Solvent effects on the absorption and fluorescence spectra of Zaleplon: Determination of ground and excited state dipole moments

Abstract

Solvent effects on the absorption and fluorescence spectra of Zaleplon, a nonbenzodiazepine sedative/hypnotic drug that is mainly used for the short term treatment of insomnia, were investigated in 18 different solvents with diverse polarities. Dipole moments of the ground and excited state (μg and μe) were determined by Lippert-Mataga, Bakhshiev, Reichardt, McRae and Suppan solvatochromic methods. The dipole moment of Zaleplon ground state in the gas phase has been calculated as μg = 10.95 D (TD-DFT) with B3LYP/cc-pVTZ functional. There is a good agreement of theoretical data with Reichardt, McRae, and Suppan correlations, while some dissidence with Lippert-Mataga and Bakhshiev equations is suggesting the occurrence of specific solute-solvent interactions. Additionally, multiple linear regression analysis with Kamlet-Taft and Catalan solvatochromic models was applied to solute-solvent interactions. Dominant property of the solvent that affects the absorption band and Stokes shifts of Zaleplon is polarity of the solvent while the emission band is influenced mainly by solvent basicity.