Multistate Photoswitches: Macrocyclic Dihydroazulene/Azobenzene Conjugates

Article abstract of DOI:10.1002/anie.201712942

Molecules comprised of three covalently linked bi-stable switches can exist in states described by a combination of binary numbers, one for each individual switch: ?000?, ?001?, etc. Here we have linked three photo-/thermoswitches together in a rigid macrocyclic structure, one azobenzene (bit no 1) and two dihydroazulenes (DHAs; bits no 2 and 3) and demonstrate how electronic interactions and unfavorable strain in some states can be used to control the speed by which a certain state is reached. More specifically, upon irradiation of state ?000?, the AZB isomerizes from trans to cis and the two DHAs to vinylheptafulvenes (VHFs), generating ?111?. The thermal VHF-to-DHA back-reactions from this state also occur stepwise and can be accelerated by photo-induced AZB cis-to-trans conversion, proceeding via ?011? to ultimately furnish ?000?. Overall, the accessibility to a specific state of one bit was found to depend on the states of its neighboring bits.

Full text of DOI:10.1002/anie.201712942

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Multistate Photoswitches: Macrocyclic Dihydroazulene/
Azobenzene Conjugates
Authors: Alexandru Vlasceanu, Mads Koerstz, Anders B. Skov, Kurt V.
Mikkelsen, and Mogens Broendsted Nielsen
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201712942
Angew. Chem. 10.1002/ange.201712942
Link to VoR: http://dx.doi.org/10.1002/anie.201712942
http://dx.doi.org/10.1002/ange.201712942

10.1002/anie.201712942
Angewandte Chemie International Edition
COMMUNICATION
Multistate Photoswitches: Macrocyclic
Dihydroazulene/Azobenzene Conjugates
Alexandru Vlasceanu,[a] Mads Koerstz,[a] Anders B. Skov,[a] Kurt V. Mikkelsen,[a] and Mogens
Brøndsted Nielsen*[a]
Abstract: Molecules comprised of three covalently linked bi-stable
switches can exist in states described by a combination of binary
numbers, one for each individual switch: <000>, <001>, etc. Here we
enantiomers. Figure 1 lists the Gibbs free energies of the lowest-
energy conformers, calculated using the CAM-B3LYP/6-
311G(d,p) method in Gaussian09.[5] trans-AZB-DHA-DHA
(RR/SS) is most stable, while cis-AZB-VHF-VHF is least.
have linked three photo-/thermoswitches together in
a rigid
macrocyclic structure, one azobenzene (bit no 1) and two
dihydroazulenes (DHAs; bits no 2 and 3) and demonstrate how
electronic interactions and unfavorable strain in some states can be
used to control the speed by which a certain state is reached. More
specifically, upon irradiation of state <000>, the AZB isomerizes
from trans to cis and the two DHAs to vinylheptafulvenes (VHFs),
generating <111>. The thermal VHF-to-DHA back-reactions from
this state also occur stepwise and can be accelerated by photo-
induced AZB cis-to-trans conversion, proceeding via <011> to
ultimately furnish <000>. Overall, the accessibility to a specific state
of one bit was found to depend on the states of its neighboring bits.
N
N
cis-AZB-VHF-VHF
73.6 kJ mol-1
O
O
O
O
trans-AZB-VHF-VHF
32.9 kJ mol-1
cis-AZB-VHF-VHF
NC
CN
CNNC
cis-AZB-DHA-VHF
60.1 kJ mol-1
trans-AZB-DHA-VHF
O
O
O
18.9 kJ mol-1
N
N
Multimode photoswitches that can exist in several states have
found interest in areas ranging from molecular electronics,
optical data storage, and fluorescence emission modulation to
molecular machines, sensors, and storage of solar
energy.[1] When individual units are combined into a single
molecular system, the state of one unit (bit) may be used to
control the state of a neighboring one. The accessibility to a
specific state of one bistable molecular bit can thereby depend
on the state of its neighbors. Access to <111> might be allowed
from <110> but not from <011>, or allowed at different rates.
The dihydroazulene/vinylheptafulvene (DHA/VHF) system
is a photo-/thermoswitch as first reported by Daub and co-
workers,[2] and we have found that macrocyclic dimers can exist
in three states (DHA-DHA, DHA-VHF, VHF-VHF).[3] Conversion
from DHA-DHA to VHF-VHF via DHA-VHF is stimulated by light,
while return of the VHF-VHF to DHA-DHA is thermally stimulated.
O
trans-AZB-DHA-DHA
a (RR / SS)
cis-AZB-DHA-DHA
a (RR / SS): 47.8 kJ mol-1
b (RS; meso): 54.5 kJ mol-1
H
H
CN
CN
NC
NC
trans-AZB-DHA-DHA
a (RR / SS): 0 kJ mol-1
b (RS; meso): 0.4 kJ mol-1
Figure 1. Relative Gibbs free energies of formation (CAM-B3LYP/6-
311G(d,p)) of isomeric macrocycles.
Herein we show that three out of six states can be reached
by appropriate application of light and heat stimuli. We shall
label the lowest- and highest-energy states by <000> and <111>,
respectively, where the first number refers to AZB (trans/cis) and
the second and third to DHA/VHF. The <001> and <010> states
are degenerate (as stereoisomers are ignored) as are <101>
and <110>.
Alternatively,
azobenzene
(AZB)
undergoes
cis/trans
photoisomerization and has been integrated in various
macrocyclic structures.[4] By cyclizing two DHA units and one
AZB unit at least six distinct isomers may result (Figure 1). The
trans/cis-AZB-DHA-DHA states can each exist as pairs of
diastereoisomers (one meso and a pair of enantiomers), and the
trans/cis-AZB-DHA-VHF states can exist as pairs of
Synthesis of trans-AZB-DHA-DHA
(<000>) was
accomplished in a cyclization between acid chloride 1[6] and diol
2[3a] in the presence of N,N-dimethylaminopyridine (DMAP)
(Scheme 1). The reaction provides
a
mixture of
[a]
Dr. A. Vlasceanu, M. Koerstz, A. B. Skov, Prof. Dr. K. V. Mikkelsen,
Prof. Dr. M. B. Nielsen
Department of Chemistry and Center for Exploitation of Solar
Energy
University of Copenhagen
Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark
E-mail: mbn@chem.ku.dk
diastereoisomers a and b in yields of 11 and 9%, which exhibit
similar UV-Vis absorption spectra. The structure of the meso
form (b) was confirmed by X-ray crystallography (Figure 2),
revealing a dimeric packing arrangement in which the DHA-DHA
moieties of two cycles occupy each other’s cavities.
http://chem.ku.dk/research_sections/solarenergy/
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201712942
Angewandte Chemie International Edition
COMMUNICATION
O
Cl
trans-AZB
OH
HO
50000
45000
40000
35000
30000
25000
20000
15000
10000
5000
DHA-DHA a
cis-AZB
VHF-VHF
DMAP
N
+
N
CH2Cl2 20%
4 h, rt
CN
CN
CN NC
1
2
trans-AZB-DHA-DHA
(a+b)
O
Cl
0
Scheme 1. Synthesis of trans-AZB-DHA-DHA (a/b diastereoisomers).
300
400
500
600
700
800
Wavelength " (nm)
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
cis-AZB
VHF-VHF
DHA-VHF
Figure 2. Left: Molecular structure of trans-AZB-DHA-DHA (b isomer) with
thermal ellipsoids shown at 50% probability level; H atoms were omitted for
clarity. Right: Crystal packing of two macrocycles. CCDC 1588810.
trans-AZB
DHA-DHA a
0
1000
2000
3000
4000
Irradiation time (s)
Photoisomerization of trans-AZB-DHA-DHA
a
was
50000
45000
40000
35000
30000
25000
20000
15000
10000
5000
conducted by irradiation with 365 nm light until a photostationary
state was reached. A large absorption decrease was observed
in the range of 300-400 nm (trans-AZB and DHA), and a
simultaneous increase in the range of 420-620 nm (VHF) (Figure
3, top). By considering the characteristic absorptions of the
trans-AZB
VHF-VHF
monomeric parent trans-AZB (λmax = 317 nm) and DHA (λmax
=
354 nm) (Figures S1 and S2), the changes above are accounted
for by a simultaneous isomerization of trans- to cis-AZB as well
as both DHAs to VHFs, leading to a state predominated by cis-
AZB-VHF-VHF (<111>) (possibly also some trans-AZB-VHF-
VHF is present). The spectrum of the resulting cis-AZB-VHF-
VHF presents a lower than expected molar absorptivity in the
region of λmax = 492 nm. Previous studies suggest that this can
be the result of structural (out-of-plane) distortion of VHF.[3b],[7]
This is supported by computational geometry optimizations
conducted for cis-AZB-VHF-VHF (Figures S21-S22), showing a
symmetrical distortion in both VHFs and hence an equal
absorbance contribution from both, yet with individually lower
molar absorptivities than expected for two structurally
undistorted VHFs. Although we cannot exclude the presence of
residual DHA-VHF, 1H-NMR studies do reveal isomerization of
the second DHA. Based on rate constants from UV-Vis studies
we estimate a photostationary state with ca. 86% VHF-VHF
under our experimental conditions. Photoisomerization of trans-
AZB-DHA-DHA was monitored by following formation of VHF at
494 nm over time (Figure 3, middle). Similar to previously
studied macrocycles,[2] the increase in absorbance as a function
of irradiation time could be modeled by a sum of two exponential
functions, A(t) = c1 exp(-t/τ1) + c2 exp(-t/τ2) + A∞ (with τ2/τ1 = 11);
the DHA-to-VHF conversions hence seem approximately
independent of the AZB state.
cis-AZB
VHF-VHF
0
300
400
500
600
700
800
Wavelength " (nm)
Figure 3. Top: UV-Vis absorption spectra showing conversion of trans-AZB-
DHA-DHA a (<000>) to cis-AZB-VHF-VHF (<111>) in MeCN by irradiation at
365 nm. Middle: Absorbance at 494 nm plotted as a function of irradiation time
and fitted by: A(t) = c1 exp(-t/τ1) + c2 exp(-t/τ2) + A∞. Bottom: Spectra showing
conversion of cis-AZB-VHF-VHF (<111>) to trans-AZB-VHF-VHF (<011>) in
MeCN by irradiation at 410 nm.
cis-AZB-VHF-VHF only has one photochromic subunit,
namely cis-AZB, and two solely thermochromic VHFs. By
irradiation at 410 nm and stimulation of the cis-AZB n à π*
transition, a photostationary state consisting of trans-AZB-VHF-
VHF (<011>) (and possibly also some cis-AZB isomer) was
observed (Figure 3, bottom). Not only are we stimulating the cis-
AZB to trans-AZB conversion by choosing a wavelength where
cis-AZB has a stronger absorption, but trans-AZB-VHF-VHF is
also calculated to be more stable than cis-AZB-VHF-VHF (by
40.7 kJ mol-1). The conversion of cis- to trans-AZB-VHF-VHF
was accompanied by the emergence of the trans-AZB π à π*
This article is protected by copyright. All rights reserved.

10.1002/anie.201712942
Angewandte Chemie International Edition
COMMUNICATION
absorption (318 nm) along with no significant decrease observed
for the VHF absorption (492 nm). Minor changes in the area
around 462 nm can be assigned to changes in VHF absorption
pathways from cis-AZB-VHF-VHF to trans-AZB-DHA-DHA, one
fully thermally activated and the other first light-activated and
then thermally (Scheme 2), it is notable that the first VHF à
DHA, <x11> à <x01>, is unaffected by the state of AZB; x = 1
(cis) or 0 (trans). The major effect of cis-/trans-AZB is on the
second VHF ring closure, <x01> à <x00>, lowering ΔGslow‡ from
as
calculations
311G(d,p)) also show only
a
result of cis/trans-AZB isomerization. Excited state
(CAM-B3LYP/6-311+G(d,p)//CAM-B3LYP/6-
minor difference in optical
a
o
properties of the VHF-VHF in the two macrocycles (SI, Table
S1).
105 to 101 kJ mol-1 (30 C) when changing x from 1 to 0 (3-fold
faster reaction) (Figure 5). Based on studies in solvents of
different polarity, we hypothesize that DHA-VHF to DHA-DHA
proceeds as <101> à <001> à <000> with the former being the
rate-determining step (cis-AZB to trans-AZB). The rate of VHF
ring closure is usually slower in an apolar solvent.[1f] This, was
indeed observed for conversion of VHF-VHF to DHA-VHF in
cyclohexane/CHCl3 1:1, while the subsequent conversion into
DHA-DHA was not significantly influenced.
Thermal isomerization of VHF-VHF to DHA-DHA can be
initiated from two starting points, either trans-AZB-VHF-VHF or
cis-AZB-VHF-VHF. These two processes were monitored at 30,
40, 50, 60, and 70 °C in MeCN and in each case observed to
occur stepwise via an intermediate DHA-VHF. The decay in VHF
absorbance was modelled by the sum of two exponential decay
functions. Neither cis- nor trans-AZB exhibits a significant
absorbance in the 494-nm region nor does their isomerization
significantly effect the absorbance of the VHFs. The effect of
AZB isomerization is thus only reflected in the rate of the VHF-
to-DHA reactions.
<111>
Relaxation of cis-AZB-VHF-VHF to trans-AZB-DHA-DHA
was observed to initially proceed via a fast decay (t = 36 min at
½
o
30 C) followed by a much slower process (t = 1900 min at 30
½
cis-AZB-VHF-VHF
oC). The isomerizations were monitored at the VHF λmax of 494
nm as well at the combined AZB and DHA λmax of 332 nm. By
comparing the changes at these two wavelengths, it is
observable that the first event exhibits a decrease in the VHF
absorption but no significant increase in the trans-AZB
absorption at 318 nm. In fact, conversion of half of the VHF
species to DHA (one moiety per macrocycle) is observed before
any significant switching of cis- to trans-AZB (Figure 4). This first
event can thus be assigned to relaxation of cis-AZB-VHF-VHF
(<111>) to cis-AZB-DHA-VHF (<101>) (Scheme 2). The cis-
AZB-VHF-VHF absorption at 492 nm is assigned to two
individual but structurally similar VHFs, which sequentially switch
to DHA.
<011>
<101>
hv
!
hv
hv
trans-AZB-VHF-VHF
cis-AZB-DHA-VHF
hv
!
hv
!
hv
!
trans-AZB-DHA-VHF
cis-AZB-DHA-DHA
!
!
!
hv
<001>
<100>
trans-AZB-DHA-DHA
2.4
2.2
2.0
1.8
1.6
<000>
cis-AZB-VHF-VHF
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
cis-AZB-DHA-VHF
Scheme 2. Two pathways of isomerization from cis-AZB-VHF-VHF to trans-
AZB-DHA-DHA: thermally via cis-AZB-DHA-VHF (dark green arrows) and
photo/thermally via trans-AZB-VHF-VHF (maroon arrows).
trans-AZB-DHA-DHA
300
400
500
600
700
800
Wavelength λ (nm)
Figure 4. UV-Vis absorption spectra showing the thermal isomerization of cis-
AZB-VHF-VHF (<111>) to cis-AZB-DHA-VHF (<101>) and then to trans-
AZB-DHA-DHA (<000>).
The relaxation of trans-AZB-VHF-VHF (<011>) to trans-
AZB-DHA-DHA (<000>) also proceeded via a fast and a slow
thermal decay, accounting for two VHF à DHA isomerizations
with half-lives of 31 and 620 min at 30 oC. By comparing the two
This article is protected by copyright. All rights reserved.

10.1002/anie.201712942
Angewandte Chemie International Edition
COMMUNICATION
6168; c) J. Zhang, Q. Zhou, H. Tian, Adv. Mater. 2013, 25, 378-399; d)
W. Szymánski, J. M. Beierle, H. A. Kistemaker, W. A. Velema, B. L.
Feringa, Chem. Rev. 2013 113, 6114-6178; e) M. Irie, T. Fukaminato, K.
Matsuda, S. Kobatake, Chem. Rev. 2014, 114, 12174-12277; f) S. L.
Broman, M. B. Nielsen, Phys. Chem. Chem. Phys. 2014 16, 21172-
21182; g) A. Lennartson, A. Roffey, K. Moth-Poulsen, Tetrahedron Lett.
2015, 56, 1457-1465; h) B. L. Feringa, Angew. Chem. Int. Ed. 2017, 56,
11060-11078; i) J.-P. Sauvage, Angew. Chem. Int. Ed. 2017, 56,
11080-11093; j) J. F. Stoddart, Angew. Chem. Int. Ed. 2017, 56, 11094-
11125.
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
trans-AZB-VHF-VHF
cis-AZB-VHF-VHF
[2]
[3]
J. Daub, T. Knöchel, A. Mannschreck, Ang. Chem. Int. Ed. Engl. 1984,
23, 960-961.
a) A. Vlasceanu, S. L. Broman, A. S. Hansen, A. B. Skov, M. Cacciarini,
A. Kadziola, H. G. Kjaergaard, K. V. Mikkelsen, M. B. Nielsen, Chem.
Eur. J. 2016, 22, 10796-10800; b) A. Vlasceanu, B. N. Frandsen, A. B.
Skov, A. S. Hansen, M. G. Rasmussen, H. G. Kjaergaard, K. V.
Mikkelsen, M. B. Nielsen, J. Org. Chem. 2017, 82, 10398-10407.
a) N. Tamaoki, K. Koseki, T. Yamaoka, Angew. Chem. Int. Ed. Engl.
1990, 29, 105-106; b) E. Tauer, R. Machinek, Liebigs Ann. 1996, 1213-
1216; c) M. Asakawa, P. R. Ashton, V. Balzani, C. L. Brown, A. Credi,
O. A. Matthews, S. P. Newton, F. M. Raymo, A. N. Shipway, N.
Spencer, A. Quick, J. F. Stoddart, A. J. P. White, D. J. Williams, Chem.
Eur. J. 1999, 5, 860-875; d) Y. Norikane, K. Kitamoto, N. Tamaoki, J.
Org. Chem. 2003, 68, 8291-8304; e) Y. Norikane, N. Tamaoki, Org. Lett.
2004, 6, 2595-2598; f) E. Bassotti, P. Carbone, A. Credi, M. Di Stefano,
S. Masiero, F. Negri, G. Orlandi, G. P. Spada, J. Phys. Chem. A 2006,
110, 12385-12394; g) Y. Norikane, N. Tamaoki, Eur. J. Org. Chem.
2006, 1296-1302; h) M. Liu, X. Yan, M. Hu, X. Chen, M. Zhang, B.
Zheng, X. Hu, S. Shao, F. Huang, Org. Lett. 2010, 12, 2558-2561; i) R.
Reuter, H. A. Wegner, Chem. Commun. 2011, 47, 12267-12276; j) E.
Uchida, K. Sakaki, Y. Nakamura, R. Azumi, Y. Hirai, H. Akiyama, M.
Yoshida, Y. Norikane, Chem. Eur. J. 2013, 19, 17391-17397; k) L.
Schweighauser, D. Häussinger, M. Neuburger, H. A. Wegner, Org.
Biomol. Chem. 2014, 12, 3371-3379.
0
50 100 150 200 250 300 350 400
Time (min)
Figure 5. Absorbance decay at 494 nm corresponding to the conversions of
trans-AZB-VHF-VHF (maroon; <011>) and cis-AZB-VHF-VHF (dark green;
<111>) to trans-AZB-DHA-DHA (<000>).
[4]
In conclusion, if we assign the trans-AZB-DHA-DHA state
as <000>, cis-AZB-VHF-VHF as <111> and trans-AZB-VHF-
VHF as <011>, photoisomerization of <000> leads to <111>.
Regeneration of <000> can be achieved thermally from <111> in
a slow process or in a fast by first photoisomerizing <111> to
<011>. The macrocyclic structure thus presents a convenient
way of controlling accessibility to specific states; however, a
data density of 3 bits per molecule is only hypothetical as data is
stored in an ensemble of molecules.
Acknowledgements
[5]
[6]
Gaussian09E01, M. J. Frisch et al. Gaussian 09, Revision C.01;
Gaussian, Inc.: Wallingford CT, 2009.
University of Copenhagen is acknowledged for financial support.
a) K. Faghihi, N. Fouroghifar, K. Zamani, M. Hajibeygi, S. Mallakpour,
Iranian Polymer Journal 2003, 12, 339-346; b) J. Yao, Y. You, H. Liu, L.
Dong, C. Xiong, J. Mater. Sci. 2011, 46, 3343-3348.
Keywords: Azo compounds • Electrocyclic reactions •
[7]
N. C. M. Lubrin, A. Vlasceanu, B. N. Frandsen, A. B. Skov, M. D. Kilde,
K. V. Mikkelsen, M. B. Nielsen, Eur. J. Org. Chem. 2017, 2932-2939.
Isomerization • Macrocycles • Photochromism
[1]
a) M.-M. Russew, S. Hecht, Adv. Mater. 2010, 22, 3348-3360; b) C.-J.
Carling, J.-C. Boyer, N. R. Branda, Org. Biomol. Chem. 2012, 10, 6159-
This article is protected by copyright. All rights reserved.

10.1002/anie.201712942
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Alexandru Vlasceanu,[a] Mads Koerstz,[a]
Anders B. Skov,[a] Kurt V. Mikkelsen,[a]
and Mogens Brøndsted Nielsen*[a]
fast
slow
<011>
<000>
<111>
Page No. – Page No.
Multistate Photoswitches:
Macrocyclic
Dihydroazulene/Azobenzene
Conjugates
Switching switching: Three photochromic units (two
dihydroazulenes/vinylheptafulvenes, blue/red, and one azobenzene, green/orange)
influence each other’s photo/thermal switching behavior when incorporated in a
macrocyclic structure, meaning that accessibility to one specific state described by
a combination of three binary numbers depends on the pathway to this state.
This article is protected by copyright. All rights reserved.