Hussan K P Safna, Sahra M, Lekshmi S, Thayyil M Shahin, Babu Thekkekara D
Micro/Nano Technology Center, Tokai University, Hiratsukashi, Kanagawa 259-1292, Japan; Amala Cancer, Research Center, Thrissur, Kerala 680 555, India; Ayurgreen Scientifica Research Institute, Edapal, Malappuram 679 582, Kerala, India.
Cranfield Forensic Institute, Cranfield University, UK.; State Forensic Science Laboratory, Thiruvananthapuram, Kerala, India.
Spectrochim Acta A Mol Biomol Spectrosc. 2026 Jan 15;345:126773. doi: 10.1016/j.saa.2025.126773. Epub 2025 Aug 5.
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× 10 kcal/mol) and Gibbs free energy (∆G = -3.88× 10 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 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. polyvinylpyrrolidone (PVP) confinement reduced fragility (m = 36), suppressed ionic hopping, and improved stability with a T 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.
盐酸普鲁卡因（PrHCl）是一种质子离子液体（PIL），由于离子和中性物种之间的相互作用而呈现出复杂的弛豫现象。然而，其玻璃形成能力有限。为了克服这些限制，本研究探索了一种新型PIL，PrHIb的合成方法，即将Cl替换为体积较大的不对称布洛芬阴离子。这种修饰预计会引入空间位阻，限制分子流动性，并使弛豫过程解耦，从而提高热稳定性、玻璃形成能力和药物功能。
合成并表征一种新型质子离子液体PrHIb，重点研究其弛豫动力学、玻璃形成能力和双重治疗潜力。
通过密度泛函理论（DFT）、傅里叶变换红外光谱（FTIR）和傅里叶变换拉曼光谱（FT-RS）验证PrHIb的合成。评估PrHIb的抗菌和抗炎性能。通过差示扫描量热法（DSC）和宽带介电谱（BDS）研究热性能和分子动力学。评估分子流动性以解读离子和中性分子的解耦情况。通过限制分子流动性来探索聚合物基质以提高性能和适用性。
DFT证实PrHIb的形成在标准条件下是吸热的且非自发的，具有正焓（∆H = -3.88×10 kcal/mol）和吉布斯自由能（∆G = -3.88×10 kcal/mol），而负熵（∆S = -56.43 cal/molK）反映系统无序度降低。FTIR和FT-RS验证了普鲁卡因和布洛芬官能团的掺入。与PrHCl相比，PrHIb对大肠杆菌（62%）和假单胞菌（80%）表现出增强的抗菌效果，并保留了较强的抗炎活性（95%）。DSC和BDS研究证实了玻璃形成行为，玻璃化转变温度为266 K。用Ibu取代Cl导致弛豫解耦且缺乏二级弛豫。M″(ω)中的两种不同弛豫归因于离子电导率和结构弛豫。所有数据均符合Havriliak-Negami方程。Vogel-Fulcher-Tammann（VFT）显示出高脆性（m = 102），表明在玻璃化转变温度附近粘度变化剧烈。聚乙烯吡咯烷酮（PVP）限制降低了脆性（m = 36），抑制了离子跳跃，并在约269 K的玻璃化转变温度下提高了稳定性。
在PrHIb中用体积较大的不对称Ib取代Cl限制了分子流动性，导致弛豫过程解耦并增强了动态不均匀性。在PVP基质中的限制通过降低脆性和提高其玻璃形成能力进一步稳定了PrHIb。这些特性以及双重抗菌和抗炎活性突出了其作为多功能药物离子液体的潜力。
