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.

Construction of a Near-Infrared Fluorescent Probe for Dynamic Monitoring and Early Diagnosis of Heart Failure

“…In our previous work, the pyridazinone skeleton has been centralized as the core of a fluorophore which is favorable for the design of cardiovascular drug candidates. − For example, we developed a smart probe as the fluorescent indicator of cardiac fibrosis . Herein, three elements are necessary for the development of a practical tool for cardiac diagnosis.…”

Early Diagnosis of Cerebral Ischemia Reperfusion Injury and Revelation of Its Regional Development by a H3R Receptor-Directed Probe

“…Herein, we consider pyridazinone due to its structural advantages as the pharmacophore of the histamine H 3 receptor agonist that is applicable for brain-directed requirement. Previously, we have proved that pyridazinone diversification generates a series of fluorophores with properties of large two-photon cross section, high photostability, low toxicity, and potent membrane permeability. − We assume that delicate modification of both the C 6 and N 2 substitutions of pyridazinone is necessary for its properties of brain targeting and two-photon excitability. , Thus, to build the brain-targeting moiety, we chose different alkyl linkers to bridge 6-(4-hydroxyphenyl)­pyridazin-3­(2 H )-one and various terminal cycloamines including pyrroline, piperidine, morpholine, and pure 2-methylpyrrolidine enantiomers. In addition, modification of the N 2 substituent endows the scaffold fluorescent emission and selective response toward H 2 O 2 .…”

Photoinduced electron transfer (PeT) based fluorescent probes for cellular imaging and disease therapy

“…Therefore, Zhao, Liang, Xu and co-workers have developed a highly sensitive and selective probe (probe 17) for the real-time detection of NO. 95 Pyridazinone was selected as one part of the fluorophore, [96][97][98] with o-phenylenediamine (OPD) used as the NO ''recognition group'', both due to its high selectivity and ability to quench the fluorescence via the PeT process (Fig. 15A).…”