Mechanistic Insights into the Stabilizing Role of Deep Eutectic Solvents for Nucleic Acids: An

The cold chain system poses a significant obstacle to equitable global access to safe and effective nucleic acid-based vaccines. There is, therefore, a critical need to eliminate or improve this vaccine coverage gap by minimizing the costly and labor-intensive cold chain process, thereby providing equitable access to these life-saving therapeutics. In this work, quantum chemical evaluation qualitatively compared the interactions of a choline chloride/trehalose-based deep eutectic solvent (DES) with model bases (adenine (A), guanine (G), cytosine (C), thiamine (T), and uracil (U)) and their base pairs AT, AU, and GC in nucleic acids. We found that unpaired purines primarily interacted with the DES through C-H···π and hydrogen bonding, leading to cage-like structures, while pyrimidines primarily engaged through hydrogen bonding. In DES/base pair complexes, the AT base pair weakened and partially lost planarity due to C-H···π interactions, while the AU base pair was disrupted by additional hydrogen bonding with Cl