Gian Piero Spada

Supramolecular architectures generated by self-assembly of guanosine derivatives

Natures use of a simple genetic code to enable lifes complex functions is an inspiration for supramolecular chemistry. DNA nucleobases carry the key information utilizing a variety of cooperative and non-covalent interactions such as hydrophobic, van der Waals, pi-pi stacking, ion-dipole and hydrogen bonding. This tutorial review describes some recent advances in the form and function provided by self-assembly of guanine (G) based systems. We attempt to make connections between the structures of the assemblies and their properties. The review begins with a brief historical context of G self-assembly in water and then describes studies on lipophilic guanosine analogs in organic solvents. The article also focuses on examples of how G analogs have been used as building blocks for functional applications in supramolecular chemistry, material science and nanotechnology.

Topological Characterization of Nucleic Acid G‐Quadruplexes by UV Absorption and Circular Dichroism

The emergence of nucleic acid four-stranded architectures, denominated G-quadruplexes as a prolific area of research, has led to an interest in the development of inexpensive methods for the rapid assessment of their structural characterization in solution. Research in this area is motivated by their potential impact in regulation of biological mechanisms and technological applications. For many applications, light absorption techniques, such as circular dichroism (CD) and UV, have been sufficient to discriminate the quadruplex fold from other architectures. CD is also useful to discriminate a single quadruplex topology from all other 25 generic folding topologies. Here we demonstrate the use of these techniques for characterizing three different types of G-quadruplex topologies classified through the sequence of glycosidic bond angles (GBA) adopted by guanosines of the G-quadruplex stem.

Dynamers at the Solid–Liquid Interface: Controlling the Reversible Assembly/Reassembly Process between Two Highly Ordered Supramolecular Guanine Motifs

Complex systems and phenomena in nature are dominated by reversible noncovalent interactions. Nucleobases, which are essential components of the genetic material in all living organisms, encode sophisticated programs for self-assembly into highly ordered and complex architectures, such as the fascinating double helix of DNA. Alongside Watson–Crick base pairing, which directs the formation of the helical structure of DNA, nucleobases can interact through other hydrogen-bonded motifs to form various complex supramolecular architectures, such as guanine (G) quadruplexes. The G quartet G4 , an hydrogen-bonded macrocycle typically formed by cation-templated assembly, was first identified in 1962 as the basis for the aggregation of 5’guanosine monophosphate (5’-GMP), and fits particularly well with contemporary studies in molecular self-assembly and noncovalent synthesis. Guanine is an extremely versatile building block: depending on its environment, it is able to self-assemble into various discrete architectures including dimers, ribbons, and macrocycles. 12] In the presence of certain cations, either G4-based octamers or columnar aggregates (supramolecular polymers) can be formed, depending on the concentration of the cation and nucleobase. The guanine-based structures are interesting for applications in organic electronics and synthesis of supramolecular hydrogels, whereas G quartets are known to have potential in several biological processes and in anticancer drug design, as they can act as enzyme telomerase inhibitors, and therefore are of importance for controlling tumor immortalization. 16, 17] While the self-assembly of guanines into G4-based architectures (not templated by a metal center) on solid surfaces has been studied by STM under ultrahigh vacuum (UHV), 19] STM explorations at the solid–liquid interface have been primarily carried out on guanosine derivatives. Although the structure of a guanine quadruplex templated by a metal center was introduced over 40 years ago, its visualization by STM once assembled at the solid–liquid interface has not been reported to date. We have studied the metal-templated reversible assembly/ reassembly process of a N-alkylguanine into highly ordered quartets and ribbons. Herein, we present a submolecularresolution STM visualization of such a process at the solid– liquid interface on highly oriented pyrolitic graphite (HOPG) surfaces. We focused our attention on the octadecyl guanine derivative 1 (see the Supporting Information for preparation). The presence of a long aliphatic side chain and the absence of the sugar with respect to previously studied guanosines were expected to promote the molecular physisorption on HOPG. The self-assembly of 1 alone on HOPG has been studied, and, upon subsequent addition of [2.2.2]cryptand, potassium picrate (K(pic) ), and trifluoromethanesulfonic acid (HTf), the reversible interconversion between two different highly ordered supramolecular motifs is triggered (Scheme 1). This process was previously indirectly shown by H NMR and circular dichroism spectroscopy to occur in solution. In general, the generation of hydrogen-bond-stabilized ordered motifs at the solid–liquid interface requires fine tuning of the interplay between interactions that involve solvent molecules, solute molecules, and the substrate. The STM observation of a conformational or assembly switching process that occurs at the solid–liquid interface cannot be obtained by operating when concentrated solutions are used, as dictated by the thermodynamics of physisorption at the solid–liquid interface. In a solution containing a large number of identical molecules that have two or more conformations, the component with a greater affinity for the substrate, that is, the component that offers a minimization of the free interface energy per unit area, will assemble on the surface, whereas the other components will remain in the supernatant solution. 27] To have full control over the switching process and immobilize all the components on the surface, and thus achieve a complete physisorption of all different components at the solid–liquid interface, it is mandatory to tune the stoichiometry of the molecules absorbed at surface. 29] At the solid–liquid interface, the number of molecules that are in [*] A. Ciesielski, Prof. P. Samor ISIS/UMR CNRS 7006, Universit de Strasbourg 8 all e Gaspard Monge, 67000 Strasbourg (France) E-mail: samori@unistra.fr

Guanosine Hydrogen-Bonded Scaffolds: A New Way to Control the Bottom-Up Realisation of Well-Defined Nanoarchitectures

Over the last two decades, guanosine-related molecules have been of interest in different areas, ranging from structural biology to medicinal chemistry, supramolecular chemistry and nanotechnology. The guanine base is a multiple hydrogen-bonding unit, capable also of binding to cations, and fits very well with contemporary studies in supramolecular chemistry, self-assembly and non-covalent synthesis. This Concepts article, after reviewing on the diversification of self-organised assemblies from guanosine-based low-molecular-weight molecules, will mainly focus on the use of guanine moiety as a potential scaffold for designing functional materials of tailored physical properties.

The Self‐Assembly of Lipophilic Guanosine Derivatives in Solution and on Solid Surfaces

The self-assembly of lipophilic deoxyguanosine derivatives 1 and 2 has been studied in solution by NMR spectroscopy and ESI-MS (electrospray ionization mass spectrometry). NMR data show the existence of two types of self-assembled, ribbonlike structures (A and B), which are connected at the guanine moieties through two different H-bonded networks. The first species (A), which is stable in the solid state and characterised by cyclic NH(2)-O(6) and NH(1)-N(7) hydrogen bonds, is detected soon after dissolving the polycrystalline powder in rigorously anhydrous CDCl3. In solution it slowly undergoes a structural transition towards a thermodynamically stable ribbon characterised by NH(1)-O(6) and NH(2)-N(3) cyclic hydrogen bonds (B). On the other hand, at surfaces, self-assembled ribbon nanostructures have been grown from solutions of derivative 1 both on mica and at the graphite-solution interface. They have been investigated by means of tapping mode scanning force microscopy (SFM) and scanning tunnelling microscopy (STM), respectively. SFM revealed dry, micrometer-long nanoribbons with a molecular cross-section. while STM imaging at submolecular resolution indicates a molecular packing of type A, like the one detected in the solid state. This indicates that, upon adsorption at the solid-liquid interface, the guanosine moieties undergo a structural rearrangement from a B-type to an A-type ribbon.

Gel-Like Lyomesophases Formed in Organic Solvents by Self-Assembled Guanine Ribbons

Lipophilic guanosine derivatives are self-assembled into ribbonlike aggregates, both in the crystal state and in solution. The structure of the ribbons has been characterised by single-crystal X-ray diffraction and, in solution, by NMR spectroscopy and ESI-MS. Two different ribbons with different patterns of hydrogen bonds are present in the solid state and in chloroform solutions. The gel-like phases obtained in hexadecane, toluene and chloroform have been investigated by optical microscopy and small-angle X-ray diffraction: the type of phase observed is related to the molecular structure of the compounds and depends dramatically on the solvent. The structures of the phases are discussed, with the presence of the two different ribbons being taken into account.

Induced Cholesteric Mesophases: Origin and Application

Abstract The relationship between the twisting power (β) and the molecular structure of the dopant and neraatic solvent are discussed. High values of β are observed whenever two (or more) planar or quasi-planar moieties, chirally distorted one with respect to the other, are present in the dopant. For high twisting powers, the mechanism of induction seems to be connected to the transfer of chirality from the solute to the solvent via chiral conformations of the latter. Sterochemical and analytical applications are briefly discussed.

Photodetectors fabricated from a self-assembly of a deoxyguanosine derivative

A metal–semiconductor–metal (MSM) photodetector has been fabricated using as the semiconductor, a self-assembled layer of a DNA basis, namely a deoxyguanosine derivative, deposited between two gold electrodes. These were defined lithographically on a SiO2 substrate, separated by a distance of about 120 nm. The resulting self-assembled guanosine crystal has been deposited in such a way to achieve striking semiconducting properties. We show that with these conditions, the I–V characteristics are independent of the crystal orientation. The device shows a high current response (differential resistance at room temperature ranges in MΩ) which is symmetric with respect to bias sign and dependent on the illumination conditions. This behavior can be explained by taking into account the standard MSM theory and its applications as a photodetector.

THE SELF-ASSEMBLY OF A LIPOPHILIC DEOXYGUANOSINE DERIVATIVE AND THE FORMATION OF A LIQUID-CRYSTALLINE PHASE IN HYDROCARBON SOLVENTS

The lipophilic 3′,5′-di-O-decanoyl-2′-deoxyguanosine (1) in CHCl3 undergoes extensive self-assembly, mediated by H-bonding between the guanine bases, to give ribbon-like aggregates. X-Ray investigation of the platelets obtained from CHCl3 reveals a disordered fibre-like structure consisting of stacks of the ribbon-like aggregates. The aggregates are completely different from the columnar structures, based on G-quartets, which are the building blocks of the mesophases formed by deoxyguanosine oligonucleotides in H2O. In pure hydrocarbons or in CHCl3/hydrocarbons, 1 forms a lyotropic liquid-crystalline phase.

Identifying guanosine self assembly at natural isotopic abundance by high-resolution 1H and 13C solid-state NMR spectroscopy.

By means of the (1)H chemical shifts and the proton-proton proximities as identified in (1)H double-quantum (DQ) combined rotation and multiple-pulse spectroscopy (CRAMPS) solid-state NMR correlation spectra, ribbon-like and quartet-like self-assembly can be identified for guanosine derivatives without isotopic labeling for which it was not possible to obtain single crystals suitable for diffraction. Specifically, characteristic spectral fingerprints are observed for dG(C10)(2) and dG(C3)(2) derivatives, for which quartet-like and ribbon-like self-assembly has been unambiguously identified by (15)N refocused INADEQUATE spectra in a previous study of (15)N-labeled derivatives (Pham, T. N.; et al. J. Am. Chem. Soc.2005, 127, 16018). The NH (1)H chemical shift is observed to be higher (13-15 ppm) for ribbon-like self-assembly as compared to 10-11 ppm for a quartet-like arrangement, corresponding to a change from NH···N to NH···O intermolecular hydrogen bonding. The order of the two NH(2)(1)H chemical shifts is also inverted, with the NH(2) proton closest in space to the NH proton having a higher or lower (1)H chemical shift than that of the other NH(2) proton for ribbon-like as opposed to quartet-like self-assembly. For the dG(C3)(2) derivative for which a single-crystal diffraction structure is available, the distinct resonances and DQ peaks are assigned by means of gauge-including projector-augmented wave (GIPAW) chemical shift calculations. In addition, (14)N-(1)H correlation spectra obtained at 850 MHz under fast (60 kHz) magic-angle spinning (MAS) confirm the assignment of the NH and NH(2) chemical shifts for the dG(C3)(2) derivative and allow longer range through-space N···H proximities to be identified, notably to the N7 nitrogens on the opposite hydrogen-bonding face.