Stefano Lena

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.

Triggering of Guanosine Self‐Assembly by Light

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. In particular, self-assembly processes that can be controlled by photochemical stimuli are an actively pursued research field and one ultimate goal in supramolecular chemistry. In recent years, lipophilic guanine derivatives (lipoGs) have received increasing attention because of their rich supramolecular behavior. 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).

Ruthenium-Catalyzed Synthesis of 5-Amino-1,2,3-triazole-4-carboxylates for Triazole-Based Scaffolds: Beyond the Dimroth Rearrangement

The 5-amino-1,2,3-triazole-4-carboxylic acid is a suitable molecule for the preparation of collections of peptidomimetics or biologically active compounds based on the triazole scaffold. However, its chemistry may be influenced by the possibility of undergoing the Dimroth rearrangement. To overcome this problem, a protocol based on the ruthenium-catalyzed cycloaddition of N-Boc ynamides with azides has been developed to give a protected version of this triazole amino acid. When aryl or alkyl azides are reacted with N-Boc-aminopropiolates or arylynamides, the cycloaddition occurs with complete regiocontrol, while N-Boc-alkyl ynamides yield a mixture of regioisomers. The prepared amino acids were employed for the preparation of triazole-containing dipeptides having the structural motives typical of turn inducers. In addition, triazoles active as HSP90 inhibitors (as compound 41, IC50 = 29 nM) were synthesized.