Jeffery T. Davis

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.

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl(-)/HCO(3)(-) exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems.

Large and stable transmembrane pores from guanosine-bile acid conjugates.

United States Department of Energy, Office of Basic Energy Sciences and the Maryland Department of Economic and Business Development for support from the Maryland Nano-Biotechnology Initiative.

Structurally simple lipid bilayer transport agents for chloride and bicarbonate

A new series of structurally simple compounds containing thiourea groups have been shown by a combination of ion-selective electrode and 13C NMR techniques to be potent chloride-bicarbonate exchange agents that function at low concentration in POPC and POPC/cholesterol membranes.

Ion‐Pair Recognition by Nucleoside Self‐Assembly: Guanosine Hexadecamers Bind Cations and Anions

G-Quartets can bind anions as well as cations: Solid-state and solution data indicate that self-assembled ion-pair receptors are formed from 16 guanosine monomers, 2 divalent cations, and 4 picrate anions. Hydrogen-bonding, ion-dipole, and base-stacking interactions combine to give a tubular complex with a cation-loaded interior. An array of hydrogen-bond donors on the receptors surface then enables anion coordination (see schematic representation, shaded rectangles=G-quartets, shaded circles=cations).

A G4·K+ Hydrogel Stabilized by an Anion

Supramolecular hydrogels derived from natural products have promising applications in diagnostics, drug delivery, and tissue engineering. We studied the formation of a long-lived hydrogel made by mixing guanosine (G, 1) with 0.5 equiv of KB(OH)4. This ratio of borate anion to ligand is crucial for gelation as it links two molecules of 1, which facilitates cation-templated assembly of G4·K(+) quartets. The guanosine-borate (GB) hydrogel, which was characterized by cryogenic transmission electron microscopy and circular dichroism and (11)B magic-angle-spinning NMR spectroscopy, is stable in water that contains physiologically relevant concentrations of K(+). Furthermore, non-covalent interactions, such as electrostatics, π-stacking, and hydrogen bonding, enable the incorporation of a cationic dye and nucleosides into the GB hydrogel.

Catechols as Membrane Anion Transporters

We report that an amphiphilic bis-catechol (3) functions as a transmembrane anion transporter. Activity depends on the catechols substitution and amphiphilicity. We also describe a liposomal assay that allows one to readily measure anion transport selectivity. This assay reveals that anion transport selectivity for this amphiphilic bis-catechol follows a Hofmeister sequence wherein anions that are easier to dehydrate are made more permeable to the membrane by 3.

G4-Quartet·M + Borate Hydrogels

The ability to modulate the physical properties of a supramolecular hydrogel may be beneficial for biomaterial and biomedical applications. We find that guanosine (G 1), when combined with 0.5 equiv of potassium borate, forms a strong, self-supporting hydrogel with elastic moduli >10 kPa. The countercation in the borate salt (MB(OH)4) significantly alters the physical properties of the hydrogel. The gelator combination of G 1 and KB(OH)4 formed the strongest hydrogel, while the weakest system was obtained with LiB(OH)4, as judged by (1)H NMR and rheology. Data from powder XRD, (1)H double-quantum solid-state magic-angle spinning (MAS) NMR and small-angle neutron scattering (SANS) were consistent with a structural model that involves formation of borate dimers and G4·K(+) quartets by G 1 and KB(OH)4. Stacking of these G4·M(+) quartets into G4-nanowires gives a hydrogel. We found that the M(+) cation helps stabilize the anionic guanosine-borate (GB) diesters, as well as the G4-quartets. Supplementing the standard gelator mixture of G 1 and 0.5 equiv of KB(OH)4 with additional KCl or KNO3 increased the strength of the hydrogel. We found that thioflavin T fluoresces in the presence of G4·M(+) precursor structures. This fluorescence response for thioflavin T was the greatest for the K(+) GB system, presumably due to the enhanced interaction of the dye with the more stable G4·K(+) quartets. The fluorescence of thioflavin T increased as a function of gelator concentration with an increase that correlated with the systems gel point, as measured by solution viscosity.

Cation-directed self-assembly of lipophilic nucleosides: the cation's central role in the structure and dynamics of a hydrogen-bonded assembly

Abstract This paper focuses on the cations central role in controlling the self-assembly of a lipophilic nucleoside, isoguanosine (isoG) 2 , in organic solvents. First, we use 1H NMR spectroscopy to show that a Ba2+ cation directs a mixture of the isomers isoG 2 and guanosine (G) 1 to self-sort into separate assemblies, without any detectable G–isoG cross-association. Next, we use electrospray ionization mass spectrometry to show that the cation controls the reversible self-assembly of isoG 2 . Final section focuses on the dynamic exchange of components between two different assemblies, namely, a (isoG 2 )5–Li+ pentamer and a (isoG 2 )10–Li+ decamer. Our 1H and 7Li NMR data is consistent with a cation-filled pentamer, (isoG 2 )5–Li+, moving as a unit during a bimolecular pentamer–decamer exchange. These data highlight crucial aspects regarding the cation-templated self-assembly of lipophilic nucleosides: (1) the structural information encoded within each nucleoside dictates the size and shape of the hydrogen-bonded assembly; (2) a cation is required to template and stabilize these discrete hydrogen-bonded assemblies, and (3) dynamic exchange of cation-filled, hydrogen-bonded units is likely to be a hallmark of these multi-layered nucleoside assemblies.

Stabilizing guanosine-sterol ion channels with a carbamate to urea modification in the linker.

The use of a bis-urea lithocholamide linker within a guanosine-sterol dimer resulted in formation of large and stable ion channels. The channels were longer-lived than those formed by the corresponding bis-carbamate.