Guanosine-based hydrogen-bonded 2D scaffolds: Metal-free formation of G-quartet and G-ribbon architectures at the solid/liquid interface

Article abstract of DOI:10.1039/c5cc03197d

We report on the synthesis and self-assembly of three novel lipophilic guanosine derivatives exposing a ferrocene moiety in the C(5′) position of the sugar unit. Their self-association in solution, and at the solid/liquid interface, can be tuned by varying the size and nature of the C(8)-substituent, leading to the generation of either G-ribbons, lamellar G-dimer based arrays or the G₄ cation-free architectures.

Full text of DOI:10.1039/c5cc03197d

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Guanosine-based hydrogen-bonded 2D scaffolds:
metal-free formation of G-quartet and G-ribbon
architectures at the solid/liquid interface†
Cite this: Chem. Commun., 2015,
51, 11677
Received 17th April 2015,
Accepted 9th June 2015
Mohamed El Garah,‡a Rosaria C. Perone,‡b Alejandro Santana Bonilla,cd
Sebastien Haar,a Marilena Campitiello,b Rafael Gutierrez,c Gianaurelio Cuniberti,*ce
´
Stefano Masiero,*b Artur Ciesielski*a and Paolo Samorı*a
`
DOI: 10.1039/c5cc03197d
www.rsc.org/chemcomm
We report on the synthesis and self-assembly of three novel lipophilic G-quartets (hereafter G4), which further pile up into octamers
guanosine derivatives exposing a ferrocene moiety in the C(50) position or higher order columnar aggregates. It is commonly believed
of the sugar unit. Their self-association in solution, and at the solid/ that templating alkali metal cations such as Na+ and K+ as well as
liquid interface, can be tuned by varying the size and nature of the alkaline earth and lanthanide cations are needed to stabilize the G4
C(8)-substituent, leading to the generation of either G-ribbons, formation.10 However, suitably designed guanosines, e.g. derivatives
lamellar G-dimer based arrays or the G4 cation-free architectures.
exposing a sterically demanding N,N-dimethylaniline moiety in the
C(8) position of the guanine core, were found to form cation-free G4
The controlled self-assembly of suitably designed molecular building structures both in solution and in the solid state of the bulk.11
blocks is a viable approach towards the construction of highly
On solid surfaces, G-based H-bonded supramolecular architec-
sophisticated nanostructured materials.1 Among various molecular tures were self-assembled into highly ordered motifs and studied by
components, supramolecular architectures with ad hoc structural scanning tunnelling microscopy (STM) under ultra-high vacuum.12
motifs can be obtained through the non-covalent self-association However, the STM explorations at the solid/liquid interfaces have
of natural2 and unnatural3 nucleobases on flat surfaces. Such shown numerous advantages, e.g. they provide an excellent
structures, when decorated with appropriate electrically/optically environment for in situ chemical modifications of adsorbed
active units, can be used as scaffolds to locate such units in pre- molecules.13 When guanosine derivatives are physisorbed at
determined positions in 2D,4 thereby paving the way towards a the solution/graphite interface, thermodynamically stable supra-
wide range of applications, e.g. in opto-electronics.5 Among the molecular ribbons, characterized by N(2)–Hꢀ ꢀ ꢀO(6) and N(1)–
four nucleobases of DNA, guanine (G)6 exhibits a very rich self- Hꢀ ꢀ ꢀN(7) H-bonds, were observed.
assembly behaviour: depending on the environmental conditions
Given the possibility of functionalizing the guanosines in
it can undergo different self-assembly pathways resulting in the sugar moiety, they represent ideal building blocks for the
various well-distinct architectures including dimers,7 tetramers,8 fabrication of conformationally rigid and structurally complex
ribbons,9 and helical structures.10 In the presence of certain metal architectures based on ribbons or G4 motifs. Yet, the formation
ions, G can form cyclic tetrameric architectures, also known as of G4 at the solid/liquid interface was observed only upon using
a templating metal center.2c
Ferrocenes are organometallic compounds possessing unique
a
´
´
ISIS & icFRC, Universite de Strasbourg & CNRS, 8 allee Gaspard Monge,
opto-electronic properties, which made them important active
components for applications in medicine and materials science.
In this context, the control over the self-assembly of ferrocene-
based architectures through molecular engineering is crucial in
order to control and improve their opto-electronic properties.
Here we have designed and synthesized three novel lipophilic
guanosine derivatives G1–G3 (see Scheme 1 and the ESI† for
synthetic details), exposing a ferrocene moiety in the C(50) position
of the sugar unit.
In order to tune the molecular self-assembly process at the
graphiteꢁsolution interface we substituted the nucleobase C(8)
position with different sterically demanding groups. The presence
of a long stearate side chain in the C(30) position of the sugar
67000 Strasbourg, France. E-mail: samori@unistra.fr, ciesielski@unistra.fr
b
`
Alma Mater Studiorum – Universita di Bologna,
Dipartimento di Chimica ‘‘G. Ciamician’’, Via S. Giacomo 11, 40126 Bologna,
Italy. E-mail: stefano.masiero@unibo.it
c Institute for Materials Science and Max Bergmann Center of Biomaterials,
Dresden University of Technology, 01062 Dresden, Germany
d Max Planck Institute for the Physics of Complex Systems, 01187 Dresden,
Germany
e Center for Advancing Electronics Dresden, Dresden Center for Computational
Materials Science, Dresden University of Technology, 01062 Dresden, Germany.
E-mail: g.cuniberti@tu-dresden.de
† Electronic supplementary information (ESI) available: Experimental details,
synthesis, full characterisation of new compounds, NMR spectra, and DFT. See
DOI: 10.1039/c5cc03197d
‡ These authors contributed equally to this work.
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Scheme 1 Chemical formulae of the investigated guanosine derivatives.
unit is expected to promote the molecular physisorption
on HOPG.
In line with previous studies on other guanosines,2a,b in the
absence of metal ions, G1 in solution forms an H-bonded
ribbon-like structure that involves the pairing N(2)–HꢀꢀꢀO(6) and
N(1)–HꢀꢀꢀN(7). 1H NMR spectra in CDCl3 (Fig. S1 in the ESI†) show
a progressive downfield shift of both N(1)–H and N(2)–H signals
upon cooling, while considerable line broadening occurs (e.g. see
the C(8)–H signal at d = 7.8 in Fig. S1, ESI†). G1 can complex alkali
metal ions to form a C4 symmetric octamer consisting of two
stacked G14, as evidenced from the characteristic changes both
in the 1H NMR and in the CD spectrum (Fig. S2, ESI†). The self-
assembly of G1 at the solid–liquid interface has been explored
by applying a 4 mL drop of a (100 ꢂ 2) mM G1 solution in
1-phenyloctane on HOPG. The STM image showed a crystalline
structure consisting of ribbon-like architectures forming a
lamellar motif (Fig. 1a). In this 2D crystal, the stearate side
chains are physisorbed flat on the surface and they are inter-
digitated between adjacent lamellae. The unit cell parameters
amount to a = (7.4 ꢂ 0.1) nm, b = (1.0 ꢂ 0.1) nm, and a = (88 ꢂ 2)1,
leading to an area A = (7.4 ꢂ 0.2) nm2, where each unit cell contains
four molecules. Thus, the area occupied by a single molecule G1
corresponds to (1.85 ꢂ 0.10) nm2. Given the size of the unit cell there
is not enough space to accommodate the ferrocene units on the
basal plane of the HOPG surface, thus it is most likely that they are
Fig. 1 STM images of physisorbed monolayers of the investigated guanosine
derivatives self-assembled on HOPG from solutions in 1-phenyloctane.
Ribbon-like structure of (a) G1 and (c) G2. (e) G4-based structure of G3. The
packing motifs are shown in (b), (d) and (f), respectively. Tunneling parameters
in (a), (c) and (e): average tunnelling current (It) = (35 ꢂ 2) pA, bias voltage (Vt) =
(400 ꢂ 25) mV.
either back-folded into supernatant solution or physisorbed as a and a = (90 ꢂ 2)1, lead to an area A = (3.7 ꢂ 0.1) nm2, where each
second layer on top of the guanosine first layer. Unfortunately, unit cell contains two molecules. Thus, the area occupied by a
despite the high spatial resolution achieved by STM imaging, we single molecule G2 amounts to (1.85 ꢂ 0.10) nm2. While the area
are unable to rule out any of these two scenarios. The monitored occupied by single molecule G2 is identical to that of G1, their
supramolecular motif can be well-described by the formation of a 1D self-assembled patterns are markedly different (see Fig. 1a vs. c).
hydrogen-bonded ribbon that involves the pairing N(2)–HꢀꢀꢀO(6) In particular, the appearance of hollow features within the G2
and N(1)–Hꢀ ꢀ ꢀN(7) (see the model in Fig. 1b and Fig. S12, ESI†). ribbon core (indicated with arrows in the inset of Fig. 1c) as well
This self-assembly behaviour is in good agreement with NMR as different orientations of stearate side chains vs. the main
solution data.
lamellar axis (601 and 901 for G1 and G2 patterns, respectively)
In order to steer the G self-assembly towards different provides unambiguous evidence for a different self-assembly motif.
supramolecular motifs, we explored the effect of the functionaliza- In fact, the G2 supramolecular motif can be well-described by the
tion of the C(8) position of the guanine core, by substituting the formation of H-bonded dimers, which involves the pairing N(1)–
proton with a Br atom (G2). Monolayers of G2 have been generated HꢀꢀꢀO(6) (see models in Fig. 1d and 2). Each dimer interacts
by applying on the HOPG surface a 4 mL drop of a (100 ꢂ 2) mM laterally with neighbouring dimers via N(2)–HꢀꢀꢀBr(8) bonding,
solution of G2 in 1-phenyloctane. The STM imaging (Fig. 1c) displays resulting in the formation of 1D lamellar arrays. Similarly to the
a crystalline structure consisting of lamellar architectures. In a case of G1 ribbons, ferrocene units are likely back-folded into
G2-based 2D crystal, the stearate side chains are physisorbed flat supernatant solution or adsorbed as a second layer. Formation of
on the surface and are interdigitated between adjacent lamellae. such structures highlights the role played by bulky bromine atoms
The unit cell parameters, a = (4.1 ꢂ 0.1) nm, b = (0.9 ꢂ 0.1) nm, in the C(8) position of the G core, which introduced N(2)–HꢀꢀꢀBr(8)
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formation of all-syn isolated G34. Although no direct and conclusive
evidence could be gathered from the spectra, an in-depth inspection
of the models suggests anti G34 or anti G3-dimers, analogous to
those found for G2 on surfaces, as the possible structure for the
minor species. STM investigation of sub-monolayer-thick films
obtained from a (100 ꢂ 2) mM solution of G3 revealed the formation
of a new type of pattern. In this 2D crystal, because of steric
hindrance brought into play by the phenol unit, only three out of
four stearate side chains are physisorbed flat on the surface. The unit
cell parameters amount to a = (4.5 ꢂ 0.1) nm, b = (1.8 ꢂ 0.1) nm, and
a = (90 ꢂ 2)1, leading to an area A = (8.1 ꢂ 0.1) nm2, where each unit
cell contains two molecules. Thus, the area occupied by a single
molecule G3 corresponds to (4.1 ꢂ 0.1) nm2. The packing of G3
molecules is very loose as evidenced by the large discrepancy
between the areas occupied by single molecules G1, G2 and G3.
The STM inset in Fig. 1e clearly shows the presence of macrocyclic
bright features decorated with four small protrusions (indicated with
white arrows in the inset), which can be assigned to G34 and
ferrocene groups (backfolded into the supernatant solution), respec-
tively. Because of the presence of sterically demanding phenol
Fig. 2 Calculated structures of G1 H-bonded ribbon, G2 lamella and G34
cation-free quartet.
bonding, thus forcing self-assembly towards an unprecedented substituents in the C(8) position of G3, the formation of H-bonded
ribbon structure.
ribbon-like structures is hindered,11 leading to the generation of
1H-NMR spectra of G2 recorded upon cooling a solution in cyclic tetrameric H-bonded structures characterized by the N(1)–
CDCl3 (Fig. S3, ESI†) show a progressive splitting of the broad HꢀꢀꢀO(6) and N(2)–HꢀꢀꢀN(7) motif, whose the existence was also
N(2)–H singlet at d = 6.1 into two signals (bonded and free N(2)–H, at indicated by NOE data in solution. While NOE analysis suggests the
d = 8.7 and d = 5.7, respectively). The chemical shifts for the N(2)–H presence of all-syn isolated G34, as the main species, once adsorbed
protons are close to those reported for a similar compound (d = 8.50 on the surface both all-syn and all-anti G34 will occupy the same
and d = 5.44),10b but differ from those of the two stacked G4 formed areas, therefore we cannot unambiguously exclude the existence of
by G1 in the presence of metal ions (marked signals in Fig. S1, ESI†) the former over the latter. Noteworthily, some G34 appear brighter in
as well as from those of an isolated G4 (d = 9.81 and d = 5.15).11 the STM image, which can be explained by the interference of the
Previously,10b some of us have studied the self-assembly of a similar supramolecular lattice and the underlying HOPG surface.
8-bromo lipophilic guanosine derivative in solution by NMR spectro-
To provide a molecular understanding of the self-assembly of the
scopy. It was concluded that this signal splitting can be attributed to three G derivatives in 2D and gain insight into the formation and
the existence of isolated G4 on the basis of the well-known preference stability of supramolecular structures, we have performed density
of 8-bromo guanosine to adopt a syn conformation around the functional theory (DFT) calculations using the hybrid Gaussian and
glycosidic bond and the lack of any liquid crystalline behavior. plane-wave method (GPW), implemented in the QUICKSTEP module
Although G2 behaves similarly and the lack of substantial line of the CP2K package.14 We used the B3LYP hybrid exchange–
broadening points to the existence of small size aggregates, the correlation potential,15 whereas Grimme’s DFT-D2 method16
present results suggest to reconsider the supramolecular behavior was employed for taking into account the dispersion forces. The
of G2 in solution, taking into account the existence of small, additional details of the computational methodology, as well as of
possibly dimer-like, aggregates.
the results for the structural and electronic properties of the different
We then decided to replace the Br atom with a more neutral assembly motifs, are provided in the ESI.† To bestow information on
group, which is also more sterically demanding, i.e. phenol (G3). The the intermolecular binding mechanisms, we have focused our
behaviour of G3 in solution is very peculiar. In analogy to G2, the G3 attention on unravelling the interplay between H-bonds, holding
molecule is unable to complex metal ions to form G4 stacked together the guanine cores and the effective metallic repulsion
structures, as no changes can be detected both on CD (Fig. S4 and coming from the four iron cations present in the ferrocenes.
S8, ESI†) and on 1H NMR spectra after the addition of K+. Further-
Noteworthily, as can be seen in the suggested monolayer
more, in the absence of added ions, both N(1)–H and N(2)–H signals packing motifs, two types of intramolecular interactions can be
split upon cooling. In particular, the N(2)–H signal splits into two distinguished, i.e., the hydrogen-bonding (or N(2)–Hꢀ ꢀ ꢀBr(8)
couples of new signals in a 2:1 ratio (Fig. S5, ESI†). A couple of interactions in the case of the G2 structure) between G cores
signals at ca. d = 8 can be attributed to H-bonded N(2)–Hs, while the and the van der Waals interaction, resulting from the inter-
other couple of signals appearing at ca. d = 3 ppm can be ascribed to digitation of the stearate chains. In order to determine their
free N(2)–Hs. The existence of two sets of resonances for both imino contribution to the total cohesive energy, we calculated the
and amino protons in a 2 : 1 ratio points to the existence of two intermolecular dissociation energy for each of the different
different supramolecular species. On the basis of NOE experiments four-molecule-based configurations (see Fig. 2) exhibited in
(Fig. S6 and S7, ESI†), the major species can be ascribed to the three G-based complexes, and the results are reported in Table 1.
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Table 1 Calculated bonding energiesa
Agence Nationale de la Recherche through the LabEx project
Chemistry of Complex Systems (ANR-10-LABX-0026_CSC) and
the International Center for Frontier Research in Chemistry
(icFRC).
System
Etot
EH-bond
EBr–HN
G1
G2
G3
ꢁ52.1
ꢁ50.8
ꢁ40.1
ꢁ13.0
ꢁ11.9
ꢁ10.0
—
ꢁ13.9
—
a
Notes and references
Etot
,
total intermolecular interaction energy, EH-bond
,
average
hydrogen-bond energy, EBr–HN, energy of bromine–NH interactions, all
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The presented first-principle calculations have not only elucidated
the different mechanically stable molecular arrangements, but
more importantly, have shed light on the energetics of intra-
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