The formation of cyclic duplexes (pairing) of known oxymethylene-linked self-complementary U*[o]A ( * ) dinucleosides contrasts with the absence of pairing of the ethylene-linked U*[c a ]A ( * ) analogues. The origin of this difference, and the expected association of U*[x]A ( * ) and A*[x]U ( * ) dinucleosides with x ยผ CH 2 , O, or S was analysed. According to this analysis, pairing occurs via constitutionally isomeric Watson -Crick, reverse Watson -Crick, Hoogsteen, or reverse Hoogsteen Hbonded linear duplexes. Each one of them may give rise to three diastereoisomeric cyclic duplexes, and each one of them can adopt three main conformations. The relative stability of all conformers with x ยผ CH 2 , O, or S were analysed. U*[x]A ( * ) dinucleosides with x ยผ CH 2 do not form stable cyclic duplexes, dinucleosides with x ยผ O may form cyclic duplexes with a gg-conformation about the C(4')รC(5') bond, and dinucleosides with x ยผ S may form cyclic duplexes with a gt-conformation about this bond.
The temperature dependence of the chemical shift of HรN(3) of the self-complementary, oxymethylene-linked U*[o]A ( * ) dinucleosides 1 -6 in CDCl 3 in the concentration range of 0.4 -50 mm evidences equilibria between the monoplex, mainly linear duplexes, and higher associates for 3, between the monoplex and cyclic duplexes for 6, and between the monoplex, linear, and cyclic duplexes as well as higher associates for 1, 2, 4, and 5.
The self-complementary, thiomethylene-linked U*[s]A ( * ) dinucleosides 27 -32 and the sequence isomeric A*[s]U ( * ) analogues 33 -38 were prepared by S-alkylation of the 6-(mesyloxymethyl)uridine 12 and the 8-(bromomethyl)adenosine 22. The required thiolates were prepared in situ from the C(5')acetylthio derivatives 9, 15, 19, and 25. The association in CHCl 3 of the thiomethylene-linked dinucleoside analogues was studied by 1 H-NMR and CD spectroscopy, and by vapour-pressure osmometric determination of the apparent molecular mass. The U*[s]A ( * ) alcohols 28, 30, and 31 form cyclic duplexes connected by Watson -Crick H-bonds, while the fully protected dimers 27 and 29 form mainly linear duplexes and higher associates. The diol 32 forms mainly cyclic duplexes in solution and corrugated ribbons in the solid state. The nucleobases of crystalline 32 form reverse Hoogsteen H-bonds, and the resulting ribbons are cross-linked by H-bonds between HOCH 2 รC(8/I) and N(3/I). Among the A*[s]U ( * ) dimers, only the C(8/I)-hydroxymethylated 37 forms (mainly) a cyclic duplex, characterized by reverse Hoogsteen base pairing. The dimers 34 -36 form mainly linear duplexes and higher associates. Dimers 34 and particularly 38 gelate CHCl 3 . Temperature-dependent CD spectra of 28, 30, 31, and 37 evidence p-stacking in the cyclic duplexes. Base stacking in the particularly strongly associating diol 32 in CHCl 3 solution is evidenced by a melting temperature of ca. 28.
2 ) For the duplex formation of a self-complementary AU dimer connected by an anthracene-1,8diethynyl linker, see [8]. This linker does not allow the preparation of oligomers. 3 ) Conventions for abbreviated notation: The substitution at C(6) of pyrimidines and C(8) of purines is denoted by an asterisk (*); for example, U* and A* for hydroxymethylated uridine and adenosine derivatives, respectively. U ( * ) and A ( * ) represent both unsubstituted and hydroxymethylated nucleobases. The moiety linking C(6)รCH 2 or C(8)รCH 2 of unit II and C(5') of unit I is indicated in square brackets, i.e., [c] for a C-, [o] for an O-, and [s] for a S-atom. The indices y, e, and a indicate a triple, double, or single bond, respectively.
Results and Discussion. -1. Evaluation of the Pairing Propensity of Self-Complementary Ethylene-, Oxymethylene-, and Thiomethylene-Linked Uridine-and Adenosine-Derived Dimers. The propensity of forming cyclic duplexes of U*[x]A ( * ) and of A*[x]U ( * ) dimers was evaluated by comparing the conformations of the monoplexes and the corresponding cyclic duplexes. As mentioned in the Introduction, analysis of the duplex formation of ethynylene-linked dimers showed the critical role of the torsion angles c and h 1 /h 2 (cf. Fig. 1,a, for the definition of the torsion angles). Analysis of the pairing of dinucleosides with X ยผ CH 2 , O, and S requires the analysis also of the torsion angles q, i, and k, and of the effect of the nature of X, i.e., of the centre unit of the linker between C(4') and C(6 or 8). angles (large distance of 5 -6 between the base pairs). Conformational analysis based on Maruzen models. 8 ) Graphical and numerical analysis of the SCC of 4 led to a K ass value of 280 [7] and of 260 AE 58 m ร1 , respectively. These values are too low considering K ass ยผ 970 m ร1 of 3. The error induced by the H/H exchange may partly be corrected by adding a value of 7.70 ppm for a concentration of 0.0001 mm. This leads to an increased association constant for 4 (K ass ยผ 13300 AE 2150 m ร1 ). K ass of the other duplexes are similarly corrected, for 1 from 1890 to 18400 AE 2350 m ร1 , for 2 from 2500 to 12300 AE 1240 m ร1 , for 5 from 3220 to 6820 AE 660 m ร1 , and for 3 from 970 to 1610 AE 110 m ร1 . These values reflect well the bending of the curves. Scheme 2 TDS ยผ Thexyl(dimethyl)silyl (thexyl ยผ 1,1,2-trimethylpropyl), MMTr ยผ (monomethoxy)trityl. a) MeO-Na, MeOH; 85% of 27; 62% of 29; 77% of 33; 75% of 35. b) (HF) 3
โข Et 3 N, THF; 58% of 28; 83% of 30; 80% of 32; 58% of 34; 93% of 36; 78% of 38. c) Cl 2 CHCO 2 H, Et 3 SiH, CH 2 Cl 2 ; 87% of 31; 67% of 37.