Effects of structural variations on the hydrogen bond pairing between adenine derivatives and thymine

Abstract

The hydrogen bonding between substituted adenines and thymine was investigated by density functional theory computations at the B3LYP/6-311+G(2d,2p) level. The effect of 20 different polar substituents at position 8 in adenine was examined in detail. Three different theoretical parameters, reflecting the electrostatics at the atoms involved in hydrogen bonding, were applied. An excellent correlation between electrostatic potentials at the bonding atoms in the monomer adenines and interaction energies was derived (Eqn. 2). It can be employed in designing bioactive adenine derivatives that are able to bind with a finely adjusted strength to thymine bioreceptor sites. NBO and Hirshfeld atomic charges are found to be less successful as reactivity predictors in these interactions.Keywords: DNA base pair; adenine; thymine; hydrogen bonding; electrostatic potential; atomic charges ЕФЕКТИ НА СТРУКТУРНИТЕ ВАРИЈАЦИИ ВРЗ СПАРУВАЊЕТО НА АДЕНИНСКИ ДЕРИВАТИ И ТИМИН СО ПОМОШ НА ВОДОРОДНО СВРЗУВАЊЕИстражувано е водородното сврзување помеѓу супституирани аденини и тимин со помош на пресметки според теоријата за функционал на електронската густина на нивото B3LYP/6-311+G(2d,2p). Детално е изучуван ефектот на 20 различни поларни супституенти на аденин во позицијата 8. Применети се три различни теоретски параметри кои ја рефлектираат електростатиката на атомите вклучени во водородното сврзување. Добиена е одлична корелација помеѓу електростатските потенцијали на сврзувачките атоми во мономерните аденини и интеракционите енергии (р-ка 2). Тоа може да се примени при дизајнирање на биоактивни аденински деривати кои можат да се сврзат со фино нагодена јачина со тиминските биорецепторски сајтови. Најдено е дека т.н. NBO и Хиршфилдовите (Hirshfeld) атомски полнежи се помалку успешни како претскажувачи на реактивноста во овие интеракции.Клучни зборови: ДНК базен пар; аденин; тимин; водородно сврзување; електростатски потенцијал; атомски полнежи  Dedicated to Academician Gligor Jovanovski on the occasion of his 70 th birthday.

Substituent effects on the stability of the four most stable tautomers of adenine and purine

“…14 It was found that the stability of tautomers of substituted adenine molecules strongly depends on solvation. It was also found 15 that, for 20 different substituents in the position 8 of adenine, electrostatic potentials at the bonding atoms of monomers correlate nicely with interaction energies of adenine-thymine pairs.…”

Effect of the Solvent and Substituent on Tautomeric Preferences of Amine-Adenine Tautomers

“…They may lead to substantial changes in its electronic structure − and, in consequence, to changes in its chemical/physicochemical/biochemical properties. , Therefore, knowledge of changes in the electronic structure of adenine caused by both the solvent and well-defined factors (e.g., introduction of substituents) exhibiting specific electron donating/accepting properties is of fundamental importance. It should be emphasized that their influence on hydrogen bonds was most often studied in structurally modified Watson-Crick base pairs, − whereas their influence on properties of nucleic acid bases is much less represented in the literature. , …”

Theoretical Investigation on the Substituent Effect of Halogen Atoms at the C8 Position of Adenine: Relative Stability, Vibrational Frequencies, and Raman Spectra of Tautomers

“…The relative stability of different conformations of adenosine was investigated due to the protonation at a low ab initio level . Recently, density functional theoretical calculations were used to explore the stability of different tautomers and hydrogen bonding pairs of DNA bases, but these studies mainly focused on analyses of the substituent effect on geometries, energies, charge distributions and hydrogen bonding interactions. ,,− Until now, there have only been a few studies on theoretical analysis of vibrational spectra of these halogen-substituted adenine derivatives. , The assignment of observed Raman bands still limited to the optimized structures at the SCF/STO-3G level and the assignment of adenine analogues. , …”