Decoupling relaxation dynamics and enhancing the glass-forming ability of a double-active ionic liquid-procaine...

Procaine HCl (PrHCl), a protic ionic liquid (PIL), exhibits intricate relaxation due to ionic and neutral species interactions. However, its glass-forming ability is limited. To overcome these limitations, this study explores the synthesis of a novel PIL, PrHIb, by replacing Cl^- with the bulky, asymmetric ibuprofen anion. This modification is expected to introduce steric hindrance, restrict molecular mobility, and decouple relaxation processes, thereby enhancing thermal stability, glass-forming ability, and pharmaceutical functionality.

To synthesize and characterize a novel protic ionic liquid, PrHIb, with a focus on relaxation dynamics, glass-forming ability, and dual therapeutic potential.

PrHIb synthesis was validated by density functional theory (DFT), Fourier Transform Infrared Spectrscopy (FTIR), and Fourier Transform Raman Spectroscopy (FT-RS). The antibacterial and anti-inflammatory properties of PrHIb were evaluated. Thermal and molecular dynamics were studied by differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). Molecular mobility was assessed to decipher the decoupling of ionic and neutral molecules. The polymer matrices were explored to enhance performance and applicability by restricting molecular mobility.

DFT confirmed PrHIb formation as endothermic and non-spontaneous under standard conditions with positive enthalpy (∆H = -3.88× 10⁵ kcal/mol) and Gibbs free energy (∆G = -3.88× 10⁵ kcal/mol), while negative entropy (∆S = -56.43 cal/molK) reflects reduced system disorder. FTIR and FT-RS validated the incorporation of functional groups from procaine and ibuprofen. PrHIb exhibited enhanced antimicrobial efficacy against E. coli (62 %) and Pseudomonas (80 %) compared to PrHCl and retained strong anti-inflammatory activity (95 %). DSC and BDS studies confirmed glass-forming behavior, with a T_g of 266 K. Replacement of Cl^- with Ibu^- led to decoupled relaxation and the lack of secondary relaxation. Two distinct relaxations in M″(ω) were attributed to ionic conductivity and structural relaxation. All data were fit the Havriliak-Negami equation. Vogel-Fulcher-Tammann (VFT) showed high fragility (m = 102), indicating sharp viscosity changes near T_g. polyvinylpyrrolidone (PVP) confinement reduced fragility (m = 36), suppressed ionic hopping, and improved stability with a T_g of ∼269 K.

Replacing Cl^- with bulky, asymmetric Ib^- in PrHIb restricts molecular mobility, leading to decoupled relaxation processes and enhanced dynamic heterogeneity. Confinement in a PVP matrix further stabilizes PrHIb by reducing fragility and improving its glass-forming ability. These features, along with dual antimicrobial and anti-inflammatory activity, highlight its potential as a multifunctional pharmaceutical ionic liquid.