Dynamics of a supramolecular capsule assembly with pyrene

Article abstract of DOI:10.1021/ja301278p

Water-soluble octaacid cavitands (OAs) form dimeric capsules suitable for guest incorporation. Our studies reveal that the mechanism of pyrene (Py) binding involves the rapid (<1 ms) formation of the Py?OA complex followed by slower binding with the second OA. The dissociation of the capsular OA?Py?OA complex occurs with a lifetime of 2.7 s, which is 5 orders of magnitude slower than the microsecond opening/closing ("breathing") previously observed to provide access of small molecules to the encapsulated guest. These different dynamics of the capsules have a potential impact on how the chemistry of included guests could be altered.

Full text of DOI:10.1021/ja301278p

Communication
pubs.acs.org/JACS
Dynamics of a Supramolecular Capsule Assembly with Pyrene
†
†,§
†
‡
,‡
Hao Tang, Carla Santos de Oliveira, Gage Sonntag, Corinne L. D. Gibb, Bruce C. Gibb,*
,†
and Cornelia Bohne*
†Department of Chemistry, University of Victoria, P.O. Box 3065, Victoria, BC, Canada V8W 3V6
‡Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, United States
*
S Supporting Information
hydrophobic effect by the addition of cosolvents denatures
these assemblies.
28
ABSTRACT: Water-soluble octaacid cavitands (OAs)
form dimeric capsules suitable for guest incorporation.
Our studies reveal that the mechanism of pyrene (Py)
binding involves the rapid (<1 ms) formation of the
Py·OA complex followed by slower binding with the
second OA. The dissociation of the capsular OA·Py·OA
complex occurs with a lifetime of 2.7 s, which is 5 orders of
magnitude slower than the microsecond opening/closing
In part, the properties of the supramolecular complexes formed
by OA are dictated by the nature of the guest. An understanding
of the complicated relationship between the host and guest can be
garnered using many different physicochemical techniques. For
example, the dynamics of encapsulated guest movement have
1
been probed on both the millisecond ( H NMR) and nanosecond
29,30
(EPR) time scales.
Furthermore, a microsecond-time-scale
(
“breathing”) previously observed to provide access of
opening of the dimeric capsule sufficient to allow access of small
molecules without dissociation of one of the OAs or guest release
small molecules to the encapsulated guest. These different
dynamics of the capsules have a potential impact on how
the chemistry of included guests could be altered.
20,31
has been inferred from excited-state quenching studies.
Nevertheless, missing from the current state of affairs are studies
providing knowledge of the formation/dissociation dynamics of
these encapsulation complexes. Indeed, the formation/dissociation
dynamics of host−guest complexes in general has been
elf-assembled container molecules provide ready access to a
32,33
S
wide range of phenomena arising through controlled
compartmentalization, including unusual chemical reactivity,
separation technologies, and storage and/or transport. A
growing focus of the field is the formation of containers in
underexploited because of the lack of suitable methodology.
Toward addressing this, here we measured in real time the kinetics
of the formation of 1:1 and 2:1 host−guest complexes formed
between OA and the guest pyrene (Py). Our results reveal the
different rates of the processes shown in Scheme 1 and demon-
1
−4
5−11
aqueous solution, and in this regard, metal coordination
12−16
and the hydrophobic effect
have proven useful as methods
to drive assembly. Regarding the latter, the Gibb group has
developed deep-cavity cavitands that dimerize into capsules via
the hydrophobic effect. These hosts, such as the so-called octa-
acid (OA), possess water-solubilizing outer coats, deep hydro-
phobic pockets, and a hydrophobic rim of the cavity that
promotes self-assembly.
Scheme 1. Cartoon Representation of the Formation of
OA·Py (Equation 1) and OA·Py·OA (Equation 2) and
Definitions of K21 and β21 (Equations 3 and 4)
OA forms monodispersed and kinetically stable dimeric
assemblies thatby dint of their water-free, low-polarity
17,18
inner space can encapsulate molecules and act as yoctoliter
1
7,19−22
strate for the first time that complex disassembly and concomitant
guest release are kinetically very different from the “breathing” of
the complex that allows small molecule entry and egress.
reaction vessels for photochemical transformations,
1
3
bring about the separation of hydrocarbon gases, engender
molecular protection for the kinetic resolution of struc-
2
3
turally similar molecules, engender unusual self-sorting
2
4
properties, and lead to the electrochemical modulation
Received: February 8, 2012
Published: March 14, 2012
2
5−27
of encapsulated guests.
Nevertheless weakening of the
©
2012 American Chemical Society
5544
dx.doi.org/10.1021/ja301278p | J. Am. Chem. Soc. 2012, 134, 5544−5547

Journal of the American Chemical Society
Communication
1
Previous H NMR experiments showed that OA forms a 2:1
constants for both different quenchers and different excited
states of the same guest.
1
7,18
host−guest complex with Py.
marked red shifts (5−6 nm) in its excitation (Figure 1) and
Py encapsulation leads to
An understanding of the kinetics of assembly and
disassembly of the host−guest complex requires knowledge of
the types of complexes present at equilibrium and their
respective equilibrium constants. Measurements of the
fluorescence intensity change as a function of OA concentration
were carried out to determine the overall binding constant
(
Figure S4). The resulting binding isotherm (Figure 2 and
Figure 1. Fluorescence excitation spectra for Py (0.2 μM, λem = 390 nm)
in the absence (a, solid line) and presence (b, dashed line) of OA
(
4 μM) at pH 8.9 (10 mM borate buffer). The arrows show the
direction of the intensity change when Py is encapsulated within OA.
The inset shows the kinetics for mixing of Py (0.2 μM) with OA
(
3 μM) upon excitation at 340 nm (c, blue) or 335 nm (d, red). The
Figure 2. Binding isotherm for the complexation of Py (0.2 μM, λ =
340 nm) with OA obtained from steady-state fluorescence experi-
ments. The data were fit to the sequential model shown in Scheme 1.
ex
intensities for the mixing of Py with buffer (e, green, λex = 340 nm; f,
black, λ = 335 nm) were normalized to 1. The higher signal-to-noise
ratio for excitation at 335 nm reflects the higher intensity of the
ex
Hg−Xe excitation lamp at this wavelength.
Figure S5) fit the expected 2:1 binding model and gave an
overall β21 value of (3.19 ± 0.06) × 10 M .
Because of the transient nature of the 1:1 complex, the
12
−2
absorption spectra (Figure S1 in the Supporting Information).
Theoretically, such spectral changes could be due to the
equilibrium constant for this species (K ) can be determined
34
11
formation of Py dimers. However, there was no evidence of
accompanying broadening of the absorption/excitation spectra
nor detection of any excimer emission (Figures S1 and S2). Red
shifts of 3−8 nm between the Py absorption in homogeneous
solution and when bound to hosts as a monomer were previously
only from kinetic studies. Stopped-flow experiments revealed
that the kinetics for complex formation followed a two-phase
behavior (Figure 3). First, an initial offset between the intensity
35
observed for Py binding to bile salt aggregates and a macro-
36
cycle. A consequence of the large absorption shift observed for
OA-encapsulated Py is that depending on the excitation wave-
length either a positive or negative change in the fluorescence is
observed (Figure 1 inset).
Time-resolved fluorescence measurements provided further
evidence of monomeric Py complexation, its isolation from the
aqueous phase in the dimeric OA capsule, and the absence of
any significant equilibrium amount of the 1:1 complex. The
fluorescence lifetime of 361 ± 1 ns for Py (0.5 μM) in the
presence of OA (10 μM) was much longer than that in aqueous
borate buffer (130 ± 1 ns) and is similar to that previously
Figure 3. Kinetics for Py (0.2 μM, λex = 335 nm) upon mixing with (a)
buffer or (b−d) OA at a concentration of (b, red) 1 μM, (c, blue) 2 μM,
or (d, green) 4 μM.
1
8
−
reported. Furthermore, the iodide anion (I ) quenching rate
constant for singlet-excited-state Py in the capsule was
5
−1 −1
measured to be (5.9 ± 0.7) × 10 M
s
(Figure S3), a
for Py in water (black line) and the intensities for Py in the
presence of OA (colored lines) was observed. This result
indicates that a reaction occurred within the 1 ms mixing time
of the stopped-flow experiment. Furthermore, the magnitude of
this offset intensity increased as the concentration of OA was
raised. Consequently, a series of stopped-flow experiments in
which the initially measured fluorescence intensity was plotted
against [OA] revealed a 1:1 binding isotherm (Figure S6). This
fit to a 1:1 model confirmed that the initial fast reaction was the
binding of Py to OA and revealed an equilibrium constant for
value much lower than that in aqueous buffer [(1.0 ± 0.2) ×
0 M s ]. Both of these metrics confirm the efficient
9
−1 −1
1
protection afforded by the capsule. Additionally, no other Py
emission with a lifetime intermediate between those of free and
encapsulated Py was observed, indicating that the 1:1 complex
was not present in any appreciable amount.
The iodide quenching rate constant for singlet-excited Py
encapsulated in OA·Py·OA is similar to that previously deter-
mined for oxygen quenching of encapsulated triplet-excited Py
5
−1 −1 31
(
5 × 10 M s ). This similarity supports the interpretation
5
−1
that the quenching rate constant for an excited guest in the
capsule is determined by a partial opening (or “breathing”) of
the capsular complex that allows small guests to enter and
this process of K11 = (4.5 ± 0.6) × 10 M . With K11 and β21
6
−1
in hand, a K21 value of (7 ± 1) × 10 M was calculated using
eq 4 in Scheme 1. The determination of both K11 and K21 for
the guest Py represents the first glimpse of the effect of
31
egress the complex. Such a mechanism predicts similar rate
5
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3
8
desolvating the rim defined by the “uppermost” aromatic rings
around the portal of the host (see the structure shown above).
In the formation of the 1:1 complex, one hydrophobic pocket
and half a guest are desolvated. In the capping of the 1:1
complex to form the capsular 2:1 complex, there is this same
desolvation, plus the additional desolvation of the rims as the
hosts clamp together around the guest. This additional factor
means that the assembly demonstrates positive cooperativity
constant for guests binding to cyclodextrins and for the
39
binding of a napththalene derivative to cucurbit[7]uril were
8
−1 −1
determined to be (4−10) × 10 M s . A similar rate constant
for Py·OA formation would explain the fast (<1 ms)
equilibration observed. The lower rate for the binding of the
second OA is analogous to the lower rates observed for the
4
0
formation of the 2:2 β-cyclodextrin:Py complex. Similarly, the
results presented here demonstrate that the dynamics of the
OA capsule system is defined by the dissociation rate constant
of the higher-order complex (i.e., OA·Py·OA). Where OA
capsules differ from cyclodextrins is in the slow release of the
guest from the OA capsule in comparison with the much faster
“breathing” dynamics. These two kinds of opening processes
suggest that selective enhancement of “bimolecular” reactions
involving the ingress of small molecules while maintaining the
general structure of the complex should be possible. Previous
results showed that capsule confinement affects the bimolecular
(
K < K ) and explains why the 1:1 complex is not present at
11 21
equilibrium in any appreciable amount.
Although the kinetic experiments shown in Figure 3 revealed
the value of K , they could not provide any kinetic information
11
on the formation of OA·Py because the formation of the 1:1
complex is faster than the time resolution of the stopped-flow
experiments.
The fast initial intensity offset observed in the stopped-flow
experiments was followed by a further slow decrease in the Py
emission intensity (Figure 3). The kinetics leveled off within
4
1,42
reactivity of guests,
and reactions with encapsulated guests
can occur when small external molecules enter the capsule.
20
1
0 s (only 0.6 s are shown in Figure 3; see Figure S7 for the
complete data set). The normalized intensity change measured
at equilibrium in the kinetic experiment was the same as the
intensity obtained from the steady-state experiments (Figure S8),
showing that the kinetics were complete within 10 s. This result
eliminated the possibility of any change in the assembly
occurring over longer periods of time. The kinetics of this
slower process followed a monoexponential decay (Figures S9
and S10) that was assigned to the formation of OA·Py·OA via
the bimolecular reaction between OA·Py and OA. Overall rate
constants for relaxation processes always correspond to the sum
of the rate constants for the forward and backward reactions,
where an increase in the observed rate constant is expected
when the concentrations of reagents involved in the
Our results suggest that it may be possible to filter out
competing reactions with larger reagent molecules attempting
to enter the complex. The origin of this separate dynamic
“breathing” process resides in the fact that the OA capsule leads
to true compartmentalization, a phenomenon that cannot occur
with simple macrocyclic hosts. Consequently, the use of OA
capsules as host systems offers more versatility to influence
competitive reaction pathways of guests differentially. Future
exploitation of the differences in the capsule dynamics will aid
the rational design of functional OA supramolecular systems
and are currently underway.
ASSOCIATED CONTENT
Supporting Information
■
3
2,33
bimolecular process are raised.
The faster decay of the
*
S
kinetics observed at higher OA concentrations (Figure 3)
confirmed that this process corresponds to a bimolecular
reaction involving OA.
Experimental details, absorption and fluorescence spectra,
quenching plots, models for binding isotherms and analysis of
stopped-flow kinetics. This material is available free of charge
via the Internet at http://pubs.acs.org.
A global analysis method was employed in which kinetic
traces at different OA concentrations were simultaneously fit to
two models based on eqs 1 and 2, where in both cases the value
of K11 was fixed. In one model, the dissociation rate constant
was included, while in the second model, this rate constant was
considered to be infinitesimally small. Both models produced
AUTHOR INFORMATION
Corresponding Author
bgibb@tulane.edu; cornelia.bohne@gmail.com
■
Present Address
the same value for k 2+ (Figure S11 and Table S1), supporting
§
1
CCBS, Universidade Federal de Mato Grosso do Sul, Caixa
the conclusion that the contribution of the dissociation process
to the observed rate constant is negligible. The average value
Postal 549, CEP 79070-900, Campo Grande, MS, Brazil.
+
Notes
for k determined from two independent experiments was (2.6
2
1
6
−1 −1
−
−1
The authors declare no competing financial interest.
±
0.2) × 10 M s , while a value for k of (0.37 ± 0.06) s
21
was calculated using eq 3 in Scheme 1. This latter rate constant
corresponds to a lifetime of 2.7 s for the dissociation of the
OA·Py·OA capsule.
ACKNOWLEDGMENTS
■
This work was supported by the Natural Sciences and
Engineering Council of Canada (NSERC) and the National
Institutes of Health (GM074031).
As discussed above, the opening/closing of OA·Py·OA to
−
provide access of small molecules (e.g., O or I ) to Py without
2
release of Py was estimated to occur on the microsecond time
37
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