Remote photoregulated ring gliding in a [2]rotaxane via a molecular effector

Article abstract of DOI:10.1021/acs.orglett.6b03457

A molecular barbiturate messenger, which is reversibly released/captured by a photoswitchable artificial molecular receptor, is shown to act as an effector to control ring gliding on a distant hydrogen-bonding [2]rotaxane. Thus, light-driven chemical communication governing the operation of a remote molecular machine is demonstrated using an information-rich neutral molecule.

Full text of DOI:10.1021/acs.orglett.6b03457

Letter
pubs.acs.org/OrgLett
Remote Photoregulated Ring Gliding in a [2]Rotaxane via a
Molecular Effector
Arnaud Tron,† Isabelle Pianet,† Alberto Martinez-Cuezva,‡ James H. R. Tucker,§ Luca Pisciottani,†
Mateo Alajarin,‡ Jose Berna,*,‡ and Nathan D. McClenaghan*,†
†Institut des Sciences Molec
́ ́
ulaires, CNRS UMR 5255, Universite de Bordeaux, 33405 Talence, France
‡Departamento de Química Organ
́
ica, Facultad de Química, Universidad de Murcia, E-30100 Murcia, Spain
§School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom
S
* Supporting Information
ABSTRACT: A molecular barbiturate messenger, which is reversibly released/
captured by a photoswitchable artificial molecular receptor, is shown to act as an
effector to control ring gliding on a distant hydrogen-bonding [2]rotaxane. Thus,
light-driven chemical communication governing the operation of a remote molecular
machine is demonstrated using an information-rich neutral molecule.
Scheme 1. Supramolecular System Where Photoregulated
hemical communication is ubiquitous in nature and is
Cnotably moderated by ion transfer in neurons, muscle
contraction, and mammalian vision.1 Equally, molecules such as
hormones constitute a major signaling pathway in the
endocrine system.2 On the other hand, while a wealth of
photoionic systems is known,3 artificial molecular systems4
utilizing chemical transfer between functional molecules are
scarce and typically rely on transfer of metal ions or protons.5
Concerning the latter, photoactive variants have been reported
using spiropyran chromophores for reversible ion binding.6
Utilization of molecules, rather than ions, as messengers in such
a scheme has not been duly considered. Molecules offer the
advantage of greater structural diversity and are inherently
information-rich. Here, we report a unique supramolecular
system where photomodulation of the amplitude of the
translational motion of a macrocycle along the thread of a
two-station [2]rotaxane is achieved by the intermediacy of a
molecular effector, which is reversibly taken up/released by a
distinct switchable receptor.
Binding of a Barbiturate Messenger Modulates the
Amplitude of the Translational Motion of a Ring in an
Interlocked Architecture
In order to design such a system, a judicious combination of
functional molecules is required. The receptor should be a
bistable species where one form binds the molecular effector
strongly (Kassoc1), while conversely in the second state, binding
is much weaker (Kassoc1′), such that Kassoc1 ≫ Kassoc 1′. Ideally,
interconversion should be triggered by an external stimulus
without chemical build up. Molecule 1 (Scheme 1) strongly
binds barbital (B) in its open form (Kassoc1 = 38000 M−1) using
six hydrogen bonds (with H-bonding pattern DADDAD:A-
DAADA).7 Photoirradiation of 1 effects a [4π + 4π] anthracene
cyclomerization reaction giving 1C, rendering the receptor site
ill-adapted to accommodate B (Kassoc1′ ≤ 10 M−1), thereby
promoting photorelease and transfer of autonomous effector B.
In order to demonstrate photopromoted transfer of B, a
second hydrogen-bonding molecule is required with an affinity
for B (Kassoc2) that is intermediate between 1 and 1c, i.e., Kassoc
1
> Kassoc2 > Kassoc1′. Benzylic amide rotaxane 2 having two
diamidopyridine units can bind B to form 1:1 and 1:2
complexes with stability constants Kassoc2(1:1) = 787 M−1
and Kassoc2(1:2) 108 M−1, respectively.8a Indeed, this ordering
may be anticipated on the basis of the number of available
hydrogen bonds formed between a barbital guest and 1, 2, and
Received: November 19, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b03457
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Organic Letters
Letter
1c, namely 6 (with H-bonding pattern DADDAD:ADAADA) vs
3 (DAD:ADA) vs <3, respectively. Additionally, considering
translational motion of the ring in 2, some of us reported that
guest binding at both rotaxane diamidopyridine sites had a
direct influence on the amplitude of the ring shuttling.8,9
Therefore, as represented in Scheme 1, in the initial state B
would be anticipated to reside quasi-exclusively at receptor 1,
and an unimpeded, large amplitude translational motion of the
macrocycle would occur in rotaxane 2. Photoirradiation would
provoke release of B, chemical transfer, and effective chemical
communication with the rotaxane, thereby restricting the
forward and backward ring motion through the formation of
a ternary aggregate (2B·2).
Hydrogen bonding between amide functions of 1/2 and
imide functions of messenger barbiturate B was followed by 1H
NMR and UV−vis spectroscopies. Thus, the state of the system
and average instantaneous position of effector and ring
components could be read out. Based on relative and absolute
association constants for B with receptor 1 and rotaxane 2, a
mixture of 1, B, and 2 ensuring preponderant complexation at 1
(89% B⊂1; ≈ 2% 2B·2) was determined to be a molar ratio of
1:1:0.5, respectively, at 2 mM concentration of 1.7,8 Following
irradiation, a dramatic population inversion was anticipated
(B⊂1C ≈ 2%; 2B·2 = 65%). Direct titration of barbiturate into
mixtures of 1 and 2 or 1C and 2 gave similar values, showing the
rapid redistribution of B (Figures S1 and S2) compatible with
reversible binding. Furthermore, moderate barbiturate binding-
induced fluorescence quenching of 1 was observed (from Φf =
0.32 to Φf = 0.27 for B⊂1 (20:1, [1] = 5 μM), Figure S6).7,10
Meanwhile, addition of [2]rotaxane 2 to 1 did not perturb the
emission (Φf = 0.31; 1:0.5, [1] = 5 μM).7
Figure 1. Partial 1H NMR spectra (600 MHz, CD2Cl2, 298 K) of (a) a
mixture of 1 and B (1:1, [B] = 2 mM); (b) a mixture of 1, B and 2
(1:1:0.5, [B] = 2 mM); (c) 2 (1 mM), (d) complex 2B·2 (1:0.5, 2
mM); (e) mixture ofs 1C, B, and 2 (1:1:0.5, 2 mM); (f) mixture of 1C
and B (1:1, [B] = 2 mM). Assigned resonances correspond to labeled
protons in Scheme 1 (see the Supporting Information for full
attribution). Space-filling structures generated by PM6 modeling.
1H NMR spectra in Figure 1 show the various states of the
system,11 denoted by the chemical shifts of H-bonding N−H
resonances of 1 and B. The spectrum of the B⊂1+2 mixture
(1:1:0.5; [B] = 2 mM, Figure 1b) shows a marked difference
between the amide protons Hc and Hg of 2, imide protons HI
and HJ of B compared to the mixture in the presence of
cyclized 1C (2B·2+1C; 1:1:0.5, [B] = 2 mM, Figure 1e).
Addition of B (1 equiv) to the acyclic receptor 1 (2 mM,
CD2Cl2, Figure 1a and Figure S3b) resulted in strong downfield
shifts of the N−H resonances of B (Δδ = 3.70 ppm) and those
of the amide protons of the receptor (Δδ = 1.25 and 1.30
ppm), cf. Figures S3a and S3c. Meanwhile, in the case of poorly
binding 1C (2 mM, CD2Cl2, Figure 1f and Figure S3d), addition
of B resulted in small downfield shifts of the corresponding
barbiturate (Δδ = 0.50 ppm) and receptor (Δδ = 0.15 and 0.05
ppm) resonances. Addition of B (2 equiv) to the homoditopic
[2]rotaxane 2 (1 mM, CD2Cl2, Figure 1d and Figure S4) results
in formation of 2B·2 as indicated by downfield shifts of imide
NH protons of barbiturate messenger (Δδ = 0.50 ppm) as well
as NH amide protons (Hc and Hg) of [2]rotaxane (Δδ = 0.30
and 0.29 ppm) compared to uncomplexed B (Figure S4c) and
2 (Figure 1c and Figure S4a). This complexation with 2
induces a restriction of the translational motion amplitude of
the macrocycle of the interlocked architecture shown by small
downfield proton resonance shifts compared to the free
[2]rotaxane (Figure S4).8a Further evidence for the feasibility
of the transfer system came from the non-interaction between
receptor 1 and [2]rotaxane 2 (Figure S5). The ensemble of
these observations is consistent with an effective transfer of
guest B between acyclic receptor 1 and the target rotaxane 2.
Photoinduced evolution of B⊂1+2 (1:1:0.5, CD2Cl2, [B] = 2
Figure 2. 1H NMR spectra (300 MHz, CD2Cl2, 298 K) of a mixture of
1, B, and 2 (1:1:0.5, [B] = 2 mM) after irradiation (λ = 350−400 nm)
for 0, 10, 15, 35, 80, and 150 min.
Figure S7) as a function of irradiation time (λ = 350−400 nm;
see the SI for irradiation conditions. Degassed solutions were
used throughout this study). A gradual upfield shift of the imide
NH protons of B (Δδ = 12.1 to 8.6 ppm) and disappearance of
1
mM) was followed by H NMR spectroscopy (Figure 2 and
B
DOI: 10.1021/acs.orglett.6b03457
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Letter
NH amide protons of receptor 1 were synchronous with the
appearance of 1C. Complete disappearance of anthracene
proton signals (δ = 7.90−7.95 and 7.48−7.42 ppm in CD2Cl2)
of the acyclic receptor 1 (Figure 2) was observed, and four
multiplet signals assigned to the aromatic protons of the
dimerized anthracene moiety in receptor 1C appeared at 6.65,
6.72, 6.85, and 7.09 ppm, after cyclization of receptor 1. A
downfield shift of the Hc and Hg NH proton signals was
observed relative to the mixture 2B·2 (Figure S4b), associated
with a restriction of ring shuttling amplitude induced by the
complexation of B on the ditopic [2]rotaxane 2. Thermal
reversibility was studied by heating to 110 °C, resulting in
retrocyclomerization of 1C, as judged by 1H NMR (Figure S8).
After 780 min, a quasi-complete return of the system to its
initial state was noted.
between identical stations in 2 could be estimated at 4900 s−1 at
223 K. Meanwhile, in the presence of B, under otherwise
analogous conditions, a higher exchange value (14000 s−1) was
measured. This infers that the photoregulated remote effector
can modulate not only the magnitude but also the net velocity
of the ring movement within the rotaxane.
Photomodulation of the mixture of receptor 1, [2]rotaxane 2,
and barbital (1:0.5:1, [B] = 2 mM) in dichloromethane was
further followed by UV−vis and fluorescence spectroscopy.
The structured absorption band (330−400 nm) of 1
disappeared upon photodimerization (λ = 365 nm in degassed
CH2Cl2), yielding nonbinding 1C (Figure 4). This allowed
Dynamic ordering spectroscopy (DOSY) NMR experiments
gave further information on the formation of supramolecular
aggregates of increased mass/hydrodynamic radius. This
translates into a lowered diffusion rate for both constituent
components, allowing instantaneous determination of the
messenger position.12 Free B, being a small, highly mobile
molecule (average diffusion coefficient (D) of 14.6 × 10−10 m2
s−1 in CD2Cl2, Figure S13) was used as a probe to follow its
complexation. In the presence of receptor 1, its diffusion rate
slows (13.0 × 10−10 m2 s−1, Figure S11a) showing association in
solution, while photoirradiation and subsequent molecule
release increase its diffusion rate value (14.4 × 10−10 m2 s−1,
Figure S11b), showing lower association with 1C. Upon
irradiation of the system B⊂1+2 (1:1:0.5, [B] = 2 mM) for 3
h, the measured weighted average diffusion coefficient of the
barbiturate messenger increased from 9.8 × 10−10 to 12.9 ×
10−10 m2 s−1 (Figure 3a,b). The lowering of the diffusion
Figure 4. (a) Electronic absorption spectra (1 mm path length) of a
mixture of 1, B, and 2 (1:1:0.5, [B] = 2 mM) in CH2Cl2. On
irradiation (λ = 350−400 nm), the disappearance of the anthracene
moieties (Abs370 nm, b) continued to 94% conversion. (c) Cycles of
photoirradiation and thermal reversion, corresponding to shuttling of
B between 1 and 2.
studies of the evolution of the release of barbital as a function of
the irradiation time. Quantum yield determination (Φr)13 of
the photodimerization reactions afforded a measure of the
efficiency of the photoprocesses for the system (receptor 1 in
presence and in absence of barbital and [2]rotaxane 2). These
yields were invariant at micro-to-millimolar concentrations,
consistent with an intramolecular reaction, while the presence
of rotaxane did not affect the determined value.7
Reversible disassembly of the photoadduct (Scheme 1)
allows system reset, and subsequent stimulus-triggered cycles.
Reversibility of the photocontrol process over multiple cycles
was studied using a mixture of 1, B, and 2 (Figure 4c) by
repeated cycles of irradiation at 365 nm for 3 h and thermal
retrodimerization at 110 °C over 14 h. The percentage of 1C
after each opening process was determined by absorption
changes at 370 nm. A fatigue study showed that >94% of the
anthracene chromophore was recovered after each cycle
(Figure 4c), with a total fatigue of 16% after four cycles.
Photochemical reversion on irradiating the (λ = 280 nm)
resulted in a higher degree of fatigue and buildup of irreversible
photoproducts.14
In conclusion, combination of a photoswitchable receptor for
a neutral multiple hydrogen-bonding molecular effector and a
two-station [2]rotaxane constitutes a system where modulation
of the ring shuttling is controlled remotely via the intermediacy
of a neutral molecule. This system was implemented based on
knowledge of binding constants and absorption profiles and
opens the way to future phototriggered supramolecular systems
involving chemical communication with a diversity of molecular
Figure 3. DOSY NMR spectra (600 MHz, CD2Cl2, 298 K) of a
mixture of 1, B, and 2 (1:1:0.5, [B] = 2 mM): (a) before irradiation;
(b) after irradiation (λ = 350−400 nm) for 150 min.
coefficient D of the rotaxane (from 5.6 × 10−10 to 5.3 × 10−10
m2 s−1) and the D increase of the barbiturate upon
photoirradiation of the three-component mixture is indicative
1
of the phototransfer process. Analysis of H spectra acquired
over a wide range of temperatures is commonly used to obtain
information on fast molecular dynamic processes, such as the
ring movement rate. Thus, by observing the coalescence of
resonances at low temperature (see the SI for a description and
Figures S14 and S15), the rate of exchange/ring shuttling
C
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80, 988. (b) Molard, Y.; Bassani, D. M.; Desvergne, J.-P.; Moran, N.;
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A.; Carro-Guillen, F.; Pastor, A.; Marin-Luna, M.; Orenes, R.-A.;
Alajarin, M.; Berna, J. ChemPhysChem 2016, 17, 1920.
(9) For studies on the ring shuttling in two-station [2]rotaxanes see:
́
(a) Bissell, R. A.; Cordova, E.; Kaifer, A. E.; Stoddart, J. F. Nature
1994, 369, 133. (b) Xue, M.; Yang, Y.; Chi, X.; Yan, X.; Huang, F.
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Ed.; CRC: Boca Raton, 1989; Vol. 1.
species. Ongoing work concerns development of biocompatible
systems to interface biomacromolecules.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b03457.
1
Experimental procedures, fluorescence spectra, H NMR
characterization data, and diffusion-ordered NMR of 1, 2,
1C, B, and mixtures B⊂1, B⊂1C, 2B·2, B⊂1+2, 2B·2+1C,
2+1, and 2+1C (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
(11) All species (Figures S16−S19) and mixtures (Figure S20−S31)
1
were fully characterized by H NMR spectroscopy.
*E-mail: ppberna@um.es.
*E-mail: nathan.mcclenaghan@u-bordeaux.fr.
ORCID
́
(12) (a) Toumi, I.; Torresani, B.; Caldarelli, S. Anal. Chem. 2013, 85,
11344. (b) Noor, A.; Moratti, C.; Crowley, J. D. Chem. Sci. 2014, 5,
4283. (c) Saha, S.; Santra, S.; Akhuli, B.; Ghosh, P. J. Org. Chem. 2014,
79, 11170. (d) Abet, V.; Evans, R.; Guibbal, F.; Caldarelli, S.;
Rodriguez, R. Angew. Chem., Int. Ed. 2014, 53, 4862.
Isabelle Pianet: 0000-0002-2694-3133
Nathan D. McClenaghan: 0000-0003-0285-1741
Notes
(13) Montalti, M.; Credi, A.; Prodi, L.; Gandolfi, M. T. In Handbook
of Photochemistry, 3rd ed.; CRC Press: New York, 2006; pp 601−604.
(14) (a) Bouas-Laurent, H.; Castellan, A.; Desvergne, J.-P.;
Lapouyade, R. Chem. Soc. Rev. 2000, 29, 43. (b) Bouas-Laurent, H.;
Castellan, A.; Desvergne, J.-P.; Lapouyade, R. Chem. Soc. Rev. 2001, 30,
248.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial support from the European Research Council (ERC,
■
FP7-2008-2013, grant no. 208702), Reg
́
ion Aquitaine; Uni-
e de la Recherche
ieur (A.T.) are gratefully acknowledged.
versity of Bordeaux; CNRS and Minister
l’Enseignement Super
̀
́
This work was also supported by the MINECO (CTQ2014-
56887-P and Contract No. FPDI-2013-16623, A.M.-C.),
FEDER, and the Fundacion
PI/14).
́
Seneca-CARM (Project 19240/
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