Towards a Molecular Understanding of Cation‐Anion Interactions and Self‐aggregation of Adeninate Salts in DMSO by NMR and UV Spectroscopy and Crystallography

Abstract

Rare anionic forms of nucleic acids play a significant biological role and lead to spontaneous mutations and replication and translational errors. There is a lack of information surrounding the stability and reactivity of these forms. Ion pairs of monosodium and -potassium salts of adenine exist in DMSO solution with possible cation coordination sites at the N1, N7 and N9 atoms of the purine ring. At increasing concentrations π-π stacked dimers are the predominant species of aggregates followed by higher order aggregation governed by coordination to metal cations in which the type of counter ion present has a central role in the aggregate formation.

Coordination Sites for Sodium and Potassium Ions in Nucleophilic Adeninate Contact ion-Pairs: A Molecular-Wide and Electron Density-Based (MOWED) Perspective

“…Hence, from a net atomic charge perspective, the Na + and K + counter ions can potentially coordinate to any of the four N-atoms of the endo-purine ring and, notably, M + would be preferentially coordinated to N1-over the N9-atom due to a stronger electrostatic attraction between the oppositely charged atoms. This is in total contradiction to experimental data and computational MOWED-based data (included in Table 1) pointing to the preference of N9-over the N1-coordination site [24]. This is an excellent example showing that focusing on a single atom or atom-pair might lead to incorrect conclusions.…”

“…This energy difference is slightly larger for the K-Ade complexes where the N7-and N1-CIP are 2 to 4 kcal mol −1 higher in energy than the N3N9-CIP. These small ∆E values suggest, in contrast to the spectroscopic data, that at least four CIPs (N3, N9, N3N9, and N7) might be present at significant concentrations in DMSO solution [24]. It is then clear that classical computational protocol involving relative energy differences was not able to provide a decisive answer and failed to pinpoint the preferred complexation site.…”

“…In contrast to the general perception, a recent NMR and UV spectroscopy study revealed that the adeninate anion does not exist as a free anion in DMSO, but rather as its contact ion-pair (CIP) with the base counter ions Na + and K + [24]. The interpretation of the NMR spectroscopic data proved to be challenging, and it was proposed that the base counter ions coordinate at either the N3 or N9 atom of the adeninate purine ring [24].…”

“…Hence, to understand the chemical behavior of the reaction system of a CIP, it is imperative to establish the coordination site for the metal cation. From the previous NMR experimental study on the CIP formation, the authors were unable to pinpoint and confirm where the counter ion is coordinated [24]. Therefore, combining experimental and computational studies should provide the most reliable models due to cross-validation between the two approaches.…”

Fluorescent nano-sized aggregates of halogen bonded complexes formed using perfluoropropyl iodides: a systematic comparison between two isomeric halogen bond acceptors, aniline and 4-methyl pyridine

“…10 As a result, the MEP for this system indicated a negative region around F atoms relative to the positive region around the methyl group in the para position. The plot of the MEP mapped over the electron density provides hints concerning the possible aggregation among the XB complexes dominated by electrostatic forces, similarly to the aggregation of ion pairs, [30][31][32][33] which will alter the morphology of the bulk system. With fewer F b atoms, a different degree of aggregation of XB complexes with n-C 3 F 7 I is expected compared to the XB systems with iso-C 3 F 7 I.…”