UV–Vis spectroscopy and solvatochromism of the tyrosine kinase inhibitor AG-1478

• AG-1478 fluorescence is sensitive to hydrogen-bonding and polarity of solvent.
• Absorption spectra of AG-1478 contain two overlapping band maxima.
• AG-1478 has larger extinction coefficients in protic than in aprotic solvents.
• AG-1478 has larger fluorescence quantum yields in aprotic than in protic solvents.

The effect of twenty-one solvents on the UV–Vis spectrum of the tyrosine kinase inhibitor AG-1478 was investigated. The absorption spectrum in the range 300–360 nm consisted of two partially overlapping bands at approximately 340 nm and 330 nm. The higher energy absorption band was more sensitive to solvent and exhibited a peak position that varied from 327 nm to 336 nm, while the lower energy absorption band demonstrated a change in peak position from 340 nm to 346 nm in non-chlorinated solvents. The fluorescence spectrum of AG-1478 was particularly sensitive to solvent. The wavelength of peak intensity varied from 409 nm to 495 nm with the corresponding Stokes shift in the range of 64 nm to 155 nm (4536 cm− 1 to 9210 cm− 1). We used a number of methods to assess the relationship between spectroscopic properties and solvent properties. The detailed analysis revealed that for aprotic solvents, the peak position of the emission spectrum in wavenumber scale correlated with the polarity (dielectric constant or ET(30)) of the solvent. In protic solvents, a better correlation was observed between the hydrogen bonding power of the solvent and the position of the emission spectrum. Moreover, the fluorescence quantum yields were larger in aprotic solvents as compared to protic solvents. This analysis underscores the importance of polarity and hydrogen-bonding environment on the spectroscopic properties of AG-1478. These studies will assume relevance in understanding the interaction of AG-1478 in vitro and in vivo.

The emission maxima (in wavenumber) of AG-1478 exhibits a correlation with Reichardt transition energy ET(30) solvent parameter. Note the distinct correlations for protic and aprotic solvents.Figure optionsDownload as PowerPoint slide