Stereoelectronic Effects in Nucleosides and Nucleotides

An excellent review of this subject was published in 2005 by Chattopadhyaya etal. [1], 

It has been shown that stereoelectronic effects play an important role in many enzyme-catalyzed biochemical reactions, as, for example, in ribozymes [2-4], serine proteases [5], lysozymes [6], and ribonucleases [3, 7], While most of the studies on stereoelectronic effects were conducted on pyranoid forms of sugars, the relationship between stereoelectronic effects and furanoid ring conformations, to the best of our knowledge, is almost totally neglected. This is a big void since the conformations of furanoid forms of sugars are of great importance for overall conformations of ribo- and deoxyribonucleic acids (RNA and DNA). 

The reason for this is most likely due to the fact that the saturated five-membered rings are very flexible due to pseudorotation and are involved in complex conformational equilibria in which the individual conformations were very difficult if not impossible to identify, whereas the pyranoid rings are rather stiff and consequently have much simpler conformational equilibria. 

Early experimental studies have shown qualitatively how the anomeric and gauche effect control the conformational equilibria of pentofuranoses in nucleofs) tides. Chattopadhyaya et al. [8 0] made accurate estimates of the magnitude of stereoelectronic effects driving the two-state North South pseudorotational equilibrium in nucleos(t)ides (Fig. 6.1). 

Recent studies on modified oligonucleotides have shown that a modification of one of the three components of the constituent nucleotides, i.e., the nucleobase, the sugar moiety, and the phosphate backbone, alters both their stability and overall structure. The actual involvement of stereoelectronic effects in the observed structural changes has been initially addressed only qualitatively [41-45]. 

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C. Thibaudeau and J. Chattopadhyaya, Stereoelectronic effects in nucleosides and nucleotides and their structural implications, Uppsala University Press, Uppsala, 1999. 

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