. C. F.; Parker, A. J.; Broston, T. J. J. Am.
Chem. Soc. 1968, 90, 5049.
The authors declare no competing financial interest.
(13) For instance, Shinkai et al. reported this kind of “remote
control” over the reactivity of a flavin analogue by means of metal
complexation to a distal crown ether attached to the coenzyme core.
See: Shinkai, S.; Kameoka, K.; Ueda, K.; Manabe, O. J. Am. Chem. Soc.
1987, 109, 923.
ACKNOWLEDGMENTS
■
This research was supported by Ministerio de Ciencia e
Innovacion
thanks Ministerio de Ciencia e Innovacion
́
and FEDER (CTQ2010-16484/BQU). E.M.L.-V.
(FPI Program).
́
(14) This inhibitory effect could not be studied with ligand 4·NO3
because no complexation between 4·NO3 and pyrene occurs, and
consequently, no solubilization of pyrene was detected.
(15) Pliego, J. R., Jr.; Pilo-Veloso, D. Phys. Chem. Chem. Phys. 2008,
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