The stepwise supramolecular organisation of guanosine derivatives

Several supramolecular architectures generated by guanosine derivatives are described. The research started from the fortuitous observation of a lyotropic behavior exhibited by a guanylic nucleotide in water. This observation stimulated extensive research on several natural and lipophilic guanosine derivatives which self-assemble in different architectures (discs, ribbons, helices...), according to their structure and environment. These ordered structures can be used as scaffolds for photo- or electro-active moieties and for the fabrication of molecular electronic devices.     

N,N'-disubstituted ureas: influence of substituents on the formation of supramolecular polymers

Symmetrical N,N'-disubstituted ureas have been synthesized and characterized. Among them, the branched dialkylureas prepared are highly soluble in organic media. Moreover, the solutions obtained are very viscous in heptane, if the branched alkyl groups are not too bulky (i.e. a methyl group on the alpha carbon, or an ethyl group on the beta carbon). Due to the strong, bifurcated hydrogen bonds between the urea moieties, linear supramolecular polymers are formed. The degree of association of these supramolecular polymers has been determined by FTIR spectroscopy.     

Self-assembly of folic acid derivatives: induction of supramolecular chirality by hierarchical chiral structures

Hierarchical chiral structures made up of dendritic oligo(L- or D-glutamic acid) moieties of folic acid derivatives induce supramolecular chirality in the self-assembled columnar structures of the folic acids. These folic acids self-assemble through the intermolecular hydrogen bonds of the pterin rings to form disklike tetramers. In the neat states, the stacked tetramers form thermotropic hexagonal columnar phases over wide temperature ranges, including room temperature. Addition of alkali metal salts induces chirality in the columnar phases. In dilute solution states in a relatively polar solvent (chloroform), the folic acid derivatives form non-chiral, self-assembled structures. In the presence of sodium triflate, the folic acid forms chiral columnar assemblies through the oligo(L-glutamic acid) moiety, similar to those formed in the liquid-crystalline (LC) states. The enantiomer of the folic acid induces columnar assemblies with reversed helicity. In the case of the diastereomer, no induced helicity is observed. Application of an apolar solvent (dodecane) drives the folic acid derivatives to form chiral assemblies in the absence of ions. In this case, lipophilic interactions promote nanophase segregation, which enhances the formation of chiral columns. Interestingly, the chiral supramolecular structure of the diastereomer induces the most intense circular dichroism. In both cases, the molecular chirality in the oligo(glutamate) moieties yields supramolecular chirality of the folic acids that self-assemble through cooperative molecular interactions.     

Using Diffusion NMR To Characterize Guanosine Self‐Association: Insights into Structure and Mechanism

This paper presents results from a series of pulsed field gradient (PFG) NMR studies on lipophilic guanosine nucleosides that undergo cation‐templated assembly in organic solvents. The use of PFG‐NMR to measure diffusion coefficients for the different aggregates allowed us to observe the influences of cation, solvent and anion on the self‐assembly process. Three case studies are presented. In the first study, diffusion NMR confirmed formation of a hexadecameric G‐quadruplex [G 1 ]₁₆ ? 4 K⁺ ? 4 pic^? in CD₃CN. Furthermore, hexadecamer formation from 5′‐TBDMS‐2′,3′‐isopropylidene G 1 and K⁺ picrate was shown to be a cooperative process in CD₃CN. In the second study, diffusion NMR studies on 5′‐(3,5‐bis(methoxy)benzoyl)‐2′,3′‐isopropylidene G 4 showed that hierarchical self‐association of G₈‐octamers is controlled by the K⁺ cation. Evidence for formation of both discrete G₈‐octamers and G₁₆‐hexadecamers in CD₂Cl₂ was obtained. The position of this octamer–hexadecamer equilibrium was shown to depend on the K⁺ concentration. In the third case, diffusion NMR was used to determine the size of a guanosine self‐assembly where NMR signal integration was ambiguous. Thus, both diffusion NMR and ESI‐MS show that 5′‐O‐acetyl‐2′,3′‐O‐isopropylidene G 7 and Na⁺ picrate form a doubly charged octamer [G 7 ]₈ ? 2 Na⁺ ? 2 pic^? 9 in CD₂Cl₂. The anion's role in stabilizing this particular complex is discussed. In all three cases the information gained from the diffusion NMR technique enabled us to better understand the self‐assembly processes, especially regarding the roles of cation, anion and solvent.     

Self‐Assembly of 3,6‐Bis(4‐triazolyl)pyridazine Ligands with Copper(I) and Silver(I) Ions: Time‐Dependant 2D‐NOESY and Ultracentrifuge Measurements

Two 3,6‐bis(R‐1H‐1,2,3‐triazol‐4‐yl)pyridazines (R=mesityl, monodisperse (CH₂ CH₂O)₁₂CH₃) were synthesized by the copper(I)‐catalyzed azide–alkyne cycloaddition and self‐assembled with tetrakis(acetonitrile)copper(I) hexafluorophosphate and silver(I) hexafluoroantimonate in dichloromethane. The obtained copper(I) complexes were characterized in detail by time‐dependent 1D [¹H, ¹³C] and 2D [¹H‐NOESY] NMR spectroscopy, elemental analysis, high‐resolution ESI‐TOF mass spectrometry, and analytical ultracentrifugation. The latter characterization methods, as well as the comparison to analog 3,6‐di(2‐pyridyl)pyridazine (dppn) systems and their corresponding copper(I) and silver(I) complexes indicated that the herein described 3,6‐bis(1H‐1,2,3‐triazol‐4‐yl)pyridazine ligands form [2×2] supramolecular grids. However, in the case of the 3,6‐bis(1‐mesityl‐1H‐1,2,3‐triazol‐4‐yl)pyridazine ligand, the resultant red‐colored copper(I) complex turned out to be metastable in an acetone solution. This behavior in solution was studied by NMR spectroscopy, and it led to the conclusion that the copper(I) complex transforms irreversibly into at least one different metal complex species.     

N.Br halogen bonding: one-dimensional infinite chains through the self-assembly of dibromotetrafluorobenzenes with dipyridyl derivatives

The N.Br halogen bonding drives the self-assembly of 1,4-dibromotetrafluorobenzene (1 a) and its 1,3 or 1,2 analogues (1 b,c, respectively) with dipyridyl derivatives 2 a,b. The isomeric supramolecular architectures 3 a-f are obtained as cocrystals that are stable in the air at room temperature. The solid-state features of these 1D infinite chains 3 have been fully characterized by single-crystal X-ray, Raman, and IR analyses. The occurrence of N.Br halogen bonding in solution has been detected with (19)F NMR spectroscopy. The N.Br halogen bonding is highly selective and directional and the geometry of the single strands of noncovalent copolymers 3 is programmed by the geometry of halogen-bonding donor and acceptor sites on the starting modules. The composition and topology of the instructed networks can be predicted with great accuracy. Experiments of competitive cocrystal formation established the strength of the N.Br interaction relative to other halogen bondings and the ability of different modules 1 to be involved in site-selective supramolecular syntheses.     

Self-assembly of an alkylated guanosine derivative into ordered supramolecular nanoribbons in solution and on solid surfaces

We report on the synthesis and self-assembly of a guanosine derivative bearing an alkyloxy side group under different environmental conditions. This derivative was found to spontaneously form ordered supramolecular nanoribbons in which the individual nucleobases are interacting through H-bonds. In toluene and chloroform solutions the formation of gel-like liquid-crystalline phases was observed. Sub-molecularly resolved scanning tunneling microscopic imaging of monolayers physisorbed at the graphite-solution interface revealed highly ordered two-dimensional networks. The recorded intramolecular contrast can be ascribed to the electronic properties of the different moieties composing the molecule, as proven by quantum-chemical calculations. This self-assembly behavior is in excellent agreement with that of 5'-O-acylated guanosines, which are also characterized by a self-assembled motif of guanosines that resembles parallel ribbons. Therefore, for guanosine derivatives (without sterically demanding groups on the guanine base) the formation of supramolecular nanoribbons in solution, in the solid state, and on flat surfaces is universal. This result is truly important in view of the electronic properties of these supramolecular anisotropic architectures and thus for potential applications in the fields of nano- and opto-electronics.     

One Ligand in Dual Roles: Self‐Assembly of a Bis‐Rhomboidal‐Shaped,Three‐Dimensional Molecular Wheel

A facile high yield, self‐assembly process that leads to a terpyridine‐based, three‐dimensional, bis‐rhomboidal‐shaped, molecular wheel is reported. The desired coordination‐driven supramolecular wheel involves eight structurally distorted tristerpyridine (tpy) ligands possessing a 60° angle between the adjacent tpy units and twelve Zn²⁺ ions. The tpy ligand plays dual roles in the self‐assembly process: two are staggered at 180° to create the internal hub, while six produce the external rim. The wheel can be readily generated by mixing the tpy ligand and Zn²⁺ in a stoichiometric ratio of 2:3; full characterization is provided by ESI‐MS, NMR spectroscopy, and TEM imaging.     

Self-assembled ionophores from isoguanosine: diffusion NMR spectroscopy clarifies cation's and anion's influence on supramolecular structure

Cation-templated self-assembly of the lipophilic isoguanosine (isoG 1) with different monovalent cations (M(+)=Li(+), Na(+), K(+), NH(4) (+), and Cs(+)) was studied in solvents of different polarity by using diffusion NMR spectroscopy. Previous studies that did not use diffusion NMR techniques concluded that isoG 1 forms both pentamers (isoG 1)(5)M(+) and decamers (isoG 1)(10)M(+) in the presence of alkali-metal cations. The present diffusion NMR studies demonstrate, however, that isoG 1 does not form (isoG 1)(5)M(+) pentamers. In fact, the diffusion NMR data indicates that both doubly charged decamers of formula (isoG 1)(10)2 M(+) and singly charged decamers, (isoG 1)(10)M(+), are formed with lithium, sodium, potassium, and ammonium tetraphenylborate salts (LiB(Ph)(4), KB(Ph)(4), NaB(Ph)(4) and NH(4)B(Ph)(4)), depending on the isoG 1:salt stoichiometry of the solution. In the presence of CsB(Ph)(4), isoG 1 affords only the singly charged decamers (isoG 1)(10)Cs(+). By monitoring the diffusion coefficient of the B(Ph)(4) (-) ion in the different mixtures of solvents, we also concluded that the anion is more strongly associated to the doubly charged decamers (isoG 1)(10)2 M(+) than to the singly charged decamers (isoG 1)(10)M(+). The (isoG 1)(10)2 M(+) species can, however, exist in solution without the mediation of the anion. This last conclusion was supported by the finding that the doubly charged decamers (isoG 1)(10)2 M(+) also prevail in 1:1 CD(3)CN:CDCl(3), a solvent mixture in which the B(Ph)(4) (-) ion does not interact significantly with the self-assembled complex. These diffusion measurements, which have provided new and improved structural information about these decameric isoG 1 assemblies, demonstrate the utility of combining diffusion NMR techniques with conventional NMR methods in seeking to characterize labile, multicomponent, supramolecular systems in solution, especially those with high symmetry.     

Investigation of guanosine-quartet assemblies by vibrational and electronic circular dichroism spectroscopy, a novel approach for studying supramolecular entities

The self-assembly of guanosine-5'-hydrazide G-1 in D(2)O, in the presence and absence of sodium cations, has been investigated by chiroptical techniques: electronic (ECD) and the newly introduced vibrational (VCD) circular dichroism spectroscopy. Using a combination of ECD and VCD with other methods such as IR, electron microscopy, and electrospray ionization mass spectrometry (ESI-MS) it was found that G-1 produces long-range chiral aggregates consisting of G-quartets, (G-1)(4), subsequently stacked into columns, [(G-1)(4)](n), induced by binding of metal cations between the (G-1)(4) species. This process, accompanied by gelation of the sample, is highly efficient in the presence of an excess of sodium cations, leading to aggregates with strong quartet-quartet interaction. Thermally induced conformational changes and conformational stability of guanosine-5'-hydrazide assemblies were studied by chiroptical techniques and the melting temperature of the hydrogels formed was obtained. The temperature-dependent experiments indicate that the long-range supramolecular aggregates are dissociated by increasing temperature into less ordered species, monomers, or other intermediates in equilibrium, as indicated by MS experiments.     

Octahydroxypyridine[4]arene self-assembles spontaneously to form hexameric capsules and dimeric aggregates

In recent years it has been observed that resorcin[4]arenes and pyrogallol[4]arenes form hydrogen-bonded hexameric capsules in nonpolar solvents. In the present study we have used NMR spectroscopy, with an emphasis on diffusion NMR, to investigate the self-assembly and the aggregation mode of solutions of octahydroxypyridine[4]arene (1 b) in chloroform. In spectroscopic studies, the hexameric capsule of C-undecylresorcin[4]arene (2 b) was used as a reference compound and in some cases also as an internal reference. The current diffusion NMR spectroscopy study shows, in contrast to a previous report, that compound 1 b self-assembles spontaneously into hexameric and dimeric aggregates in solutions in chloroform. The (1)H NMR and diffusion NMR spectroscopic studies on a solution of 1 b in CHCl(3) show the presence of new upfield-shifted peaks, which diffuse with the same diffusion coefficient as the hexameric peaks in the spectrum. Therefore, these new upfield-shifted peaks were attributed to encapsulated CHCl(3) molecules. Interestingly, diffusion NMR measurements showed that the addition of trifluoroacetic acid (6.7 equiv), which had no effect on the hexameric capsules of 2 b, led to the disassembly of the hexamer and the dimer of 1 b into its monomers. Therefore, we conclude that compound 1 b self-assembles spontaneously into hexameric capsules in nonpolar organic solvents, as do resorcin[4]arenes 2 b and 2 c and pyrogallol[4]arenes 3 a and 3 b.