Fluorogenic probes are important tools to image proteinsw ith high contrast and no wash protocols. In this work, we rationally designed and synthesized as mall set of four protein fluorogens with red or near-infrared emission. The fluorophores were characterizedinthe presence of albumin as am odel protein environment and exhibited good fluorogenicitya nd brightness (fluorescenceq uantum yield up to 36 %). Oncec onjugatedt oahaloalkanel igand, the probes reactedw ith the protein self-labelingt ag HaloTag with ah igh fluorescencee nhancement (up to 156-fold). The spectroscopic properties of the fluorogens and their reaction with HaloTag were investigated experimentally in vitro and with the helpo fm olecular dynamics. The two most promising probes, one in the red and one in the near-infrared range,w eref inally applied to image the nucleus or actin in live-cell and in wash-free conditions using fluorogenica nd chemogenetic targeting of HaloTag fusion proteins.

Ten borylated bipyridines (BOBIPYs) have been synthesized and selected structural modifications have been made that allow useful structure-optical property relationships to be gathered. These systems have been further investigated using DFT calculations and spectroscopic measurements, showing blue to green fluorescence with quantum yields up to 41%. They allow full mapping of the structure to determine where selected functionalities can be implemented, to tune the optical properties or to incorporate linking groups. The best derivative was thus functionalised with an alkyne linker, which would enable further applications through click chemistry and in this optic, the stability of the fluorophores has been evaluated.

We report the development of HaloTag fluorogens based on dipolar flexible molecular rotor structures. By modulating the electron donating and withdrawing groups, we have tuned the absorption and emission wavelengths...

Summary[2 + 2]-Cycloadditions of cyclopentene and 2,3-dimethylbut-2-ene to furanone were investigated under continuous-flow conditions. Irradiations were conducted in a FEP-microcapillary module which was placed in a Rayonet chamber photoreactor equipped with low wattage UVC-lamps. Conversion rates and isolated yields were compared to analogue batch reactions in a quartz test tube. In all cases examined, the microcapillary reactor furnished faster conversions and improved product qualities.

The aza-Diels–Alder cycloaddition of 1,2,4-triazines with alkynes offers a rapid and convenient method for the synthesis of highly substituted pyridines, but often requires harsh conditions and long reaction times. The present study offers a solution to these limitations by use of a temporary tether established by a Lewis acid–base complexation of in situ generated alkynylboranes and triazines bearing a Lewis basic donor. The cycloaddition reactions take place within 20 min at 40 °C and provide direct access to a broad range of pyridines with complete and predictable regiocontrol. The carbon—boron bond can be further functionalised by cross-coupling allowing further functionality to be introduced after cycloaddition.

A synthetic sphingolipid related to a ring-constrained hydroxymethyl pyrrolidine analog of FTY720 that was known to starve cancer cells to death was chemically modified to include a series of alkoxy-tethered 3,6-substituted 1,2-pyridazines. These derivatives exhibited excellent antiproliferative activity against eight human cancer cell lines from four different cancer types. A 2.5-to 9-fold reduction in IC 50 in these cell lines was observed relative to the lead compound, which lacked the appended heterocycle.

We introduce a strategy for the fluorogenic and genetic targeting of a calcium indicator by combining a protein fluorogen with the BAPTA sensing group. The resulting dual-input probe acts like...

We report that axially chiral biaryl boronic esters can be generated with control of atroposelectivity by a Binol-mediated dynamic thermodynamic resolution process. These intermediates can be progressed to enantioenriched products through stereoretentive functionalization of the carbon-boron bond. Finally, we have exploited this method in the first highly stereoselective total synthesis of P-streptonigrin.