Work

The Electronic Properties of Cordycepin in the Adenine Nucleoside Landscape: A Theoretical Approach

Year: 2025

Type: article

Abstract: The anticancer activity of 3′-deoxyadenosine (Cordycepin, or dCor) is known to be linked to the inhibition of the MAPK/ERK signalling and Hedgehog pathways, as well as the termination of primer elongation by primase in DNA lagging-strand synthesis. In this study, the electronic properties of dCor, 7,8-dihydro-8-oxo-3′-deoxyadenosine (OXOdCor), and 8-hydroxy-3′deoxyadenosie (HOdCor), together with their spin densities, charge distributions, and global reactive descriptors, have been taken into consideration at the M06-2x/6-31++G** level of theory in the aqueous phase. It was found that dCor predominantly adopts a 3′-endo,anti conformation, while OXOdCor and HOdCor adopt a 2′-endo,syn conformation. Also, the keto form of oxidised dCor was found to be energetically preferred to its enolic form. The adiabatic ionisation potentials (AIPs) were noted as follows (in eV): 6.29 for dCor, 6.21 for OXOdCor, and 6.17 for HOdCor. The lowest adiabatic electron affinity among all the discussed adenine nucleosides analogues was assigned for OXOdCor at 1.12 eV. A thorough analysis of the spin density distribution of the adiabatic radical cation reveals that it has a higher accumulation at N6 > C5 > C8 > 3 of dCor, C5 > N6 > N7 > O8 of OXOdCor, and N6 > C5 > C8 > C2 of HOdCor. The results suggest that Cordycepin is more easily converted to OXOdCor and HOdCor than canonical adenine nucleosides. Much like typical drugs, after its administration and release, Cordycepin is exposed to various physiological factors and can be exposed to ionisation radiation during combined therapy. These factors can influence the therapeutic potential of Cordycepin. Therefore, further studies on its stability are of utmost importance.

Source: Molecules

DOI: 10.3390/molecules30112289

Author: Boleslaw T. Karwowski

Institution: Medical University of Lodz

Language: English

Topic: Advanced Chemical Physics Studies

Subfield: Atomic and Molecular Physics, and Optics

Field: Physics and Astronomy

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $3,258

Funders: Uniwersytet Łódzki, Uniwersytet Medyczny w Lodzi, Infrastruktura PL-Grid, Academic Computer Centre Cyfronet, AGH University of Science and Technology