Four-Component Catalytic Machinery: Reversible Three-State Control of Organocatalysis by Walking Back and Forth on a Track

Article abstract of DOI:10.1021/acs.inorgchem.7b02703

A three-component supramolecular walker system is presented where a two-footed ligand (biped) walks back and forth on a tetrahedral 3D track upon the addition and removal of copper(I) ions, respectively. The addition of N-methylpyrrolidine as a catalyst t

Full text of DOI:10.1021/acs.inorgchem.7b02703

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Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
Four-Component Catalytic Machinery: Reversible Three-State
Control of Organocatalysis by Walking Back and Forth on a Track
̈
Nikita Mittal, Merve S. Ozer, and Michael Schmittel*
Center of Micro and Nanochemistry and Engineering, Organische Chemie I, Universitat
Siegen, Germany
̈
Siegen, Adolf-Reichwein-Strasse 2, D-57068
*
S Supporting Information
ABSTRACT: A three-component supramolecular walker
system is presented where a two-footed ligand (biped) walks
back and forth on a tetrahedral 3D track upon the addition and
removal of copper(I) ions, respectively. The addition of N-
methylpyrrolidine as a catalyst to the walker system generates a
four-component catalytic machinery, which acts as a three-
state switchable catalytic ensemble in the presence of
substrates for a conjugate addition. The copper(I)-ion-initiated
walking process of the biped ligand on the track regulates the
int
catalytic activity in three steps: ON versus ON (intermediate
ON) versus OFF. To establish the operation of the four-
component catalytic machinery in a mixture of all constituents,
forward and backward cycles were performed in situ
illustrating that both the walking process and catalytic action are fully reversible and reproducible.
INTRODUCTION
a three-component walker system that is based on self-sorted
■
22,23
metal−ligand interactions
and capable of controlling a
Nature’s design of protein-based molecular walkers (dynein,
kinesin, and myosin) is amazing. These startling systems walk
1
conjugate addition depending on its position on the track when
a proper catalyst is added. As demonstrated below, the walker 2
is able to walk reversibly on the four-station track 1 upon the
addition and removal of copper(I) ions requiring a
sophisticated stoichiometry-dependent self-sorting (Chart
step by step on microtubule or actin filament tracks, with each
step driven by adenosine triphosphate hydrolysis, thereby
executing essential tasks such as cargo transport, muscle
contraction, cell division, etc. They utilize weak noncovalent
interactions like hydrogen bonding, electrostatic interactions,
etc., to attach each foot to the track. Inspired by these
biomolecular machines, several synthetic molecular walker
systems, for instance based on dynamic covalent bond
formation and cleavage, have been designed to mimic the
walking process while keeping the directionality and
2
−6
24,25
1).
In detail, the three-component system is composed of track 1
with its four binding sites [two sterically hindered phenanthro-
lines (phenAr ) and two zinc(II) porphyrin (ZnPor) sites], the
2
biped ligand 2, and copper(I) ions (Scheme 1). In the absence
of copper(I) ions, the biped ligand 2 with its two 2-
methylpyridine binding terminals will coordinate to both
ZnPor sites of track 1. Upon the addition of copper(I) ions,
the biped ligand 2 is expected to depart in two steps from the
two ZnPor stations of 1 and thus walk toward the copper(I)-
filled phenanthroline stations. The removal of copper will
reverse the process. The addition of a catalyst to the three-
component walker generates the four-component catalytic
machinery. When this machinery is commanded to undergo
stepwise walking in a solution containing the substrates for the
catalytic process, then three-state catalysis emerges with ON
7
−14
processivity of the system intact.
Alternatively, labile
1
5
transition-metal coordination motifs have been utilized by
1
6
Leigh’s group in preparing a two-footed ligand (biped)
consisting of a platinum(II) complex as the kinetically inert foot
and a palladium(II) complex as the labile foot, with the latter
being able to step back and forth on the track via reversible
protonation. At present, such walker systems using dynamic
metal−ligand coordination remain scarce, although detachment
of the foot from the track can be more easily accomplished than
that with covalent systems.
7
Among the known artificial walker systems, very few have
been successfully coupled with additional functions, like
fluorescence quenching, although the processivity could be
used for sequence-specific functionalization. On the basis of
our experience with allosteric artificial switches that are able to
regulate catalytic processes such as click cycloaddition,
int
versus ON (intermediate ON) versus OFF activity.
17
18
Special Issue: Self-Assembled Cages and Macrocycles
Received: October 24, 2017
19−21
cyclopropanation, Knoevenagel reactions, etc.,
we present
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.7b02703
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Inorganic Chemistry
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Chart 1. Track 1 and Biped 2
Scheme 1. Reversible Stepwise Walking of Biped 2 on the Tetrahedral Track 1, Forming Different States upon the Addition and
+
Removal of Cu Metal Ions
RESULTS AND DISCUSSION
switch, ZnPor is intermolecularly bound either to the catalyst
usually a secondary amine) or to an intramolecular pyridine
arm.
The conception of the four-component catalytic machinery is
required to reconcile the operation of a three-component
walker with the catalyst release as developed in our nanoswitch
work. Track 1 was thus designed to provide a tetrahedral
arrangement of two identical ZnPor and two sterically shielded
■
(
Design. The structural design of the present four-
component catalytic machinery was inspired by recent insights
26,27
19−21
gained from our nanorotor
and nanoswitch
work. For
20
instance, in a recently elaborated nanoswitch system, the
pyridylpyrimidine switching arm binds intramolecularly either
to a ZnPor [in the absence of copper(I) ions] or to a phenAr2
unit [in the presence of copper(I) ions], which allows control
of catalyst release from the ZnPor unit into solution. The
release is based on the fact that ZnPor systems can only
phenanthroline (phenAr ) stations. In state I, two NMepy →
2
ZnPor interactions ensure the formation of complex [(1)(2)].
28−30
accommodate one additional ligand;
thus, in the nano-
The phenAr ligands are required for the uptake of copper(I)
2
B
DOI: 10.1021/acs.inorgchem.7b02703
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Inorganic Chemistry
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Chart 2. Ligands 3−7 and Complexes C1−C3
ions. Their steric shielding is a prerequisite to guarantee clean
in CD Cl . As expected, the formation of complex [(1)(2)] is
2
2
+
31
NMepy → [Cu(phenAr )] complexation (HETPYP =
confirmed by strong upfield shifts of protons a-, b-, and c-H of
the biped ligand 2 from 8.47, 7.21, and 7.28 ppm to 5.98, 6.52,
and 6.61 ppm, respectively, due to immersion of those protons
in the π ring cloud of the ZnPor stations of track 1 (Figure
S13). Formation was additionally established by UV−vis data
(Figure S41) because the Q band exhibits a 10 nm shift from
550 nm (track 1) to 560 nm (state I), similar to that in other
2
heteroleptic pyridine and phenanthroline complexation) upon
the addition of copper(I) ions to 1.
The walking process needs a distinct thermodynamic driving
+
force for the biped to move from ZnPor to the [Cu(phenAr )]
2
site. After various model studies with different pyridine
derivatives, we decided on 2-methylpyridine as the terminal
19
for the biped ligand 2 because it binds significantly with both
Npy → ZnPor interactions. Complex [(1)(2)] is further
+
1
binding units, i.e., with [Cu(phenAr )] (log K = 3.43 ± 0.01;
characterized by H DOSY NMR, showing a single species with
2
3
2
−10
2
−1
Figure S42) and ZnPor (log K = 2.3 ), which are available on
diffusion coefficient D = 3.5 × 10 m s (r ∼ 15.1 Å) and
track 1. The required clean self-sorting upon going from
confirming clean formation (Figure S32).
To prepare state III, i.e., [Cu (1)(2)] , track 1, biped ligand
+
2+
[
(1)(2)] to [Cu(1)(2)] was tested ahead of finalizing the
2
structural design of the track and biped. For instance, complex
2, and [Cu(CH CN) ]PF were mixed in a 1:1:2 ratio. As
anticipated, H NMR analysis shows the characteristic upfield
3
4
6
1
C1 formed from zinc porphyrin 3 and 4-bromo-2-methylpyr-
1
idine (5) mixed in a 1:1 ratio (Chart 2). In the H NMR
shifts of phenAr protons 9-H from 6.96 ppm (in track 1) to
2
spectrum, the signals of protons a- and b-H are shifted upfield
from 8.38 and 7.28 ppm in 5 to 6.44 and 6.81 ppm in C1,
respectively, because of the protons’ immersion in the
6.71 ppm and of 2-methylpyridine protons a-H from 8.47 ppm
(in biped 2) to 7.52 ppm, suggesting the formation of a
+
[Cu(phenAr )(2-methylpyridine)] complex unit (Figure S17).
2
1
1
2+
porphyrin’s ring current (Figure S9). In the H NMR spectrum
Indeed, a comparison of the H NMR data of [Cu (1)(2)]
2
of complex C2, prepared by mixing ligands 4 and 5 and
with that of complex C2 confirms the binding of both 2-
I
[
Cu(CH CN) ]PF in a 1:1:1 ratio in CD Cl , characteristic
methylpyridine terminals of biped ligand 2 to the Cu phenAr
3
4
6
2
2
2
upfield shifts of proton 9-H of ligand 4 from 6.93 to 6.74 ppm
and proton a-H of ligand 5 from 8.38 to 7.61 ppm are seen
stations of 1 (Figure S18). In agreement with this assignment,
the Q band of state III is shifted back to 550 nm (Figure S41),
i.e., to the same position as that in track 1. ESI-MS of the
(
Figure S11). Complex C2 was further characterized by
2
+
electrospray ionization mass spectrometry (ESI-MS), which
mixture shows a single peak at m/z 1829.1 for [Cu (1)(2)] ,
2
+
shows a single peak at m/z 652.0 for [Cu(4)(5)] (Figure S39).
suggesting the quantitative formation of state III (Figure S40).
1
Another control ensured that the intramolecular 2-methyl-
pyridine unit of 2 is a better binder to the ZnPor subunit of 1
than the intermolecularly present catalyst, N-methylpyrrolidine.
This finding suggests that in the presence of complex [(1)(2)]
the catalyst is available in solution.
Synthesis and Characterization of a Three-Compo-
nent Walker. We synthesized the tetrahedral track 1
consisting two phenAr2 and two ZnPor units as stations
A single set of signals in the H DOSY NMR at D = 3.36 ×
−
10
2
−1
10 m s (r ∼ 15.7 Å) further confirms our claim (Figure
S34).
After the successful formation of states I and III of the
walking system, we interrogated the crucial state II, i.e.,
+
[Cu(1)(2)] , because it requires a stoichiometry-dependent
self-sorting. Thus, a CD Cl solution of track 1, biped ligand 2,
2
2
1
and [Cu(CH CN) ]PF in a 1:1:1 ratio was subjected to H
3
4
6
(
Chart 1) via a series of Sonogashira coupling steps; details are
NMR measurement without any purification. Two types of
mesityl protons 9-H emerge, one for the complexed phenAr2
unit at 6.72 and 6.75 ppm and the other for the uncomplexed
mentioned in the Supporting Information (SI). Equally, several
Sonogashira coupling reactions were used to synthesize the
biped ligand 2 (Chart 1) with 2-methylpyridine units as
terminals. Both compounds were fully characterized by
spectroscopic techniques, i.e., H NMR, C NMR, DOSY
NMR, ESI-MS, and elemental analysis (see the SI). Before
studying the in situ three-state walking of the biped ligand 2
from the ZnPor to phenAr stations of 1, we decided to
individually characterize each walking state. State I was
prepared by mixing track 1 and biped ligand 2 in a 1:1 ratio
phenAr unit at 6.96 and 6.95 ppm (Figure S15). The two sets
2
of signals are actually strong support for the identity of state II.
1
13
Two racemic diastereomers are expected because the central
+
carbon and the NMepy → [Cu(phenAr )] linkage are
2
stereogenic. Since all peaks of track 1 (complexed as well as
uncomplexed sites) show up in two sets at a 1:1 ratio, the
formation of two diastereomers is warranted in a 1:1 ratio.
Reciprocally, a mixture of states I and III rather than state II is
2
C
DOI: 10.1021/acs.inorgchem.7b02703
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Inorganic Chemistry
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1
Figure 1. H NMR (400 MHz, 298 K, CD Cl ) showing in situ reversible stepwise walking of biped 2 on track 1 upon the sequential addition and
2
2
+
removal of Cu ions, thereby switching between different states of the system; (a) state I ([(1)(2)]) obtained after mixing track 1 and biped 2 in a
:1 ratio; (b) the addition of 1 equiv of [Cu(CH CN) ]PF to state I depicted in spectrum a generates state II, i.e., [Cu(1)(2)]PF ; (c) the addition
1
3
4
6
6
of 1 equiv more of [Cu(CH CN) ]PF to state II depicted in spectrum b generates state III, i.e., [Cu (1)(2)](PF ) ; (d) the addition of 2 equiv of
3
4
6
2
6 2
+
ligand 7 to state III displayed in spectrum c to remove 1 equiv of Cu regenerates state II and complex C3; (e) the addition of 2 equiv more of ligand
to remove the remaining Cu regenerates state I along with complex C3. The subscripts UC and C denote uncomplexed and complexed sites.
+
7
1
ruled out by the presence of two H NMR sets. In the case of a
mixture, the complexed and uncomplexed sites should display a
station on track 1. The addition of 2 equiv more of ligand 7
causes walking of ligand 2 back to both ZnPor sites,
regenerating state I (Figure 1e). Thus, as anticipated by our
design, the system was reversed in a stepwise process (Figure
1d,e) without any loss.
+
single set each. The identity of [Cu(1)(2)] is additionally
substantiated by UV−vis data (Figure S41) as the Q band
shifted from 550 nm (track 1) to 554 nm (state II).
33
Furthermore, a single peak in the DOSY NMR with a diffusion
coefficient D = 3.44 × 10 m s (r ∼ 15.3 Å) suggests clean
formation of state II (Figure S33).
Four-Component Catalytic Machinery. After establish-
ing the full reversibility of the walker, we decided to transform
the walker into four-component catalytic machinery. As
−10
2 −1
15
The clean formation of all states suggested to study in situ
the reversible walking of the walker system (Scheme 1)
depending on the copper(I) ion stoichiometry. Initially, track 1
and biped ligand 2 were mixed in a 1:1 ratio in CD Cl to form
delineated above in the design chapter, we envisioned that
the ZnPor units present in the walking system may be
programmed to capture or release catalytically active secondary
20
35
amines, such as piperidine or N-methylpyrrolidine, by the
addition or removal of copper(I) ions. In the presence of the
substrates for an organocatalytic reaction, stepwise regulation of
2
2
state I with both feet at the ZnPor stations of track 1 (Figure
a). Now, upon the addition of 1 equiv of [Cu(CH CN) ]PF
6
1
3
4
1
int
to state I, the H NMR demonstrates the formation of state II;
thus, one foot of ligand 2 has walked to one of the free phenAr2
stations of track 1 (Figure 1b). After the addition of a further 1
catalysis (ON, ON, and OFF) should be possible by
addressing the various states I−III.
For instance, as long as biped ligand 2 is bound to both
ZnPor stations in [(1)(2)], all of the added catalyst should be
available in solution, resulting in 100% activity (ON state).
Upon the addition of 1 equiv of copper(I) ions to this solution,
the formation of [Cu(1)(2)]+ will take place, where one
liberated ZnPor unit should capture 1 equiv of the added
catalyst. The yield of the catalytic reactions should thus drop,
1
equiv of [Cu(CH CN) ]PF into the latter solution, the H
3
4
6
NMR (Figure 1c) confirms that ligand 2 is now attached to
both copper(I)-filled phenAr stations of track 1, representing
2
state III. Thus, the designed two-step walking of ligand 2 from
ZnPor stations to phenAr stations of 1 has taken place.
2
After the two forward walking steps by the sequential
addition of copper(I) ions were realized, the reverse walking
was studied by removing them. We used the electron-rich 2-
ferrocenyl-9-mesityl-1,10-phenanthroline (7) to remove
copper(I) ions because it forms the highly stable homoleptic
int
representing an ON state. After the addition of 1 equiv more
of copper(I) ions, both 2-methylpyridine terminals of the biped
I
ligand 2 should locate on the Cu phenAr stations, exposing
2
both ZnPor stations to capture the remaining catalyst from the
solution. No further catalytic product formation is expected in
+
34
complex [Cu(7) ] (C3; log K = 11.0; Chart 2). The addition
2
2+
of 2 equiv of ligand 7 (Chart 2) to state III leads to the
the presence of [Cu (1)(2)] , i.e., a catalytic OFF state.
2
formation of state II (Figure 1d) within seconds. Thus, the high
For a proof of concept, we selected N-methylpyrrolidine
(10) as the catalyst because it is able to catalyze the conjugate
addition of thiophenol (8) to 2-cyclopentenone (9; Scheme 2).
Moreover, 10 has a significant binding affinity toward the
+
dynamics about the NMepy → [Cu(phenAr )] binding, as
2
2
4
established already earlier in other systems, allows the fast
trapping of 1 equiv of copper(I) ions by 7 and thus the rapid
35
movement of one foot of ligand 2 from phenAr to the ZnPor
ZnPor unit (log K = 4.2) of 1 so that its catalytic activity is
2
D
DOI: 10.1021/acs.inorgchem.7b02703
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Inorganic Chemistry
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Scheme 2. Reaction Scheme for the Model Reaction
evaluated for its catalytic activity. After track 1, biped ligand 2,
and [Cu(CH CN) ]PF were mixed in a 10:10:10 ratio in
3
4
6
CD Cl and substrates 8 and 9 and catalyst 10 were added in a
2
2
2
00:200:18 ratio, the mixture was heated at 40 °C for 2 h.
1
Quantification by H NMR analysis corroborated the product
formation in (12 ± 2)% yield (Figure S28). Thus, CatState II
indeed acts as an ON state, demonstrating that the ZnPor
int
+
unit in [Cu(1)(2)] is able to capture a defined part of the
catalyst, leaving the rest of the catalyst free in the solution.
Finally, the study of in situ product formation and inhibition
during forward and backward walking of biped ligand 2 on
track 1 was investigated (Figure 2). Hereunto, track 1 and
biped ligand 2 (10:10) were mixed to form CatState I, and then
substrates 8 and 9 and catalyst 10 (200:200:18) were added.
basically zero in a complex with the ZnPor unit. The switching
of the overall catalytic machinery should then be visible from
the amounts of product 11.
Before in situ regulation of the conjugate addition reaction by
the addition and removal of copper(I) ions in the full catalytic
machinery (Scheme 3) was studied, several control experiments
were undertaken. When the reaction of 8 and 9 (both 100 mol
The resulting mixture in CD Cl was heated for 2 h in an NMR
2
2
1
tube at 40 °C. H NMR showed 27% product 11 (Figure
S30a). Now 1 equiv of [Cu(CH CN) ]PF and the consumed
%
) is run in the presence of 9 mol % organocatalyst 10 using
standardized conditions [dichloromethane (DCM), 40 °C, 2
h], then product 11 is detected in (32 ± 2)% yield (Figure
S22). In the presence of 4 mol % catalyst 10, the yield is (16 ±
3
4
6
1
amounts of substrates 8 and 9 were added. After heating, H
NMR showed 39% product 11 (Figure S30b), thus an increase
by 12%. This finding indirectly confirms the formation of
2)% (Figure S23). In contrast, no product 11 is formed in the
int
CatState II in solution ( ON state) because the catalytic
presence of both zinc(II) tetraphenylporphyrin (3; 9 mol %)
and 10 (9 mol %), confirming that formation of the strong
complex [(3)(10)] inhibits the reaction between 8 and 9
activity in solution has come to roughly half of that in CatState
I. Finally, 1 equiv of [Cu(CH CN) ]PF and again the
3
4
6
consumed amounts of 8 and 9 were added. After this mixture
(
Figure S24).
1
After these model experiments, we studied the conjugated
had been heated (2 h at 40 °C), H NMR analysis still showed
addition reaction in the presence of each individual state of the
catalytic machinery. First, we examined the OFF state, i.e.,
CatState III (a six-component mixture). Here both free ZnPor
stations of track 1 are expected to fully capture catalyst 10,
preventing catalysis. We mixed track 1, biped ligand 2,
39% product 11 (Figure S30c). Apparently, the present mixture
represents an OFF state of catalysis, as we would expect for
CatState III. To reverse the walking and to regenerate CatState
II, 2 equiv of 7 was added as well as the consumed amounts of
1
substrates 8 and 9. Upon heating for 2 h at 40 °C, H NMR
[
Cu(CH CN) ]PF , substrates 8 and 9, and catalyst 10 in a
analysis indicated an increase of the product yield by 12%
(Figure S30d), in agreement with the formation of CatState II.
The addition of 2 equiv more of 7 and used-up substrates gave
rise to a 24% increase in product 11 (Figure S30e), in
agreement with the regeneration of CatState I.
To challenge the reproducibility of the catalytic walker
machinery, we now began the catalytic cycle with CatState III
as the OFF state using the same stoichiometric ratios as before.
We evaluated the product yields starting with CatState III,
added the required amounts of 7 to probe CatStates II and I,
and studied the backward cycle in the same mixture by the
3
4
6
1
0:10:20:200:200:18 ratio in CD Cl and heated the resulting
2 2
solution at 40 °C for 2 h. No product formation was observed
in the H NMR, confirming that CatState III is indeed an OFF
1
state for catalysis (Figure S29). Thereafter, we studied the
formation of product 11 in the presence of CatState I as 100%
ON state (for yield calculations, tetrachloroethane is used as an
internal reference). After track 1, biped ligand 2, substrates 8
and 9, and catalyst 10 were mixed in a 10:10:200:200:18 ratio
in CD Cl , the mixture was heated for 2 h at 40 °C, furnishing
2
2
(
28 ± 2)% product 11 (Figure S27). Now, CatState II was
int
Scheme 3. Cartoon Representation of the Stepwise (ON/ ON/OFF) Regulation of a Conjugate Addition Reaction at the
+
Different States (CatStates) by the Addition and Removal of Cu Ions
E
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Figure 2. Product formation in each state in forward and backward cycles: (a) table; (b) bar graph representation.
addition of [Cu(CH CN) ]PF , probing CatStates II and III.
and δ
C
= 53.8 ppm; CDCl
3
, δ
H
= 7.26 ppm and δ
C
= 77.2 ppm). The
3
4
6
following abbreviations were utilized to describe the peak patterns: s =
singlet, d = doublet, t = triplet, dd = doublet of doublets, td = triplet of
doublets, dt = doublet of triplets, br = broad, bs = broad singlet, bd =
broad doublet, and m = multiplet. The numbering of the carbon atoms
in the molecular formulas (vide infra) is used only for the assignments
of the NMR signals and thus is not necessarily in accordance with
IUPAC nomenclature. Electrospray ionization mass spectrometry
All CatStates were evaluated for their catalytic activity under
standardized conditions (DCM, 40 °C, 2 h). The total yield of
1
1 in this sequence (0, 12%, 35%, 46%, and 48%) allows us to
calculate the yields in the various CatStates: CatState III (0%)
→
→
CatState II (12%) → CatState I (23%) → CatState II (11%)
CatState III (2%) (Figure S31). An examination of the
averaged yields for all in situ probed CatStates provides the
following results: CatState I [(24.7 ± 2.1)%], CatState II
(ESI-MS) spectra were recorded on a Thermo-Quest LCQ Deca
spectrometer. Melting points were measured on a Buchi SMP-20
̈
instrument. IR spectra were recorded using a Varian 1000 FT-IR
instrument. UV−vis spectra were recorded on a Varian Cary 100
BioUV/Vis spectrometer. Elemental analysis was done on the EA 3000
CHNS analyzer.
[
(11.75 ± 0.5)%], and CatState III [(0.3 ± 0.6)%]. As a result,
CatState II furnishes 47.6% of the yield observed in CatState I,
in good agreement with the different amounts of catalyst
available under ideal walking behavior [CatState I (18 mol %
catalyst), defined as 100%; CatState II (8 mol % out of 18 mol
Synthesis of State I. Track 1 (811 μg, 0.282 μmol) and biped ligand
2
(184 μg, 0.282 μmol) were loaded into an NMR tube and dissolved
%
of the catalyst should be available): 44.4%]. Thus, the yields
in CD Cl . The resultant mixture was subjected to characterization
2
2
obtained in the in situ forward and backward cycles reveal that
the two-step walking of the biped ligand 2 on track 1 in the
catalytic machinery is reversible, reproducible, and a means to
successfully regulate the conjugate addition reaction in a
1
without any further purification. Yield: quantitative. H NMR (400
MHz, CD Cl ): δ 8.88 (d, J = 4.6 Hz, 4H, β-H), 8.73 (d, J = 4.6 Hz,
H, β-H), 8.67 (s, 8H, β-H), 8.36 (d, J = 8.4 Hz, 2H, [4/7]-H), 8.34
d, J = 8.2 Hz, 2H, [7/4]-H), 8.23 (d, J = 8.2 Hz, 4H, [15/14]-H),
7.94 (d, J = 8.2 Hz, 4H, [14/15]-H), 7.91 (s, 4H, 5- and 6-H), 7.68
d, J = 8.6 Hz, 4H, [13/10]-H), 7.62 (d, J = 8.7 Hz, 4H, [10/13]-H),
.57 (d, J = 8.4 Hz, 2H, [3/8]-H), 7.56 (d, J = 8.2 Hz, 2H, [8/3]-H),
.54 (t, J = 1.6 Hz, 2H, g-H), 7.47 (dt, J = 7.6 Hz, J = 1.6 Hz, 2H,
d/f]-H), 7.43 (d, J = 8.7 Hz, 4H, [11/12]-H), 7.40 (d, J = 8.6 Hz,
H, [12/11]-H), 7.37 (dt, J = 7.6 Hz, J = 1.6 Hz, 2H, [f/d]-H), 7.31
t, J = 7.6 Hz, 2H, e-H), 7.28 (s, 12H, 16- and 17-H), 6.98 (s, 2H, h-
H), 6.97 (s, 4H, 9-H), 6.61 (s, 2H, c-H), 6.52 (d, J = 5.6 Hz, 2H, b-
3
3
2
2
3
4
(
3
3
36
3
systems-chemistry approach.
3
3
(
7
7
[
4
3
3
CONCLUSIONS
■
3
3
4
In conclusion, a novel walker system based on metal−ligand
binding and cleavage is designed as a special metallomacrocycle
3
3
3
4
37
3
that changes its connectivity with each input. Upon the
addition/removal of copper(I) ions, the biped ligand 2 walks
forward and backward on the tetrahedral track 1 from the
ZnPor to phenAr2 stations in two steps. The sequential
addition and removal of copper ions allows access to all states
of the system in a clean manner. The addition of 10 as the
catalyst to the walker system generates a four-component
catalytic machinery. After the addition of the required
substrates, the different catalytic states were utilized to control
a conjugate addition reaction in a stepwise manner by
regulating the release and uptake of 10 as the catalyst. The
present work is the first example, in which an artificial
molecular walker system is able to regulate a catalytic
(
3
3
H), 5.98 (br, 2H, a-H), 3.99 (t, J = 6.4 Hz, 4 H, i-H), 2.61 (s, 18H, f′-
and h′-H), 2.57 (s, 12H, [b′/a′]-H), 2.34 (s, 6H, d′-H), 2.05 (s, 12H,
c′-H), 1.96 (s, 12H, [a′/b′]-H), 1.82 (s, 12H, g′-H), 1.81 (s, 24H, e′-
H), 1.82−1.75 (m, 4 H, j-H), 1.58−1.48 (m, 4 H, k-H), 0.96 (m, 12 H,
Me- and l-H). IR (KBr): ν 3435, 2950, 2920, 2850, 2211, 1599, 1503,
−
1
1
478, 1379, 1337, 1279, 1203, 1062, 995, 852, 826, 797, 725 cm .
UV−vis (CH Cl ): λ = 560 nm (Q band; ε = 1.43 × 10 M
cm ). Anal. Calcd for C247H204N O Zn ·2CH Cl : C, 80.81; H, 5.66;
4
−1
2
2
max
−1
14
2
2
2
2
N, 5.30. Found: C, 81.15; H, 5.53; N, 5.19.
Synthesis of State II. Track 1 (1.71 mg, 0.594 μmol), biped ligand 2
(388 μg, 0.594 μmol), and [Cu(CH CN) ]PF (221 μg, 0.594 μmol)
3
4
6
were loaded into an NMR tube and dissolved in CD Cl . The resultant
2
2
3
8
reaction. The regulation defines three different levels of
mixture was subjected to analytical characterization without any
int
1
further purification. Yield: quantitative. H NMR (400 MHz, CD Cl )
catalytic activity from ON to ON to OFF. Thus, the present
2
2
of two diastereomers in a ratio of 1:1 (diastereotopic characteristic
protons marked as asterisks and subscript C and UC in proton
assignments are used for complexed and uncomplexed phenanthroline,
catalytic ensemble that requires a mixture of seven components
represents switchable and highly reliable advanced molecular
machinery.
3
respectively): δ = 8.86 (d, J = 4.8 Hz, 1H, β-H), 8.83−8.81 (m, 3H, β-
H), 8.74−8.62 (m, 14H, 4 -, 7 - and β-H), 8.38−8.32 (m, 2H, 4
-
C
C
UC
EXPERIMENTAL SECTION
■
and 7UC-H), 8.23−8.15 (m, 6H, 5
-, 6 -, and [14/15]-H), 7.96−7.88
C C
General Information. All commercial reagents were used without
further purification. Solvents were dried with the appropriate
(m, 8H, 8 -, 3 -, 5UC-, 6UC-, and -[15/14]-H), 7.69−7.50 (m, 12H, g-,
C
C
13-, 14-, 3UC-, 8UC-, d-, and f-H), 7.44−7.39 (m, 4H, 11- and 12-H),
7.34−7.18 (m, 8H, e-, c-, and mes-H), 7.05 (s, 2H, h-H), 6.96 (s, 1H,
1
13
desiccants and distilled prior to use. H and C NMR were recorded
on a Bruker Avance 400 (400 MHz) or on a Varian-S 600 (600 MHz)
spectrometer using a deuterated solvent as the lock and a residual
protiated solvent as the internal reference (CD Cl , δ = 5.32 ppm
9
*-H), 6.95 (s, 1H, 9 -H), 6.82 (bs, 2H, b-H), 6.75 (s, 1H, 9 *-
UC C
3
UC
H), 6.72 (bs, 3H, a- and 9 -H), 4.01 (t, J = 6.0 Hz, 4H, i-H), 2.60 (s,
C
18H, f′- and h′-H), 2.56 (s, 3H, [b′/a′]UC*-H), 2.54 (s, 3H, [b′/a′]UC
-
2
2
H
F
DOI: 10.1021/acs.inorgchem.7b02703
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Forum Article
H), 2.38 (s, 3H, [b′/a′] *-H), 2.36 (s, 3H, [b′/a′] -H), 2.34 (s, 1.5H,
substrates 8 and 9 were added. After heating for 2 h at 40 °C, a further
increase in the yield of product 11 (total of 35%) was observed in the
NMR (Figure S31c). To start the reverse cycle, 1 equiv of
[Cu(CH CN) ]PF (103 μg, 0.278 μmol) and the used-up 8 and 9
C
C
d′ *-H), 2.32 (s, 1.5H, d′ -H), 2.15 (s, 3H, d′ -H), 2.05 (s, 3H,
UC
UC
C
c′ *-H), 2.04 (s, 3H, c′ -H), 2.02 (s, 6H, c′ -H), 1.96 (s, 3H, [a′/
UC
UC
C
b′] *-H), 1.94 (s, 3H, [a′/b′] -H), 1.92 (bs, 6H, [a′/b′] -H),
UC
UC
C
3
4
6
1
.82−1.77 (m, 40H, j-, g′-, and e′-H), 1.57−1.47 (m, 10H, k- and Me-
were added to regenerate CatState II. After heating, a further increase
in the yield of product 11 (total of 46%) was observed in the NMR
(Figure S31d). Now, to regenerate CatState III (OFF state), 1 equiv
more of [Cu(CH CN) ]PF (103 μg, 0.278 μmol) and the consumed
3
H), 0.94 (t, J = 7.2 Hz, 6H, l-H). IR (KBr): ν 3436, 2922, 2858, 2219,
1
9
641, 1610, 1511, 1463, 1376, 1333, 1272, 1220, 1202, 1083, 1060,
−1
97, 979, 852, 829, 798 cm . UV−vis (CH Cl ): λ = 554 nm (Q
2
2
max
3
4
6
4
−1
−1
band;
ε
=
1.46
×
10
M
cm ). Anal. Calcd for
amounts of substrates 8 and 9 were added. After heating for 2 h at 40
°C, a minute (2%) increment in the product yield of 11 was observed
(Figure S31e).
C247H204CuF N O PZn ·2.5CH Cl : C, 75.83; H, 5.33; N, 4.96.
Found: C, 75.59; H, 4.94; N, 4.69.
6
14
2
2
2
2
Synthesis of State III. Track 1 (811 μg, 0.282 μmol), biped ligand 2
(
184 μg, 0.282 μmol), and [Cu(CH CN) ]PF (210 μg, 0.564 μmol)
3
4
6
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.7b02703.
■
were loaded in an NMR tube and dissolved in CD Cl . The resultant
2
2
*
S
mixture was subjected to characterization without any further
1
purification. Yield: quantitative. H NMR (400 MHz, CD Cl ): δ
2
2
3
3
8
8
.89 (d, J = 4.6 Hz, 4H, β-H), 8.76 (d, J = 4.6 Hz, 4H, β-H), 8.75−
3
.69 (m, 12H, β-, 4-, and 7-H), 8.23 (d, J = 7.6 Hz, 2H, [15/14]-H),
3
8
.21 (s, 4H, 5- and 6-H), 7.95 (d, J = 8.4 Hz, 2H, [3/8]-H), 7.94 (d,
Synthesis and characterization of 1 and 2, spectroscopic
data for all new complexes and ligands, and all catalytic
experiments and controls (PDF)
3
3
J = 8.4 Hz, 2H, [8/3]-H), 7.90 (d, J = 7.6 Hz, 4H, [14/15]-H), 7.81
(
bs, 2H, g-H), 7.62−7.48 (m, 14H, a-, d-, f-, 10-, and 13-H), 7.43−7.30
(
m, 10H, 11-, 12-, and e-H), 7.29 (s, 6H, 16- and 17-H), 7.17 (bs, 2H,
c-H), 7.12 (s, 2H, h-H), 7.06 (bd, 2H, b-H), 6.71 (s, 4H, 9-H), 4.00 (t,
3
J = 6.0 Hz, 4H, i-H), 2.61 (s, 18H, f′- and h′-H), 2.41 (s, 12H, [b′/
AUTHOR INFORMATION
Corresponding Author
E-mail: schmittel@chemie.uni-siegen.de.
■
a′]-H), 2.15 (s, 6H, d′-H), 2.02 (s, 12H, c′-H), 1.93 (s, 12H, [a′/b′]-
H), 1.92 (s, 6H, Me-H), 1.84 (s, 12H, g′-H), 1.83 (s, 24H, e′-H),
*
1
.76−1.72 (m, 4 H, j-H), 1.49−1.46 (m, 4 H, k-H), 0.88 (t, 6 H, l-H).
IR (KBr): ν 3435, 2920, 2213, 1642, 1612, 1512, 1463, 1376, 1336,
ORCID
−1
1
275, 1204, 1085, 998, 979, 892, 853, 826, 799, 774, 756, 725 cm .
Michael Schmittel: 0000-0001-8622-2883
Notes
The authors declare no competing financial interest.
2
+
ESI-MS: m/z (%) 1829.1 (100; [M − 2PF ] ). UV−vis (CH Cl ):
λ
C247H204Cu F N O P Zn ·3CH Cl : C, 71.44; H, 5.04; N, 4.67.
Found: C, 71.24; H, 4.71; N, 4.58.
In Situ Cycle 1 Starting with CatState I. The forward catalytic
reaction was started with CatState I prepared directly in the NMR
tube. Track 1 (830 μg, 0.288 μmol) and biped ligand 2 (188 μg, 0.288
μmol) were dissolved in 500 μL of CD Cl . To generate CatState I,
6
2
2
4
−1
−1
= 550 nm (Q band; ε = 1.36 × 10 M cm ). Anal. Calcd for
max
2
12 14
2
2
2
2
2
ACKNOWLEDGMENTS
■
We are highly indebted to the DFG (Schm 647/19-2 and 20-1)
and the University of Siegen for their continued support of this
research.
2
2
compounds 8 (635 μg, 5.76 μmol), 9 (470 μg, 5.76 μmol), and 10
44.1 μg, 0.518 μmol) were added and the resultant mixture was
heated at 40 °C for 2 h. The reaction mixture was then cooled to 0 °C
(
DEDICATION
■
1
(
to stop the reaction) and immediately subjected to H NMR analysis.
This work is dedicated to Prof. Dr. W. H. E. Schwarz on the
occasion of his 80th birthday.
The formation of product 11 (27%) was observed (100% ON; Figure
S30a). Thereafter, 1 equiv of [Cu(CH CN) ]PF (107 μg, 0.288
3
4
6
μmol) was added along with the consumed amounts of substrates 8
and 9 (CatState II). The mixture was heated for 2 h at 40 °C. The
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Inorg. Chem. XXXX, XXX, XXX−XXX