Photorelease of an organic molecule in solution: Light-triggered blockage of a hydrogen-bonding receptor site

Article abstract of DOI:10.1002/anie.200461946

Bathed in light, the acyclic receptor 1 that binds a neutral guest molecule through hydrogen bonding (1-2) undergoes an intramolecular anthracene photodimerization reaction to yield a macrocyclic structure. The dramatic change in the structure of 1 from o

Full text of DOI:10.1002/anie.200461946

Communications
Host–Guest Chemistry
Herein, we demonstrate how light controls the binding
affinity of a hydrogen-bonding receptor towards a neutral
organic molecule to such an extent that the bound guest
(barbital) is effectively released upon photoirradiation.
Receptors 1a and 2a (Scheme 1; a denotes acyclic) were
synthesized through a five-step reaction pathway starting
from anthrone and were fully characterized (see Supporting
Information).[4] Each receptor was designed to contain two
Photorelease of an Organic Molecule in Solution:
Light-Triggered Blockage of a Hydrogen-Bonding
Receptor Site**
Yann Molard, Dario M. Bassani,
Jean-Pierre Desvergne,* Peter N. Horton,
Michael B. Hursthouse, and
James H. R. Tucker*
The selective recognition of a guest by a
molecular host is a fundamental process
whose understanding has led to the design of
systems that are capable of controlled asso-
ciative/dissociative behavior.[1] Such systems
rely on an external physical or chemical
stimulus to modulate reversible intermolecu-
lar forces that are responsible for the associ-
ation of two or more species, and they are
ubiquitous to all living organisms, wherein
they play a vital role in complex signal-trans-
mission, regulation, and amplification proc-
esses. There are now several examples of
receptor molecules that contain photorespon-
sive units for which the strength of a binding
interaction with a particular guest species in
solution can be controlled by light.[2] The vast
majority of these receptors rely on a photo-
chromic auxiliary to impart a light-induced
structural modification of a crown-ether-like
cavity. Although the flexibility of the crown
ether units facilitates the modulation of their
binding properties, such systems have so far
been focused on the binding of metal ions,
Scheme 1. Receptors 1a and 2a bind barbital (3) strongly in solution; photoirradiation
of the receptors gives the macrocycles 1c and 2c, which are weaker binders of 3.
whereas reports of photoresponsive receptors
that bind organic species through multiple
hydrogen-bonding interactions are rare.[2e,3]
pyridine-2,6-diamide units connected by a phenyl spacer
group to generate a motif that has been shown to bind barbital
(3) strongly in chlorinated solvents through six complemen-
tary hydrogen bonds.[5] The binding site was connected by an
alkyl spacer group of variable length to two anthracene units,
which were expected to undergo the well-characterized and
thermally reversible 4p+4p photocycloaddition reaction
through an intramolecular pathway[6] to result in a change
in the structure of the receptor from acyclic to macrocyclic.
Anthracene photodimerization is particularly versatile as it
can proceed smoothly in a range of solvents.[6a]
[*] Dr. D. M. Bassani, Dr. J.-P. Desvergne
Laboratoire de Chimie Organique et Organomꢀtallique
Universitꢀ Bordeaux I
351, Cours de la Libꢀration, 33405 Talence (France)
Fax: (+33)5-4000-6994
E-mail: jp.desvergne@lcoo.u-bordeaux1.fr
Dr. Y. Molard, Dr. J. H. R. Tucker
Department of Chemistry
University of Exeter
Stocker Road, Exeter EX44QD (UK)
Fax: (+44)1392-263-434
As expected, both receptors 1a and 2a bound barbital
strongly in chlorinated organic solvents to give complexes of
E-mail: j.h.r.tucker@ex.ac.uk
Dr. P. N. Horton, Prof. M. B. Hursthouse
EPSRC National Crystallography Service
School of Chemistry, University of Southampton
Highfield, Southampton SO171BJ (UK)
1
1:1 stoichiometry as determined by H NMR spectroscopy.
The addition of one equivalent of 3 to a solution of 1a in
CDCl3 (8.5 mm) induced downfield shifts in the two signals
that correspond to the four NH protons of the receptor (from
d = 8.04 to 9.62 ppm for Ha; from d = 8.40 to 9.88 ppm for Hb).
The addition of further amounts of 3 brought about no further
significant changes to the spectrum which indicates the
[**] Financial support for this work was provided by the EPSRC (GR/
S07438/01 to Y.M.)
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200461946
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formation of a strongly bound 1:1 complex. As shown in
Figure 1, the addition of 3 to a solution of 2a in CH2Cl2 (2.15 ꢀ
10ꢀ5 m) did not affect the anthracene 1La absorption band
(300–400 nm) in the UV/Vis spectrum of the receptor,[2b] but
Figure 2. 1H NMR spectra of 2a in CDCl3 before and after photoirradia-
tion: a) initial spectrum of 2a and b) spectrum after 5 h (compound
2c).
confirms the 4p+4p photocycloaddition reaction between the
central rings on each anthracene unit.[2b] A close inspection of
the H NMR spectral pattern for the aromatic resonances of
1c and 2c suggests a head-to-tail (HT) structure rather than
the anticipated head-to-head (HH) structure.[9] This was
confirmed by X-ray diffraction studies of crystals of 1c and
2c, which were grown from CDCl3 and THF/hexane, respec-
tively (Figure 3).[10] A plausible explanation is the much lower
Figure 1. The binding of 3 by receptor 2a as followed by UV/Vis
spectroscopy; [2a]=2.15ꢁ10ꢀ5 m with additions of 0, 0.5, 1, 2, 3, 5,
and 8 equivalents of 3. The inset shows the increase in the observed
molar absorption coefficient (e) at l=315 nm upon addition of 3.
1
induced a bathochromic shift in the pyridine band (from
lmax = 298 to 304 nm) which reflects a bonding interaction
between the guest and both pyridine units.[7] The binding
constants K = [complex]/[host] ꢀ [3] (host = 1a or 2a) were
determined for each receptor by using the Letagrop pro-
gram.[8] The values (Table 1) are in the same range as those for
previously described acyclic barbiturate receptors in chlori-
nated solvents.[5a,c]
Table 1: Binding constants for the complexation of barbital (3) by the
receptors in their acyclic (1a and 2a) and macrocyclic forms (1c and 2c).
K [mꢀ1
]
Receptor
Acyclic form (a)
Cyclic form (c)
1
2
38000ꢁ2500[a]
38ꢁ6[b]
27000ꢁ3000[a]
8320ꢁ575[a]
[a] Determined by UV/Vis spectroscopy measurements in CH2Cl2,
receptor concentrationꢂ2ꢁ10ꢀ5 m. [b] Determined by 1H NMR
spectroscopy measurements in CD2Cl2, receptor concentration=1.7ꢁ
10ꢀ3 m.
Figure 3. Representations of the head-to-tail structures of a) 1c (tri-
clinic, space group P1) and b) 2c (monoclinic, space group C2/c)
obtained by X-ray crystallography. Solvent molecules (CDCl3 for 1c and
THF for 2c) have been omitted for clarity.
¯
Continued irradiation (Hg lamp, lead filter) of solutions of
1a and 2a (5 ꢀ 10ꢀ4 m) in degassed dichloromethane during
five hours resulted in the disappearance of the 1La anthracene
band in the absorption spectra of the receptors. Upon removal
of the solvent, the photodimers 1c and 2c (Scheme 1, c
denotes cyclic) were isolated as air-stable solids in essentially
thermal stability of 9-alkoxy-substituted anthracene HH
photodimers,[6b] which, if formed, would be expected to
undergo a relatively rapid thermal retrocyclization reaction
to yield the starting materials. In the case of 1c (Figure 3a),
the size and shape of the binding cavity are strongly affected
by the four bulky ortho-xylene units of the photodimer.
1
quantitative yield according to the H NMR spectra of 2a in
CDCl3 before and after photoirradiation (Figure 2, see
1
ꢀ
Supporting Information for H NMR spectra of 1a and 1c).
Furthermore, one of the four N H bonds points away from
The new signal at d = 4.43 ppm (Figure 2b) corresponds to
the cavity. In 2c (Figure 3b), although all six hydrogen-
the two bridgehead protons on the photodimer subunit and
bonding groups point inwards, the binding site is distinctly
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nonplanar with an angle of 77.5(2)8 between the pyridine
planes.
Preliminary studies revealed that 1c and 2c are fairly
stable at room temperature (as usually observed for HT
anthracene photodimers[6b]), but can be switched back to the
starting materials (open form) upon gentle heating (e.g., after
heating a solution of 1c in toluene at ꢂ 808C for two days,
ꢃ 90% of the starting material 1a was regenerated).
is likely that, at any one time, only one side of the guest is
weakly bound by one pyridinediamide unit, whereas the other
unit is blocked by the photoadduct. The value of the binding
constant is, in fact, lower than those obtained for unhindered
three-point hydrogen-bonding interactions with the pyridine-
2,6-diamide motif in chlorinated solvents.[12]
As found for the 1a/1c system, photodimerization of 2a
into 2c lowers the binding constant with barbital (Table 1),
but the decrease is less significant at approximately threefold,
with K(2a)/K(2c) = 3.3 ꢁ 0.6. From the crystal structure of 2c
(Figure 3b), it is clear that the longer spacer unit prevents the
photoadduct from blocking the cavity and enables the guest to
be stabilized by six hydrogen bonds. This was borne out by the
1H NMR spectra in CDCl3 which indicated relatively large
shifts of the signals for the protons Ha and Hb upon addition of
approximately one equivalent of barbital (from d = 7.88 and
8.05 ppm to 9.23 and 9.61 ppm, respectively). The presence of
3 also has a strong influence on the excited-state behavior of
1a and 2a. In particular, the observed decrease in the
quantum yield for photodimerization (0.07 and 0.07 versus
0.01 and 0.05 for the formation of 1c and 2c in the absence
and presence of 3, respectively) probably reflects a lowered
photoreactivity of the complexes 1a·3 and 2a·3.
To assess the photoswitched binding behavior of these
systems, the binding of barbital by the two photoproducts was
evaluated by 1H NMR spectroscopy (1c) and by UV/Vis
spectroscopy (2c). It was immediately apparent that the
binding between 3 and 1c was much weaker than with its
acyclic counterpart because in contrast to 1a, a large excess of
guest was required to bring about significant changes to the
NMR spectra. Figure 4 depicts the aromatic and aliphatic
Finally, a photoirradiation experiment was performed on
the 1a/1c system in the presence of barbital to examine
whether photoswitched binding could be observed in situ. A
solution of 1a in CD2Cl2 (5 ꢀ 10ꢀ4 m) which contained
0.95 equivalents of 3 (to ensure that the guest was fully
complexed) was continuously irradiated and monitored by
1H NMR spectroscopy over time (see Supporting Informa-
tion). The study revealed that the signal for the proton of the
imide group of barbital shifted upfield from d = 12.16 ppm
(before irradiation) to d = 9.79 ppm (after 3 h irradiation). At
the same time, the signals for the receptor changed from those
of almost fully complexed 1a (Ha and Hb signals at d = 9.20
and 9.47 ppm respectively) to those of essentially uncom-
plexed 1c (Ha and Hb signals at d = 7.82 and 8.41 ppm,
respectively; signal for the proton at C-2 of the isophthaloyl
group at d = 7.31 ppm). These observations are consistent
with the ejection of the guest from the receptor upon
photodimerization [Eq. (1)].
Figure 4. Evolution of the 1H NMR spectrum of 1c in CD2Cl2 upon addition of 3.
[1c]=1.7ꢁ10ꢀ3 m and remains constant during the titration. a) 1c, b) [3]/[1c]=1,
c) [3]/[1c]=6, d) [3]/[1c]=11, and e) [3]/[1c]=15.
1
regions of the H NMR spectra of 1c in CD2Cl2 (1.7 mm) in
the presence of increasing amounts of 3. Upon the addition of
15 equivalents of barbital, changes were observed in the
signals for the protons of the photoadduct: the bridgehead
protons moved upfield from d = 4.42 to 4.29 ppm, the proton
at C-2 of the isophthaloyl group shifted from d = 7.32 to
7.52 ppm, and the amide protons Ha and Hb (see Scheme 1)
underwent relatively small downfield shifts (Ha: from d = 7.82
to 8.56 ppm), which is consistent with a weak hydrogen-
bonding interaction. The binding constant for a 1:1 complex
was calculated from the chemical shift values for proton Ha by
using the EQNMR program.[11] The value obtained (K =
38mꢀ1, Table 1) confirms that photodimerization of 1a
dramatically affects the ability of 1c to form a strong complex
with barbital, with an approximately 1000-fold decrease
observed in the binding constant. An explanation for this
change can be obtained from the X-ray crystal structure of 1c
(Figure 3a), which clearly shows that it is impossible for the
receptor to accommodate barbital within its cavity. Instead, it
hn
1 a ꢄ 3
1 c þ 3
ð1Þ
ƒ!
In conclusion, these studies have shown how light can be
used to control both the binding and the in situ release of a
neutral guest molecule through structural changes to a
hydrogen-bonding receptor. The latter, designed to bind
barbital and other biologically relevant molecules such as
urea derivatives, offers the possibility to photoregulate the
release of such species in a reversible manner.
Received: September 10, 2004
Revised: October 13, 2004
Published online: January 11, 2005
Keywords: host–guest systems · molecular devices · molecular
recognition · photochemistry · supramolecular chemistry
.
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Chemie
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[4] 1a: FAB-MS: m/z calcd for C58H53N6O6: 929.4027 [M++H];
found: 929.4015; elemental analysis calcd (%) for
C58H52N6O6·0.5H2O: C 74.26, H 5.69, N 8.96; found: C 74.44,
H 5.65, N 8.88. 2a: FAB-MS: m/z calcd for C62H61N6O6: 985.4653
[M++H]; found: 985.4659; elemental analysis calcd (%) for
C62H60N6O6·0.5H2O; C 74.90, H 6.18, N. 8.45; found: C 74.95, H
6.14, N 8.35.
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[7] Preliminary studies indicate that complexation leads to a
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[8] a) L. G. Sillen, B. Warnqvist, Ark. Kemi 1968, 31, 377; b) L. G.
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[10] CCDC-249540 and CCDC-249539 (1c and 2c, respectively)
contain the supplementary crystallographic data for this paper.
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