title: Solvatochromism and linear solvation energy relationship of the kinase inhibitor SKF86002.
abstract: 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 19.68kJ·mol(-1) and 6.65kJ·mol(-1) due to H-bonds, and produce the three major UV-Vis absorption bands at 325nm, 260nm and 210nm in cyclohexane solutions. This environment-sensitive fluorophore exhibited emission in the 400-500nm 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 397.5nm in cyclohexane to 436nm in DMSO. While the emission maximum in hydrogen donating solvents ranged from 420nm in t-butanol to 446nm 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 R(2) values 0.78, 0.80 and 0.80, respectively. Additionally, the multicomponent linear regression analysis of Kamlet-Taft (R(2)=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 (R(2)=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 R(2)=0.90. The dipole moment difference between excited and ground state was calculated to be 3.4-3.5debye.
authors.affiliation: Centre for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122, Australia. Electronic address: mkhattab@swin.edu.au.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Khattab
authors.affiliation: Molecular Model Discovery Laboratory, Department of Chemistry and Biotechnology, School of Science, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122, Australia.
authors.forename: Madeline
authors.initials: M
authors.lastname: Van Dongen
authors.affiliation: Molecular Model Discovery Laboratory, Department of Chemistry and Biotechnology, School of Science, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122, Australia. Electronic address: fwang@swin.edu.au.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Centre for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122, Australia. Electronic address: aclayton@swin.edu.au.
authors.forename: Andrew H A
authors.initials: AH
authors.lastname: Clayton
mesh_terms: D003510:Cyclohexanes / Q000737:chemistry; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D016014:Linear Models; D008968:Molecular Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D012996:Solutions; D012997:Solvents; D013844:Thiazoles; C506365:Cyclohexane; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole
keywords: Anti-inflammatory drug; Kinase inhibitor; Photophysics; SKF86002; Solvatochromism; UV–Vis spectroscopy