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The mononucleoside, 5‘-(tert-butyldimethylsilyl)-2‘,3‘-O-isopropylidene isoguanosine (isoG) 2, has a strong affinity for alkali metal cations. Previously, it was shown that isoG 2 self-assembles via hydrogen bonds to give a stable tetramer, (isoG)4 4, in organic solvents (Davis et al. J. Org. Chem. 1995, 60, 4167−4176). The isoG tetramer 4 can then coordinate metal cations. In this present study, vapor phase osmometry and further 1H NMR experiments confirmed that isoG 2 self-assembles via complementary hydrogen bonds to form tetramer 4. Molecular models obtained from molecular dynamics and MM2 energy minimization indicate that the isoG tetramer 4 is bowl-shaped, with four C2 oxygens located on the tetramer's convex surface. It is likely that these four oxygens on the tetramer's convex face coordinate cations. Potassium picrate was used to determine the stoichiometry of the isoG-K+ complex and its K+ binding affinity. Both 1H NMR and UV−vis spectroscopic analysis demonstrated that isoG 2 forms an octamer, (isoG)8-K+ (5), in the presence of potassium picrate in CDCl3 and CD3CN. The octamer (isoG)8-K+ (5) has a single set of 1H NMR resonances, even at −90 °C, consistent with a D 4-symmetric head-to-head stacking of two tetramers around the central K+ cation. Analysis of the picrate's optical spectra indicated that the picrate salt of (isoG)8-K+ (5) is a separated ion pair in CDCl3, consistent with the K+ being sandwiched between two isoG tetramers. Picrate extraction experiments revealed that (isoG)8 5 is an impressive ionophore, with a K+ association constant (log K a = 8.2 M-1) approaching that of 18-crown-6 ether derivatives. Indeed, NMR competition experiments for K+ binding between dicyclohexano-18-crown-6 and isoG 2 confirm that the K+ binding constants in CDCl3 for the crown ether and for the self-assembled ionophore are of the same magnitude (K a = 108 M-1).

Two-dimensional NMR was used to determine the solution structure of an undecanucleotide duplex, d(CGGTCACGAGG).d(CCTCGTGACCG), in which (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene is covalently bonded to the exocyclic N(6)() amino group of the central deoxyadenosine, dA(6), through trans addition at C10 of the epoxide (to give a 10S adduct). The present study represents the first NMR structure of a benzo[a]pyrene (10S)-dA adduct in DNA with a complementary T opposite the modified dA. Exchangeable and nonexchangeable protons of the modified duplex were assigned by the use of TOCSY (in D(2)O) and NOESY spectra (in H(2)O and D(2)O). Sequential NOEs expected for a B-type DNA conformation with typical Watson-Crick base pairing are observed along the duplex, except at the lesion site. We observed a strong intraresidue NOE cross-peak between H1' and H8 of the modified dA(6). The sugar H2' and H2' ' of dC(5) lacked NOE cross-peaks with H8 of dA(6) but showed weak interactions with H2 of dA(6) instead. In addition, the chemical shift of the H8 proton (7.51 ppm) of dA(6) appears at a higher field than that of H2 (8.48 ppm). These NOE and chemical shift data for the dA(6) base protons are typical of a syn glycosidic bond at the modified base. Restrained molecular dynamics/energy minimization calculations show that the hydrocarbon is intercalated from the major groove on the 3'-side of the modified base between base pairs A(6)-T(17) and C(7)-G(16) and confirm the syn glycosidic angle (58 degrees ) of the modified dA(6). In the syn structure, a weak A-T hydrogen bond is possible between the N3-H proton of T(17) and N7 of dA(6) (at a distance of 3.11 A), whereas N1, the usual hydrogen bonding partner for N3-H of T when dA is in the anti conformation, is 6.31 A away from this proton. The 10(S)-dA modified DNA duplex remains in a right-handed helix, which bends in the direction of the aliphatic ring of BaP at about 42 degrees from the helical axis. ROESY experiments provided evidence for interconversion between the major, syn conformer and a minor, possibly anti, conformer.

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