Hemiindigo: Highly Bistable Photoswitching at the Biooptical Window

Article abstract of DOI:10.1021/jacs.7b07531

Hemiindigo is a long known chromophore that absorbs in the blue part of the spectrum but has almost completely been ignored as potential photoswitch. Herein we show how the absorption of hemiindigo is shifted to the red part of the visible spectrum and how nearly perfect photoswitching can be achieved using blue or green and red light. Five derivatives were investigated giving very high isomeric yields in both switching directions, i.e. >90% E isomer after irradiation with 470 to 530 nm light and 99% Z isomer with 590 up to 680 nm light. At the same time the thermal bistability is extraordinarily high leading to half-lives of the pure isomeric states of up to 83 years at 25 °C. The herein developed photoswitches show photochromism in the visible enabling the two isomeric states to be distinguished by the naked eye. Substituted hemiindigos therefore constitute extremely promising new photoswitches with excellent properties for applications in biology, chemistry, or material sciences.

Full text of DOI:10.1021/jacs.7b07531

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Article
Hemiindigo - Highly Bistable Photoswitching at the Biooptical Window
Christian Petermayer, Stefan Thumser, Florian Kink, Peter Mayer, and Henry Dube
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b07531 • Publication Date (Web): 25 Sep 2017
Downloaded from http://pubs.acs.org on September 25, 2017
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Hemiindigo - Highly Bistable Photoswitching at the Biooptical Window
†
†
†
†
†
Christian Petermayer, Stefan Thumser, Florian Kink, Peter Mayer, Henry Dube *
†
LudwigꢀMaximiliansꢀUniversität München, Department für Chemie and Munich Center for Integrated Protein
Science CIPSM, Dꢀ81377 Munich, Germany.
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Abstract
Hemiindigo is a long known chromophore that absorbs in the blue part of the spectrum but has
almost completely been ignored as potential photoswitch. Herein we show how the absorption of
hemiindigo is shifted to the red part of the visible spectrum and how nearly perfect
photoswitching can be achieved using blue or green and red light. Five derivatives were
investigated giving very high isomeric yields in both switching directions, i.e. >90% E isomer
after irradiation with 470 to 530 nm light and 99% Z isomer with 590 up to 680 nm light. At the
same time the thermal bistability is extraordinarily high leading to half-lives of the pure
isomeric states of up to 83 years at 25 °C. The herein developed photoswitches show
photochromism in the visible enabling the two isomeric states to be distinguished by the naked
eye. Substituted hemiindigos therefore constitute extremely promising new photoswitches with
excellent properties for applications in biology, chemistry, or material sciences.
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Introduction
Shifting the wavelengths for photoswitching into the red part of the spectrum while maintaining high
thermal stability of the induced metastable states is a topic of very high current interest in many
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chemistry related fields.
multiresponsive molecular systems
reactions of harmful UV irradiation, and offers deep signal penetration into tissue
This combination of properties opens up new opportunities for
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or towards orthogonal photoswitching,
eliminates side
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for biological and
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photomedical applications.
Even without complete visible light responsiveness the establishment
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of highly bistable photoswitching remains a challenge at the current state of the art.
On this topic we have recently reported a hemithioindigo photoswitch that can be operated using green
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and red light with a thermal halfꢀlife of the metastable E isomer of 30 days at 25 °C. Hemiindigo is
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structurally related to hemithioindigo
and consists of an indigo and a stilbene fragment sharing a
common central double bond (Figure 1a). It is known as a chromophore for more than 100 years and
was first described by Adolf von Baeyer in 1883 naming the compounds obtained from condensation
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of indoxylic acid and aldehydes “Indegonide”. Despite its facile synthesis,
established
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spectroscopic properties,
and relation to hemithioindigo
and aurone
the photochemistry of
hemiindigo is essentially unexplored especially with regard to applications as photoswitch. As the
absorption profile of unsubstituted hemiindigo resides partially in the visible part of the
electromagnetic spectrum the possibility of reversible double bond photoisomerization using
exclusively visible light is highly tempting. However, the very few earlier investigations in this
direction show a rather unfavorable photochemistry of hemiindigo where unwanted behavior such as
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light induced [2+2] cycloadditions
or triplet generation seem to hamper stable and efficient
photoswitching. To the best of our knowledge only one such example was reported so far using a
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pyroleꢀderivative and UV/vis light for excitation.
In this work we show how donor substitution of hemiindigo leads to formidable photoswitches with
nearly perfect reversible switching behavior in the red part of the visible spectrum. We prepared 5
derivatives of hemiindigo with different amineꢀsubstituents at the stilbene fragment as well as
different substituents at the nitrogen atom of the indigo fragment (Figure 1) and analyzed their
photophysical properties in detail. Amine substituents were used to establish a strong push (electronꢀ
donating stilbene) ꢀ pull (electronꢀaccepting carbonyl group) character across the central double bond,
which leads to a significant redshift of the absorption. These derivatives offer precise photocontrol of
their geometry at wavelengths up to 565 nm in the Z to E switching direction and up to 680 nm in the
E to Z direction, consistent switching behavior in different solvents, and an extraordinarily high
thermal stability of the individual isomeric Z and E states. Combined with their easy access via a
simple twoꢀstep synthesis substituted hemiindigos therefore constitute a highly promising new
photoswitching system for broad applications in all chemistryꢀrelated fields.
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Figure 1. Hemiindigos 1 to 5 investigated in this work. (a) Molecular structures of 1 to 5. (b) Crystal
structures of hemiindigos Zꢀ1, Zꢀ2, Eꢀ3 and Eꢀ4. (c) Crystals of Zꢀ2 showing strong redꢀgreen
dichroism.
Results and Discussion
Synthesis. The synthesis of hemiindigos 1 to 5 is shown in Scheme 1 and commences with a
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condensation reaction between commercially available indoxyl acetate and a benzaldehyde. The
protonated hemiindigo 1 and 2 are obtained in good yields of 82% and 69%, respectively.
Deprotonation and substitution with nꢀpropyl iodide as electrophile delivers the Nꢀpropylated
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hemiindigos 3 and 5 in very good yields of up to 92%. A BuchwaldꢀHartwig palladiumꢀcatalyzed
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cross coupling allows for facile installation of an aromatic substituent at the indigoꢀamine function
and delivers hemiindigo 4 in 50%. Purification of the derivatives 2 to 5 is best achieved using reverse
phase HPLC delivering very pure material.
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Scheme 1. Synthesis of hemiindigos 1 to 5 via condensation of indoxyl acetate and different
substituted benzaldehydes. The NHꢀproton can easily be replaced by alkyl or aromatic substituents.
Conformation of Substituted Hemiindigos. Crystal structure analysis could be provided for
hemiindigos Zꢀ1 and Zꢀ2 as well as for Eꢀ3 and Eꢀ4 (see Figure 1b). Derivatives Zꢀ1, Eꢀ3, and Eꢀ4 do
not accumulate sterical hindrance between the indigoꢀ and the stilbene fragment and are therefore
planar structures. Consequently small torsion angles around the rotatable single bond adjacent to the
double bond are found for Zꢀ1 (8.9°), Eꢀ3 (7.5°), and Eꢀ4 (6.1°). Only Zꢀ2 shows some more
pronounced twisting of the stilbene fragment (torsion angle of 14.5°). Introducing substituents at the
indoxylꢀnitrogen atom larger than hydrogen should lead to strongly increased steric repulsion with the
stilbene fragment in the Z isomeric state. Therefore, the Z isomers of hemiindigos Zꢀ3 to Zꢀ5 are not
expected to be completely planar anymore. Apparently the situation is different for their E isomers,
where a planar structure can be expected and is indeed found in the crystalline state of Eꢀ3 and Eꢀ4.
As we have incomplete record of the detailed molecular structures of all derivatives in the Z and E
isomeric state, we optimized both isomers of all five hemiindigos on the B3LYPꢀGD3BJ/6ꢀ311G(d,p)
level of theory. Additionally the polarizable continuum model (PCM) for implementation of DMSO
solvent effects was employed for the optimization. For both Z and E isomers of 3 and 4 an initial
conformational search has been conducted on the force field MM3* level of theory with a Monte
Carlo Multiple Minimum (MCMM) search algorithm and an energy threshold of 1.91 kcal/mol in the
gas phase to account for the conformationally flexible nꢀpropyl chains. The global minima geometries
were then first optimized on the MPW1K/6ꢀ311G(d,p) and subsequently reoptimized on the B3LYPꢀ
GD3BJ/6ꢀ311G(d,p) PCM(DMSO) level of theory. Frequency analysis confirmed all structures to be
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minimum structures since no imaginary frequencies have been found. We also provide the
corresponding calculated absorption spectra (see below at the “Theoretical Description of the
Absorption” section and the Supporting Information for further details on the computations).
Two cases can be distinguished: Close to planar geometry for both Z and E isomers (hemiindigos 1
and 2) and twisted Z but planar E isomer geometry (hemiindigos 3 to 5).
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For 1 and 2 the calculations show that there is a slight twist in the Z isomers around the single bond
adjacent to the central double bond (14.6° for Zꢀ1 and 14.0° for Zꢀ2) but full planarity is achieved in
the E isomeric form. The twist in Zꢀ1 therefore appears to be a bit more pronounced than suggested by
the crystal structure of (8.9°). This can be explained by the apparently nonꢀnegligible steric
interactions between the NH proton and the orthoꢀprotons of the stilbene fragment, which are
overcome in part by crystal packing forces. The planarity in the E isomers is likely a result of
…
favorable CꢀH lonepair interactions between the orthoꢀprotons of the stilbene fragment and the
carbonyl moiety favoring a short distance.
For the Z isomers of 3 to 5 the stilbene fragment is more severely twisted (34° for Zꢀ3, 37° for Zꢀ4, and
26° for Zꢀ5). This twist is however not extremely large and should therefore not strongly impede the
conjugation across the chromophore. The corresponding E isomers of 3 to 5 are consistently found to
possess a planar hemiindigo coreꢀchromophore structure. In Zꢀ5 the toluene residue at the indoxylꢀ
nitrogen atom is also twisted but only with a 40° angle. In the corresponding E isomer the toluene
residue at the indigo fragment shows an increased twist angle of 69°. The lesser 40° twist angle of this
substituent in Zꢀ5 together with its apparent close proximity to an orthoꢀhydrogen atom of the stilbene
fragment (2.70 Å) therefore suggests favorable dispersive and CHꢀπ interactions, which reduce the
twist angle in this case. These interactions could therefore also explain the comparatively small 26°
twist angle of the stilbene fragment. The theoretically obtained structures of Zꢀ1, Zꢀ2, Eꢀ3, and Eꢀ4
correspond very well with the experimentally determined structures in the crystalline state.
In solution the Z and E isomers can be assigned clearly by NOE cross signals between protons of the
indoxylꢀN substituents and the doubleꢀbond proton as well as close by protons of the stilbene
fragment. For the full analysis see the Supporting Information. Less information is available
concerning twisting of the stilbene fragment but several solution properties hint at a rather small
torsion angle, which does not strongly impede conjugation in the chromophore. For all derivatives 1 to
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the extinction is rather high for both isomers, which excludes a severe distortion. For hemiindigos
, 2, and 5 the extinction of the S ꢀS transition is considerably higher for the Z isomers compared to
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their corresponding E isomers. The trend is reversed for hemiindigos 3 and 4 where the extinctions of
this band in the E isomers is equally high or higher compared to the Z isomers. The latter behavior
hints at some conjugation impediment stemming from distortion in the Z isomeric state of 3 and 4,
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which is released in the E isomer. However, these are not very large effects and overall the
conformations of the coreꢀchromophore structure in solution can be regarded as not severely twisted
and well conjugated, resembling those found in the crystal structures and in the theoretical
descriptions.
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Figure 2. Extinction coefficients of both Z (bold lines) and E isomers (dotted lines) of hemiindigos 1
to 5 measured in solvents of different polarity (toluene in blue, THF in black, and DMSO in red): (a)
1, (b) 2, (c) 3, (d) 4, and (e) 5. (f) Individual isomers can be distinguished in solution by the naked eye:
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Physical and Photophysical Properties. For evaluation of the photophysical properties we measured
the extinction coefficients for Z and E isomers of all hemiindigo derivatives (Figure 2). The
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extinctions of derivatives 2, 4, and 5 are of special interest as they are located at the longest
wavelengths but all derivatives show considerable photochromism (e.g. 55 nm for 4 in THF). The
solvatochromism is comparatively small for all derivatives. The largest solvatochromic shift is
observed for derivative Zꢀ2 where the absorption maximum shifts 30 nm towards longer wavelengths
when going from apolar toluene to highly polar DMSO (positive solvatochromism).
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The photoisomerization was scrutinized using irradiation wavelengths between 365 nm and 680 nm in
different solvents (see the Supporting Information for the full list of conditions tested). Irradiation was
continued until the photostationary state (pss) was reached and no further changes were observed in
the isomer composition. The pss with highest isomeric ratios are reported in Table 1 for hemiindigos 1
to 5 together with the respective wavelengths of irradiation. For selected wavelengths we also report
quantum yields for the Z to E (φZ/E) and Z to E (φE/Z) photoisomerizations in selected solvents. As can
be seen the photoisomerization of 1 to 5 proceeds efficiently and gives very high isomeric ratios in
both switching directions. The photoswitching behavior is rather independent of the solvent for all
derivatives ꢀ which is again in considerable contrast to many members of the related hemithioindigo
39ꢀ41
photoswitch family.
The photoisomerization performance of derivative 4 is particularly
impressive: switching with 470 to 505 nm light gives >95% yield of the E isomer while irradiation
with wavelengths up to 680 nm delivers back the Z isomer virtually quantitatively. A similar good
performance but at somewhat shorter wavelengths is achieved for all other derivatives as shown in
Table 1. This behavior does not change even if the nature of the solvent is changed drastically (from
toluene to THF to DMSO). Additionally, we have examined the photoisomerization behavior in
mixtures of H O and small amounts of DMSO, DMF, or THF (see Supporting Information for all
2
measured spectra). In some cases tiny amounts of triethylamine have to be added to increase the
switching performance. In these solvent mixtures the photoisomerization is still efficient, especially
for derivatives 1, 3, and 4. At the same time the absorptions appear redshifted even further and the
time needed to reach the pss is considerably shorter hinting at improved switching efficiencies.
In general the isomer yield obtained under irradiation at a certain wavelength is determined by the
quantum yield
φ and the difference of the extinction coefficients of both isomers of a photoswitch. The
favorable pss compositions obtained for hemiindigos 1 to 5 are the result of significant
φZ/E and φE/Z in
combination with good photochromism, i.e. strongly different extinctions of the two isomers in the
450 nm ꢀ 500 nm range and beyond 570 nm. This pronounced photochromism is likely to be enhanced
by the conformational differences of the Z and E isomers (see the conformation discussion above),
where full planarity and conjugation of the chromophore can be achieved only in the E isomeric forms.
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Table 1
Physical and photophysical properties of hemiindigo (HI) photoswitches 1 to 5.
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-1
Polarity - E
= 45.1.
T
(30) /kcal mol of the solvents: toluene = 33.9; THF = 37.4; DMSO
Equilibraꢀ Equilibraꢀ
φ
Z/E
φ
E/Z
Isomer yield in
the pss /%
(nominal LED
nm)
ꢀG*
ꢀG*
tion halfꢀ
life of
tion halfꢀ
life of
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/%
(at
(therm.Z/E (therm.E/Z
HI
Solvent
(
equil.)
equil.)
pure Z
pure E
ꢀ1
ꢀ1
nm)
/kcal mol
/kcal mol
isomer at
25 °C
isomer at
25 °C
2
4 ±2
9 ±2
99% Z (617 nm)
1
toluene
THF
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
24.1
24.5
26.9
23.8
22.4
25.8
30.5
27.8
28.7
24.6
28.6
27.8
30.5
29.5
25.7
ꢀ
ꢀ
15 h
1.2 d
70 d
8.9 h
50 min
11 d
83 a
(467) (600) 87% E (470 nm)
4% Z (617 nm)
9% E (435 nm)
19 ±2 11 ±2 98% Z (617 nm)
467) (600) 89% E (470 nm)
9
ꢀ
ꢀ
8
DMSO
toluene
THF
ꢀ
(
9
9% Z (617 nm)
83% E (470 nm)
9% Z (617 nm)
0% E (470 nm)
16 ±2 10 ±2 95% Z (617 nm)
2
3
4
5
ꢀ
ꢀ
ꢀ
9
ꢀ
ꢀ
ꢀ
9
DMSO
toluene
THF
ꢀ
(
467) (600) 81% E (505 nm)
99% Z (617 nm)
ꢀ
ꢀ
3
2
2
0.3
8.0
8.2
60 a
1.2 a
1.7 a
1.2 d
2.0 a
0.7 a
83 a
15 a
6 d
9
3% E (470 nm)
9% Z (625 nm)
9
ꢀ
ꢀ
0.9 a
4.0 a
1.4 d
3.4 a
0.9 a
83 a
93% E (470 nm)
98% Z (617 nm)
23 ±2
9 ±2
DMSO
toluene
THF
(
467) (600) 95% E (470 nm)
99% Z (617 nm)
ꢀ
ꢀ
24.5
95% E (470 nm)
96% Z (617 nm)
90% E (470 nm)
ꢀ
ꢀ
2
2
3
2
2
8.3
7.7
0.5
9.5
5.4
22 ±2
7 ±2
99% Z (680 nm)
DMSO
toluene
THF
(467) (600) 98% E (505 nm)
9
9% Z (617 nm)
5% E (470nm)
98% Z (617 nm)
6% E (470 nm)
93% Z (625 nm)
ꢀ
ꢀ
9
ꢀ
ꢀ
15 a
8
22 ±2
2 ±1
DMSO
9 d
(
467) (625) 97% E (470 nm)
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The thermal isomerization properties of hemiindigos were tested for derivatives 1 to 5. Upon
prolonged heating we observed full conversion to the Z isomers for 1 and 2. The barriers for thermal
conversion of E to Z isomers were found to be in the range of 22.2 to 25.5 kcal/mol for 1 and 2, which
is high enough for considering these derivatives as bistable for many applications. However, an
equilibrium state with both Z and E isomers being present is observed when heating solutions of 3 to
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. The latter behavior is in stark contrast to hemithioindigo for which the Z isomer is in almost all
cases the thermodynamically most stable state, allowing full thermal conversion of the corresponding
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E isomer.
For the substituted hemiindigos 3 to 5 both isomers have very similar energies and none
is clearly preferred thermodynamically. As both the Z and E isomers are populated thermally, the first
order kinetics of thermal Z to E and the reverse E to Z equilibration are slightly different and can be
determined separately. We found that significantly higher bistabilities are observed when substituents
are present at the indoxylꢀN atom (3 ꢀ 5) as opposed to the protonated derivatives 1 and 2. Especially
high barriers were found for the thermal isomerizations of hemiindigo 3, where equilibration halfꢀlives
of up to 83 years are determined for individual isomers in solution. Changing the polarity of the
solvent significantly does not change this high bistability much ꢀ again in strong contrast to many
hemithioindigo photoswitches. Hemiindigos 4 and 5 exhibit somewhat reduced barriers for their
thermal isomerizations but the obtained stabilities are still very high warranting equilibration halfꢀlives
of individual states up to several years at 25 °C (Table 1).
According to these results the substitution pattern of hemiindigos 3 and 4 provide paramount property
profiles (Figure 3) as they combine highly efficient photoswitching at wavelengths up to 680 nm
(
nominal LED nm) with very high thermal bistability of the individual isomeric states (halfꢀlives up to
3 years at 25 °C) in solvents of vastly different polarity.
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Figure 3. Photoswitching and thermal isomerization behavior of substituted hemiindigos 3 and 4 in
solution. Photoisomerization between (a) Zꢀ3 and Eꢀ3 or (b) Zꢀ4 and Eꢀ4 in DMSO proceeds almost
quantitatively in both directions using green and red light, respectively. Clear isosbestic points are
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observed during the photoconversion. (c) H NMR spectra of a 3.0 mM solution of 3 in THFꢀd at
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7 °C measured after the pss is reached at 470 nm irradiation wavelength (1: 93% Eꢀ3 is obtained) and
90 nm (2: 99% Zꢀ3 is obtained). (d) The thermal stability of the individual isomers of 3 and 4 remains
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high in solvents of vastly different polarity. Energy barriers for the thermal Z to E (solid bars) and E to
Z (hollow bars) isomerizations of hemiindigo 3 (black) and 4 (grey) in different solvents (tolueneꢀ d8,
8 6
THFꢀ d , and DMSOꢀ d ).
Theoretical Description of the Absorption. Based on the previously optimized structures (see the
Conformational Analysis section) time dependent B3LYP/6ꢀ311+G(d,p) PCM(DMSO) calculations
were performed to obtain UV/vis spectra for both isomers of 1 to 5. The results for hemiindigos 3 and
4
are discussed in more detail below, for all other derivatives see the Supporting Information.
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Figure 4. Theoretical description of the electronic transitions of (a) Zꢀ4; and (b) Eꢀ4. The main
transition is a HOMOꢀLUMO excitation for both Z and E isomer, which can essentially be described
as πꢀπ* excitation. Orbitals and associated energies were obtained at the TDꢀB3LYPꢀ
GD3BJ/6ꢀ311+G(d,p) PCM(DMSO) level of theory based on structures optimized at the B3LYPꢀ
GD3BJ/6ꢀ311 G(d,p) PCM(DMSO) level.
According to the theoretical description the Franck Condon S state mainly consists of a HOMOꢀ
1
LUMO excitation, which is a πꢀπ* excitation for all calculated hemiindigo photoswitches and isomers.
Additionally, a small contribution from a HOMOꢀ1 to LUMO excitation is also observed except for Zꢀ
4 (Figure 4). Comparing the shape and size of the HOMOs for the E and Z isomer pairs of each
hemiindigo no strong differences are found. However, the energies of the HOMOs are significantly
different with a larger HOMOꢀLUMO gap being consistently observed for the Z isomers. Comparing
the two different hemiindigos 3 and 4 a slight shift of HOMO localization towards the stilbene
fragment in hemiindigo 4 can be recognized.
The LUMO shapes are also very similar for Zꢀ3, Z-4, and Eꢀ4. They are characterized by a significant
loss of electron density at the indigoꢀnitrogen atom as well as the stilbene fragment. Only Eꢀ3 differs
from that LUMO distribution as it retains a sizable contribution of the indigoꢀnitrogen atom. This
LUMO is also more delocalized over the whole molecule compared to the LUMOs of Zꢀ3, Z-4, and Eꢀ
4. Energetically the LUMOs are rather similar for all isomers.
Theoretical spectra were obtained from the time dependent DFT calculations using 10 states for the
description. The calculated spectra are in good agreement with the experimentally obtained ones
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regarding both the position of maxima as well as photochromicity between Z (hypsochromic
absorption) and E isomers (bathochromic absorption). The observed photochromicity can essentially
be traced back to a larger HOMOꢀLUMO gap for the Z isomers compared to the corresponding E
isomers ꢀ regardless of the degree of planarization of the molecule in the different isomeric states (see
details in the Supporting Information). The reasons for the different HOMOꢀLUMO gaps in both
isomers are: 1. A large stabilization of the HOMO in the Z isomers compared to the E isomers and 2.
To a lesser degree a destabilization of the LUMO of the Z isomer compared to the E isomer.
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Conclusions
In this work we have developed the photochemistry of the virtually unexplored hemiindigo
chromophore and present a substitution pattern that gives access to nearly perfect photoswitching
behavior in the red region of the visible spectrum. Synthetically easily accessible hemiindigos 1 to 5
show a highly beneficiary property profile with almost quantitative Z to E and E to Z
photoisomerization using blue or green and yellow to red light, respectively. They show pronounced
photochromism that can be discerned by the naked eye, possess very high thermal stability of the
individual isomeric states, and give sizable quantum yields for their photoreactions. This behavior is
scarcely influenced by solvent polarity, which renders substituted hemiindigos into a very reliable
photoswitching system. We believe that these new photoswitches are highly promising tools for very
broad applications in all chemistry related fields especially in cases where damaging UV light needs to
be avoided and exclusive photocontrol should be maintained without thermal deterioration of the
switching states. With 680 nm responsiveness of its E isomer hemiindigo 4 reaches the biooptical
window and should therefore be of special high interest to pharmaceutical and bioꢀmedicinal
applications.
Associated Content
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: xxx
Synthetic procedures for 1 - 5 as well as a full set of characterization data including melting
1
13
points, H NMR, C NMR, IR, (HR)MS, and elemental analyses, conformational analysis in
solution and in the crystal, photophysical data including extinction coefficients, isomer
compositions in the pss at different wavelengths, quantum yields, kinetic analyses of the
interconversion of isomers at different temperatures, and computational details.
Xꢀray crystal file/data sheet for Zꢀ1, Zꢀ2, Eꢀ3, and Eꢀ4 (CIF).
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Author Information
Corresponding Author
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*heduch@cup.uniꢀmuenchen.de
Notes
The authors declare no competing financial interest.
Acknowledgements
†
We dedicate this work to Adolf von Baeyer ( 20.08.1917)
H. Dube and C. Petermayer thank the Deutsche Forschungsgemeinschaft (SFB 749, A12) for financial
support. We further thank the “Fonds der Chemischen Industrie” for a Liebig fellowship, the Deutsche
Forschungsgemeinschaft (DFG) for an EmmyꢀNoether fellowship, and the Cluster of Excellence
’
Center for Integrated Protein Science Munich’ (CIPSM) for financial support.
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