Evolution of catalytic machinery: three-component nanorotor catalyzes formation of four-component catalytic machinery

Article abstract of DOI:10.1039/d1cc02805g

The three-component nanorotor [Cu₂(S)(R)]²⁺(k₂₉₈= 46.0 kHz) that is a catalyst for a CuAAC reaction binds the click product at each of its copper centers thereby creating a new platform and a dynamic slider-on-deck system. Due to this sliding motion (k₂₉₈= 65.0 kHz) the zinc-porphyrin boundN-methylpyrrolidine is efficiently released into solution and catalyzes a follow-up Michael addition.

Full text of DOI:10.1039/d1cc02805g

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Evolution of catalytic machinery: three-
component nanorotor catalyzes formation
of four-component catalytic machinery†
Cite this: Chem. Commun., 2021,
57, 7180
Received 28th May 2021,
Accepted 24th June 2021
Abir Goswami,‡ Merve S. O¨ zer,‡ Indrajit Paul and Michael Schmittel
*
DOI: 10.1039/d1cc02805g
rsc.li/chemcomm
The three-component nanorotor [Cu2(S)(R)]2+ (k298 = 46.0 kHz) that (S = stator; R = rotator/slider) via CuAAC chemistry catalyzes
is a catalyst for a CuAAC reaction binds the click product at each of formation of the four-component slider-on-deck [Cu2(S)(R)
its copper centers thereby creating a new platform and a dynamic (P)2]2+ (Scheme 1), where the latter acts as catalytic machinery
slider-on-deck system. Due to this sliding motion (k298 = 65.0 kHz) turning ON a Michael addition reaction.
the zinc-porphyrin bound N-methylpyrrolidine is efficiently
The design of this unique transformation is based on the
nanorotor [Cu2(S)(R)]2+ (Scheme 1) whose catalytic activity for
azide–alkyne cycloadditions has been established.10a In that
released into solution and catalyzes a follow-up Michael addition.
For many chemists, the unmatched performance of Nature’s work, we demonstrated that the click product was expelled
multicomponent machinery has been an inspiration for developing from the catalytic site by the nanomechanical motion in the
supramolecular machines that exhibit mechanical motion and nanorotor.12 For the present project, we chose the reactants 1
perform useful tasks.1 However, one aspect of Nature’s road to and 2 in such a way that their bidentate click product P would
machinery has received little attention so far: new enzymes with block the catalytic site of the nanorotor by a strong HETPHEN-
alternative architectures and new functions are constantly being type (HETeroleptic bis-PHENanthroline) complexation.1b Since
evolved from their ancestral enzymes.2,3 Evolution of new artificial product P possesses a zinc porphyrin (ZnPor) site, the binding
machinery from a dynamic information–handling mixture4 or
directly from multicomponent machines5 is thus a persuasive
vision. However, despite remarkable developments in the field of
useful molecular machines,6 only an outstanding paper by Leigh
reports on a manmade machine building another functional
device, in this case, a homooligomeric peptide for asymmetric
catalysis.7
Knowledge of adaptive dynamic supramolecular devices8 is
continuously growing and will eventually help to approach the
complexity and seamless organization of biological systems.9
Recently, we have reported catalytic multicomponent machi-
nery10 like rotors, walker, and sliders based on heteroleptic
metal–ligand complexation and demonstrated how emergent
functionality evolved from well-conceived self-sorting.11 Yet,
transformation of a manmade machine to new dynamic
catalytic machinery remains without precedent. Here, we
demonstrate how the three-component nanorotor [Cu2(S)(R)]2+
Center of Micro and Nanochemistry and Engineering, Organische Chemie I,
¨
Universitat Siegen, Adolf-Reichwein-Str. 2, Siegen D-57068, Germany.
E-mail: schmittel@chemie.uni-siegen.de; Tel: +49(0) 2717404356
† Electronic supplementary information (ESI) available: Experimental proce-
dures, compound characterizations, spectral data, UV-vis titrations data. See
DOI: 10.1039/d1cc02805g
Scheme 1 Transformation of the nanorotor [Cu2(S)(R)]2+ to the slider-
on-deck [Cu2(S)(R)(P)2]2+
¨
.
‡ Abir Goswami and Merve S. Ozer contributed equally.
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of P should establish a new coordination site for the rotary
biped in the nanorotor. With two ZnPor units coordinated to
[Cu2(S)(R)]2+, another type of nanomechanical motion is
expected in [Cu2(S)(R)(P)2]2+ because it is formally a slider-on-
deck system (Scheme 1), where the biped R should move
between altogether three zinc porphyrins.10c
At first, we carried out a model catalytic study (Scheme 2)
with the alkyne-terminated zinc(II) porphyrin 1 and 2-(azido-
methyl)pyridine (2). They were allowed to react in a 1 : 1 ratio in
CD2Cl2 : CDCl3 (4 : 1) at 50 1C in the presence of an equimolar
amount of [Cu(Phen)]+, the copper(I)-loaded 2,9-dimesityl-1,10-
phenanthroline. Progress of the reaction was followed by the
Fig. 1 Comparison of the partial 1H NMR spectra (400 MHz, 298 K) in
CD2Cl2 of (A) [Cu(Phen)]+, (B) 1, (C) [Cu(Phen)(P)]+.
1
signals of protons r-H and j0-H in the H NMR (Fig. 1).
Disappearance of the signal of proton CRCH (j0-H) and a
single set of zinc porphyrin r-H, s-H, q-H, t-H and p-H signals in
the 1H NMR as well as the clean formation of [Cu(Phen)(P)]+
indicated completion of the azide–alkyne cycloaddition reac-
tion after B24 h (ESI,† Fig. S19). Moreover, the signal of
phenanthroline proton 20-H experienced a diagnostic upfield
shift from 7.01 to 6.74 ppm, showing that the copper(I)-loaded
ligand was now coordinated to platform P (Fig. 1A and C). The
emergence of a broad signal for the methylene protons i-H
confirmed formation of the click product P. Finally, the single
peak at m/z = 1205.3 in the ESI-MS proved the integrity of the
heteroleptic complex [Cu(Phen)(P)]+ (ESI,† Fig. S30).
After these exemplary catalytic investigations, we wanted to
test the analogous click reaction with the rotor system as
catalyst (Scheme 1). First of all, nanorotor [Cu2(S)(R)]2+ was
prepared by mixing S, R and 2.0 equiv. of Cu+ in CD2Cl2.10a The
data unambiguously demonstrated that one pyridine foot of
rotator R (= biped) was attached to the ZnPor unit of stator S by axial
Fig. 2 Partial comparison 1H NMR (400 MHz, 298 K) in CD2Cl2 of
(A) nanorotor [Cu2(S)(R)]2+, (B) deck [Cu2(S)(P)2]2+, (C) slider-on-deck
[Cu2(S)(R)(P)2]2+
.
coordination while the other foot toggled between the Cu+-loaded (ESI,† Fig. S32). The upfield shift of proton signal 9-H from 7.03
phenanthroline stations at a frequency k298 = 46.0 kHz. Activation to 6.79 ppm indicated that platform P was coordinated to the
parameters of the nanorotor [Cu2(S)(R)]2+ were reported earlier as Cu+-loaded phenanthroline stations of stator S (Fig. 2A and C).
DH‡ = 49.1 ꢀ 0.4 kJ molꢁ1 and DS‡ = 9.5 ꢀ 1.7 J molꢁ1 Kꢁ1 10a
.
Furthermore, the proton signal b0-H of rotator R shifted from
Finally, reactants 1 and 2 were heated with nanorotor 6.89 to 5.77 ppm as a result of the pyridine arm moving from
[Cu2(S)(R)]2+ as a CuAAC13 catalyst in a 2 : 2 : 1 ratio in CD2Cl2 : the Cu+-loaded phenanthroline station to the ZnPor platform.
CDCl3 (4 : 1) at 50 1C. Formation of [Cu2(S)(R)(P)2]2+ was mon- After 24 h, all the signals corresponding to 1 had disappeared
itored by 1H NMR spectroscopy and ESI-MS. Similar to the and [Cu2(S)(R)(P)]2+ was furnished quantitatively.
model reaction, the formation of platform P was followed by
To clearly establish the Npy - ZnPor coordination in slider-
the disappearance of proton signals j0-H and meso r0-H of 1 and on-deck [Cu2(S)(R)(P)2]2+, we separately prepared deck [Cu2(S)
appearance of the meso r-H signal of P in 1H NMR (Fig. 2C). (P)2]2+ by mixing S, P and [Cu(CH3CN)4]PF6 in a 1 : 2 : 2 ratio in
1
Parallel, the peaks at m/z = 1970.8, 1606.0 and 1358.9 in CD2Cl2 and compared it with [Cu2(S)(R)(P)2]2+. In the H NMR,
the ESI-MS showed the expected mass signals for [Cu2(S)(R) the proton signal r-H resonating at 10.30 ppm experienced a
(P)2]2+, [Cu2(S)(R)(P)]2+ and [Cu2(S)(P)(CH3CN)]2+, respectively notable upfield shift to 10.22 ppm when rotator R was added
due to the axial pyridine coordination in slider-on-deck
[Cu2(S)(R)(P)2]2+. Furthermore, the DOSY spectrum yielded a
single diffusion coefficient (D = 3.3 ꢂ 10ꢁ10 m2 sꢁ1) indicating
that the multi-component slider-on-deck [Cu2(S)(R)(P)2]2+ was a
single species. The experimental hydrodynamic radius was
derived as 16.1 Å (ESI,† Fig. S17) in agreement with the
theoretical value (ESI,† Fig. S34, S35). The system was further
analyzed by UV-vis. In the final slider-on-deck, there are two
different types of ZnPor units present; one emerging from
stator S and two from both platforms P. The Q-band of S at
Scheme 2 Model study for self-sorting of platform P after formation with
Click reaction.
550 nm was reported earlier to undergo a red shift upon
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Fig. 3 (A) Comparison of the UV-vis spectra of [Cu2(S)(P)2]2+ and
[Cu2(S)(R)(P)2]2+ in 1,1,2,2-tetrachloroethane (c = 1.00 mM, 298 K) in
1.0 mm cuvette. (B) Partial VT 1H NMR (600 MHz) of slider-on-deck
[Cu2(S)(R)(P)2]2+ in CD2Cl2.
formation of rotor [Cu2(S)(R)]2+.10a In order to assign the ZnPor
absorptions in [Cu2(S)(R)(P)2]2+, the position of the ZnPor
Q-band of 1 (536 nm) was determined in 1,1,2,2-tetrachlo-
roethane (ESI,† Fig. S33). The Q-band absorption of the multi-
component deck [Cu2(S)(P)2]2+ without rotator R (Fig. 3A) was
observed at lmax = 539 nm with a shoulder at 549 nm. The
former absorption belongs to the ZnPor chromophore of P and
the shoulder to the ZnPor unit of S. The Q-band absorption of
the slider-on-deck system exhibited a lmax = 550 nm with a
hump at 542 nm (Fig. 3). As expected, upon coordination of R to
the deck, the Q-bands experienced a red shift in agreement with
our previous reports.14
Scheme 3 (A) Catalyst liberation due to the sliding motion enables
catalysis. (B) N-methylpyrrolidine (5) catalyzed Michael addition. Binding
of 5 to ZnPor prevents catalysis.
was strong enough to prevent catalytic activity of the nitrogen
heterocycle whereas sliding motion in slider-on-deck systems
was found to liberate the bound catalyst (N-methylpyrrolidine
- ZnPor-based sliders) into the solution thus turning ON
catalysis.10c Hence, we expected that the catalyst N-methyl-
pyrrolidine would be initially bound at the ZnPor unit of 1
thus being inactive for catalysis. However, after formation of
the slider-on-deck [Cu2(S)(R)(P)2]2+, the pyridyl end of the slider
R would move from the Cu+-loaded phenanthroline stations to
the newly bound ZnPor platform and should liberate catalyst
5. If this concept was correct, one would see that the
N-methylpyrrolidine catalyzed reaction was turned ON.
To first check the ability of the slider-on-deck to act as a
catalytic machinery in combination with organocatalyst 5, we
mixed S (1.9 mM), P, R, [Cu(CH3CN)4]PF6, 3, 4 and 5 in
1 : 2 : 1 : 2 : 20 : 100 : 2 ratio in CD2Cl2 : CDCl3 (4 : 1) and heated
at 50 1C. Indeed, 46% of the product 6 was formed after 4 h as
evidenced by 1H NMR (Scheme 3A). The reference reaction
itself, the mixture of 3, 4 and free catalyst 5 (3.8 mM) in
10 : 50 : 1 ratio in CD2Cl2 : CDCl3 (4 : 1), furnished 54% of pro-
duct 6 after heating at 50 1C for 4 h (Scheme 3B). This indicated
that the dynamic slider-on-deck liberated most of the available
catalyst 5 into solution as its activity is close to that of free 5.
In the next step, the in situ evolution of the catalytic slider-
on-deck and its effect on the Michael addition were tested. For
that purpose, we mixed 1, nanorotor [Cu2(S)(R)]2+ (E 2.0 mM)
as well as 3, 4 and catalyst 5 in 2 : 1 : 20 : 100 : 2 ratio in CD2Cl2 :
CDCl3 (4 : 1) and heated at 50 1C. No Michael addition product
6 was formed after 4 h because the static N-methylpyrrolidine
(5) - ZnPor binding of 1 was strong enough to prevent catalytic
activity (ESI,† Fig. S25).
After establishing the slider-on-deck system [Cu2(S)(R)
(P)2]2+, we examined the sliding motion of R across the three
ZnPor units of deck [Cu2(S)(P)2]2+ by VT (variable temperature)
1H NMR (Fig. 3B and ESI,† Fig. S27, S28). The meso proton r-H
(10.22 ppm) appearing as a singlet at 25 1C due to dynamic
sliding showed coalescence at ꢁ30 1C and split at ꢁ50 1C into
two singlets at a ratio of ca. 2 : 1. At ꢁ70 1C, splitting to 2 : 1 ratio
can be seen more clearly. The signal at 10.28 ppm represents
the Npy - ZnPor complexed site and the one at 10.22 ppm the
pyridine-free ZnPor site. The software WinD-NMR15 was used to
1
simulate the VT H NMR for the determination of the motion.
The rate of exchange at room temperature was determined
as k25 = 65.0 kHz and the corresponding activation para-
meters were calculated as DH‡ = 49.4 ꢀ 0.2 kJ molꢁ1 and
DS‡ = 13.1 ꢀ 0.8 J molꢁ1 Kꢁ1 (Table 1). The kinetic barrier for
exchange DG‡ = 45.5 kJ molꢁ1 in [Cu2(S)(R)(P)2]2+ is almost
identical to that of a nanoslider that undoubtedly operates via a
single Npy - ZnPor dissociation (DG‡ = 47.3 kJ molꢁ1).14
Finally, we coupled the slider-on-deck system with a base-
catalyzed reaction (Scheme 3). From former work it had been
established that the N-methylpyrrolidine (5) - ZnPor binding
Table 1 Experimental activation parameters of nanorotors and rotational
frequency at 25 1C in CD2Cl2
To the same mixture, we added 2.0 equiv of azide 2 (with
respect to the nanorotor) and heated at 50 1C. Now, 25% of the
Michael addition product 6 formed after 4 h (ESI,† Fig. S24).
The reduced yield of 6 may readily be rationalized by the fact
that only 47% of the slider-on-deck was furnished after 4 h of
heating. This yield agrees well with that of a control experiment
Machines
DH‡/kJ molꢁ1 DS‡/J molꢁ1 Kꢁ1 DG‡/kJ molꢁ1 k298/kHz
[Cu2(S)(R)]2+
49.1 ꢀ 0.4a 9.5 ꢀ 1.7a
46.6a
45.5
46.0a
65.0
[Cu2(S)(R)(P)2]2+ 49.4 ꢀ 0.2
13.1 ꢀ 0.8
a
Ref. 10a
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In detail, the protocol involves the transformation of a
nanorotor into a slider-on-deck system via copper(I)-catalyzed
azide–alkyne cycloaddition (CuAAC).13 While the motion of the
nanorotor was dictated by the cleavage the coordinative Npy-
[Cu(phenAr2)]+ bond, after click reaction that of the slider-on-
deck was guided by the Npy - ZnPor interaction. Consequently,
the exchange speed changed, i.e. from 46.0 kHz (nanorotor) to
65.0 kHz (slider-on-deck). Moreover, the sliding motion was
utilized to liberate a catalyst into the solution to turn ON a
Michael addition. The formation of new catalytic machinery
from a catalytically active nanorotor is a lucid example of an
adaptive evolutionary process leading to new properties.
We are indebted to the Deutsche Forschungsgemeinschaft
(Schm 647/20-2) for financial support and Dr. T. Paululat for VT
NMR measurements.
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Conflicts of interest
There are no conflicts to declare.
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