The nature of conformational correlations in alpha- and beta-anomers of nucleic acid components in aqueous solution by nuclear magnetic resonance

The solution distribution of combinations of the sugar ring puckering domains, C2'endo(S), C3'endo(N), and C4'-C5' rotamers, +sc(g+), ap(t), -sc(g-), in alpha and beta-anomers in ribo- and deoxyribo- pyrimidine nucleic acid components can be determined from vicinal coupling constants (M. Remin, J. Biomol. Str. Dyn. 2, 211 (1984). A general correlation pattern with a conformational constant lambda reflecting an intrinsic physical property of the sugar-side chain ensemble, is developed and expressed in terms of four principles: I) The +sc rotamer contributes to the C3'endo population to a higher extent (1-Yt) than to C2'endo, (1-Yt-Yg-/Xs). II) The ap rotamer contributes to both C2'endo and C3'endo populations to the same extent (Yt). III) The -sc rotamer contributes only to the C2'endo population, (Yg-/Xs). IV) The molar fractions Xs, Yt and Yg- of conformations C2'endo, ap and -sc, respectively, are strongly correlated, lambda = (Yg-/Xs)/Yt approximately 0.5, and therefore Yt is a basic variable parameter which determines all others in the correlation pattern. In alpha-anomers, regardless of the type and conformation of the sugar ring and base, the molar fraction Yt = 0.37 +/- 0.02. This finding means that different alpha-anomers show one correlation pattern free of the influence of the base. In beta-anomers, structure and conformation of the base are important factors which modulate (through Yt) the correlation pattern, conserving its fundamental features. Yt is considerably increased by a syn-oriented pyrimidine base, but decreases when the base is anti. The transition from anti to syn orientation of the base is followed by destabilization of (C2'endo, +sc) in favor of (C3'endo, ap). The principles of conformational correlations rationalize a variety of correlations observed in the past.