Fluorescent Flippers: Small‐Molecule Probes to Image Membrane Tension in Living Systems

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(20)

Published: Feb. 3, 2023

Flipper probes have been introduced as small molecule fluorophores to image physical forces, that is, membrane tension in living systems. Their emergence over one decade is described, from evolution design and synthesis spectroscopic properties. Responsiveness compression equilibrium at the ground state identified ideal origin of mechanosensitivity cells. A rich collection flippers described deliver release any subcellular interest a leaflet-specific manner. Chalcogen-bonding cascade switching dynamic covalent are developed for super-resolution imaging dual-sensing hydration. Availability broad use community validate flipper fine example power translational supramolecular chemistry, moving fundamental principles success on market.

Language: Английский

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Introduction of Lipophilic Side Chains to NH-Sulfoximines by Palladium Catalysis Under Blue Light Irradiation

Organic Letters, Journal Year: 2022, Volume and Issue: 24(11), P. 2238 - 2241

Published: March 16, 2022

Palladium catalysis under blue (LED) light irradiation allows conversion of NH-sulfoximines into products with long lipophilic side chains attached to the S═N moiety. The three-component reactions involve both radicals and organometallic intermediates stemming from alkyl bromides butadienes. substrate scope is broad, are formed in moderate good yields.

Language: Английский

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Core‐Alkynylated Fluorescent Flippers: Altered Ultrafast Photophysics to Track Thick Membranes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(31)

Published: May 17, 2024

Fluorescent flippers have been introduced as small-molecule probes to image membrane tension in living systems. This study describes the design, synthesis, spectroscopic and imaging properties of that are elongated by one two alkynes inserted between push pull dithienothiophene domains. The resulting mechanophores combine characteristics flippers, reporting on physical compression ground state, molecular rotors, torsional motion excited take their photophysics new level sophistication. Intensity ratios broadened excitation bands from differently twisted conformers core-alkynylated thus report mechanical compression. Lifetime boosts ultrafast excited-state planarization lifetime drops competitive intersystem crossing into triplet states viscosity. In standard lipid bilayer membranes, too long for leaflet tilt or extend disordered interleaflet space, which preserves rotor-like disorder weak, blue-shifted fluorescence. Flipper-like occurs only highly ordered membranes matching thickness, where they light up selectively these thick with red-shifted, sharpened maxima, high intensity lifetime.

Language: Английский

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Dithieno[3,2-b:2′,3′-d]thiophene (DTT): an emerging heterocyclic building block for future organic electronic materials & functional supramolecular chemistry

RSC Advances, Journal Year: 2022, Volume and Issue: 12(55), P. 36073 - 36102

Published: Jan. 1, 2022

DTT: a potential electron rich building block and its diverse application in organic electronic materials.

Language: Английский

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Fluorogenic In Situ Thioacetalization: Expanding the Chemical Space of Fluorescent Probes, Including Unorthodox, Bifurcated, and Mechanosensitive Chalcogen Bonds

JACS Au, Journal Year: 2023, Volume and Issue: 3(9), P. 2557 - 2565

Published: Aug. 21, 2023

Progress with fluorescent flippers, small-molecule probes to image membrane tension in living systems, has been limited by the effort needed synthesize twisted push-pull mechanophore. Here, we move a higher oxidation level introduce new design paradigm that allows screening of flipper rapidly, at best situ. Late-stage clicking thioacetals and acetals simultaneous attachment targeting units interfacers exploration critical chalcogen-bonding donor same time. Initial studies focus on plasma develop chemical space thioacetals, from acyclic amino acids cyclic 1,3-heterocycles covering dioxanes as well dithiolanes, dithianes, dithiepanes, derived also classics biology like cysteine, lipoic acid, asparagusic DTT, epidithiodiketopiperazines. From functional point view, sensitivity imaging cells could be doubled, lifetime differences FLIM images increasing 0.55 1.11 ns. theoretical complexity mechanically coupled chalcogen bonding is explored, revealing, among others, intriguing bifurcated bonds.

Language: Английский

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The Dynamic Range of Acidity: Tracking Rules for the Unidirectional Penetration of Cellular Compartments

ChemBioChem, Journal Year: 2022, Volume and Issue: 23(15)

Published: May 10, 2022

Labeled ammonium cations with pK

Language: Английский

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G‐Quartets, 4‐Way Junctions and Triple Helices but Not DNA Duplexes: Planarization of Twisted Push–Pull Flipper Probes by Surface Recognition Rather Than Physical Compression

Helvetica Chimica Acta, Journal Year: 2022, Volume and Issue: 105(8)

Published: June 16, 2022

Abstract Planarizable push–pull flipper probes have been introduced to image order and tension of membranes in living cells. In this report, we show that fluorescent flippers can also be planarized by chemical interactions on DNA architectures rather than physical forces biomembranes. Compared fluorescence water, the planarization parallel cMyc G‐quartets is characterized a 100 nm red shift excitation maximum strong increase intensity. A coinciding emission compared ordered reveals occurs water‐accessible surface within G‐quartets. Less relevant for compression ground state hydrophobic membranes, functional relevance solvatochromism excited state, reflected shifts excitation, unprecedented introduces attractive dual sensing perspectives. With decreasing efficiency, are antiparallel hTel22 G‐quartets, 4‐way junctions triple helices, while aromatic B‐DNA duplexes too small enough π stacking. These remarkably consistent results expand understanding planarizable enable applications new directions.

Language: Английский

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Fluorescent Flippers: Small‐Molecule Probes to Image Membrane Tension in Living Systems

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(20)

Published: Feb. 3, 2023

Abstract Flipper probes have been introduced as small molecule fluorophores to image physical forces, that is, membrane tension in living systems. Their emergence over one decade is described, from evolution design and synthesis spectroscopic properties. Responsiveness compression equilibrium at the ground state identified ideal origin of mechanosensitivity cells. A rich collection flippers described deliver release any subcellular interest a leaflet‐specific manner. Chalcogen‐bonding cascade switching dynamic covalent are developed for super‐resolution imaging dual‐sensing hydration. Availability broad use community validate flipper fine example power translational supramolecular chemistry, moving fundamental principles success on market.

Language: Английский

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Hydrophobic Interfacing of Fluorescent Membrane Probes

ChemistryEurope, Journal Year: 2023, Volume and Issue: 1(3)

Published: Oct. 2, 2023

Abstract Fluorescent flippers have been introduced as small‐molecule probes to image membrane tension in living systems. While the hydrophilic headgroup region has modified extensively for intracellular targeting, little is known about hydrophobic interfacing with surrounding membrane. To tackle this challenge, design, synthesis and evaluation of a glutamine‐derived flipper collection reported. Considering importance tension‐induced phase separation imaging, study focused on how modulate distribution functional between ordered disordered microdomains. Also interest was control over intermembrane transfer without loss function specific labeling plasma membranes. Evidence presented two‐step insertion mechanism through more accessible domains into better matching domains. This process also explains differences partition coefficients bioimaging. It further demonstrated that interdomain can be regulated by brightness fluorescence lifetime imaging microscopy responsiveness tension. Irreversible partitioning inhibits coincides internalization cells. These results demonstrate improve probe performance provide guidelines proceed.

Language: Английский

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Organoboron/Palladium Cocatalytic Allylation of NH-Sulfoximines Using Allylic Alcohols

Organic Letters, Journal Year: 2023, Volume and Issue: 25(46), P. 8274 - 8278

Published: Nov. 14, 2023

Synergistic organoboron/palladium cocatalysis enables dehydrative couplings of NH-sulfoximines with allylic alcohols, furnishing the corresponding N-allylated products. The reactions proceed in absence a Brønsted base and are tolerant diverse sulfoximine partners, including functionalized variants. Experimental computational studies suggest that reagent is activated by complexation to boronic acid cocatalyst.

Language: Английский

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