Essential reactive intermediates in nucleoside chemistry: cyclonucleoside cations

Area of Science:

• Organic Chemistry
• Theoretical Chemistry
• Physical Chemistry

Background:

• Keto nucleosides are important in biochemical processes.
• Their reactivity, particularly acid susceptibility, is not fully understood.
• Previous studies lacked detailed mechanistic insights into acid-catalyzed reactions.

Purpose of the Study:

• To investigate the mechanism of acid-induced degradation of keto nucleosides.
• To identify and characterize low-energy intermediates in these reactions.
• To elucidate the structural basis for the observed reactivity patterns.

Main Methods:

• Density Functional Theory (DFT)-based computational modeling.
• Experimental examination of model keto nucleosides under acidic conditions.
• Spectroscopic and analytical techniques to characterize reaction products and intermediates.

Main Results:

• DFT calculations revealed the formation of low-energy cyclonucleoside cation intermediates.
• Experimental data corroborated the theoretical findings, confirming the existence of these intermediates.
• The proposed structures of these intermediates successfully explain the reaction courses for multiple nucleoside reactions.

Conclusions:

• The high susceptibility of keto nucleosides to acids is attributed to the facile formation of specific cyclonucleoside cation intermediates.
• The theoretical elucidation of these intermediates provides a unified mechanistic explanation for a range of nucleoside reactions.
• This work offers novel insights into nucleoside chemistry and reaction mechanisms.