Hossain Mohammad, Susan Md Abu Bin Hasan
Department of Chemistry, Bangladesh University of Engineering and Technology (BUET), Dhaka 1000, Bangladesh.
Department of Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.
Phys Chem Chem Phys. 2025 May 14;27(19):10399-10412. doi: 10.1039/d4cp04889j.
In this work, volumetric, acoustic, viscometric, and photon correlation spectroscopic studies of an antidiabetic drug, ertugliflozin L-pyroglutamic acid (E.L-PGA) have been performed in aqueous medium in absence and presence of D-(+)-glucose. E.L-PGA serves as a structure-maker at intermediate concentrations ( 2.0 × 10 mol kg) while as a structure-breaker at low ((0.5-2.0) × 10 mol kg) and high ((2.0-3.5) × 10 mol kg) concentrations. The volumetric pairwise interaction coefficient, , is negative (-330 to -760) corresponding to stronger solute-solvent interactions. Structure-making occurs at low (290-305 K) and high (305-330 K) temperatures but structure-breaking occurs at intermediate ( 305 K) temperatures. The hydrodynamic diameter () of the aggregates ranges from 200 to 500 nm at 0.4456 × 10 mol kg of E.L-PGA. A breaking-making-breaking nature of the water structure is observed with increasing concentrations of D-(+)-glucose in E.L-PGA-D-(+)-glucose-water systems. The varies from 30 to 40 due to stronger solute-solute interactions. A small amount of D-(+)-glucose (up to 10.0 × 10 mol kg) causes water structure breaking and further addition helps to add water molecules around E.L-PGA. In a ternary system of 0.8993 × 10 mol kg of E.L-PGA, 5.6533 × 10 mol kg of D-(+)-glucose, and water, the of the clusters is in the range of 400-1000 nm. For both binary and ternary systems, Δ, Δ, and Δ vary from 8.4 to 9.2 kJ mol, 12 to 17 kJ mol, and 12 to 26 J mol, respectively. These results offer valuable insights into the molecular-level interactions of E.L-PGA with D-(+)-glucose under different perturbations and help understand pharmacological action and potential contraindications to open new avenues for the development of efficacious antidiabetic drugs.
在这项工作中，对抗糖尿病药物埃格列净L - 焦谷氨酸（E.L - PGA）在有无D -（+）-葡萄糖存在的水性介质中进行了体积、声学、粘度和光子相关光谱研究。E.L - PGA在中等浓度（2.0×10⁻³mol/kg）时作为结构形成剂，而在低浓度（（0.5 - 2.0）×10⁻³mol/kg）和高浓度（（2.0 - 3.5）×10⁻³mol/kg）时作为结构破坏剂。体积成对相互作用系数ϕ为负（-330至-760），对应更强的溶质 - 溶剂相互作用。在低温（290 - 305K）和高温（305 - 330K）下发生结构形成，但在中等温度（305K）下发生结构破坏。在0.4456×10⁻³mol/kg的E.L - PGA时，聚集体的流体动力学直径（Dh）范围为200至500nm。在E.L - PGA - D -（+）-葡萄糖 - 水体系中，随着D -（+）-葡萄糖浓度的增加，观察到水结构具有破坏 - 形成 - 破坏的性质。由于更强的溶质 - 溶质相互作用，ηsp/c从30变化到40。少量的D -（+）-葡萄糖（高达10.0×10⁻³mol/kg）导致水结构破坏，进一步添加有助于在E.L - PGA周围添加水分子。在含有0.8993×10⁻³mol/kg的E.L - PGA、5.6533×10⁻³mol/kg的D -（+）-葡萄糖和水的三元体系中，簇的Dh在400 - 1000nm范围内。对于二元和三元体系，ΔH、ΔG和ΔS分别在8.4至9.2kJ/mol、12至17kJ/mol和12至26J/(mol·K)范围内变化。这些结果为不同扰动下E.L - PGA与D -（+）-葡萄糖的分子水平相互作用提供了有价值的见解，并有助于理解药理作用和潜在禁忌症，为开发有效的抗糖尿病药物开辟新途径。
