Taming the complexity of donor-acceptor stenhouse adducts: Infrared motion pictures of the complete switching pathway

Article abstract of DOI:10.1021/jacs.9b00341

Switches that can be actively steered by external stimuli along multiple pathways at the molecular level are the basis for next-generation responsive material systems. The operation of commonly employed molecular photoswitches revolves around one key structural coordinate. Photoswitches with functionalities that depend on and can be addressed along multiple coordinates would offer novel means to tailor and control their behavior and performance. The recently developed donor-acceptor Stenhouse adducts (DASAs) are versatile switches suitable for such applications. Their photochemistry is well understood, but is only responsible for part of their overall photoswitching mechanism. The remaining thermal switching pathways are to date unknown. Here, rapid-scan infrared absorption spectroscopy is used to obtain transient fingerprints of reactions occurring on the ground state potential energy surface after reaching structures generated through light absorption. The spectroscopic data are interpreted in terms of structural transformations using kinetic modeling and quantum chemical calculations. Through this combined experimental-theoretical approach, we are able to unravel the complexity of the multidimensional ground-state potential energy surface explored by the photoswitch and use this knowledge to predict, and subsequently confirm, how DASA switches can be guided along this potential energy surface. These results break new ground for developing user-geared DASA switches but also shed light on the development of novel photoswitches in general.

Full text of DOI:10.1021/jacs.9b00341

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Article
Taming the complexity of donor–acceptor Stenhouse adducts:
IR motion pictures of the complete switching pathway
Habiburrahman Zulfikri, Mark A.J. Koenis, Michael M. Lerch, Mariangela Di
Donato, Wiktor Szyma#ski, Claudia Filippi, Ben L. Feringa, and Wybren Jan Buma
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b00341 • Publication Date (Web): 10 Apr 2019
Downloaded from http://pubs.acs.org on April 10, 2019
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Taming the complexity of donor–acceptor Stenhouse adducts: IR
motion pictures of the complete switching pathway
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Habiburrahman Zulfikri , Mark A.J. Koenis , Michael M. Lerch , Mariangela Di Donato , Wiktor
3
,6
1
3,*
2,7,*
Szymański , Claudia Filippi , Ben L. Feringa , Wybren Jan Buma
1
MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
Van ’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The
Netherlands.
Centre for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG
Groningen, The Netherlands.
European Laboratory for Non Linear Spectroscopy (LENS), via N. Carrara 1, 50019 Sesto Fiorentino, Italy.
Istituto Nazionale di Ottica, Largo Fermi 6, 50125 Firenze, Italy.
Department of Radiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ
Groningen, The Netherlands
2
3
4
5
6
7
Radboud University, Institute for Molecules and Materials, FELIX Laboratory, Toernooiveld 7c, 6525 ED Nijmegen,
The Netherlands
5
in applications ranging from receptors and molecular
ABSTRACT: Switches that can be actively steered by
external stimuli along multiple pathways at the molecular
level are the basis for next-generation responsive material
systems. The operation of commonly employed molecular
photoswitches revolves around one key structural coordinate.
Photoswitches with functionalities that depend on and can be
addressed along multiple coordinates would offer novel
means to tailor and control their behaviour and performance.
The recently developed donor–acceptor Stenhouse adducts
6
7–9
10,11
muscles to machines
and ‘smart’ materials.
More
recently, they have been used for biological and medicinal
applications, with photopharmacology attracting tremendous
1
2–18
19
interest.
Switches such as azobenzenes, stilbenes,
2
0
21
hemithioindigos, and diarylethenes rely, for all practical
purposes, on a simple transformation, that is, the key step for
their functioning involves one reaction coordinate such as E–
Z isomerization or electrocyclization. Going beyond the
possibilities offered by these ‘simple’ systems requires
photoswitches that undergo addressable transformations
along multiple possible reaction pathways. Such switches
open novel avenues for tailor-made, user-oriented chemical
systems whose functionalities can be manipulated by
directing the mechanistic pathway.
(DASAs) are versatile switches suitable for such
applications. Their photochemistry is well understood, but is
only responsible for part of their overall photoswitching
mechanism. The remaining thermal switching pathways are
to date unknown. Here, rapid-scan infrared absorption
spectroscopy is used to obtain transient fingerprints of
reactions occurring on the ground state potential energy
surface after reaching structures generated through light
absorption. The spectroscopic data are interpreted in terms of
structural transformations using kinetic modelling and
quantum chemical calculations. Through this combined
experimental-theoretical approach, we are able to unravel the
complexity of the multi-dimensional ground-state potential
energy surface explored by the photoswitch, and use this
knowledge to predict – and subsequently confirm – how
DASA switches can be guided along this potential energy
surface. These results break new ground for developing user-
geared DASA switches, but also shed light on the
development of novel photoswitches in general.
The recently introduced donor–acceptor Stenhouse
2
2–27
adducts (DASA),
of applications,
which have already found a wide range
feature in this respect favourable
2
7
characteristics. The visible-light-triggered transformation
starts from a strongly coloured, linear triene (‘open’) that
28
cyclizes into a colourless cyclopentenone (‘closed’, Fig.
1
used
a) – whose structure depends on the generation of DASAs
24,25
(Fig. 1b) – and then thermally reverts to the original
form. It has become clear (vide infra) that the functional use
of DASAs along a productive photoswitching pathway
depends on at least two key steps (see Fig. 1c for
2
3,29
mechanistic proposal):
a photoinduced Z–E isomerisation
within the triene and a thermal electrocyclization. Whereas
the actinic step of the reaction has been previously
2
9–32
investigated in detail,
insight into the thermal part of the
INTRODUCTION
pathway is as yet largely lacking. Here, using time-resolved
infrared absorption spectroscopy and quantum chemical
calculations, we show that competing photoswitching
pathways are indeed far more complicated than one would
have assumed a priori, and that a rational control over it
requires ‘turning knobs’ that one normally would not
consider.
Photochemical tools rely on light as external stimulus to
manipulate chemical, biological, and materials systems with
high spatiotemporal control and without contaminating the
1
,2
3
sample. Molecular photoswitches have been particularly
successful in this respect as they can be switched reversibly
4
between isomers whose distinct properties can be harnessed
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a) Donoracceptor Stenhouse adducts
b) Photoswitches studied herein:
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4
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O
O
O
OH
O
O
O
O
O
O
O
O
O
OH
OH
hv
O
O
OH
N
O
N
O
N
O
N
O
kBT
thermal
MeO
O
O
N
O
H
DASA 3
DASA 1
DASA 2
'
open'
'cyclized'
1st generation
2nd generation
colourless
strongly coloured
c) Mechanistic proposal
This work
O
O
O
0
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0
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0
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0
3
4
2
O
Previously observed
1
A
O
O
O
O
O
O
5
O
OH
OH
2
O
2
HO
N D
O
O
O
(E)
2
A
O
(E)
A
O
3
4
O
R
H
R'
OH
2
hv
3
3
1
R
A
4
(Z)
1
1
A
N
D
O
5
O
or:
R'
C2C3
isomerization
5
4
3 4
C C
isomerization
4
5
5
3
1
proton transfer
N D
R'
O
tautomerization
O
O
O
N
N
D
electrocyclization
R
R
D
R'
R
R'
3
4
2 H
O
O
1
A
A
A'
A''
5
N
D
ideal arrangement
for electrocyclization
R
R'
d) Overview of possible thermal interconversions
*
experimentally observed (previously)
* experimentally observed (this work)
O
O
O
HO
O
R
R
D N
OH
O
4
R'
N
5
O
O
O
O
O
O
(E)
(Z)
2
1
A
2
1
A
D
OH
2
5
(Z)
4
OH
2
3
(Z)
4
O
O
R'
(E)
3
A
A
R'
4
O
O
N
D
5
O
(
Z) (Z)
(Z) (Z)
R
3
1
3
1
N
D
R'
R
5
B
EZZ
*
ZZZ
ZZE
"syn"
O
O
O
O
HO
O
HO
O
O
O
1
O
O
O
OH
OH
O
4
O
2
O
4
O
O
O
(E)
2
A
(E)
2
A
A
2
1
A
2
A
A
2
O
O
1
O
R'
OH
3
O
3
O
1
O
4
3
3
3
N (
E)
2
A
O
1
(Z)
4
1
3
(E) (E)
(E)
5
5
5
5
O
HO
5
O
R
D
(Z)
5
4
O
O
O
R'
(
E)
5
3
1
4
4
ND
R
N
D
R
HN R'
N
D R
R'
R'
D
R
N
N
R
D
R'
R
D
R'
*
*
**
A
A'
EEE
A''
EZE
B
"anti"
*
**
B'
B''
"anti"
B'''
"anti"
EEZ
"anti"
O
O
O
O
O
O
O
O
O
O
OH
OH
2
2 H
A
4
A
1
O
(
Z)
2
A
(E)
O
5
O
3
3
R'
DN
(E) (Z)
1
5
3
1
(E)
4
N
4
R
D
R'
R
(Z)
D
N R'
5
R
ZEZ
ZEE
C
**
productive pathway
Figure 1. Donor–acceptor Stenhouse adducts: (a) overall photochemical transformation; (b) photoswitches studied in this work; (c)
current mechanistic proposal for the photoswitching mechanism; and (d) all possible thermal interconversions.
Previous mechanistic studies of DASAs in solution have
only focused on the initial photochemical step by means of
ultrafast pump-probe spectroscopy and density functional
theory (DFT) calculations, in combination with temperature-
dependent steady-state UV/Vis spectroscopy and
photoaccumulation experiments at low temperature.
These investigations suggested Z–E isomerization happening
on a picosecond timescale (from A to A’ in Fig. 1c).
The presence of a hydroxy group on the triene chain seems
to favour the productive photochemical isomerization
2 3
pathway around the C —C bond, but many different ‘non-
productive’ isomers can potentially be obtained by thermal
rotation or photochemical isomerization along the
conjugated bridge before and after photoactivation (Fig.
d). This increases the complexity of the switching process
continuous wave light sources are used as opposed to the
pulsed laser sources employed in high-end spectroscopic
studies.
34,35
In analogy to the Piancatelli rearrangement
and related
36
(
iso-)Nazarov-type chemistry, it has been postulated that a
productive mechanistic pathway involving a thermally
allowed 4π-electrocyclization starting from A’’ (Fig. 1c) is
followed by a proton transfer and tautomerization.
Although the primary photochemical step determines the
immediate photoresponse, the thermal steps that occur on
much longer timescales are far more important for
understanding and controlling DASA-photoswitching. To
characterize this thermal part of the switching mechanism we
2
9–31,33
30,31,33
23,29
3
1
3
2
employ
a combination of rapid-scan IR absorption
1
37
spectroscopy, quantum chemical computations, and kinetic
modelling. This approach offers the necessary time-
resolution (milliseconds to hours) and structural information
to come for the first time to a complete picture of the thermal
reaction pathways in DASAs in terms of calculated and
observed intermediates, as well as their IR absorption
tremendously. In addition, gas-phase studies have suggested
that the step following the initial photoisomerization could
also be photochemical in nature, with A’ absorbing a second
photon yielding A”. This finding can be relevant for ‘real-
life’ applications of DASA switches for which usually
32
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spectra, energies, and possible ground-state interconversions.
At the same time, it allows us to fill the gap between our
the visible spectral region, characteristic of the open form,
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and the increasing absorption in the UV region attributed to
the closed form. Time-resolved IR experiments provide
kinetic traces (Fig. 2b) that allow to distinguish three
different phases in the reaction. Immediately after irradiation
is started with broadband white light (see SI section 1.2), a
quick response of the system occurs, producing a new
equilibrium within the experimental time resolution of the
experiment (96 ms). Subsequently, an exponential behaviour
is observed both in the decay of the starting compound and
the concurrent formation of a product. Importantly, time
traces of bands in the carbonyl stretching region show
different kinetics that suggests the delayed formation of
another final product (see for instance the kinetic behaviour
of red trace in Fig. 2b as compared to the yellow trace).
2
9,30
ultrafast spectroscopy studies
and the photoswitching
outcomes. We then show that the complicated reaction
mechanisms are in fact governed by a few simple but
sometimes counterintuitive principles that provide detailed
design suggestions and guidelines for next-generation
DASAs, and that are applicable beyond the presently studied
class of photochromes.
RESULTS AND DISCUSSION
0
1
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0
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0
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0
Herein, we focused on three molecules (Fig. 1b)
2
2,23
representing both first- (1 and 2)
and second-generation
2
4–26
(3)
DASA photochromes (SI section 1.1, 2 and 7). To
elucidate the molecular basis of the thermal interconversions
and overall photoswitching mechanism, we identified the
structures of the various isomers formed upon continuous
wave illumination using rapid-scan FT-IR spectroscopy and
kinetic modelling. Interpretation and assignment of the time-
resolved spectra requires the comparison with computed
FTIR spectra of all possible intermediates. We therefore
optimized the structure of all ground-state minima and
computed the corresponding vibrational spectra using DFT at
To identify the minimum number of kinetic components
needed to describe the time-dependent behaviour of the
spectra, we analysed the rapid-scan FT-IR data using
4
4
singular-value decomposition (see SI section 1.7 for more
4
4
details). Subsequently, we used a global analysis procedure
that fits the kinetic traces recorded at all frequencies
simultaneously with a combination of exponential decay
functions. Global analysis requires the specification of a
kinetic scheme, allowing to write the differential equations
describing the change in the concentration of reactant and
products and determine the associated kinetic constants. In
view of the multitude of intermediate structures that may be
formed during the reaction, and the resulting complexity of
the kinetic scheme describing their interconversion, the
analysis was performed applying a simplified sequential
reaction scheme shown in Fig. 3a that nevertheless allows us
3
8,39
40
the B3LYP /maug-cc-pVDZ level and an implicit
4
1
SMD solvent model. For the evaluation of the energy
profile, we employed instead the M06-2X functional, since
B3LYP is known to describe incorrectly the ring-closure
step even though it produced better spectra for our systems
see SI Fig. S5.33).
4
2
4
3
(
4
4
Photoinduced thermal reaction pathways of DASA 1
to identify the timescale of formation of the main products.
The reaction scheme describes the time evolution of the
system in terms of compartments (boxes S1-S4 boxes in Fig.
Rapid-scan FT-IR spectra of DASA 1 in dichloromethane
(DCM) are shown in Fig. 2. Visual inspection of the time
3
a) representing the state of the system at a given time. The
evolution makes immediately clear that most of the intense
bands from the linear form A strongly decrease once light is
switched on. As illumination progresses, new low-intensity
bands appear as a result of cyclization, in particular in the
different compartments are connected by the kinetic
constants determined from the fit of the kinetic traces. Apart
from the kinetic constants, the analysis also determines the
spectral component associated with each compartment. We
loosely name these components “Species Associated
Differential Spectra” (SADS) even though they do not reflect
the
-1
carbonyl stretching region (1650-1750 cm ). Cyclization
under continuous illumination is also observed by steady-
state UV/Vis spectroscopy (see SI section 3), manifesting
itself in the disappearance of the intense absorption band in
a) 0.7
b)0.14
1151
-1 s
4 s
1151 cm x 0.2
1181 cm
70 s
1579 cm
0
.6
136
1765 cm x 10
0.12
2
3
5
8
38 s
38 s
38 s
38 s
0.5
0.4
0.3
0.2
0.1
0
0.1
1765
0.08
0.06
0.04
0.02
0
1720 1740 1760 1780
1
181
1579
1
200
1400
1600
1800
0
200
400
600
800
-1
Frequency (cm )
Time (s)
Figure 2. Rapid-scan FT-IR spectra of DASA 1. (a) Snapshots of spectra before and after switching on the light (broadband white light;
at t = 0) in the rapid-scan FT-IR experiment. (b) Time-dependent behaviour of key bands during the rapid-scan FT-IR experiment. For the
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765 cm-1 trace, absorption is taken relative to the absorption at 1779 cm-1 in order to eliminate the change in absorbance due to other
1
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1
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bands in the spectrum.
0
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9
0
1
2
3
4
5
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8
9
0
Figure 3. Kinetic scheme and modelling of the rapid-scan FT-IR measurement of DASA 1. (a) Schematic representation of the kinetic
model. (b) Resulting SADS (black) and their fits with computed spectra with SADS1 to SADS4 from top to bottom. The spectrum of the
elongated form A has been subtracted before fitting the data, producing the differential signals shown in panel b. The four SADS have
respectively been fitted as (see Figure 1d for isomer notation): SADS1 a 37:63 mixture of A’:EZZ, SADS2 a 14:18:34:34 mixture of
A’:EZZ:B’’:B’’’, SADS3 a 58:31:11 mixture of B’’:B’’’:C and SADS4 a 74:26 mixture of B’’:B’’’. (c) Concentration profile of the four
SADS
in
time.
differential spectra of pure intermediates (as in the case of a
complete reaction scheme) but rather of mixtures due to the
simplification here introduced. The four SADS resulting
from the kinetic analysis with estimated lifetimes of t
t =88 s, t =201 s, and t =14x10 s are shown in Fig. 3b.
2 3 4
Assigning the positive/negative vibrational bands of each
SADS to appearing/disappearing isomers during the course
of the reaction requires knowledge of the energy profile of
the productive lowest-energy pathway and the vibrational
spectra of all intermediates along this pathway, which for
clarity we split into three steps:
accompanied by
a
concomitant proton-transfer
reaction (Figs. 1c and 4) which breaks the extended
conjugation and results in the formation of the
colourless isomer B. An alternative electrocyclization
without such an associated proton transfer is only
possible in the absence of the intramolecular
hydrogen bond. This pathway would involve a
cyclized intermediate I7 also involved in the pathway
from B to C (see Fig. 4c) that is high in energy (see SI
Fig. S6.4) and is thus unlikely to occur. Another
1
=10 s,
3
possible,
electrocyclization pathway starting from the ZZE
isomer (Fig. 1d) would lead to sterically
encumbered syn-configuration in contrast to the
energetically favoured and experimentally
anti-configuration.
but
energetically
disfavoured
1
.
From A to A’’ (Fig. 4a): Our previous studies have
a
shown that the primary photochemical step consists
of photoisomerization around C
This isomer can then thermally isomerize around
—C to form A’’, so that the molecule is spatially
arranged for a thermally allowed, conrotatory 4π-
2 3
—C to form A’.
2
3,25,45
observed
C
3
4
3. From B onwards (Fig. 4c): To reach the lowest
energy products, tautomerization of B to B’’’ or C
needs to occur. While a solvent-assisted process was
3
0,33
electrocyclization step (Fig. 1b).
Importantly, our
calculations indicate that, beside the three open
isomers (A, A’ and A’’) put forward from the
mechanistic proposal, one has to consider at least the
isomer EZZ among the remaining five possible open
isomers of Fig. 1d (EZZ, ZZZ, ZZE, ZEZ and ZEE),
3
3
previously postulated,
it appears that a fast,
intramolecular proton-transfer pathway is possible
without direct involvement of solvent or another
DASA molecule. Our calculations find that the
system follows three consecutive steps to reach the
zwitterionic final product B’’’: a nitrogen inversion
1
EZZ being the second most stable structure. H-NMR
experiments confirm this finding as they show that
the elongated triene form A is in thermal equilibrium
with a minor amount of EZZ in solution at room
temperature in the dark (see SI section 8).
1 A 5 D
(B’), a rotation around C —C (B’’), and a C —N
bond rotation with a concomitant transfer of a proton
to the nitrogen atom. We note that this path is
energetically preferred among the many possible
routes resulting from the combination of the above
2. From A’’ to B (Fig. 4b): For a successful ring-closure
step, the electrocyclization of A” should be
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5
four processes, also when the possible ring-flip of the
Meldrum’s acid moiety is considered (see SI Figs.
S6.5-S6.7). The enol-keto tautomerization pathway
from either B or B’ to C (which is the primary
in CD
structures
3
CN and DMSO-d
6
and in crystal
2
4,25
1
2
3
4
5
6
7
8
9
) proceeds with a proton transfer
mediated by the oxygen of the cyclopentenone
1
cyclized product of DASA 3 as observed by H-NMR
1
1
1
1
1
1
1
1
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0
1
2
3
4
5
6
7
8
9
0
Figure 4. Possible isomers and calculated low-energy productive pathway: Energy profiles of DASA 1 in DCM for (a) backward
(
(
gray) and forward (black) isomerizations of the initial photoproduct A’, (b) triene isomerization (gray) and ring closure (black) of A”, and
c) the competing tautomerization pathways of to B’’’ (black) and (blue) and of B” to (red).
B
C
C
ring, without any need for a catalyst, external acid, or
base. Alternatively, the amine group on the
cyclopentenone ring can facilitate the tautomerization
from B” to C without any intermediates.
adequate fit. Notably, we observed bands at 1582 and
-1
1723 cm that are distinctive signatures of B’’’, while the
-1
band at 1679 cm can only be explained by B’’ (see SI Fig.
S5.17). The presence of the latter isomer is further supported
by the observation of bands associated with its N-H bending
After identifying the lowest-energy pathway connecting
-1
-1
and stretching modes at 1579 cm and 2200 cm (see SI
Figs. S5.7 and S5.17), which are significantly broadened and
shifted as a result of the internal hydrogen bond in B’’. We
therefore conclude that after the ‘instantaneous’
photoinduced transformation of A into other open isomers,
ring closure can occur on a timescale of 10 s. In terms of
Eyring’s equation, this implies a Gibbs activation energy of
18.5 kcal/mol, which is in excellent agreement with the
calculated Gibbs energy difference between A’ and the
transition state connecting A’’ to B (18.2 kcal/mol). Once the
molecule has overcome this barrier, there is a downward
energy path from B via B’ that populates B’’ and B’’’. The
fact that S2 shows contributions of A’ and EZZ is due to the
continuous generation of these isomers.
the open and closed forms, the SADS obtained from the
kinetic analysis of the experimental time-resolved IR spectra
have been interpreted using the calculated IR spectra of the
species reported in Fig. 4. To this end, we fitted the SADS
with combinations of the calculated spectra (reported in SI
section S5.1.4) using an in-house developed genetic
algorithm (see SI section S1.8).
Surprisingly, the first SADS S1 (Fig. 3b), which describes
the species formed within the time resolution of the rapid-
scan measurement (96 ms), shows a large contribution of
EZZ which was not observed in our previous femtosecond
time-resolved infrared (fs-TRIR) experiments that explored
4
6
time delays up till the nanosecond timescale. In particular,
-1
the two positive bands at 1224 and 1254 cm observed in S1
are missing in the fs-TRIR spectrum, which was previously
assigned exclusively in terms of the formation of A’ (SI Fig.
S5.20). Although the presence of a large amount of EZZ fits
well with the energy of this isomer in comparison with A’
and A’’, the mechanism by which it is generated is not
immediately clear, as the aforementioned TRIR experiments
exclude photochemical generation from A. One possible
explanation could be that a second photon absorption takes
Subsequently, formation of S3 occurs with a time constant
of about 90 s (Fig. 3b). What distinguishes this component
from S2 is the presence of the most stable closed isomer C –
which is evidenced by the appearance of three characteristic
carbonyl stretching bands in the spectrum (highlighted in
Fig. 2a) – and the absence of open isomers. The fact that the
formation of C occurs on a much longer time scale and that a
delayed ingrowth is observed (Fig. 2b, red trace) implies that
tautomerization towards C starts from the closed B-type
forms and is associated with a higher energy barrier. These
conclusions are in good agreement with our calculations
3
2
place, as recently put forward by Bieske and co-workers.
However, rapid-scan FTIR experiments in which a band-pass
filter (HQ510/80m-2p, Chroma) was used to inhibit
absorption of a second photon by either A’ or A’’, which are
both red-shifted with respect to A, show that this does not
occur, since under these conditions EZZ is still formed and
with the same temporal behaviour as without filter (see SI
Figs. S5.5 and S5.6). We therefore conclude that EZZ is
generated along a thermal reaction path from A’ (obtained
photochemically within the time resolution of the
experiment) to A’’ and then back to EZZ. Considering the
inherent uncertainties in calculated energy barriers, this path
is energetically very well possible and in line with the
observed time scales.
(Fig. 4c) which show that after isomer B is formed, the
tautomerization path with the lowest barrier is the one
leading to B’’’ via B”. However, once these two isomers
have been populated, a thermal reaction from B” to C is
possible, albeit with a higher Gibbs activation energy which
explains its slower rate of formation.
The presence of a further component S4 (Fig. 3b) showing
the presence of only B’’ and B’’’ and not of C may in first
instance seem puzzling. Important to notice is that, in the
sequential kinetic scheme adopted in Fig. 3c, a particular
SADS reports the changes that occur in the concentrations of
the pertaining components with respect to the previous
SADS. This implies that in going from S3 to S4 the
contribution of B’’ and B’’’ is affected to a major extent,
The second component (S2 in Fig. 3b) is formed on a 10 s
timescale. Importantly, the IR spectra of closed isomers, in
particular B’’ and B’’’, needed to be included for an
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while the contribution of C is much less affected. In our energetic barriers which regulate their thermal conversions,
1
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1
1
1
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1
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1
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experiments on DASA 1, dissolved in DCM, we have
observed that precipitation occurs (see SI Fig. S5.1). Such a
precipitation does not occur when DASA 1 is dissolved in
dimethyl sulfoxide (DMSO). Moreover, analyses of the
rapid-scan FT-IR data on DASA 1 in DMSO do not show a
fourth component (vide infra). The major difference between
the two solvents is that in DMSO the zwitterionic B’’’
isomer is the end product and is very well soluble, while in
DCM the solubility of B’’’ is considerably lower. We
therefore conclude that the presence of S4 for DASA 1 in
DCM is due to the precipitation of B’’’. This is in line with
the observation that the concentration of C hardly changes in
going from S3 to S4, and that the dominant changes occur in
B’’ and B’’’, with B’’ being influenced because it is on the
pathway from C to B’’’ and has a nearly equal energy as
B’’’ (Fig. 4c). Such conclusion is also in agreement with the
allows us to deliberately steer efficacies, rates, and switching
characteristics of DASAs, as will be shown in the following.
The reaction scheme depicted in Fig. 4 predicts the
stability of the transition states from A’ to A” and back from
A’ to A to be a key means to control the reaction rate of
DASAs conversion. With the electrocyclization being the
rate-limiting step, this is counterintuitive. A simple way to
tune the energy of transition states is to change the solvent.
Indeed, calculations with DMSO as a solvent show that the
transition state between A’ and A is 3.4 kcal/mol lower than
in DCM, while the transition state to A” is only slightly
higher by 0.7 kcal/mol (Fig. 5a). In agreement with these
findings, we observe experimentally that in DMSO full
conversion of DASA 1 does not occur even after 3 h of
irradiation, while in DCM ring closure proceeds in the order
of minutes. As the energy profile of the ring-closure step (A”
to B) is practically the same in both solvents, the lower
conversion rate can only be attributed to a quicker thermal
back conversion from A’ to A in addition to a possible
0
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0
3
time scale on which S4 decays (14x10 s), which, in turn, is
in line with the Gibbs energy difference between C and the
highest transition state leading to B’’’ (24.5 kcal/mol, Fig.
4
c).
33
influence of band overlap. This is confirmed by rapid scan
The detailed studies presented above for DASA 1 in DCM
FT-IR studies (Sections S5.1.2 and S5.1.3) that show almost
no evidence for the presence of A’ on the milliseconds
timescale, in agreement with the calculations that predict the
half-life of A’ to drop to around 1 ms in DMSO.
have led to a series of remarkable and unexpected findings,
highlighting the importance of thermal reaction pathways in
determining both the rate and the efficiency of DASA
photoswitching. The isomer EZZ is clearly observed and
plays a key role in the early phase of photoswitching.
Moreover, the cyclization occurs on a 10 s timescale
consistent with the computed thermal barriers to produce B,
which rapidly isomerizes to B’ and then to B’’ and B’’’.
Subsequently, on a longer timescale, the most stable isomer
C is formed.
Further support for the importance of the stabilities of the
transition states from A’ to A” and back to A is found by
analysing the photoswitching behaviour of DASA 1 in
toluene. Here, faster photoswitching than in DCM is
observed, in line with the lower/higher barrier for the
forward/backward thermal conversion of A’ predicted by the
calculations (Fig. 5a). The relative energy of the barriers can
simply be explained by analysing the bonding characteristics
in different solvents (SI Fig. S6.8). As the solvent polarity
increases, the zwitterionic resonance contribution gains more
Tailoring DASA’s reaction pathways
Our experiments and calculations on DASA 1 show that
the photoswitching process – although operationally simple –
is in reality a picture of complex interconversions among
different open and closed isomers where different tuneable
importance and, consequently, the bond order of C
2
—
C
3
/C —C decreases/increases, thereby hindering/favouring
3
4
isomerization around these bonds. The same consideration
applies to the stability of the transition state from A” to EZZ:
higher barriers are found in toluene preventing the formation
of the non-productive EZZ isomer (SI Fig. S6.9). From all
these findings, we thus conclude that to increase the forward
switching rate both the transition state from A’’ to EZZ and
from A’ to A should be destabilized as much as possible to
minimize unproductive backward reactions.
‘
knobs’ allow controlling the overall photoswitching
behaviour. The experimental insights gained on the
contribution of thermal interconversions and the developed
theoretical model enable us to account for previously
observed differences in the kinetic behaviours of DASA,
which could depend on solvents or on the nature of donor or
acceptors groups. Rationally addressing the key steps of the
reaction by tuning the stability of selected isomers or the
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Figure 5. Role of solvent and substituent in the ring-closure reaction: Energy profiles for backward (lighter color) and forward (darker
color) isomerization pathways of isomer A’ of (a) DASA 1 in toluene (red), DCM (black) and DMSO (blue) and of (b) all studied DASAs
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
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1
2
2
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6
(1
in
black,
2
in
purple,
and
3
in
green)
in
DCM.
DASA 1 and 2
rate-determining
step; higher for
DASA 2, than 1
in DCM
EZZ accumulate rapidly (see SI section 9). The fact that
upon irradiation EZZ is easily formed in DASA 3 can help
hv
3
3
A
A'
A''
A''
B
B'
C
B''
B'''
explain previously observed differences in the behaviour of
first- and second-generation DASAs. In these ultrafast time-
resolved IR spectroscopic studies, it was observed that for
nanosecond delays the spectra of compound 2 showed
solvent-dependent changes, while for compound 3 the same
spectral features were observed for all solvents. This
observation can now be understood: in first-generation
DASAs the interconversion between A’ and EZZ is a
thermal process whose barrier depends on the employed
solvents whereas for second-generation DASAs the
formation of EZZ is photoinduced and solvent independent.
We expect the photochemical forked pathway of DASA 3 to
be a direct result of a further weakening of the double bonds
in the triene due to the aromaticity of the indoline group.
Since EZZ is not part of the productive switching pathway,
the efficacy of such switches is in principle reduced.
main-product
for DASA 1
and 2
EZZ
accumulates
temporarily
lowest in energy,
but kinetically
not favoured
DASA 3
in DCM
0
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0
A'
A''
A''
B
B'
B''
B'''
hv
A
EZZ
accumulates
temporarily
C
main product
for DASA 3
Figure 6. Overview of photoswitching behaviour of DASA 1–
3
in DCM.
Being able to control the composition of photostationary
states is highly desirable when dealing with photoswitches.
Although the use of different substituents on a particular
donor is an obvious means to target this issue for DASAs –
as exemplified by the recent studies of Beves and co-
Our rapid-scan FT-IR studies on DASA 3 (SI section
S5.3) further show that in DCM only C is formed as
2
4,25
suggested previously,
in line with the prediction that this
4
5
workers – it is quite unexpected that replacing the methyl
groups in DASA 1 by ethyl groups in DASA 2 leads to
major changes in photoswitching behaviour (for DASA 2
cyclization is much reduced, see SI section 3.2). Rapid scan
FT-IR spectra of DASA 2 in DCM recorded directly after
switching on the light are very similar to those of DASA 1 in
the same solvent, indicating comparable early steps (SI Fig.
S5.20). Hence, differences in the overall photoswitching
behaviour should be a result of differences in energies at
later stages. Our calculations find indeed that the ring-
closure step (from A” to B) is responsible for the slower
photobleaching in DASA 2 (Fig. 5b), which can be related to
the steric hindrance arising from the bulkier ethyl groups.
This seems to hold for different solvents as well, since
switching experiments in toluene (SI section S3.2) found that
DASA 2 converts more slowly to the cyclized product than
DASA 1 (see also the energy profile in SI Fig. S6.18). Fine-
tuning of steric interactions thus appears to be more
instrumental in regulating DASA’s switching pathways than
expected. Thus, substitutions at the triene unit could very
well be another useful means to obtain further control over
DASA’s photoswitching behaviour, and this is indeed one of
the directions we are presently exploring.
isomer is considerably more stable than the B forms.
However, what in first instance would not have been
expected – but is in excellent agreement with the calculated
higher energy barrier between B and C – is that several
forms of B can be observed as intermediates, except B’’’
which is markedly destabilized, most likely due to the
decreased basicity of the donor. The destabilization of the
zwitterionic B’’’ helps preventing the formation of
precipitated products for DASA 3 as compared to DASA 1
in chlorinated solvents.
Overall, thermal interconversions between isomers thus
prove to be essential for DASA photoswitching (Fig. 6). First
generation DASAs 1 and 2 predominantly produce A’
through light absorption, but the unproductive EZZ isomer
can be accumulated via a solvent dependent thermal
interconversion through A’’. In contrast, DASA 3 exhibits a
forked photochemical reaction to produce both A’ and EZZ.
With a complete understanding of the thermal reaction steps
involving the electrocyclization, proton transfer and
tautomerizations leading to the cyclized forms, we now can
start acting on the molecular structure to deliberately steer
the outcome and kinetics of DASA photoswitching and to
produce application-tailored switches.
By now, several generations of DASAs have been developed
that aim for further control by modifying the electronic
properties of the donor and acceptor groups. Our studies on
DASA 3 (see SI sections S5.3 and S6.4), an example of a
second-generation DASA, demonstrate how the present
investigations allow for rationalizing in much more detail
how specific donors influence the switching behaviour.
Importantly, already the actinic step is dramatically
influenced by a change in donor: excitation of isomer A of
DASA 3 leads to the formation of both A’ and EZZ in equal
amounts, in contrast to the first-generation DASAs
CONCLUSIONS
Photoswitching of DASAs 1–3 has been studied using
rapid-scan FT-IR to elucidate the structural transformations
at work after photoexcitation and their timescales. Key to the
interpretation of these data has been a complete mapping of
the reaction pathway with all possible intermediates and
transitions states. This has led to a detailed understanding of
the switching pathways, the energies and barriers governing
the thermal equilibrium. Overall, a picture has emerged in
which thermal interconversions play a crucial role in the
photoswitching of DASAs.
(
compound 1 and 2) where only A’ is formed. Using a
1
combination of H-NMR, ultrafast TRIR, rapid-scan FTIR
experimental data and DFT calculations we find that most
While the primary photochemical step provides an initial
means to kick-start the process, the rate-limiting thermal
steps govern the overall behaviour of these switches.
likely
a
forked photochemical reaction pathway is
1
responsible for this behaviour (see Fig. 6). H-NMR in situ-
irradiation experiments support this finding as both A’ and
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Unexpectedly, thermal interconversions not only play a
Page 8 of 10
Michael M. Lerch: 0000-0003-1765-0301
Mariangela Di Donato: 0000-0002-6596-7031
Wiktor Szymański: 0000-0002-9754-9248
Claudia Filippi: 0000-0002-2425-6735
Ben L. FeringaL: 0000-0003-0588-8435
Wybren Jan Buma: 0000-0002-1265-8016
Author Contributions
1
2
3
4
5
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7
8
9
1
1
1
1
1
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1
1
1
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2
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6
central role in the electrocyclization and proton-
transfer/tautomerization steps, but also in the arrangement of
the DASA structure for electrocyclization as has been
outlined above for the role played by the EZZ isomer. The
photochemical step gives access to high-energy open
intermediates, and it is the control over the lifetime of these
intermediates that allows one to steer the reaction towards a
targeted outcome. Once electrocyclization takes place, rapid
interconversion of the primary closed species B to other B-
and C-type closed forms is possible, with a product
distribution that can be directed according to the specific
application at hand. The herein presented results have
clarified for the first time where modifications need to take
place to achieve a particular photoswitching behaviour,
enabling operators to steer DASA’s photoswitching outcome
along multiple switching pathways.
+
H.Z and M.A.J.K contributed equally to this work
Notes:
0
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The authors declare no competing financial interest.
Acknowledgements
This work was supported financially by the Netherlands
Organization for Scientific Research (NWO–CW, Top grant
to B.L.F., VIDI grant no. 723.014.001 for W.S., NWO
Chemical Innovations Project Nr. 731.014.209 to W.J.B.),
the European Research Council (ERC; Advanced
Investigator Grant, no. 694345 to B.L.F.) and the Ministry of
Education, Culture and Science (Gravitation program, no.
024.001.035). The computational work was carried out on
the Dutch national supercomputer Cartesius with the support
of the SURF Cooperative. Furthermore, the authors
acknowledge support from: Laserlab-Europe (LENS002289,
grant no. 654148) and the Royal Netherlands Academy of
Arts and Sciences (KNAW). The Swiss Study Foundation is
acknowledged for a fellowship to M.M.L.. We thank P. van
der Meulen for support with the temperature dependent
NMR in situ-irradiation studies and T. Tiemersma-Wegman
for ESI-MS analyses.
DASAs have entered the molecular nanotechnology field
only recently, but have evolved tremendously over the past
few years. The beauty of these switches relies on their
complex reaction pathway that allows tuning of their
photoswitching and overall behaviour with interventions in
structure and environment. The ’IR motion pictures’
recorded in the present work together with elaborate
quantum chemical calculations that supply crucial ‘subtitles’
have provided the insight necessary to do so in a rational
manner, at any point, and at a level that was not possible
before.
EXPERIMENTAL SECTION
Rapid-scan FT-IR: The samples were prepared in a dark
room. Subsequently 10–15 min. rapid-scan FT-IR
measurements have been performed using a Nicolet iS50 FT-
-1
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1
5599.
absorption studies on DASA 1 in DCM that have not been
30,33
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reported in our previous work.
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A.; Bussotti, L.; Szymański, W.; Buma, W. J.; Foggi, P.; Di
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