Catalysis in a porous molecular capsule: Activation by regulated access to sixty metal centers spanning a truncated icosahedron

Article abstract of DOI:10.1021/ja304513t

The 30 cationic {Mo^V₂O₄(acetate)} ⁺ units linking 12 negatively charged pentagonal "ligands," {(Mo^VI)Mo^VI₅O₂₁(H ₂O)₆}^6- of the porous metal-oxide capsule, [{Mo^VI₆O₂₁(H₂O)₆} ₁₂{Mo^V₂O₄(acetate)} ₃₀]^42- provide active sites for catalytic transformations of organic "guests". This is demonstrated using a well-behaved model reaction, the fully reversible cleavage and formation of methyl tert-butyl ether (MTBE) under mild conditions in water. Five independent lines of evidence demonstrate that reactions of the MTBE guests occur in the ca. 6 × 10 ³ A³ interior of the spherical capsule. The Mo atoms of the {Mo^V₂O₄(acetate)}⁺ linkers - spanning an ca. 3-nm truncated icosahedron - are sterically accessible to substrate, and controlled removal of their internally bound acetate ligands generates catalytically active {Mo^V₂O₄(H ₂O)₂}²⁺ units with labile water ligands, and Lewis- and Bronsted-acid properties. The activity of these units is demonstrating by kinetic data that reveal a first-order dependence of MTBE cleavage rates on the number of acetate-free {Mo^V₂O ₄(H₂O)₂}²⁺ linkers. DFT calculations point to a pathway involving both Mo(V) centers, and the intermediacy of isobutene in both forward and reverse reactions. A plausible catalytic cycle - satisfying microscopic reversibility - is supported by activation parameters for MTBE cleavage, deuterium and oxygen-18 labeling studies, and by reactions of deliberately added isobutene and of a water-soluble isobutene analog. More generally, pore-restricted encapsulation, ligand-regulated access to multiple structurally integral metal-centers, and options for modifying the microenvironment within this new type of nanoreactor, suggest numerous additional transformations of organic substrates by this and related molybdenum-oxide based capsules.

Full text of DOI:10.1021/ja304513t

Article
pubs.acs.org/JACS
Catalysis in a Porous Molecular Capsule: Activation by Regulated
Access to Sixty Metal Centers Spanning a Truncated Icosahedron
†
‡
§
§
‡
∥
́
Sivil Kopilevich, Adria
̀
Gil, Miquel Garcia-Rates
́
, Josep Bonet-Avalos, Carles Bo, Achim Muller,
̈
,
†
and Ira A. Weinstock*
†Department of Chemistry and the Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev,
Beer Sheva, 84105, Israel
§
Department of Chemical Engineering, ETSEQ, Universitat Rovira i Virgili, Tarragona, 43007, Spain
‡Institute of Chemical Research of Catalonia, ICIQ, Tarragona, 43007, Spain
∥Faculty of Chemistry, University of Bielefeld, Bielefeld, D-33501, Germany
*
S Supporting Information
V
+
ABSTRACT: The 30 cationic {Mo O (acetate)} units
2
4
VI
linking 12 negatively charged pentagonal “ligands,” {(Mo )-
Mo O (H O) } of the porous metal-oxide capsule,
{Mo O (H O) } {Mo O (acetate)} ]
VI
6−
5
21
2
6
VI
V
2
42−
[
provide active
6
21
2
6
12
4
30
sites for catalytic transformations of organic “guests”. This is
demonstrated using a well-behaved model reaction, the fully
reversible cleavage and formation of methyl tert-butyl ether
(
MTBE) under mild conditions in water. Five independent
lines of evidence demonstrate that reactions of the MTBE
guests occur in the ca. 6 × 10 Å interior of the spherical
3
3
V
+
capsule. The Mo atoms of the {Mo O (acetate)} linkersspanning an ca. 3-nm truncated icosahedronare sterically
2
4
accessible to substrate, and controlled removal of their internally bound acetate ligands generates catalytically active
V
2+
{
Mo O (H O) } units with labile water ligands, and Lewis- and Brønsted-acid properties. The activity of these units is
2 4 2 2
demonstrating by kinetic data that reveal a first-order dependence of MTBE cleavage rates on the number of acetate-free
V
2+
{
Mo O (H O) } linkers. DFT calculations point to a pathway involving both Mo(V) centers, and the intermediacy of
2 4 2 2
isobutene in both forward and reverse reactions. A plausible catalytic cyclesatisfying microscopic reversibilityis supported by
activation parameters for MTBE cleavage, deuterium and oxygen-18 labeling studies, and by reactions of deliberately added
isobutene and of a water-soluble isobutene analog. More generally, pore-restricted encapsulation, ligand-regulated access to
multiple structurally integral metal-centers, and options for modifying the microenvironment within this new type of nanoreactor,
suggest numerous additional transformations of organic substrates by this and related molybdenum-oxide based capsules.
INTRODUCTION
We now report that ligand-regulated access to multiple
structurally integrated high-valent (formally) Mo(V) centers of a
porous molybdenum-oxide capsule with approximately icosahe-
■
The rational design of self-assembled structures based on the
ligand-directing properties of metal cations and the dimensions
and binding motifs of bridging ligands has generated a large
library of one-, two-, and three-dimensional coordination
dral- (I ) symmetry (Figure 1), results in catalysis of a model
h
organic reaction in water, the fully reversible cleavage and
formation of methyl tert-butyl ether (MTBE).
1
polymers. Among these are numerous supramolecular
The representative complex used in this work, Na
3
4
structures that serve as “hosts” for a variety of molecular
guests”. The chemically unique and spatially restricted
VI
V
[
∼
{Mo O (H O) } {(Mo O ) (OAc) (H O) }]·
6
21
2
6
12
2
4
30
22
2
16
“
4
a
300H O (abbreviated as Na 1 · ca. 300 H O), belongs to a
2 34 2
environments inside these host structures can accelerate
reactions of guest substrates, stabilize reactive intermediates,
and lead to enhanced selectivities and novel stereochemical
family of molecular metal-oxide-based coordination polymers
with spherical periodicity (see ref 3a for the definition), in
which 12 (formally) negatively charged pentagonal “ligands”,
2
outcomes. In many cases, catalysis is achieved through
VI
VI
6−
IV 2+
{
(Mo )Mo O (H O) } , are linked by 30 cationic V O ,
hydrophobic and/or electrostatic interactions, involving both
substrates and host complexes, and in others, organometallic
catalysts are noncovalently bound inside the frameworks.
Generally, however, the structurally integrated, and typically
low-valent late-transition metals used in the coordination-driven
self-assembly of these capsules are not directly involved in
reactions with guest substrates.
5 21 2 6
3
+
3+
V
2+
3
Cr , Fe , or Mo O
“spacers”, giving I -symmetry
h
2
4
structures of the metal skeletons. Compound 1 (Figure 1)
V
2+
4
V
contains 30 Mo O linkers, abbreviated {Mo }, 22 of which
2
2
Received: May 9, 2012
©
XXXX American Chemical Society
A
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Article
size and flexibility of the Mo O pores. In solid-state oxides, the
9
9
entry of substrates larger than the sizes of the rigid pores in
those materials is effectively blocked. In solutions of 1, however,
the pores of the molecular capsule are considerably more
flexible, allowing the passage of guests larger than the
4a
crystallographic dimensions of the pores.
After 24 h, ca. 0.5 equiv. of MTBE is encapsulated, as
indicated by broad signals at 1.7 and −0.2 ppm, assigned to
−
CH and −C(CH ) , respectively. No MeOH is observed.
3
3 3
After 12 days (Figure 3A), 1.4 equiv. of MTBE are present
Figure 1. Structure of 1. Mo(VI) atoms are shown in blue and green,
and Mo(V) atoms in red. Exchangeable acetate ligands are bound to
the interior of the capsule by bidentate coordination to 22 of the
V
{
Mo } linkers.
2
are coordinated by labile acetate ligands bound in a bidentate
V
2
fashion to the two Mo centers, with the remaining 8 {Mo }
units each occupied by two labile H O ligands. Coordination of
2
V
the 12 pentagonal “ligands” to the 30 {Mo } linkers creates 20
2
Mo O rings, 3.2 Å in diameter based on the van der Waals
9
9
4a,c
radii of opposing O atoms. These flexible rings serve as pore-
like openings to the interior of the water-soluble capsules.
RESULTS AND DISCUSSION
■
(
Figure 3. Encapsulation and cleavage of MTBE by 1. A: H-1 NMR
spectra of 1 (3.6 mM) and MTBE (182 mM) after 12 days at room
temperature. The signals due to the acetate ligands (insets) are small
relative to those from MTBE; 1.4 equiv. of encapsulated MTBE give
rise to broad signals at 1.7 and −0.2 ppm. B: After 44 h at 65 °C,
MeOD and tert-BuOH (ca. 50% conversion), are observed in the bulk
solution outside the capsule, and a new sharp signal 1.6 ppm, due to an
isobutene intermediate (discussed later), is indicated by an asterisk.
Reversible Cleavage of methyl tert-butyl ether
1
+
MTBE). The H NMR spectrum of the Na salt of 1 is
4a,b
shown in Figure 2; see figure caption for assignments. The
inside 1, and traces of MeOH and tert-BuOH are observed.
Once heated to 65 °C, however, the concentration of MTBE
inside 1 increases rapidly, reaching ca. 4.5 equiv. after 24 h, and
tert-BuOH (TBA) and MeOD are observed (eq 1); a
representative spectrum (ca. 50% conversion after 44 h at 65
1
Figure 2. The H NMR spectrum of 1 (in D O) shows a broad signal
2
°
C) is shown in Figure 3B.
of the internally bound acetate ligands (illustrated in the inset), in
dynamic equilibrium with those in solution outside the capsule (1.8
ppm).
tert‐BuOMe + D O ⇌ tert‐BuOD + MeOD
(1)
2
In control experiments involving both MTBE and pH 4.5
acetate buffer, only a trace amount of methanol (0.1%
conversion) was observed after 24 h at 65 °C, compared to
25.5% conversion in the presence of 1 at the concentrations
used in Figure 3. These values indicate that the initial rate of
MTBE cleavage in the presence of 1 is >200 times that for the
control.
The formation of MTBE from tert-BuOH and MeOH, and
the reversibility of the cleavage reaction in eq 1 were
simultaneously established by carrying out parallel experiments
in two NMR tubes, each containing identical volumes of 3.6
signal arising from the methyl protons of the acetate ligands
inside the capsule is shifted to lower-frequency (smaller)
chemical shift values, as is typical for encapsulations of
4
carboxylate ligands inside 1, and of other guests such as
4d
aliphatic alcohols that do not bind to the Mo(V) centers.
Characteristic broad signals arise from encapsulating guests in
large macromolecules, which influences the relevant relaxation
times, T and especially T .
1
2
Hydrophobic effects are known to result in the uptake of
several equivalents n-butanol by a propionate-ligand form of the
mM solutions of 1 in D O. One contained MTBE (182 mM),
2
4
d
capsule, and by 1 (this work). Apart from the presence of the
acetate ligands, these effects provide a driving force for the
uptake of MTBE. The entry of MTBE may also result (at least
in part) from the concentration gradient established upon its
addition to solutions of 1.
and the second, a 1:1 mixture of tert-BuOH and MeOH (Figure
S1 of the Supporting Information, SI). Both tubes were flame-
sealed to avoid evaporative loss of MTBE (bp 55.2 °C). After
ca. 12 days (288 h) at 65 °C, both solutions contained the same
concentrations of all three species (Figure 4). These concen-
trations gave an equilibrium constant, K, for the cleavage
Nevertheless, at room temperature, diffusion of MTBE into 1
through the smaller yet flexible Mo O pores is slow. The rates
o
reaction in eq 1 of 18 ± 1 M, from which, ΔG (at 338K) =
9
9
−1
at which organic guests enter the capsule are controlled by the
−1.94 ± 0.04 kcal mol .
B
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Journal of the American Chemical Society
Article
Evidence for Reaction Inside 1. The first-order depend-
ence of rate on both [1] and [MTBE] establishes that MTBE
cleavage is catalyzed by 1. Five lines of evidence were then used
to demonstrate that ether cleavage occurs inside the capsule,
rather than on its exterior surface.
First, MTBE was reacted with the isopolymolybdates
6−
(
predominantly heptamolybdate, [Mo O ] ) obtained by
7 24
acidification of Na MoO (final concentration 0.41 M) to pH
2
4
4
.5 by acetic acid. Only trace amounts of methanol were
observed after 24 h at 65 °C. Moreover, no MeOH was
detected after refluxing MTBE in an aqueous solution of the
bis-(triphenylphosphine)iminium salt of MoO42
−
.
5
Second, when the size of the substrate was modestly
increased by changing the methyl group on oxygen to ethyl
(
B in Chart 1), conversion after 24 h at 65 °C decreased from
Figure 4. Cleavage of MTBE to tert-BuOD and MeOD (blue squares),
and its reverse, the formation of MTBE (red diamonds) from tert-
Chart 1. MTBE and Two Larger Derivatives
BuOD and MeOD at 65 °C in D O. At equilibrium, the ratio of
2
MTBE to MeOD is 1:99; see inset.
For ether cleavage (blue squares in Figure 4), the initial
−1
turnover rate (i.e., far from equilibrium) was ∼1 h , and
2
5 to 14% (concentrations used were the same as those in
equilibrium was reached after ∼50 turnovers. (No decom-
1
Figure 3). After adding a −CH OH group to the already large
tert-butyl group of MTBE, to give 3-methyl-3-methoxy-butanol
2
position of 1 was detected by H NMR; see Figure S2 of the
4
c
SI. )
Rate Expression for MTBE Cleavage. Given the small
(
C), much less of the substrate was encapsulated (ca. 2 equiv.
after 24 h 65 °C), and conversion dropped to 7%.
equilibrium concentration of MTBE, the progress of the
cleavage reaction can be closely approximated by treating the
rate of ether cleavage to 90% completion as an exponential
function of [MTBE], eq 2. Using eq 2, the linear plot in Figure
A third line of evidence was provided by replacing acetate
1
ligands in 1 by 12 equiv. of benzoate (Figure 6; an H NMR
5A shows that the cleavage reaction is first order in [MTBE],
with k = k·[1].
obs
ln([MTBE]/[MTBE] ) = −k ·t
(2)
0
obs
Figure 6. Partial replacement of interior acetate ligands by 12 benzoate
ligands inhibits the entry of MTBE and dramatically decreases the rate
of MTBE cleavage.
Figure 5. Kinetic plots showing that MTBE cleavage is first order in
MTBE] (A) and in [1] (B). Data in A are from Figure 4 (blue
[
squares); data in B were obtained by quantifying MTBE cleavage in
reactions with incrementally larger concentrations of 1.
6
spectrum is provided in Figure S3 of the SI), so that the larger
ligands might inhibit access of MTBE to the capsule’s interior.
MTBE-cleavage was then carried out under the same
conditions as those used in Figure 3. After 24 h, the amount
of MTBE discernible by H NMR inside the capsule was small,
and an order-of-magnitude less MeOD was produced: ca. 2%
conversion, compared to 25%.
Molecular dynamics simulations confirmed that the hydro-
phobic benzoate ligands are less labile than are acetate ligands
in 1, and decrease the amount of water inside the capsule (see
the SI). This unique microenvironment, along with steric
effects, both inhibit the entry of MTBE into the capsule.
A fourth line of evidence was provided by using 1 to catalyze
the cleavage of p-dimethoxybenzene (p-DMB) (Figure 7).
The dependence of rate on the concentration of 1 was
evaluated by measuring the percent conversion of MTBE to
tert-BuOH and MeOD. For this, initial concentrations of
1
MTBE, [MTBE] , were kept constant in a series of reactions
0
involving incrementally larger concentrations of 1. Final
1
concentrations of MTBE, [MTBE], were determined by H
NMR after 14.5 h. The linear dependence of ln[MTBE]/
[
MTBE] on [1] in Figure 5B shows that ether cleavage is first
0
order in [1].
These data give the rate expression for ether cleavage shown
in eq 3, where, from both plots in Figure 5, k = 1.07 ± 0.04 ×
−3
−1 −1
10
M
s .
Upon heating to 65 °C in D O, MeOD was observed in the
2
−
d[MTBE]/dt = k[MTBE][1]
(3)
bulk solution outside the capsule, while the (larger) phenolic
C
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Journal of the American Chemical Society
Article
coordination polymers, the restricted internal dimensions of
those capsules inhibit the access of substrates to the metal
3
3
cations. The ca. 6 × 10 Å interior of 1 is substantially larger,
V
however, such that MTBE can readily access the {Mo } units
2
that span the capsule’s I -symmetry metal-oxide skeleton.
h
Reaction Mechanism. Information about the mechanism
V
of catalysis at the {Mo } linkers was provided by MTBE
2
cleavage in 18O-labeled H O. As shown in eq 4, the O label
18
2
Figure 7. Upon cleavage of p-dimethoxybenzene (p-DMB), the larger
product is initially “trapped” inside the capsule. A: p-DMB is
encapsulated by 1; B: Initially, MeOD is the only product observed
was found exclusively on tert-BuOH (by GC MS; Figures S10
and S11 of the SI). Hence, MTBE hydrolysis occurs exclusively
1
by H NMR in bulk solution outside 1; C: p-Methoxyphenol (p-MP),
whose rate of egress is much slower than that of MeOD, was identified
via cleavage of the Me C−O bond, ruling out an associative
3
1
by H NMR (inset) after “cracking open” the capsule (NaOH and
mechanism involving (sterically difficult) nucleophilic attack on
the tert-butyl group.
O ). Control experiments ruled out the formation of p-MP during the
2
1
oxidative hydrolysis of 1. (See Figures S4−S8 of the SI for H NMR
spectra related to all three stages.)
At this juncture, DFT calculations (Figures S12−S14 of the
SI) indicated that the (formal) elimination of methanol from
MTBE to give an olefinic intermediate, isobutene, would be
product, p-methoxyphenol (p-MP) was initially observed
exclusively inside 1.
A fifth and highly informative line of evidence was obtained
after further analysis of the rate constant, k, in eq 3. Namely,
after reacting MTBE (182 mM) with 1 (3.6 mM) for 3 h at 65
kinetically viable if it occurred via a concerted process involving
V
both Mo(V) atoms of each {Mo } linker (Figure 9).
2
°
C, the concentration of MTBE inside 1 was 6 times that of
MeOD. Hence, the entry of MTBE through the Mo O pores
9
9
of 1 is not rate limiting, such that k (eq 3) must refer to ether
cleavage inside the capsule. Having established this, it was
possible to determine whether rate constants for MTBE
V
cleavage varied as the number of {Mo } linkers occupied by
2
water versus acetate ligands was systematically varied.
For this, a series of capsules was prepared in which internal
Figure 9. Proposed transition state for isobutene formation at a
acetate ligands were incrementally replaced by water (two per
V
V
V
bifunctional {Mo } linker. The {Mo } unit, with Mo atoms in green,
2
2
{
Mo } unit). Rate constants for MTBE cleavage were then
2
is shown between two pentagonal units, at left and right. The ether
found to increase linearly with the number of water-bound
7a
oxygen is bound to one Mo(V) atom, acting as a Lewis acid, while a
V
{
Mo } linkages (Figure 8). This not only proves that MTBE
2
water molecule on the adjacent Mo(V) atom serves as a “proton-
shuttle” in a six-membered transition-state.
The proposed transition-state structure involves one Mo(V)-
bound water molecule acting as a proton “shuttle”, and one
Mo(V) center serving as a Lewis-acid. On the basis of pD
values of 3.6 mM solutions of 1 in D Owhich vary from 3 to
2
5
depending on the number of internal acetate ligands
presentthe pK values of water molecules bound to Mo(V)
a
centers are estimated at ca. 3.5 to 5.0, similar to water ligands
7a,b
on Ti(IV) in titanocene. However, the water ligands in the
V
2+
{
Mo O (H O) } linkers are labile (have a rather short
2 4 2 2
11
residence time): On the basis of published data, exchange
V
2
Figure 8. Effect of the number of “available” (water-bound) {Mo }
5
−1 11b
3
rates are estimated at between 10 and 10 s .
linkers on rate constants for MTBE cleavage. The plot includes a
correction to the x-axis; see additional data and discussion of this
procedure in the SI.
Consistent with bond breaking in an organized transition
state, the temperature dependence of the rate constant for
2
MTBE cleavage (R = 0.9998 for five temperatures) gave
‡
enthalpies and entropies of activation of ΔH = 21.6 ± 0.2 kcal
−
1
‡
−1 −1
cleavage occurs inside 1, but also reveals that catalysis occurs
mol and ΔS = −8.6 ± 0.5 cal mol
K
(Figure 10).
V
V
2+
exclusively at the hydrated {Mo } linkers, {Mo O (H O) } ,
The subsequent hydration of isobutene in D Ocatalyzed
2
2
4
2
2
2
VI
VI
6−
V
rather than under the {(Mo )Mo O (H O) } pentagons.
by the {Mo } linkers, but with a smaller activation energy
5
21
2
6
2
More generally, it shows that access of substrates to Mo(V)
active sites inside 1 can be deliberately regulated by varying the
number of internally bound carboxylate ligands.
based on DFT resultsshould incorporate deuterium into the
methyl groups of the tert-BuOD product (eq 5). This was
8
definitively confirmed by ESI MS (Figure S15 of the SI).
In line with this, the small signal at 1.6 ppm consistently
observed during MTBE cleavage and formation (labeled with
When organic ligands are combined with small numbers of
transition-metal ions to give, e.g., T - and O -symmetry
d
h
D
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Journal of the American Chemical Society
Article
ligands, suggest numerous additional prospects for catalytic
transformations of organic substrates in water by porous
molybdenum-oxide based nanocapsules.
EXPERIMENTAL SECTION
■
Materials and Reagents. Regenerated-cellulose dialysis mem-
branes (45-mm flat-width tubes; 12−14 000 Da MWCO) were
purchased from VWR Scientific, treated before use to remove glycerin
and traces of sulfur compounds, and stored under high-purity water
(
17 MΩ, Millipore) at 5 °C. tert-Butyl methyl ether (≥99.5%; Fisher
Scientific), methanol (≥99.5%; Bio Lab), 1,4-dimethoxybenzene
(
oxide (≥99.9% D; CIL), ammonium acetate (ACS, Mallinckrodte),
ammonium molybdate 4-hydrate (ACS; Mallinckrodte), hydrazine
≥99%; Aldrich), 4-methoxyphenol (≥99%; Aldrich), deuterium
Figure 10. Eyring plot of ln(k/T) vs 1/T from the temperature
dependence of rate constants for MTBE cleavage.
1
8
sulfate (≥98%; Fluka), oxygen-18 enriched water (≥98% O;
Dchem), 3-methoxy-3-methyl-1-butanol (≥98%; Aldrich), 3-methyl-
3
-butene-1-ol (≥97%; Aldrich), and 3-methyl-1,3-butanediol (≥97%;
VI V
Aldrich) were used as received. Na [{Mo O (H O) } {(Mo O -
34
6
21
2
6
12
2
4
)30
(OAc) (H O) }]·∼300H O (abbreviated as Na 1 · ca. 300 H O)
22
2
16
2
34
2
4a
was prepared as previously described. All reactions were carried out
an asterisk in Figure 3B) was positively identified as isobutene.
Moreover, when a water-soluble analogue, (B in eq 6), or the
in 17 MΩ Millipore water or D O. All other reagents were obtained
2
from commercial sources and used as received.
related ether or alcohol (A or C, respectively), was reacted with
Instrumentation. pH values were measured using a EuTech pH
510 Bench-Top pH meter equipped with a Ag/AgCl electrode
(Thermo Electron, U.K) and temperature compensation. A digital hot
plate/stirrer MH-220 (MRC) equipped with a PT-100 sensor was
used to control the oil-bath temperatures. Proton-NMR spectra were
acquired on Bruker 400 and 500 MHz spectrometers, and the HDO
1
1
and MeOH, all three species were observed by H NMR (eq 6,
shown for simplicity in H O).
2
signal in D O samples was used as an internal chemical-shift reference
2
(relative to tetramethylsilane, TMS). Spectral data were processed
using Mnova version 6.1. Gas chromatographic mass spectral (GCMS)
data were obtained using an Agilent 6850 GC equipped with an
Agilent 5973 MSD working under standard conditions and an Agilent
HP5-MS column.
The reversible nature of MTBE cleavage (Figure 4) requires
that each elementary step in the 1-catalyzed process must be
microscopically reversible. A plausible mechanistic cycle based
on DFT calculationsincluding the transition-state structure
in Figure 9consistent with all the above findings, and that
Internal Integration Standard. Methane sulfonic acid (MSA)
(0.0183 g, 0.189 mmol) was dissolved in 3 mL of D O in a 5 mL
2
9
volumetric flask, and neutralized using a solution of NaOH in D O
fully satisfies microscopic reversibility, is provided in Figure S16
2
until the pH reached 4.0. Additional D O was added to bring the
of the SI. The proposed mechanistic sequence, involving
2
7
10
volume to 5 mL. The final pH was 4.5 and the final concentration of
bifunctional (Lewis acid and general acid/base ) sites at each
1
V
MSA was 37.89 mM. This solution used as an internal standard for H
{
Mo } unit, is an attractive possibility insofar as bifunctionality
is a hallmark of many enzymatic processes.
2
2
b,12
NMR.
External integration standard. Methane sulfonic acid (MSA)
(
0.0354 g, 3.66 mmol) was dissolved in 600 μL of D O. Then, 60 μL
2
CONCLUSIONS
In summary, the 30 Mo O linkers, {Mo }, that combine
with the 12 negatively charged {(Mo )Mo O (H O) }
■
of this solution was transferred to coaxial inner cell (″micro tube″; NE-
5-CIC, New Era). Sodium tetraphenylborate (TPB; 0.0250 g, 72.4
μmol) was dissolved in 5 mL D O. Then, 500 μL of this solution
V
2+
4
V
2
2
VI
VI
6−
5
21
2
6
2
pentagonal “ligands” of a porous metal-oxide capsule are active
sites for catalysis of a well-behaved model reaction, the fully
reversible cleavage and formation of methyl tert-butyl ether.
The data provided systematically demonstrate that the
transferred to a thin walled 5-mm precision NMR tube (ML-5, New
Era). The “micro tube” was inserted into the 5-mm tube, and the
number of equivalents of MSA relative to tetraphenylborate was
1
calculated from H NMR signal-intensity ratios. To increase accuracy,
3
3
the calibration was repeated using three different TPB solutions.
Kinetics and Reversible Cleavage of Methyl tert-Butylether
reactions occur in the ca. 6 × 10 Å interior of the porous
capsule, and that control over the number of internally bound
acetate ligands can be used to generate specific numbers of
(
MTBE). For MTBE cleavage, 15 μL of pure MTBE were added to an
NMR tube containing 1.81 μmol of Na 1 in D O (50 mg in 485 μL
34
2
V
2
2+
catalytically active {Mo O (H O) } units. The tert-butyl
D O). After addition, the NMR tube was flame-sealed under air and
2
4
2
2
groups of the substrate “guests” are larger than the crystallo-
transferred to an oil bath kept at a constant temperature of 65 °C. H-1
NMR spectra were acquired every ∼24 h. For MTBE formation, 5.1
μL MeOH and 11.8 μL of tert-ButOH were added to an NMR tube
containing 1.81 μmol of Na 1 in D O (50 mg in 485 μL D O). After
graphic dimensions of the Mo O pores through which they
9
9
4
must pass to enter or leave the capsule, and catalytic activity is
a consequence of the long residence times of the relatively large
substrates inside the capsule, combined with the capsule’s
tunable internal microenvironment.
34
2
2
addition, the NMR tube was flame-sealed under air and transferred to
an oil bath kept at a constant temperature of 65 °C. NMR spectra were
acquired every ∼24 h.
More generally, pore-restricted encapsulation, ligand-regu-
lated access to multiple structurally integral metal center based
18
MTBE Cleavage in O-Labeled Water. The sample was
18
prepared as immediately above, but in H2 O rather than in D O,
2
V
2+
{
Mo O (H O) } groups acting as both Lewis acid and
2 4 2 2
and kept at 65 °C for 120 h. The solution was then transferred to a 4
general-acid/base sites, combined with ready options for
modification of the internal microenvironment through the
introduction of e.g., chiral, hydrophobic, and/or reactive
mL vial and extracted with 2 mL of ethyl acetate. The extracts were
18
dried over MgSO , and the O labeled products were identified by
4
GC-MS.
E
dx.doi.org/10.1021/ja304513t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Dependence of Cleavage Rate on [Na 1]. For this, 20, 30, 40,
and 10 h), aliquots of the solution were drawn from the membrane
bag, and dried by rotary evaporation to a dark red-brown solid. These
34
5
0, 60, and 70 mg amounts of Na 1 were each dissolved in 485 μL
34
D O. The solutions were transferred to separate NMR tubes, and 15
were quantitatively dissolved in D O (50 mg in 500 μL) containing an
internal MSA integration standard, and H NMR spectra were
acquired. After 3, 7, and 10 h, 18.2, 14.9, and 11.8 equiv. of acetate
were found inside the capsule, respectively.
For the molybdenum-site dependence study, 100 mg (3.62 μmol)
of each acetate/water capsule (20.4, 18.2, 14.9, and 11.8 equiv. of
2
2
1
μL of pure MTBE were added to each tube. The NMR tubes were
closed tightly (but not flame-sealed) and placed in an oil bath kept at a
constant temperature of 65 °C. H-1 NMR spectra were acquired after
1
4 h 40 min.
Preparation of Na37[{MoVI6
O −
(H O) } {(MoV2O4)30
21 2 6 12
(
(
OAc)13(C H CO ) (H O) }], Abbreviated as Na 1-
CH CO ) (C H CO ) . Two 0.1 M benzoate buffer solutions (0.5
internally bound acetate) were dissolved in 970 μL of D O, followed
6
5
2
12
2
10
37
2
3
2 13
6
5
2 12
by 30 μL of pure MTBE to achieve total volumes of 1000 μL (3.61
mM 1). Then, 500 μL of each solution were transferred to an NMR
tube, which was flame-sealed and placed in a 65 °C. Proton-NMR
spectra were acquired at regular time intervals, which differed
depending on the relative rates of MTBE cleavage.
mL of each) were prepared by combining 1.7 mg benzoic acid and 5.7
+
mg sodium benzoate in 0.5 mL D O, to give a 1:3 ratio of acid to Na
2
forms. Two ligand-exchange reactions were then carried out in parallel
by adding 50 mg of Na 1 (1.81 μmol, 3.61 mM) to 0.5 mL of the 0.1
34
M benzoate buffer solutions in 4 mL vials containing a small magnet to
provide mixing. The vials were then placed in a 65 °C oil bath for 18 h.
One of the solutions was then transferred to a thin-walled 5-mm
precision NMR tube and H and C NMR spectra were acquired. The
second solution was concentrated to dryness by rotary evaporation in
warm (40 °C) water to give a dark red-brown solid. IR: 1617 (m),
Preparation and Reactions of Capsules, 1, With Inaccessible,
Acetate-Blocked Mo(V) Sites. To four separate vials each
containing 200 mg (7.24 μmol) of Na341 in 1840, 1860, 1908, and
1
13
1924 μL of D O, 100, 80, 32, and 16 μL (respectively) of aqueous
2
+
+
acetate buffer solution (1:1 Na : H forms; 4.5 M; pH = 4.7) were
added to achieve, in each case, a total volume of 1940 μL (3.73 mM
1). Then, 500 μL of each solution were transferred to an NMR tube,
and NMR spectra were acquired using an external (coaxial) integration
standard to quantify the numbers of acetate ligands inside each
capsule. The integration standard indicated that 26, 24.4, 23.7, and
22.6 acetates, respectively, were bound inside 1.
1
5
3
522 (m), 1410 (m), 975 (m), 938 (m), 858 (m), 803 (s), 731 (s),
−1
72 (s) cm . Raman: 943 (m), 882 (s) ν
11 (m), 212 (m) cm . The UV−vis spectrum shows a broad intense
, ∼843 (sh), 370 (s),
MoO
−1
band with a maximum at 455 nm. H-1 NMR (400 MHz, D O;
2
referenced to HDO at 4.65 ppm relative to external tetramethylsilane):
−
To determine the dependence of rate constants on the number of
δ = 7.74, 7.43, 7.35 (m, C H COO in bulk solution), 7.2−5.25
6
5
V
−
−
available (water-occupied) {Mo } linkages, 970 μL of each of the 4
(
broad, internally coordinated C H COO ), 1.84 (s, CH COO in
2
6
5
3
solutions described above were transferred to separate vials, and 30 μL
of pure MTBE were added to give a total volume of 1000 μL (3.61
mM 1). Then, 500 μL of each solution were transferred to an NMR
tube, flame-sealed, and placed in a constant-temperature 65 °C oil
bath. Proton-NMR spectra were acquired at regular time intervals,
based on the relative rates of MTBE cleavage in each NMR-tube
reaction.
bulk solution), −1.5−0.85 ppm (broad, internally coordinated
−
CH COO ). C-13 NMR (400 M Hz, D O; referenced to external
3
2
−
tetramethylsilane): δ = 179.3 (s, CH COO in bulk solution), 174.6
s, C H COO in bulk solution), 134.8, 131.6, 128.8, 128.2 (s,
3
−
(
6
5
−
C H COO in bulk solution), 125.6 (broad, internally coordinated
6
5
−
−
C H COO ), 21.9 ppm (s, CH COO in bulk solution).
6
5
3
Reaction of MTBE with Na 1(CH CO ) (C H CO ) . MTBE
15 μL, 91 μmol) was added directly to an NMR tube containing the
37
3
2 13
6
5
2 12
Formation of 3-Methoxy-3-methyl-1-butanol from 3-Meth-
yl-3-butene-1-ol and MeOH. 3-Methyl-3-butene-1-ol, 20 μL (0.198
mmol) and 20 μL (0.494 mmol) of MeOH were added to an NMR
tube containing 1.81 μmol of Na 1 in D O (50 mg in 500 μL D O,
(
benzoate-ligand substituted capsule, prepared as described immedi-
ately above. Then, the NMR tube was flame-sealed under air and kept
in an oil bath at 65 °C for 23 h, 40 min. H-1 NMR spectra were
acquired before and after the reaction.
3
4
2
2
1
3
.61 mM). The NMR tube was closed tightly, and an H NMR
spectrum was acquired 7 min after the addition. The NMR tube was
then kept in a 65 °C oil bath for 65 h, and a second H NMR
spectrum was acquired.
Cleavage of p-Dimethoxybenzene (p-DMB) to p-Methox-
yphenol (p-MP) and Methanol. 1,4-Dimethoxybenzene (para-
DMB; 4.5 mg, 32.6 μmol) was added to a solution of 50 mg Na 1
1
34
(
1.81 μmol, 3.61 mM) in 500 μL D O. After 19 h 30 min at 65 °C, a
2
1
ASSOCIATED CONTENT
Supporting Information
Computational details; spectroscopic, analytical, and computa-
tional data; and discussion. This material is available free of
charge via the Internet at http://pubs.acs.org.
H NMR spectrum was acquired. Next, 50 μL of a 12.5 M solution of
NaOH in D O in air were added (to effect the oxidative alkaline
hydrolysis of 1). The color of 1 was discharged, solid products of
hydrolysis that formed immediately were removed by centrifugation,
■
*
S
2
1
and a H NMR spectrum was acquired.
Temperature Dependence of the Rate Constant for MTBE
‡
‡
Cleavage. To obtain ΔH and ΔS , 150 μL of pure MTBE were
added to an NMR tube containing 18.1 μmol of Na 1 in D O (500
mg in 4.850 mL D O). After addition, 500 μL of the solution were
AUTHOR INFORMATION
Corresponding Author
iraw@bgu.ac.il
Notes
■
34
2
2
transferred to the NMR tube, and the tube was flame-sealed under air.
An additional four NMR-tube samples were prepared in the same way.
The NMR tubes were placed in separate oil baths, kept at constant
temperatures of 55 °C, 60 °C, 65 °C, 70 and 75 °C. Proton-NMR
spectra were acquired at regular time intervals, which differed
depending on the relative rates of MTBE cleavage. Rate constants
associated with MTBE cleavage at each temperature were calculated,
and activation parameters were derived from the plot of ln(k/T) vs 1/
k (i.e., from a linear form of Eyring equation).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
I.A.W. and A.M. thank the Deutsche Forschungsgemeinschaft,
for support, Prof. William H. Casey for estimates of water-
exchange rates, and Dr. Pere Miro for graphics. C.B. thanks the
MINECO of Spain (CTQ2011-29054-C02-02/BQU) and the
ICIQ Foundation for support. Dedicated to Prof. Adam
Bielanski on the occasion of his 100th birthday.
Preparation and Reactions of Capsules, 1, With Accessible,
Water-Bound Mo(V) Sites. To replace part of the acetate ligands in
1
2
by H O, 10 mL of concentrated Na 1 (initially with an average of
2 34
0.4 acetates inside; 4.5 mM in water) were placed in a dialysis
membrane bag, and immersed in 0.5 L of 0.1 mM methanesulfonic
acid (MSA) at pH 4. The slight acidity was used to keep the pH at a
value close to the native pH of Na 1 in water, thus preventing
hydrolytic decomposition. The 0.1 mM MSA was replaced by fresh
MSA solutions four times over a 10-h period, during which (after 3, 7,
REFERENCES
■
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34
F
dx.doi.org/10.1021/ja304513t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
(
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̈
(
̈
̈
2
̈
̈
̈
̈
̈
̈
2
(
1
(
affects ligand exchange, the entry of benzoate (ref 4a) was revisited.
+
After 24 h at 65 °C, and using the Na -salt (more soluble than the acid
form used earlier)benzoate is indeed observed inside 1 (see SI).
(
7) (a) Breno, K. L.; Ahmed, T. J.; Pluth, M. D.; Balzarek, C; Tyler,
D. R. Coord. Chem. Rev. 2006, 250, 1141−1151. (b) This is difficult to
quantify more precisely because observed pD values result from the
dissociation of protons from multiple water ligands on numerous
V
{
Mo } linkages.
2
1
(
8) Accordingly, the intensity ratio of H NMR signals of tert-BuOD
“
(CH ) C-“ and methanol “-CH ” groups after MTBE cleavage in D O
3
3
3
2
was 8:3, smaller than the 9:3 ratio for unreacted MTBE.
(
(
9) Blackmond, D. G. Angew. Chem., Int. Ed. 2009, 48, 2648−2654.
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(
(
(
12) Catalytic cycles involving a single Mo(V) centerwhether as a
Lewis acid, or with a bound water ligand acting as a Brønsted acid
require the inclusion of elementary steps whose microscopically
reverse processes appear much less plausible (see Figures S17 and S18
of the SI).
G
dx.doi.org/10.1021/ja304513t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX