Structural modifications of nucleosides in ionic liquids

Abstract

Nucleoside chemistry represents an important research area for drug discovery, as many nucleoside analogs are prominent drugs and have been widely applied for cancer and viral chemotherapy. However, the synthesis of modified nucleosides presents a major challenge, which is further aggravated by poor solubility of these compounds in common organic solvents. Most of the currently available methods for nucleoside modification employ toxic high boiling solvents; require long reaction time and tedious workup methods. As such, there is constant effort to develop process chemistry in alternative medium to limit the use of organic solvents that are hazardous to the environment and can be deleterious to human health. One such approach is to use ionic liquids, which are ‘designer materials’ with unique and tunable physico-chemical properties. Studies have shown that methodologies using ionic liquids are highly efficient and convenient for the synthesis of nucleoside analogs, as demonstrated by the preparation of pharmaceutically important anti-viral drugs. This article summarizes recent efforts on nucleoside modification using ionic liquids.

Ionic liquids: prospects for nucleic acid handling and delivery

“…In spite of the scientific significance of these promising studies, the majority of the available publications on nucleic acids and ionic liquids describe the possibilities of applying common ILs as stabilizing media for DNA or RNA storage (Table 1 ). So far, several reviews on interactions between nucleic acids and ILs or deep eutectic solvents (DES), as well as on application of ILs in synthesis of nucleoside-containing drugs, have been published ( 54–57 ). Nevertheless, the field is developing rapidly, and dozens of new papers on the topic are published yearly.…”

High Nucleobase-Solubilizing Ability of Low-Viscous Ionic Liquid/Water Mixtures: Measurements and Mechanism

“…Among all ILs studied for such unique solvation abilities, 1-alkyl-3-methyl imidazolium acetates ([R n mim]­[Ac]) have received particular attention, owing to the exceptional hydrogen bonding ability of the acetate anion. Thus, Araújo et al carried out a series of studies to solubilize nucleobases in [R n mim]­[Ac] ILs and obtained a phenomenal ∼100-fold increase in solubilities of adenine, uracil, and thymine in [emim]­[Ac] and [bmim]­[Ac] relative to their solubilities in water. − The authors ascribed this high solubility to strong hydrogen bonding between the polar groups on the nucleobases and the IL ions. , Earlier, Kumar et al examined the solubilities of nucleobase derivatives in imidazolium-based ILs containing the closely related trifluoroacetate anion and found manifold increased solubility compared to their solubilities in conventional organic solvents. , Interestingly, ILs containing other commonly used anions, like BF 4 – and PF 6 – , showed poor solubility for these nucleobase derivatives, suggesting a prominent role of the anion in base dissolution . However, the major drawback of these experiments was that ILs were highly viscous and addition of large amounts of nucleobases increased the viscosity of the solution further.…”

Physicochemical Properties ofN-Butyl-N-methyl-2-oxopyrrolidonium Bromide and Its Binary Mixtures with Water or Methanol

“…The specified and attractive properties, of ILs may present clear advantages in different pharmaceutical and biomedical applications, − prompted their use in battery as a electrolytes, − fuel cells, , nanotechnology, , polymerization reactions − as well as commercial and technical applications. − …”