C2'-F Stereoconfiguration As a Puckering Switch for Base Stacking at the Dinucleotide Level

Area of Science:

• Nucleic acid chemistry
• Organic chemistry
• Biophysical chemistry

Background:

• Base stacking in dinucleotides influences their structure and function.
• Fluorine substitution is a common strategy to modify nucleotide properties.

Purpose of the Study:

• To investigate the impact of C2 ahydrogen fluorine stereoconfiguration on intramolecular base stacking in bis(2 ahydrogen-fluorothymidine) dinucleotides.
• To elucidate the relationship between fluorine configuration, dinucleotide conformation, and photoreactivity.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy to analyze dinucleotide structure and dynamics.
• Natural Bond Orbital (NBO) analysis to scrutinize electronic properties and conformational preferences.

Main Results:

• The C2 ahydrogen-β fluorine configuration significantly reduces intramolecular base stacking compared to the C2 ahydrogen-α configuration.
• Stereochemical configuration at C2 ahydrogen dictates significant variations in sugar puckering.
• The 2 ahydrogen-β F-isomer exhibits markedly reduced photoreactivity relative to the 2 ahydrogen-α F-isomer.

Conclusions:

• Intramolecular base stacking in fluorinated dinucleotides is tunable via C2 ahydrogen fluorine stereochemistry.
• Conformational changes induced by fluorine configuration directly impact base stacking and photoreactivity.
• This study provides insights into the design of modified nucleic acids with tailored properties.