Triggering of guanosine self-assembly by light

Article abstract of DOI:10.1002/anie.201000805

Chemical Representation Light switches: The introduction of a photoactive moiety into a lipophilic guanosine derivative allows photocontrol over the self-assembly of the molecule. The existence of C-quartets can be alternately switched on and off (see pic

Full text of DOI:10.1002/anie.201000805

Angewandte
Chemie
DOI: 10.1002/anie.201000805
Supramolecular Chemistry
Triggering of Guanosine Self-Assembly by Light**
Stefano Lena, Paolo Neviani, Stefano Masiero, Silvia Pieraccini, and Gian Piero Spada*
Controlling a function at the molecular level by means of
external stimuli is one of the key requirements in the
development of “smart” materials, and light is a very
appealing trigger because of its ready availability, easy
manipulation, and noninvasive character.[1] In particular,
self-assembly processes that can be controlled by photo-
chemical stimuli are an actively pursued research field and
one ultimate goal in supramolecular chemistry.[2]
In recent years, lipophilic guanine derivatives (lipoGs)
have received increasing attention because of their rich
supramolecular behavior.[3,4] Most of the supramolecular
architectures obtained from lipoGs and so far reported in
the literature require the presence of a cation (usually an
alkali-metal cation, but also an alkaline-earth or lanthanide
cation) that stabilizes the G-quartet-based assemblies
through dipole–ion interactions (Figure 1a). However, even
in the absence of metal cations suitable lipoGs are able to
undergo extensive self-assembly mediated by H-bonding
between guanine bases, thus leading to the formation of
ribbonlike architectures (e.g., Figure 1b).
Scheme 1. Synthesis of (E)-1. a) NBS; b) trans-2-phenylvinylboronic
acid, Na2CO3, TPPTS, Pd(OAc)2; c) acetic anhydride, DMAP. NBS=N-
bromosuccinimide, TPPTS=tris(3-sulfophenyl)phosphine trisodium
salt, DMAP=4-dimethylaminopyridine.
the molecule is reverted to the E isomer by either thermal or
photochemical back isomerization.
Following our experience with photoswitchable sys-
tems,[2f,7] for the introduction of photochemical control over
guanosine self-assembly our first approach was to introduce
an azobenzene moiety in the 8-position of the guanine base.
We expected that, if the photoactive moiety were placed close
to the sites of base recognition, the geometrical changes
associated with photoisomerization of the azo chromophore
would have resulted in strong effects over guanine self-
assembly. Unfortunately, the compounds obtained did not
show the desired supramolecular behavior. While this work
was in progress, interesting results were reported by Ogasa-
wara and Maeda[8] for oligonucleotides containing a modified
guanosine, in which an arylvinyl moiety had been introduced
at the 8-position. We therefore turned our attention to the 8-
styrylguanine moiety as the photoswitching unit.
Figure 1. a) D4-symmetric octamer and b) ribbonlike architectures.
We have already demonstrated the chemically driven
switching between different supramolecular motifs for lipoGs
both in solution[5] and at the solid/liquid interface.[6] Herein,
we report the photocontrolled self-assembly of a modified
guanosine nucleobase. Compound (E)-1 (Scheme 1) in the
presence of a measured amount of KI self-assembles into a
D4-symmetric complex consisting of two stacked G-quartets.
Photoisomerization to the Z isomer determines the decom-
position of the octameric complex, which is re-formed when
Derivative (E)-1 was obtained in three steps from natural
guanosine (Scheme 1). Bromination at the 8-position with
NBS followed by Suzuki coupling with 2-phenylvinylboronic
acid and esterification of the hydroxy functions with acetic
anhydride afforded (E)-1 in a 48% overall yield as the pure
isomer.
[*] Dr. S. Lena, P. Neviani, Prof. S. Masiero, Dr. S. Pieraccini,
Prof. G. P. Spada
Dipartimento di Chimica Organica “A. Mangini”, Alma Mater
Studiorum—Universitꢀ di Bologna
Compound (E)-1 dissolves readily in MeCN. The
1H NMR spectrum of (E)-1 (Figure 2a) in CD3CN (5 mm)
shows sharp signals, which suggests that extensive self-
assembly to form ribbonlike aggregates does not occur
under these conditions.[9] This finding is supported by
Via San Giacomo 11, 40126 Bologna (Italy)
E-mail: gianpiero.spada@unibo.it
[**] This work was supported by the University of Bologna.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201000805.
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Figure 3. a) Absorption spectra for photoisomerization of (E)-1 (5 mm
in MeCN) upon irradiation at 365 nm; initial spectrum (c) and
spectra recorded after 2 (a), 6 (b), 22 (d), and 28 min (g).
b) Absorption spectra for photoisomerization of (Z)-1 upon irradiation
at 254 nm; initial spectrum (c) and spectra recorded after 3 (g),
7 (a), 20 (d), and 30 min (b).
Figure 2. 1H NMR spectra for a) a 5 mm solution of (E)-1 in CD3CN,
b) a 30 mm solution of (E)-1 in CD3CN, and c) a 5 mm solution of (E)-
1/KI in CD3CN.
spectrum: this suggests the formation of an octameric species
composed of two stacked G-quartets arranged in a D4
symmetry. NOESY spectra show a correlation between H1’
and HA for both diluted and concentrated samples, which
implies that in the octameric supramolecular complex all of
the guanosine units adopt a syn conformation around the
glycosidic bond, regardless of concentration.
In the CD spectrum (Figure 4a) of the (E)-1/KI octameric
complex, a positive band at 255 nm and a very strong, positive
band at 350 nm can be observed. Although no detailed
NOESY spectra, which show no cross peak attributable to
intermolecular correlations. Extensive self-assembly takes
place upon increasing the concentration above 20 mm: the
imino N1-H and amino N2-H protons, which resonate at d =
9.30 and 5.50 ppm, respectively, in 5 mm solution, shift
downfield to d = 10.47 and 6.33 ppm in a 30 mm solution
(Figure 2b). This indicates progressive involvement of these
groups in H-bonding. Accordingly, the NOESY spectrum now
clearly shows an intermolecular correlation between the N2-
H and H1’ of adjacent guanosine moieties. Interestingly, these
spectra (see the Supporting Information) indicate a confor-
mational change around the glycosidic bond as a function of
concentration. In diluted samples (below 5 mm), a cross peak
correlating H1’ and HA suggests a syn conformation around
the glycosidic bond, but at higher concentrations (20 mm and
above) this cross peak is no longer apparent. The presence of
an intermolecular peak relating the N2-H and H1’ of adjacent
guanosine units indicates that a ribbonlike architecture is
present and the anti conformation is now predominant.
The CD spectrum of (E)-1 in MeCN at 5 mm concen-
tration (see the Supporting Information) shows only a weak
(negative) signal. The profile is almost superimposable on the
CD spectrum of (E)-1 in MeOH, a competing solvent for
hydrogen bonding, thus suggesting the presence of a disag-
gregate form of (E)-1. Upon irradiation of this MeCN
solution at 365 nm, (E)-1 isomerizes to the Z form and a
Z photostationary state (Z-PSS, Z = 85%) is reached in
28 min, as estimated from UV/Vis spectroscopy by spectral
subtraction[10] (Figure 3). The process is perfectly reversible:
the Z isomer reverts back to the E form either by irradiation
at 254 nm (30 min) or thermally in the dark (150 min).
Figure 4. a) CD and b) UV/Vis spectra of a 5 mm solution of (E)-1/KI
(a), of 1/KI at the Z-PSS (g), and of 1 at the Z-PSS (c) in
MeCN.
information on the electronic transitions are available so far
for the 8-styrylguanine chromophore, the spectral changes
observed upon addition of potassium ion closely resemble
those reported for other unmodified lipophilic guanosi-
nes.[3a,b,d] The strong increase of the CD signal associated
with the formation of the (E)-1/K+ aggregate can analogously
be attributed to interchromophore couplings taking place in
the stacked complex. When samples of the (E)-1/K+ octa-
meric complex are irradiated at 365 nm, photoconversion to
the Z isomer takes place and the Z-PSS is reached in 30 min
for a 5 mm sample. The photoisomerization has a dramatic
effect on the assembled species. The CD spectrum of the
solution of 1/KI recorded at the Z-PSS shows very weak
signals: this spectrum is practically superimposable on the CD
spectrum of (Z)-1 prior to KI addition and it is similar to that
of uncomplexed (E)-1.
When a weighed amount of KI (0.125 mol per mol of
guanine, that is, 1/8) is added to a MeCN solution of (E)-1, the
1H NMR and CD spectra change dramatically, as expected
when the formation of stacked G-quartets templated by the
cation occurs. In particular, in the 1H NMR spectrum
(Figure 2c) the imino proton shifts downfield more than d =
3 ppm while the H1’ signal moves upfield by d = 0.4 ppm and
the amino signal becomes unobservably broad at room
1
temperature. No doubling of signals appears in the H NMR
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A comparison of the CD and UV spectra for (E)-1 before
and after K+ extraction points to the conclusion that the
intensity of the CD signal is mainly attributable to interchro-
mophoric interactions. In particular, the E form before K+
complexation shows a weak CD spectrum, in spite of the
strong absorbance in the corresponding UV spectrum.
Accordingly, the weak CD signal shown by the system at
the Z-PPS results from the disaggregation of the stacked
supramolecular complex and is not directly related to the
lower molar absorptivity of the Z isomer. The disappearance
of the strong CD bands at 255 and 350 nm is evidence of
decomposition of the complex: stacked G-quartets no longer
exist in solution.
absorptivity was observed for both the E and Z states after
five cycles.
In conclusion, by the introduction of a photoactive moiety
at C8 in a lipophilic guanosine derivative it is possible to
operate photocontrol over the self-assembly of the molecule,
such that the existence of G-quartets can be alternately
switched on and off (Figure 6).
The observation that (Z)-1 does not form (stacked) G-
quartets is most likely because in the Z form the phenyl group
of the styryl unit is twisted[11] with respect to the G-quartet
plane. The consequent steric hindrance could force quartets
away from van der Waals contact or it could produce a
conformational change around the glycosidic bond, which, in
turn, would hamper the stacking. Additionally, in the Z form
the N7 atom is probably shielded by the styryl unit and is no
longer available for H-bonding.
Figure 6. Phototriggering of guanosine self-assembly.
Unfortunately, no NMR studies could be carried out on
the Z-PSS solution: photoisomerization with standard Hg
lamps of samples large enough to be suitable for NMR
analysis produced substantial amounts of photocycloaddition
products, in the time required to attain the Z-PSS under these
conditions (see the Supporting Information). Hence, direct
detailed information on the type and extent of self-assembly
undergone by 1 when in the Z form in the presence of K+
could not be obtained. Although the disappearance of the
stacked octameric structure is evident from the CD spectrum,
the organization of (Z)-1 into other self-assembled species
cannot be ruled out.
As stated above, the Z form can be converted back to the
E form either photochemically, by irradiation at 254 nm, or
thermally. Retroisomerization to the E isomer determines, at
the supramolecular level, the re-creation of the octameric
complex: the CD spectrum of the solution at this point
perfectly overlaps the starting [(E)-1]8K+ trace.
Experimental Section
The photoisomerization of (E)-1 in spectrophotometric-grade aceto-
nitrile was performed at room temperature by irradiating the samples,
contained in 0.01 cm quartz cells, with the 150 W xenon lamp of the
dichrograph (JASCO J-710). The monochromator of the instrument
(slit width 3 mm) was employed to select the UV irradiation
wavelengths (365 and 254 nm).
Received: February 9, 2010
Published online: April 9, 2010
Keywords: G-quartet · guanine · photoisomerization ·
.
self-assembly · supramolecular chemistry
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