Solvatochromism and linear solvation energy relationship of the kinase inhibitor SKF86002

• SFK is a kinase inhibitor yet displays fluorescence sensitive to environment.
• The emission wavelength maximum is sensitive to environmental polarity and H-bonding.
• Quantum chemical calculations reveal intra-molecular H-bonds.
• SKF holds promise as both a drug and a probe of biological environment.

We studied the spectroscopic characteristics of SKF86002, an anti-inflammatory and tyrosine kinase inhibitor drug candidate. Two conformers SKF86002A and SKF86002B are separated by energy barriers of 19.68 kJ·mol− 1 and 6.65 kJ·mol− 1 due to H-bonds, and produce the three major UV–Vis absorption bands at 325 nm, 260 nm and 210 nm in cyclohexane solutions. This environment-sensitive fluorophore exhibited emission in the 400–500 nm range with a marked response to changes in environment polarity. By using twenty-two solvents for the solvatochromism study, it was noticed that solvent polarity, represented by dielectric constant, was well correlated with the emission wavelength maxima of SKF86002. Thus, the SKF86002 fluorescence peak red shifted in aprotic solvents from 397.5 nm in cyclohexane to 436 nm in DMSO. While the emission maximum in hydrogen donating solvents ranged from 420 nm in t-butanol to 446 nm in N-methylformamide. Employing Lippert-Mataga, Bakhshiev and Kawski models, we found that one linear correlation provided a satisfactory description of polarity effect of 18 solvents on the spectral changes of SKF86002 with R2 values 0.78, 0.80 and 0.80, respectively. Additionally, the multicomponent linear regression analysis of Kamlet-Taft (R2 = 0.94) revealed that solvent acidity, basicity and polarity accounted for 31%, 24% and 45% of solvent effects on SKF86002 emission, respectively. While Catalán correlation (R2 = 0.92) revealed that solvatochromic change of SKF86002 emission was attributed to changes in solvent dipolarity (71%), solvent polarity (12%), solvent acidity (11%) and solvent basicity (6%). Plot of Reichardt transition energies and emission energies of SKF86002 in 18 solvents showed also a linear correlation with R2 = 0.90. The dipole moment difference between excited and ground state was calculated to be 3.4–3.5 debye.

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