Comprehensive NMR Investigation of Imidazolium-Based Ionic Liquids [BMIM][OSU] and [BMIM][Cl] Impact on Binding and Dynamics of the Anticancer Drug Doxorubicin Hydrochloride

• Published in: The journal of physical chemistry. B 2023-11, Vol.127 (47), p.10226-10235
• Main Authors: Hari Krishnan, Sanjana, Eswaran, Vaishnavi Devi D, Lobo, Nitin Prakash, Phani Kumar, Bandaru V N
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents; Doxorubicin; Ionic Liquids - chemistry; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Water
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/acs.jpcb.3c06036

For the design of an efficient drug delivery system utilizing an ionic liquid (IL) as a carrier, it is prudent to gain molecular/atomistic level insights of a drug with IL in terms of binding and dynamics. In this scenario, the influence of anionic counterpart of imidazolium-based ILs, namely, 1-butyl-3-methyl-imidazolium octyl sulfate [BMIM][OSU] and 1-butyl-3-methyl-imidazolium chloride [BMIM][Cl] in their submicellar region ([IL] = 20 mM) on the model water-soluble anticancer drug doxorubicin hydrochloride (DOX) was probed by employing an arsenal of nuclear magnetic resonance (NMR) approaches. The salient feature of the present study includes the significant interaction of DOX with [BMIM][OSU], whereas the lack of such an interaction with [BMIM][Cl] is gauged by H NMR translation self-diffusometry and is further corroborated by C chemical shift perturbation. The two-step model was utilized to estimate the bound fraction (p ) and equivalent partition coefficient ( ) of DOX with [BMIM][OSU]. A combination of selective and nonselective spin-lattice relaxation rates ( and , respectively) enables to gauze the significant interaction of DOX with [BMIM][OSU] over [BMIM][Cl]. Furthermore, 1D transient and truncated driven nuclear Overhauser enhancement (NOE) data analyses in the initial rate limit permits the evaluation of the cross-relaxation efficacy of DOX with the investigated ILs. An Arrhenius-type temperature dependence of the drug's self-diffusion was observed for DOX, DOX-[BMIM][OSU], and DOX-[BMIM][Cl] aqueous mixtures and the corresponding activation energies were evaluated.