Quantitative structure-fluorescence property relationship analysis of a large BODIPY library

A quantitative structure-fluorescence property relationship (QSPR) analysis of a large 288-membered library based on a single fluorescent BODIPY scaffold is presented for the first time. BODIPY is a versatile fluorescent scaffold with outstanding photophysical properties. Absorption (λ_abs) and fluorescence emission (λ_em) wavelength maxima were modeled with help of stepwise multiple linear regression (MLR) and support vector regression (SVR). The models were rigorously validated by 10-times 10-fold cross-validation (CV), y-scrambling CV and with an external validation set. Non-linear SVR models (R² =0.92 and Q² =0.71 for λ_abs; R²=0.89 and Q²=0.69 for λ_em) performed significantly better than linear models. A small root mean squared error (RMSE) of 5.62 nm and 11.07 nm was achieved for λ_abs and λ_em, respectively, and confirmed by external validation. A novel intramolecular charge transfer descriptor was developed based on the QSPR analysis and its inclusion in the modeling significantly improved models of λ_em· We conclude that QSPR is a useful tool for modeling λ_abs and λ_em of BODIPY fluorophores and suggest QSPR as an ideal partner for the design of compounds with tailored fluorescence properties in a diversity-oriented fluorescence library approach (DOFLA).