Adenine nucleosides in solution: circular dichroism studies and base conformation

Area of Science:

• Biochemistry
• Molecular Biophysics
• Spectroscopy

Background:

• Adenosine analogs are crucial in biological and medicinal chemistry.
• Circular dichroism (CD) spectroscopy is a powerful tool for studying molecular conformation.
• Understanding the relationship between CD spectra and molecular structure is vital for drug design and biological studies.

Purpose of the Study:

• To investigate the circular dichroism (CD) spectra of various adenosine analogs.
• To correlate CD spectral variations with structural parameters, particularly the glycosyl torsion angle.
• To explore the utility of CD spectroscopy in predicting the base conformation of novel nucleoside structures.

Main Methods:

• Synthesis and characterization of over 25 synthetic adenosine analogs.
• Measurement of circular dichroism (CD) spectra for all synthesized compounds.
• Analysis of proton magnetic resonance (1H NMR) spectroscopy to determine base conformation (anti-conformation).

Main Results:

• Adenosine analogs exhibited distinct groups of CD spectra with positive and negative Cotton effects.
• CD spectral variations were correlated with the glycosyl torsion angle (phiCN), with specific ranges associated with different conformations.
• The anti-conformation of the adenine base was prevalent in most derivatives, as confirmed by NMR.

Conclusions:

• Circular dichroism spectroscopy effectively differentiates adenosine analogs based on their conformation.
• CD spectral analysis provides a reliable method for predicting the base conformation of novel nucleoside structures.
• The study highlights the structure-determining influence of modifications at the 4' position and the glycosyl torsion angle on CD spectra.