title: Quantitative Structure-Fluorescence Property Relationship Analysis of a Large BODIPY Library.
abstract: 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 (λabs ) and fluorescence emission (λem ) 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 (R(2) =0.92 and Q(2) =0.71 for λabs ; R(2) =0.89 and Q(2) =0.69 for λem ) performed significantly better than linear models. A small root mean squared error (RMSE) of 5.62 nm and 11.07 nm was achieved for λabs and λem , 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 λem . We conclude that QSPR is a useful tool for modeling λabs and λem 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).
authors.affiliation: Duke-NUS Graduate Medical School, Program in Emerging Infectious Diseases, 8 College Road, Singapore 169857.|Medicinal Chemistry Programme, National University of Singapore, 3 Science Drive 3, Singapore 117543.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schüller
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 phone: +65 6516 6774, fax: +65 6779 1691.
authors.forename: Garrett Benjamin
authors.initials: GB
authors.lastname: Goh
authors.affiliation: Medicinal Chemistry Programme, National University of Singapore, 3 Science Drive 3, Singapore 117543.|Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 phone: +65 6516 6774, fax: +65 6779 1691.
authors.forename: Hanjo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Life/Health Division, Integrated Omics Center, Korea Institute of Science and Technology (KIST), Seoul, South Korea, 136-791.
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Medicinal Chemistry Programme, National University of Singapore, 3 Science Drive 3, Singapore 117543. chmcyt@nus.edu.sg.|Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 phone: +65 6516 6774, fax: +65 6779 1691. chmcyt@nus.edu.sg.|Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Biomedical Research Council, Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way, #02-02 Helios, Singapore 138667. chmcyt@nus.edu.sg.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
keywords: Absorption/fluorescence emission wavelength (λabs/λem); DOFLA; Multiple linear regression (MLR); QSPR, BODIPY; Support vector regression (SVR)