SELF-ASSEMBLED IONOPHORES FROM ISOGUANOSINE

The isoguanosine (isoG) mononucleoside 3 forms a C-4-symmetric tetramer in organic solvents. The isoG tetramer 6 has been characterized by 2D NMR spectroscopy, UV spectroscopy, and FAB mass spectrometry. Specific NOEs between the exocyclic C6NH2 amino protons and the ribose H1' and H2' protons confirmed the isoG self-association and was the basis for the tetramer model. Molecular models of isoG dimers, trimers, and tetramers show that only the C-4-symmetric tetramer 6 is consistent with the observed NH6-H1', H2' NOEs. In the isoG tetramer, hydrogen bonds between C6NHA and a purine NS bring both exocyclic amino protons within 3-4 Angstrom of the adjacent monomer's ribose H1' and H2' protons. The isoG tetramer 6 organizes by hydrogen bonding between the Watson-Crick face of one isoG base and the complementary bottom edge of another purine. The tetramer is stabilized by an inner and outer ring of hydrogen bonds. The inner ring forms between the imino NH1 proton of one monomer and the C2 carbonyl oxygen of an adjacent monomer, while the outer ring is made up of four NH6-N3 hydrogen bonds. The isoG tetramer is thermodynamically very stable, with a K-s of ca. 10(9)-10(10) M(-3) at room temperature, and a Delta G degrees of tetramer formation of -12.5 kcal mol(-1) in d(6)-acetone at 25 degrees C. The van't Hoff plots indicated that the thermodynamic parameters for tetramer formation were Delta H degrees = -18.2 kcal mol(-1) and Delta S degrees(298) = -19.1 eu Each isoG C2 oxygen in the tetramer has a nonbonded electron pair that points into a central cavity, enabling selective cation coordination. Solutions of the isoG mononucleoside 3 in d(6)-acetone were titrated with LiCl, NaI, KI, and BaI2. Each of these ions had a dramatic effect on the isoG structural equilibrium. Thus, Li+ destabilized the tetramer and shifted the equilibrium back to the monomer. Low concentrations of Na+, on the other hand, stabilized the tetramer. Titrations of solutions of isoG 3 with the larger cations, K+ and Ba+2, indicated that 1 equiv of metal coordinated 8 nucleotide monomers, suggesting formation of a metal-stabilized octamer. The NMR analysis indicates that the isoG-K+ tetramer 6 is much more stable than the corresponding guanosine-K+ complex.