C2'-F Stereoconfiguration as a puckering switch for base stacking at the dinucleotide level.

Fluorine configuration at C2' of the bis(2'-fluorothymidine) dinucleotide is demonstrated to drive intramolecular base stacking. 2'-beta F-Configuration drastically reduces stacking compared to the 2'-alpha series. Hence, base stacking emerges as being tunable by the C2'-F stereoconfiguration through dramatic puckering variations scrutinized by NMR and natural bond orbital analysis. Accordingly, 2'-beta F-isomer photoreactivity is significantly reduced compared to that of the 2'-alpha F-isomer.