Solvent effect on the solubility and absorption spectra of meloxicam: experimental and theoretical calculations

The solubility and absorption spectra of meloxicam (MLX) in 18 pure solvents were determined. In addition, molecular modelling calculations were performed. MLX presents the lowest solubility in water and the highest in dioxane. The results indicate that the polarity/polarisability of the solvent, and the Hildebrand’s solubility parameter, have a greater influence on its solubility. The MLX absorption spectra show that a redshift occurs when the solvent polarity increases. By applying Kamlet-Taft and Catalán methods it has been suggested that the solvent polarisability is the most important solvent´s parameter in the solvatochromism of MLX. The electronic transitions were determined using the TD-DFT methodology with the B3LYP, PBE0 and LC-wPBE functional. The best results were obtained with PBE0. Also, it was determined that the main MOs responsible for the electronic transition are HOMO → LUMO with a ππ* character with a significant intraligand charge transfer from the thiazole to the oxycam group.

本研究测定了美洛昔康（meloxicam，MLX）在18种纯溶剂中的溶解度与吸收光谱。此外，本研究还开展了分子建模计算。MLX在水中的溶解度最低，在二氧六环（dioxane）中溶解度最高。结果表明，溶剂的极性/极化率与希尔德布兰德溶解度参数（Hildebrand’s solubility parameter）对其溶解度影响更为显著。MLX的吸收光谱显示，随着溶剂极性升高，会出现红移现象。通过运用卡米特-塔夫特（Kamlet-Taft）法与卡塔兰（Catalán）法，研究发现，在MLX的溶剂化显色效应（solvatochromism）中，溶剂极化率是最为关键的溶剂参数。本研究采用搭载B3LYP、PBE0及LC-wPBE泛函的含时密度泛函理论（TD-DFT）方法，确定了MLX的电子跃迁过程，其中PBE0泛函的计算结果最优。此外，研究明确，参与该电子跃迁的核心分子轨道（Molecular Orbitals，MOs）为具有π-π*跃迁特征的最高占据分子轨道（Highest Occupied Molecular Orbital，HOMO）→最低未占据分子轨道（Lowest Unoccupied Molecular Orbital，LUMO），且伴随显著的噻唑环（thiazole）向氧卡巴基团（oxycam group）的配体内电荷转移过程。