Synthesis of a new photoresponsive molecular carcerand

Article abstract of DOI:10.1016/j.jphotochem.2016.01.008

The synthesis of a covalently bonded new photoresponsive molecular capsule formed from two resorcin[4]arene cavitands by fourfold ether linkages using azobenzene subunits is reported. The new molecular capsule undergoes trans to cis isomerization upon irradiation with 365?nm light and can be reversed back from cis to trans form by means of exposure to visible light (530?nm) in benzene solution. The photo-switchable behaviour was also investigated by ¹H NMR spectroscopy which further substantiated the UV–vis experiment. The quantum chemical calculations both at PM6 as well as at the DFT (B97-D) level of approximation for various stereoisomers starting from all-trans to all-cis indicated an increasing flexibility of these molecular capsules.

Full text of DOI:10.1016/j.jphotochem.2016.01.008

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Contents lists available at ScienceDirect
Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
Synthesis of a new photoresponsive molecular carcerand
Satya Narayan Sahua, Alexander B. Rozhenkob, Jens Eberhardc,d, Jochen Mattayd,
*
a
School of Chemistry, Sambalpur University, Jyoti Vihar, Burla, Sambalpur 768019, Orissa, India
Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Murmans’ka str. 5, 02660 Kyiv, Ukraine
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Universitätscampus E8.1, 66123 Saarbrücken, Germany
b
c
d
Jochen Mattay, Department of Chemistry, Bielefeld University, P.O. Box 100131, D-33501 Bielefeld, Germany
A R T I C L E I N F O
A B S T R A C T
Article history:
The synthesis of a covalently bonded new photoresponsive molecular capsule formed from two resorcin
[4]arene cavitands by fourfold ether linkages using azobenzene subunits is reported. The new molecular
capsule undergoes trans to cis isomerization upon irradiation with 365 nm light and can be reversed back
from cis to trans form by means of exposure to visible light (530 nm) in benzene solution. The photo-
switchable behaviour was also investigated by 1H NMR spectroscopy which further substantiated the
UV–vis experiment. The quantum chemical calculations both at PM6 as well as at the DFT (B97-D) level of
approximation for various stereoisomers starting from all-trans to all-cis indicated an increasing
flexibility of these molecular capsules.
Received 1 October 2015
Received in revised form 6 January 2016
Accepted 7 January 2016
Available online xxx
Keywords:
Azobenzene
Resorcin[4]arene cavitand
Carcerand
ã 2016 Elsevier B.V. All rights reserved.
Molecular capsule
Cis–trans isomerization
DFT
1. Introduction
encapsulation of guest molecules within the cavity of such
molecular capsules is a great challenge and often depends on
The continuing growth in supramolecular chemistry for diverse
applications such as molecular recognition and sensing, catalysis,
cellular carriers and as biological mimics, demands highly
sophisticated and larger molecular architectures. Therefore to
expand the library of readily accessible and versatile organic
molecular capsules, it is envisaged that a meticulous choice of
resorcin[4]arene cavitands can often give highly symmetrical three
dimensional cages through covalent bonding driven self-assembly
processes. Early pioneering work by Cram and coworkers [1] has
demonstrated the synthesis of carcerands and hemicarcerands, in
which two resorcin[4]arene cavitands are held together by four
covalent linkages attracting considerable attention for stabilizing
reactive intermediates and for using them as microvesicles for drug
delivery. Subsequently various recent examples were reported
from the laboratories of Sherman [2], Warmuth [3], Kobayashi [4],
and Rebek [5] on the diversified synthesis of resorcin[4]arene
cavitands or capsules and their applications for host–guest
interactions utilizing the fact that the confinement of guest
molecules inside the capsules away from bulk phases may behave
differently compared to their free form. However, the controlled
the flexibility of the linkers that bound the two cavitand units [6].
Earlier examples have employed various photoresponsive linker
units where the molecular flexibility can be tuned by irradiation
process at different wavelengths of light. For instance, our group
has reported the synthesis of photoswitchable calixarenes and
molecular capsules based on the photochemically driven dimer-
ization of two anthracene moieties [7]. In a very recent example
Wang et al. have reported on a reversible photochemically gated
transformation of a hemicarcerand to a carcerand which is based
on same concept of anthracene dimerization [8]. In another report
calixarenes functionalized by other photoresponsive moieties such
as acridinium and tropylium have been reported and found to be
potentially useful for photoswitchable behavior [9].
Recent studies have demonstrated that the process of trans–cis
isomerization of azobenzene also offers the possibility to control
the flexibilityand therebygeometryof molecules [10]. Forexample,
Osorio-Planesetal. havereported onthe reversiblephotocontrolled
disintegration of a dimeric tetraurea-calix[4]pyrrole capsule with
all-trans appended azobenzene units upon exposure to visible light
[11]. Similarly Husaru et al. [12] and Yushkova et al. [13] have
reported the synthesis of azobenzene substituted calix[4]resorci-
narene and p-tert-butyl thiacalix[4]arene derivatives, respectively,
where the cavity size of the molecules can be altered through the
photoswitchable behavior of azobenzene units. In contrast to the
first concept (i.e. cyclodimerization of anthracene units) the second
* Corresponding author.
E-mail addresses: snsahu.chem@gmail.com (S.N. Sahu), a_rozhenko@ukr.net
(A.B. Rozhenko), jens.eberhard@helmholtz-hzi.de (J. Eberhard),
mattay@uni-bielefeld.de (J. Mattay).
http://dx.doi.org/10.1016/j.jphotochem.2016.01.008
1010-6030/ã 2016 Elsevier B.V. All rights reserved.
Please cite this article in press as: S.N. Sahu, et al., Synthesis of a new photoresponsive molecular carcerand, J. Photochem. Photobiol. A: Chem.
(2016), http://dx.doi.org/10.1016/j.jphotochem.2016.01.008

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Scheme 1. Synthesis of 4,40-dihydroxyazobenzene (1).
Scheme 2. Synthesis of tetrabromo-resorcin[4]arene cavitand (4).
one utilizes a photoinduced isomerization process (trans to cis
isomerization of azobenzene) leading to an altered geometry rather
than covering/opening an entrance channel of a host compound.
With thisconceptwenowreport the synthesisof a photoresponsive
molecular capsule formed from two resorcin[4]arene cavitands by
fourfold ether formation using azobenzene subunits as an example
for covalently bonded molecular cavities with a “switchable wall”.
Its photochemical behavior as well as size dependence and
flexibility on the trans–cis isomerization has been studied both
experimentally and by quantum chemical calculations.
2.1. Synthesis and characterization
The synthesis of photoactive azobenzene linker 1 (Scheme 1)
was achieved by diazonium coupling reaction of 4-aminophenol
with phenol at 0 ꢀC in 43% yield. Azo compound 1 is perfectly suited
for the linkage to a resorcinarene via nucleophilic substitution
reaction owing to its phenolic hydroxyl functions.
The octahydroxy resorcin[4]arene (2) was synthesized by acid
catalyzed condensation reaction of 2-methyl resorcinol with n-
pentanal in 73% yield. The cavitand formation was achieved by the
treatment of 2 with bromochloromethane (BrCH2Cl) in DMF with
potassium carbonate as base under standard reaction conditions
[14] to yield cavitand 3 in 92%. The complete bromination of the
four methyl groups in 3 was performed with NBS in presence of
AIBN to yield the functionalized building block 4 (55%) for the
capsule synthesis (Scheme 2). The reaction between the resorcin
[4]arene building block 4 and azobenzene linker 1 was performed
2. Results and discussion
The construction of the target molecular capsules involves the
synthesis of functionalized cavitands. These cavitands will be
further utilized to generate molecular assemblies by covalent
bonding processes.
Scheme 3. Synthesis of the covalent molecular capsule (5).
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Fig. 1. Variable temperature 1H NMR spectra of 5 in CDCl3 (a) ꢁ50 ꢀC; (b) 0 ꢀC; (c) +27 ꢀC; (d) +50 ꢀC.
in acetone with potassium carbonate as base under reflux
condition to yield the dimeric capsule 5 (Scheme 3).
The dimeric capsule was directly obtained in one step instead of
two or more consecutive reactions which is an advantage
compared to our previous work whereby tedious purification step
via HPLC could be avoided. As normal for this type of reaction the
yield of the isolated product is rather low, since the formation of
oligomer or polymer by-products is inevitable. However, MALDI
Fig. 2. (a) 1H NMR signal decays in dry CDCl3 solution of 5 at 7.559 ppm at 293.3 K as a function of the diffusion gradient strength (G); (b) plot of signal decay as a function of
the gradient strength (G).
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analysis of the crude product mixture obtained from the reaction of
4 and 1 showed a mass peak of the dimeric capsule whereas peaks
corresponding to higher order molecular capsules were absent.
All compounds were characterized by means of NMR and high
resolution mass spectrometry. Particularly the NMR spectra in
CDCl3 revealed that the symmetry of the resorcinarene core units is
maintained in the dimer 5. The aromatic protons of the
resorcinarene core can be assigned to one singlet signal at
7.34 ppm corresponding to eight protons in the 1H NMR spectrum
of 5. In addition the azobenzene units in 5 showed two distinct
aromatic signals at 7.55 ppm and 6.59 ppm. Homo-nuclear
coupling (COSY) between different aromatic protons further
corroborated the complete analysis of the aromatic protons of
the dimer molecule. The 1H NMR results of 5 furthermore indicated
that the azobenzene linkers are fixed symmetrically to each other.
Variable temperature NMR experiments were performed to
study the flexibility of the dimeric capsule. 1H NMR spectra were
recorded in CDCl3 at +50 ꢀC, +27 ꢀC, 0 ꢀC and ꢁ50 ꢀC (Fig.1). Analysis
of the protons signals of 5 at different temperatures exhibited
almost no change in the chemical shift values of aromatic protons
of the azobenzene linkers (at 7.55 ppm and 6.59 ppm) and the
methylene bridge protons (at 5.73 ppm and 4.63 ppm) of the
cavitands indicating the rigidity in the molecular structure.
However the aromatic protons of the resorcinarene core (at
7.34 ppm) and lower rim alkyl proton (at 5.03 ppm) exhibited a
slight upfield shift upon lowering the temperature from +27 ꢀC to
ꢁ50 ꢀC possibly due to restriction of thermal motions at low
temperature.
covalent interactions [15]. In contrast, this is the first example
where the particle size in solution has been estimated from the
diffusion coefficient value of a covalently linked molecular capsule.
We determined the diffusion coefficient of species existing in the
NMR sample of 5 from the gradient diffusion of the aromatic signal
at 7.559 ppm (Fig. 2) and found the coefficient value (Dt) to be
0.39 ꢂ10ꢁ5 cm2/s at 293.3 K which is very close to the coefficient
values obtained for other resorcinarene based self-assembled
noncovalent dimeric aggregates [16].
2.2. Photochemistry
The absorption spectra of compounds 1 and 5 in degassed
benzene solution are shown in Fig. 3. The capsule 5 showed a
spectrum very similar to that of the azobenzene linker 1 which
indicated the presence of symmetrical isomers of azobenzene
units (Fig. 3a). The trans–cis isomerism study of the capsule 5 was
performed at 365 nm and 530 nm wavelengths. Irradiation of 5
with 365 nm light for 30 min converted nearly all azobenzene units
into cis-form as indicated by a decrease of the trans band and
appearance of a new band at around 450 nm in the absorption
spectrum (Fig. 3b). A photochemical reversion of the cis-isomer
could be detected by irradiating the cis-5 with 530 nm light for
30 min as shown in Fig. 3b. An essential difference of the switching
behavior occurs upon changing the solvent from benzene to
chloroform. Conversion of trans-form to cis-form in 5 can be
conducted in chloroform just as in benzene solvent by means of
irradiation with 365 nm light, which was envisaged from the
decrease of trans band in the absorption spectrum (Fig. 3c).
Surprisingly the cis-form of 5 in chloroform could not be reversed
to the trans-form either by irradiation with 530 nm light for 40 min
or by keeping the sample in dark for overnight.
In addition, diffusion NMR spectroscopy provided useful data
concerning the solution state of dimeric species. To the best of our
knowledge diffusion NMR spectroscopy has been used only on
aggregated species of resorcin[4]arenes, i.e. formed through non-
Fig. 3. UV–vis spectra of compound 5 and 1 (a), 5 in benzene (b) and 5 in chloroform (c), c = ca. 1 ꢂ10ꢁ4 mol Lꢁ1
.
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5
Fig. 4. 1H NMR spectra (in C6D6) of 5 in trans-form (a), after irradiation with 365 nm for 30 min (b) and after irradiation with 530 nm for 30 min (c). [red marked signal at
8.05 and 6.63 ppm for azobenzene aromatic protons]. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
The trans–cis isomeric conversion of 5 was also evaluated by
NMR spectroscopy in deuterated benzene as solvent (Fig. 4a and b).
A comparison of the 1H NMR spectra of the trans- and cis-form
indicated a change in the symmetry of the azobenzene units during
the isomerization whereas the resorcinarene units are hardly
disturbed. For instance, aromatic protons of the azobenzene units
exhibited two broad doublets at 8.05 ppm and 6.63 ppm in the
trans-form of 5 and upon irradiation with 365 nm light for 30 min
these signals vanished completely and a series of doublets
appeared at a slightly higher field similar to that observed for
other azobenzene systems upon irradiation. Shifting signals to
high field can also be observed for the methylene bridged protons
of the cavitand as well as for the methylene protons of the linkers
(at 5.74 ppm, 5.48 ppm and 4.99 ppm in trans-form). However, the
signal at 7.69 ppm, which can be ascribed to the aromatic protons
of the resorcinarene phenyl units, was barely disturbed during the
photochemical isomerization and indicated a symmetrical ar-
rangement of the resorcinarene cores in the cis-form. The
photochemical reversion of the cis-isomer was also investigated
through NMR spectroscopy by irradiating the sample with 530 nm
light for 30 min which showed reappearance of proton signals of
the trans-form as shown in Fig. 4c.
2.3. Quantum chemical calculations
The calculated solvodynamic radius (rH) of the covalent
molecular capsule using the diffusion coefficient value was found
to be 9.6 Å. Preliminary calculations at the PM6 level showed that
the azobenzene capsule exhibits an inner cavity of approx.
dimension 8.6 Å ꢂ 22.1 Å (inter-atomic distances) (Fig. 5) which
is very close to the inner cavity size of other resorcinarene based
self-assembled non-covalent dimeric aggregates [17,18].
Further quantum chemical calculations of various structures of 5
were carried out at the DFT (B97-D) level of approximation and
predicted the lowest energy for the structure with all ꢁꢁN¼Nꢁꢁ
bonds having trans-configuration (Fig. 6a: all-trans). The starting
geometries were preliminarily relaxed using molecular dynamics
based on MM2 force field. As can be seen, the fully trans-structure is
twisted, providing
p,p-stacking and CH,p-interections with a
participation of the aromatic rings of the aza-moieties. The all-trans
structure is definitely most favorable, in complete agreement with
the experimental data discussed above. The least favorable
configuration is the structure with fully cis-oriented ꢁꢁN¼Nꢁꢁ
Fig. 5. Calculated dimension of the all-trans azobenzene capsule (5).
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Fig. 6. Jmol projections of equilibrium structures all-trans 5 and all-cis 5 and relative energy values (DG, kcal/mol).
fragment (Fig. 6b: all-cis) (
trans 5). In order to keep
structureisfoldedintheregionoftheN
structures correspond to local minima in energy, as can be
concluded from absence of calculated imaginary frequencies.
Unfortunately, due to the large size of the molecule, it is
extremely difficult to study computationally the all-trans ! all-cis
transformation, but it might be suggested that this conversion
proceeds gradually, with the inversion at only one nitrogen atom
D
p
G = 62.0 kcal/mol compared to all-
-stacking and CH, -interactions, the
N-bonds. Bothequilibrium
per step. As our calculations indicate, the total (
DE) and Gibbs free
p
,
p
energy ( G) decrease smoothly from all-trans to all-cis via
D
¼
intermediate structures with increasing portion of cis-bonds
(Fig. 7a–c). It should admitted here that the large size and
conformational lability of the various structures of 5 do not allow
to grant finding global minima in energy by geometry optimization
even starting from the structures preliminarily relaxed using
molecular dynamics. Therefore, in reality an equilibrium will exist
within a variety of the structures with very close total energy. The
Fig. 7. Jmol projections of some equilibrium structures of 5 and relative energy values (DG, kcal/mol, related to all-trans 5).
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Table 1
Calculated (RI-B97-D/TZVP) total energy values (E, Hartree), zero-point energy correction and thermal corrections to Gibbs free energy magnitudes (ZPE and TCGFE, Hartree),
corrected energy values (E + ZPE and E+ TCGFE, Hartree), lowest vibrational frequency ( E and G, kcal/mol).
n
, cmꢁ1) and corresponding relative energy values (
D
D
Structure of 5
E
ZPE
E + ZPE
TCGFE
E+ TCGFE
n
DE
DG
all-trans
ꢁ7180.717317
ꢁ7180.682355
ꢁ7180.657569
ꢁ7180.637654
ꢁ7180.613068
2.046531
2.046055
2.045452
2.044385
2.044620
ꢁ7178.670786
ꢁ7178.636300
ꢁ7178.612117
ꢁ7178.593269
ꢁ7178.568449
1.874828
1.873571
1.871210
1.870970
1.869336
ꢁ7178.842489
ꢁ7178.808784
ꢁ7178.786359
ꢁ7178.766685
ꢁ7178.743733
7.7
7.4
8.6
27.3
7.0
0.00
21.6
36.8
48.6
64.2
0.00
21.2
35.2
47.6
62.0
cis,trans,trans,trans
cis,trans,cis,trans
cis,trans,cis,cis
all-cis
optimized most favorable structures with an increasing number of
cis-inversed N N-bonds are shown in Fig. 7a–c (from cis,trans,
and host-guest type interactions can be envisaged inside the
supramolecular system.
¼
trans,trans via cis,trans,cis,trans to cis,trans,cis,cis). The calcu-
lated total energy values for these structures seem to be
intermediate cases between the fully cis- and trans-isomers
(Table 1) and the structures themselves transform gradually from
twisted to folded ones.
4. Experimental procedures
4.1. Synthesis of 4,40-dihydroxyazobenzene (1)
To a solution of 4-aminophenol (1.07 g, 9.81 mmol) dissolved in
1 N HCl solution (17.0 mL), a solution of sodium nitrite (1.13 g,
16.38 mmol), dissolved in 3.4 mL water was added dropwise at 0 ꢀC
withconstantstirring.Themixturewasdilutedbyaddingpre-cooled
to 0 ꢀC methanol (34.0 mL). In a separate flask, phenol (0.92 g,
9.78mmol) and potassium hydroxide (1.04 g, 18.54 mmol, 1.9 eq)
were dissolved in methanol (4.8 mL) and cooled to 0 ꢀC. This
phenolate solution was added dropwise under constant stirring to
the flask containing diazonium salt. The resulting red solution was
stirred for additional 24 h.1 N HCl solution was added to precipitate
the crude product, which was collected by filtration. The crude
product was then recrystallized from glacial acetic acid to give the
product as a red-black solid (0.91 g, 4.25 mmol). Yield= 43%.1H NMR
3. Conclusions
In conclusion, the synthesis of a new macrocyclic capsule 5 based
ontworesorcin[4]areneunitsandfourazobenzenelinkershasbeen
performed and the prepared compound was characterized by NMR
and high resolution mass spectrometry. The new molecular capsule
undergoes trans to cis isomerization upon irradiation with 365 nm
light and can be reversed back from its cis to trans form by means of
exposuretovisiblelight(530 nm)inbenzene. Thephoto-switchable
behaviour of 5 was also investigated by 1H NMR spectroscopy and
further substantiated by the UV–vis experiment. To the best of our
knowledge this is the first example of a covalently assembled
molecular capsule with a “switchable wall” based on these units
which can reversibly change its cavity by irradiation at different
wavelengths of light. Since the geometry of the capsule and size of
the cavity by the transformations from trans-form to cis-form and
back to trans-form can be controlled by light, a number of
interesting applications such as light driven chemical reactions
(300 MHz, acetone-d6)
d ppm: 6.97(d, 4H, J = 9 Hz), 7.77(d, 4H,
J = 9 Hz), 9.14(bs, 2H, D2O-exchangeable). ESIMS (-ve): m/z for
[C12H10N2O2 + H2O + Na]+ Calcd: 255.07; found: 255.0.
4.2. Synthesis of tetramethyl resorcin[4]arene (2)
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10.28 g (82.8 mmol) of 2-methylresorcinol was dissolved in a
mixture of 100 mL of ethanol and 50 mL of 37% aqueous hydro-
chloric acid (HCl). To this stirred solution 7.20 g (8.9 mL, 83.6
precipitate obtained was filtered and washed repeatedly till the
filtrate became neutral (controlled by pH paper). Then the solid
product was recrystallized from chloroform and dried. Yield = 92%.
mmol) of n-pentanal was added slowly through
a
syringe.
MP: > 320 ꢀC. 1H NMR (500 MHz, CDCl3)
d ppm: 0.92(t, 12H,
Immediately after the addition was complete, the reaction was
cooled in a water bath to control the exothermic reaction. The
reaction mixture was then maintained at 80 ꢀC for 16 h, and the
yellow solid that separated were collected and washed with cold 3:
l ethanol–water mixture until the washings were light yellow. The
pale colour solid material obtained was then dried at 80 ꢀC under
reduced pressure for 30 h. Yield = 73%. MP: > 230 ꢀC (decomposed).
J = 5 Hz), 1.34(m, 8H), 1.43(m, 8H), 1.97(s, 12H), 2.20(q, 8H), 4.25(d,
4H, J = 10 Hz), 4.74(t, 4H, J = 10 Hz), 5.88(d, 4H, J = 10 Hz), 6.98(s, 4H).
13C NMR (125 MHz, CDCl3)
d: 10.3, 14.1, 22.8, 29.7, 30.1, 36.9, 98.5,
117.5, 123.6, 137.9, 153.2, 162.5. EI-MS (+ve): m/z for [C52H64O8]
Calcd: 816.46; found: 816.5.
4.4. Synthesis of tetrabromoꢁresorcin[4]arene cavitand (4)
1H NMR (500 MHz, acetone-d6)
d
ppm: 0.88(t, 12H, J = 5 Hz), 1.26
A mixture of cavitand 3 (0.0.498 g, 0.61 mmol) and AIBN (0.02 g,
0.12 mmol) were dissolved in 25 mL of benzene (deaerated by
saturation with argon gas for 1 h). To this solution NBS (0.762 g,
4.28 mmol) was added and the reaction mixture was refluxed
overnight (about 12 h) under argon atmosphere followed by TLC
control. After completion of the reaction it was cooled, the solid
succinimide precipitate was filtered off and the residue was
washed with benzene (2 ꢂ 4 mL). The combined filtrate was
(m, 8H), 1.37(m, 8H), 2.04(s, 12H), 2.27(q, 8H), 4.35(t, 4H, J = 5 Hz),
7.43(s, 4H), 7.95(bs, 8H, D2O-exchangeable). 13C NMR (125 MHz,
acetone-d6) d: 10.7, 14.3, 22.6, 29.2, 35.4, 56.3, 113.6, 122.0, 124.6,
153.1.
4.3. Synthesis of resorcin[4]arene cavitand (3)
A mixture of dry resorcin[4]arene 2 (2.0 g, 2.6 mmol) and
anhydrous K2CO3 (5.75 g, 41.6 mmol) in 60 mL of dry DMF was
heated at 60 ꢀC with stirring under argon (Ar) atmosphere for
30 min. Then CH2BrCl (9.75 g, 75.35 mmol) was added to the
reaction mixture in three fractions over a period of 40 h and after
final addition of CH2BrCl the reaction mixture was heated at 60 ꢀC
with stirring under argon (Ar) atmosphere for 12 h. After
completion of the reaction, DMF was evaporated under reduced
pressure and then water was added to the reaction mixture. The
evaporated to get a pale white solid. The solid was dissolved in
a small volume of acetone and then recrystallized from acetone by
storing at low temperature to obtain a white solid. Yield = 0.38 g
(55%). MP: > 300 ꢀC. 1H NMR (500 MHz, CDCl3)
d ppm: 0.93(t, 12H,
J = 5 Hz), 1.30(m, 8H), 1.44(m, 8H), 2.20(q, 8H), 4.42(s, 12H), 4.55(d,
4H, J = 5 Hz), 4.77(t, 4H, J = 10 Hz), 6.02(d, 4H, J = 5 Hz), 7.14(s, 4H). 13
C NMR (125 MHz, CDCl3)
d: 14.1, 22.7, 22.9, 29.7, 30.0, 36.8,
99.1,120.9, 124.5, 138.0, 153.5. ESI-MS (ꢁve): m/z for
[C52H60Br4O8 + H2O + 2Na]2+ Calcd: 1192.09; found: 1193.8.
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(2016), http://dx.doi.org/10.1016/j.jphotochem.2016.01.008

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JPC 10106 No. of Pages 10
S.N. Sahu et al. / Journal of Photochemistry and Photobiology A: Chemistry xxx (2015) xxx–xxx
9
4.5. Synthesis of the covalent molecular capsule (5)
Supplementary Information to this paper. The optimized struc-
tures were graphically represented using the Jmol program [27].
A mixture of 1 (0.047 g, 0.22 mmol) and anhydrous K2CO3
(0.61 g, 4.42 mmol) were taken in 125 mL of dry acetone and
refluxed for 30 min. Then the reaction was cooled to room
temperature and cavitand 4 (0.125 g, 0.11 mmol) was added and
further refluxed for 12 h. After disappearance of starting tetra-
bromo resorcin[4]arene in the reaction mixture by TLC monitoring
(9:1 cyclohexane and ethylacetate eluent) the reaction solvent was
evaporated and 50 mL of chloroform was added to the residue. The
suspension was filtered to remove the solid K2CO3 and the
chloroform filtrate was washed with acidified 1N HCl solution
followed by distilled water. The organic layer was separated, dried
over anhydrous MgSO4 and then evaporated under vacuum to yield
a red coloured solid. This crude product was subjected to GPC
purification in chloroform to obtain the desired azobenzene-linked
molecular assembly. Yield = 11%. MP: > 300 ꢀC. 1H NMR (600 MHz,
Acknowledgements
Financial Support by the Deutsche Forschungsgemeinschaft
(SFB 613) is gratefully acknowledged. SNS is grateful for a
BOYSCAST fellowship 2009–2010 by the Department of Science
and Technology (DST), Government of India. A.B. Rozhenko thanks
the Alexander von Humboldt Foundation (Germany) for generous
donating the hardware for calculations and license to the
TURBOMOLE set of programs. The team of the SKIT computer
cluster at the V.M. Glushkov Institute of Cybernetics of NAS of
Ukraine, Kyiv is gratefully acknowledged for providing computa-
tional resources for TURBOMOLE calculations.
Appendix A. Supplementary data
CDCl3)
4.63(brs, 8H), 5.03(brs, 24H), 5.73(brs, 8H), 6.59(brs,16H), 7.34(brs,
8H), 7.55(brs, 16H). 13C NMR (125 MHz, CDCl3)
: 14.3, 22.9, 29.9,
30.3, 36.8, 60.4, 114.4, 121.9, 124.7, 128.9, 131.0, 138.7, 146.9, 154.5,
159.7. HRMS: m/z for [C152H152N8O24 + H]+ Calcd: 2475.10250;
found: 2475.10279.
d ppm: 0.90–1.03 (m, 24H),1.46–1.56(m, 32H), 2.36(q,16H),
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.jphotochem.
2016.01.008.
d
References
[1] D.J. Cram, J.M. Cram, Container Molecules and Their Guests, Royal Society of
Chemistry, Cambridge, 1994.
4.6. Details of calculations
[2] (a) A. Jasat, J.C. Sherman, Carceplexes and Hemicarceplexes, Chem. Rev. 99
All the structures were first optimized using the TURBOMOLE
(versions 6.2 and 6.4) program packet [19] with the implemented
Resolution Identity (RI) routine [20–23] and Multipole Accelerated
Resolution of Identity J-algorithm (MARIJ) [24]. RI-B97-D func-
tional [25] and standard triple-zeta basis sets (TZVP) [26] were
used. The contraction of the basis functions were (11s6p)/
[5s3p] ! {62111/411} for C, N and O, and (5s)/[3s] ! {311} for H.
One set of (five) d-functions was added for every non-hydrogen
atom and one set of p-functions was used for H’s. For all the
structures vibrational analyses were performed, computing
numerically first and second order derivatives. The absence of
imaginary frequencies for the equilibrium structures proved that
they were true local minima in energy. The corresponding zero
point energy (ZPE) corrections and thermal corrections to Gibbs
free energy (TCGFE) were derived at the RI-B97-D level of theory
(1999) 931–967;
(b) J.C. Sherman, Molecules that can’t resist templation, Chem. Commun.
(2003) 1617–1623.
[3] Z. Lin, J. Sun, B. Efremovska, R. Warmuth, Assembly of water-soluble, dynamic,
covalent, container molecules and their application in the room-temperature
stabilization of protoadamantene, Chem. Eur. J. 18 (2012) 12864–12872 and
references therein.
[4] K. Kobayashi, M. Yamanaka, Self-assembled capsules based on
tetrafunctionalized calix[4]resorcinarene cavitands, Chem. Soc. Rev. 14 (2015)
449–466.
[5] (a) J. Rebek, Molecular behavior in small spaces, Acc. Chem. Res. 42 (2009)
1660–1668;
(b) O.B. Berryman, H. Dube, J. Rebek, Photophysics applied to cavitands and
capsules, Isr. J. Chem. 51 (2011) 700–709;
(c) E. Busseron, J. Lux, M. Degardin, J. Rebek, Synthesis and recognition studies
with a ditopic, photoswitchable deep cavitand, Chem. Comm. 49 (2013) 4842–
4844.
[6] F.A. Arroyave, P. Ballester, Reversible light-controlled cargo release in
hydrogen-bonded dimeric capsules, J. Org. Chem. 80 (2015) 10866–10873.
[7] (a) S. Bringmann, R. Brodbeck, R. Hartmann, C. Schäfer, J. Mattay, Anthracene–
calixarene-based capsules: synthesis and photoswitchable features, Org.
Biomol. Chem. 9 (2011) 7491–7499;
and used for calculations of
DE and DG values with the default
scaling. The complete calculation data set can be found in the
Please cite this article in press as: S.N. Sahu, et al., Synthesis of a new photoresponsive molecular carcerand, J. Photochem. Photobiol. A: Chem.
(2016), http://dx.doi.org/10.1016/j.jphotochem.2016.01.008

G Model
JPC 10106 No. of Pages 10
10
S.N. Sahu et al. / Journal of Photochemistry and Photobiology A: Chemistry xxx (2015) xxx–xxx
(b) C. Schäfer, J. Mattay, Preparation of photocyclizable dianthracene
derivatives of resorc[4]arenes which are potential photo switches, Photochem.
Photobiol. Sci. 3 (2004) 331–333;
(c) M.C. Letzel, C. Schäfer, F.R. Novara, M. Speranza, A.B. Rozhenko, W.W.
Schoeller, J. Mattay, A kinetic study of guest displacement reactions on a host–
guest complex with a photoswitchable calixarene, J. Mass Spectrom. 43 (2008)
1553–1564;
(d) C. Schäfer, B. Decker, M.C. Letzel, F. Novara, R. Eckel, R. Ros, D. Anselmetti, J.
Mattay, On the way to supramolecular photochemistry at the single molecule
level, Pure Appl. Chem. 78 (2006) 2247–2259.
[16] (a) B. Schnatwinkel, I. Stoll, A. Mix, M.V. Rekharsky, V.V. Borovkov, Y. Inoue, J.
Mattay, Monomeric, dimeric and hexameric resorcin[4]arene assemblies with
alcohols in apolar solvents, Chem. Commun. (2008) 3873–3875;
(b) L. Avram, Y. Cohen, Spontaneous formation of hexameric resorcinarene
capsule in chloroform solution as detected by diffusion NMR, J. Am. Chem. Soc.
124 (2002) 15148–15149;
(c) T. Evan-Salem, Y. Cohen, Octahydroxypyridine[4]arene self-assembles
spontaneously to form hexameric capsules and dimeric aggregates, Chem. Eur.
J. 13 (2007) 7659–7663.
[17] N. Nishimura, K. Kobayashi, Self-assembly of a cavitand-based capsule by
dynamic boronic ester formation, Angew. Chem. Int. Ed. 47 (2008) 6255–6258.
[18] (a) T. Schröder, S.N. Sahu, Dario Anselmetti, J. Mattay, Supramolecular capsules
derived from resorcin[4]arenes by H-bonding and metal coordination:
synthesis, characterization, and single-molecule force spectroscopy, Isr. J.
Chem. 51 (2011) 725–742;
(b) T. Schröder, S.N. Sahu, J. Mattay, Molecular capsules derived from resorcin
[4]arenes by metal-coordination, Top. Curr. Chem. 319 (2012) 99–124.
[19] F. Furche, R. Ahlrichs, C. Hättig, W. Klopper, M. Sierka, F. Weigend, Turbomole,
Wiley Interdiscip. Rev. Comput. Mol. Sci. 4 (2014) 91.
[8] H. Wang, F. Liu, R.C. Helgeson, K.N. Houk, Reversible photochemically gated
transformation of a hemicarcerand to a carcerand, Angew. Chem. Int. Ed. 52
(2013) 655–659.
[9] (a) L. Grubert, W. Abraham, Photoswitchable calix[4]arenes bearing
dihydroacridine substituents at the upper rim, Tetrahedron 63 (2007)
10778–10787;
(b) M. Fehlinger, W. Abraham, Calix[4]arenes bearing a tropylium substituent
as hosts for organic cations, J. Inclus. Phen. Macrocyclic Chem. 58 (2007)
263–274.
[10] (a) D. Bleger, S. Stefan Hecht, Visible-light-activated molecular switches,
[20] B.I. Dunlap, J.W.D. Connolly, J.R. Sabin, On some approximations in
Angew. Chem. Int. Ed. 54 (2015) 2–14;
applications of Xa theory, J. Chem. Phys. 71 (1979) 3396.
(b) A.A. Beharry, G.A. Woolley, Azobenzene photoswitches for biomolecules,
Chem. Soc. Rev. 40 (2011) 4422–4437.
[22] O. Vahtras, J. Almlöf, M.W. Feyereisen, Integral approximations for LCAO-SCF
calculations, Chem. Phys. Lett. 213 (1993) 514.
[11] L. Osorio-Planes, M. Espelt, M.A. Pericas, P. Ballester, Reversible
photocontrolled disintegration of a dimeric tetraurea-calix[4]pyrrole capsule
with all-trans appended azobenzene units, Chem. Sci. 5 (2014) 4260–4264.
[12] L. Husaru, M. Gruner, T. Wolff, W.D. Habicher, R. Salzer, Photoresponsive upper-
rim azobenzene substituted calix[4]resorcinarenes, Tetrahedron Lett. 46
(2005) 3377–3379.
[13] E.A. Yushkova, E.N. Zaikov, I.I. Stoikov, I.S. Antipin, Self-assembly of nanosized
aggregates based on the photoswitchable p-tert-butyl thiacalix[4]arene
derivative and Fe III, CuII, and AgI cations, Russ. Chem. Bull. 58 (2009) 101–107.
[14] R. Wu, T.F. Al-Azemiz, K.S. Bisht, Spatially directional multiarm poly(e-
caprolactone) based on resorcin[4]arene cavitand core, Chem. Commun.
(2009) 1822–1824.
[23] K. Eichkorn, O. Treutler, H. Öhm, M. Häser, R. Ahlrichs, Auxiliary basis sets to
approximate Coulomb potentials, Chem. Phys. Lett. 240 (1995) 283.
[24] M. Sierka, A. Hogekamp, R. Ahlrichs, Fast evaluation of the Coulomb potential
for electron densities using multipole accelerated resolution of identity
approximation, J. Chem. Phys. 118 (2003) 9136.
[25] S. Grimme, J. Antony, T. Schwabe, C. Mück-Lichtenfeld, Density functional
theory with dispersion corrections for supramolecular structures, aggregates,
and complexes of (bio) organic molecules, Org. Biomol. Chem. 5 (2007) 741.
[26] A. Schäfer, C. Huber, R. Ahlrichs, Fully optimized contracted Gaussian basis sets
of triple zeta valence quality for atoms Li to Kr, J. Chem. Phys. 100 (1994) 5829.
[27] Jmol: An Open-Source Java Viewer for Chemical Structures in 3D. See Http://
jmol.sourceforge.net/ for more details
[15] L. Avram, Y. Cohen, Diffusion NMR of molecular cages and capsules, Chem. Soc.
Rev. 44 (2015) 586–602.
Please cite this article in press as: S.N. Sahu, et al., Synthesis of a new photoresponsive molecular carcerand, J. Photochem. Photobiol. A: Chem.
(2016), http://dx.doi.org/10.1016/j.jphotochem.2016.01.008