Structural and Energetic Impact of Non‐natural 7‐Deaza‐8‐azaguanine, 7‐Deaza‐8‐azaisoguanine, and Their 7‐Substituted Derivatives on Hydrogen‐Bond Pairing with Cytosine and Isocytosine

Abstract

We theoretically characterized the impact that the 7-deaza-8-azaguanine (DAG) and 7-deaza-8azaisoguanine (DAiG) modifications have on the geometry and stability of the G:C Watson-Crick (cWW) base pair and of the G:iC and iG:C reverse Watson-Crick (tWW) base pairs. In addition, we investigated the effect on the same base pairs of seven C7-substituted DAG and DAiG, some of which have been previously experimentally characterized. Our calculations indicate that all these modifications have a negligible impact on the geometry of the above base pairs, and that the modification of the heterocycle skeleton has small impact on the base pair interaction energies. Instead, base pair interaction energies are dependent on the nature of the C7 substituent. For the 7substituted DAG-C cWW systems we found a linear correlation between the base pair interaction energy and the Hammett constant of the 7-substituent, with higher interaction energies corresponding to more electron-withdrawing substituents. Therefore, the explored modifications are expected to be accommodated in both parallel and antiparallel nucleic acid duplexes without perturbing their

Occurrence and stability of anion–π interactions between phosphate and nucleobases in functional RNA molecules

“…The DMP–base anion…π interaction energies were evaluated at the coupled cluster level of theory, with iterative inclusion of single and double excitations and perturbative inclusion of triple excitations (CCSD(T)), which is considered the golden standard in electronic structure calculations including H-bonding and stacking interactions in nucleic acids ( 68 , 69 ). The domain-based local pair-natural orbital (DLPNO) approximation ( 70–72 ), as implemented in the ORCA package ( 73 ), was used to accelerate calculations.…”

Enzymatic Formation of an Artificial Base Pair Using a Modified Purine Nucleoside Triphosphate

“…In addition, binding energies of H-bonded base pairs are also calculated. This is a rather standard approach used in this kind of calculations. − …”

Unveiling structural and energetic characterization of the emissive RNA alphabet anchored in the methylthieno[3,4-d]pyrimidine heterocycle core

“…To have an immediate and intuitive understanding of the impact of a specific modification, we introduced the modification energy, E Mod , defined as the energy difference between the binding energy of the modified and of the corresponding natural base pair (in this specific case A:U and G:C base pair), 42,43,70,71 as shown in eqn (2).…”