Intrinsic Contributions of 2′‐Hydroxyl to the Hydration of Nucleosides at the Monomeric Level

Abstract

Although many reports have revealed structural differences between DNA and RNA at the polymeric level, there are no comparative studies with 2′‐deoxyribonucleoside and ribonucleoside to explore the role of the 2′‐OH group at the monomeric level under the same conditions. Inspired by this, herein, the intrinsic contributions of the 2′‐OH group in the nucleoside have been systematically investigated by directly solving the single‐crystal structures of 2′‐deoxy‐2‐aminoadenosine (1), 2‐aminoadenosine (2), and 2‐aminoarabinofuranosyladenine (3) in water. The 2′‐OH group not only influenced the conformation and base‐pair pattern of the single‐nucleoside molecule, but also played a fundamental role in the entire supramolecular structure. Interestingly, compound 1, which did not contain the 2′‐OH group, displayed strong hydration, whereas 2 and 3 (with the 2′‐OH group in the opposite direction) exhibited no hydration, which was completely different from that observed in nucleic acids. Meanwhile, compound 1 trapped water molecules to form unique trihydrol moieties, which further served as the backbone to construct the simplest double‐chain DNA‐like structures. To this end, to investigate the effect of the biological environment on these unique structures, the solvent was changed from water to phosphate‐buffered saline (PBS). Surprisingly, such a subtle adjustment led to entirely different superstructures, consisting of 2D lamellar structures in water and 3D porous structures in PBS. These large morphological differences could be attributed to delicate ion hydration, which was also confirmed through variable‐temperature X‐ray analysis, SEM, and intermolecular interaction energy calculations. In summary, this study comprehensively investigated the intrinsic contributions of 2′‐hydroxyl to the hydration of nucleosides at the monomeric level; this is helpful to further understand the differences in DNA/RNA and the impact of their surrounding environment.

High‐Strength and Injectable Supramolecular Hydrogel Self‐Assembled by Monomeric Nucleoside for Tooth‐Extraction Wound Healing

“…[ 3e,7a,9 ] Previously, upon investigating the single‐crystal structure of 2‐DA, we observed the formation of Hoogsteen‐like base‐pairs by its double NH 2 groups, indicating their roles in increasing hydrogen‐bonding density. [ 10 ] However, owing to its unique trihydrol moieties, 2‐DA exhibited a strong hydration ability and formed a clear solution, failing to self‐assemble into a hydrogel. Upon changing the 2′‐H group to a hydrophilic 2′‐OH (2‐RA) group, however, the hydration ability was significantly decreased.…”

“…Accordingly, we investigated this phenomenon through a structural analogy: 2′‐deoxy‐2′‐fluoroguanosine (FG), 2‐RA, and 2‐DA were selected for this study because 2‐FA and 2‐DA (or 2‐RA) share the same base moiety, namely 2,6‐diaminopurine (DAP), while the single‐crystal structures of 2‐FA and FG bear the same sugar moiety ( Figure a and Figure S6a,b, Supporting Information). [ 10 ] Their hydrogen‐bonding characteristics provided information regarding the mechanism underlying the 2‐FA hydrogel formation.…”

“…Our previous study revealed that the crystal structure of 2‐DA exhibits unique trihydrol characteristics, which enable it to connect with water molecules under two different conformations. [ 10 ] Conversely, no water molecules are present in the crystal structures of 2‐RA and FG. The high tendency of 2‐FA to interact with water molecules led us to hypothesize that it would exhibit a similar behavior with 2‐DA.…”