Development and application of Diels-Alder adducts displaying AIE properties

Exploring organic reactions to construct novel molecules with aggregation-induced emission (AIE) features is an essential branch of AIE research. The fast-paced application of AIE materials in various disciplines, including photoelectricity, molecular biology, medicine, and materials science, has led to an ever-growing need for new AIE molecules. Unlike the synthesis of most “earlier generations” of AIE fluorogens (AIEgens) that require tedious and harsh reactions, chemists now shift their synthetic focus to a selection of reliable and straightforward reactions. The Diels-Alder reaction has been overlooked in this field. Herein, we report a catalyst-free Diels-Alder reaction between 1,3-diphenylisobenzofuran and a series of electron-deficient alkynes to create AIEgens. Photophysical properties of our synthesized 1,3,4-triphenyl-1,4-dihydro-1,4-epoxynaphthalene (ENAP) derivatives are studied systematically, manifesting their AIE characteristics and structure-fluorescence property relationships. Finally, we highlight the diverse applications of some selected ENAP derivatives in latent fingerprint detection, cell imaging, and bacterial staining

Development and application of Diels-Alder adducts displaying AIE properties

Exploring organic reactions to construct novel molecules with aggregation-induced emission (AIE) features is an essential branch of AIE research. The fast-paced application of AIE materials in various disciplines, including photoelectricity, molecular biology, medicine, and materials science, has led to an ever-growing need for new AIE molecules. Unlike the synthesis of most “earlier generations” of AIE fluorogens (AIEgens) that require tedious and harsh reactions, chemists now shift their synthetic focus to a selection of reliable and straightforward reactions. The Diels-Alder reaction has been overlooked in this field. Herein, we report a catalyst-free Diels-Alder reaction between 1,3-diphenylisobenzofuran and a series of electron-deficient alkynes to create AIEgens. Photophysical properties of our synthesized 1,3,4-triphenyl-1,4-dihydro-1,4-epoxynaphthalene (ENAP) derivatives are studied systematically, manifesting their AIE characteristics and structure-fluorescence property relationships. Finally, we highlight the diverse applications of some selected ENAP derivatives in latent fingerprint detection, cell imaging, and bacterial staining

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs

Diversity Oriented Clicking (DOC) is a unified click-approach for the modular synthesis of lead-like structures through application of the wide family of click transformations. DOC evolved from the concept of achieving “diversity with ease”, by combining classic C−C π-bond click chemistry with recent developments in connective SuFEx-technologies. We showcase 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click-cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click-library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3- and 1,5-dipoles; while reaction with cyclic dienes yields several three-dimensional bicyclic Diels–Alder adducts. Growing the library to 278 discrete compounds through late-stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well-plates—demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin.</p

Modular synthesis of functional libraries by accelerated SuFEx click chemistry

Accelerated SuFEx Click Chemistry (ASCC) is a powerful method for coupling aryl and alkyl alcohols with SuFEx-compatible functional groups. With its hallmark favorable kinetics and exceptional product yields, ASCC streamlines the synthetic workflow, simplifies the purification process, and is ideally suited for discovering functional molecules. We showcase the versatility and practicality of the ASCC reaction as a tool for the late-stage derivatization of bioactive molecules and in the array synthesis of sulfonate-linked, high-potency, microtubule targeting agents (MTAs) that exhibit nanomolar anticancer activity against multidrug-resistant cancer cell lines. These findings underscore ASCC's promise as a robust platform for drug discovery.</p