title: Rational Design of Fluorescent Phthalazinone Derivatives for One- and Two-Photon Imaging.
abstract: Phthalazinone derivatives were designed as optical probes for one- and two-photon fluorescence microscopy imaging. The design strategy involves stepwise extension and modification of pyridazinone by 1) expansion of pyridazinone to phthalazinone, a larger conjugated system, as the electron acceptor, 2) coupling of electron-donating aromatic groups such as N,N-diethylaminophenyl, thienyl, naphthyl, and quinolyl to the phthalazinone, and 3) anchoring of an alkyl chain to the phthalazinone with various terminal substituents such as triphenylphosphonio, morpholino, triethylammonio, N-methylimidazolio, pyrrolidino, and piperidino. Theoretical calculations were utilized to verify the initial design. The desired fluorescent probes were synthesized by two different routes in considerable yields. Twenty-two phthalazinone derivatives were synthesized and their photophysical properties were measured. Selected compounds were applied in cell imaging, and valuable information was obtained. Furthermore, the designed compounds showed excellent performance in two-photon microscopic imaging of mouse brain slices.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China.|Medical and Healthy Analysis Center, Peking University, Beijing, P. R. China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, P. R. China.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, P. R. China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Shui
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China.
authors.forename: Tongliang
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Beijing National Laboratory for Molecular Science, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing, P. R.China.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Beijing National Laboratory for Molecular Science, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing, P. R.China.
authors.forename: Jun-Long
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China. pingxu@bjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Medical and Healthy Analysis Center, Peking University, Beijing, P. R. China. yuan_lan@bjmu.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China. leiliang@bjmu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
mesh_terms: D000818:Animals; D004583:Electrons; D005456:Fluorescent Dyes / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D015394:Molecular Structure; D017785:Photons
chemical_list: D005456:Fluorescent Dyes
keywords: density functional calculations; fluorescence microscopy; fluorescent probes; imaging agents; synthesis design