Interdependence of ring conformations of 2′,3′-cyclic mononucleotides by nuclear magnetic resonance spectroscopy

Abstract

The inter-relation between the conformational properties of the sugar and phosphate rings of 2′,3′-cyclic mononucleotides has been investigated using ¹H and ¹³C n.m.r. Results. ¹³C N.m.r. Measurements of ³J(³¹P, ¹³C) magnitudes have been made on a number of 2′,3′-cyclic mononucleotides to supplement results available in the literature as well as those for ³J(H,H) and ³J(¹H, ³¹P) in the same systems. It is found that certain spin coupling constants are constant, i.e. J_2′,3′ 6.8 ± 0.1; (J_2′,p+J_3′,P) 18.4 ± 0.1; (J_1′,2′+J_3′,4′) 8.2 ± 0.3; and (J_P,C-4′+J_P,C-1′) 8.3 ± 0.4 Hz. The coupling constant behaviour does not support conformational models suggested by X-ray crystallographic results but it is consistent with a two-state symmetrical conformational model for both five-membered rings. Analysis of spin-coupling constants reveals that the puckering of the sugar and phosphate rings is about the same and that the conformational equilibria of both rings are related. It is shown that there is a direct correlation between sugar and phosphate ring conformations in which the cyclic phosphate adopts the O-3′-endo, O-2′-exo(³O₂) conformation for the sugar ring in the N-type (C-3′-endo, C-2′-exo; ³T₂) conformation and the O-2′-endo, O-3′-exo(²O₃) conformation for the sugar ring in the S-type (C-2′-endo, C-3′-exo; ²T₃) conformation. One consequence of the quantitative rationalisation of the conformational behaviour of 2′,3′-cyclic mononucleotides is that it leads to the empirical determination of the electronegative substituent effect of the glycosyl nitrogen atom at C-1′ for both ¹H–¹H (J_1′2′, δJ 0.7 Hz) and ³¹P–¹³C (J_P,C-1′, δJ– 1.1 Hz) vicinal coupling paths.