C-F...H-C hydrogen bonds in ribonucleic acids

Area of Science:

• Nucleic acid chemistry
• Biophysical chemistry
• Molecular biology

Background:

• Understanding RNA duplex stability is crucial for molecular biology.
• Investigating modified nucleosides provides insights into base-pairing interactions.
• Existing research lacks comprehensive analysis of isosteric base analogues in RNA duplexes.

Purpose of the Study:

• To synthesize and characterize novel ribonucleoside analogues.
• To investigate the duplex stabilizing forces (hydrogen bonding, base stacking, solvation) of these analogues.
• To determine the potential of these analogues as universal bases in RNA.

Main Methods:

• Synthesis of 1'-deoxy-1'-(benzimidazol-1-yl)-beta-D-ribofuranose and 1'-deoxy-1'-phenyl-beta-D-ribofuranose.
• Incorporation of phosphoramidites of nine RNA analogues into a 12mer RNA sequence.
• UV- and CD-spectroscopy to analyze RNA duplex stability, melting points, and thermodynamic data.

Main Results:

• Identified analogues 1 (B) and 9 (E) as effective universal bases with low destabilization.
• Determined thermodynamic contributions of base stacking and solvation for modified building blocks.
• Demonstrated the absence of direct hydrogen bonds between natural bases and most RNA analogues.
• Observed a novel C-F.H-C hydrogen bond stabilizing force in duplexes containing fluorinated analogues.

Conclusions:

• The synthesized RNA analogues can function as universal bases, with specific analogues offering superior performance.
• Base stacking and solvation are key forces in duplex stabilization, but hydrogen bonding interactions differ with modified bases.
• A novel C-F.H-C hydrogen bond contributes to duplex stability, offering new avenues for RNA design and engineering.