A Far-Red Emitting Fluorescent Chemogenetic Reporter for In Vivo Molecular Imaging

Far-red emitting fluorescent labels are highly desirable for spectral multiplexing and deep tissue imaging. Here, we describe the generation of frFAST (far-red Fluorescence Activating and absorption Shifting Tag), a 14-kDa monomeric protein that forms a bright far-red fluorescent assembly with (4-hydroxy-3-methoxy-phenyl)allylidene rhodanine (HPAR-3OM). As HPAR-3OM is essentially non-fluorescent in solution and in cells, frFAST can be imaged with high contrast in presence of free HPAR-3OM, which allowed the rapid and efficient imaging of frFAST fusions in live cells, zebrafish embryo/larvae, and chicken embryos. Beyond enabling the genetic encoding of far-red fluorescence, frFAST allowed the design of a far-red chemogenetic reporter of protein–protein interactions, demonstrating its great potential for the design of innovative far-red emitting biosensors.     

A rhenium tris-carbonyl derivative as a single core multimodal probe for imaging (SCoMPI) combining infrared and luminescent properties

A rhenium tris-carbonyl derivative has been designed to couple infrared and luminescent detection in cells. Both spectroscopies are consistent with one another; they point out the reliability of the present SCoMPI (for Single Core Multimodal Probe for Imaging) for bimodal imaging and unambiguously indicate a localization at the Golgi apparatus in MDA-MB-231 breast cancer cells.     

One-pot Sonogashira-cyclization protocol to obtain substituted furopyrimidine nucleosides in aqueous conditions

An environmentally benign one-pot protocol was herein reported to obtain different substituted furopyrimidine nucleosides in aqueous conditions with a low catalysts loading.     

Validation of molecular mass measurements by means of diffusion-ordered NMR spectroscopy: Application to oligosaccharides

The validation of molecular mass measurements by using DOSY spectrocopy is presented. A mixture of oligosaccharides has been studied and an extended model has been used. A method has been proposed and applied to correct the imperfections due either to the lock system or the room temperature regulator.     

Ferrocenyl compounds possessing protected phenol and thiophenol groups: Synthesis,X-ray structure,and in vitro biological effects against breast cancer

We have previously shown that conjugated ferrocenyl p-phenols show strong cytotoxic effects against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines, possibly via metabolic quinone methide (QM) formation. To further evaluate this proposed mechanism, we have created a series of ferrocenyl prodrugs containing methyl and acetyl-protected thio- and oxo-phenols: 2-ferrocenyl-1,1-bis(4-acetoxyphenyl)-but-1-ene (5), 2-ferrocenyl-1,1-bis(4-thioacetylphenyl)-but-1-ene (6), 2-ferrocenyl-1,1-bis(4-methoxyphenyl)-but-1-ene (7), and 2-ferrocenyl-1,1-bis(4-thiomethylphenyl)-but-1-ene (8), which might be activated by hydrolysis enzymes in situ. Only the acetoxy 5 displayed antiproliferative effects (IC₅₀ on MDA-MB-231 of 0.5 μM) while 6–8 act as pure estrogens (proliferative on MCF-7 and little to no effect on MDA-MB-231). The behaviour of 5 is similar to that previously found for the free phenol 2-ferrocenyl-1,1-di(4-hydroxyphenyl)-but-1-ene (2), indicating that 5 is metabolized in situ to 2, which could then undergo oxidative QM formation. The observation that the thioacetyl 6 is not cytotoxic suggests that the in situ oxidative chemistry of the putative ferrocenyl thiophenol is different from that of 2. Because p-thioquinone methides are practically unknown, the negative results for 6 further implicate the bioformation of the QM in the case of 2 and related compounds. The lack of cytotoxicity of 7 and 8 can be attributed to lack of efficient hydrolysis in situ. Estrogen receptor binding affinity studies for the compounds and the X-ray structure of 8 are also reported.     

Nanoscopic Imaging of meso‐Tetraalkylporphyrins Prepared in High Yields Enabled by Montmorrilonite K10 and 3 Å Molecular Sieves

We have developed a high‐yielding synthesis of meso‐tetraalkylporphyrins, which previously have been obtained only in lower yields. By employing Montmorrilonite K10 as the acid catalyst and 3 Å molecular sieves as the dehydrating agent, yields that reached 70 % could be achieved with some aliphatic aldehydes. The free‐base porphyrins with decyl ( C10 ) or longer chains were imaged at the single‐molecule level at the solvent/surface interface. Highly oriented pyrolytic graphite (HOPG) was used as a π‐stacking surface, whereas 1‐phenyloctane and 1‐phenylnonane were used as solvents. An odd–even effect was observed from C13 to C16 . For C13 a single‐crystal X‐ray structure allowed an unprecedented insight into how packing from two dimensions is expanded into a three‐dimensional crystal lattice.     

Photoswitching Kinetics and Phase‐Sensitive Detection Add Discriminative Dimensions for Selective Fluorescence Imaging

Non‐invasive separation‐free protocols are attractive for analyzing complex mixtures. To increase selectivity, an analysis under kinetic control, through exploitation of the photochemical reactivity of labeling contrast agents, is described. The simple protocol is applied in optical fluorescence microscopy, where autofluorescence, light scattering, as well as spectral crowding presents limitations. Introduced herein is OPIOM (out‐of‐phase imaging after optical modulation), which exploits the rich kinetic signature of a photoswitching fluorescent probe to increase selectively and quantitatively its contrast. Filtering the specific contribution of the probe only requires phase‐sensitive detection upon matching the photoswitching dynamics of the probe and the intensity and frequency of a modulated monochromatic light excitation. After in vitro validation, we applied OPIOM for selective imaging in mammalian cells and zebrafish, thus opening attractive perspectives for multiplexed observations in biological samples.     

Synthesis and cross-coupling of sulfonamidomethyltrifluoroborates

Sulfonamidomethyltrifluoroborates were successfully synthesized and cross-coupled with a wide range of aryl and heteroaryl chlorides, allowing the construction of a sulfonamidomethyl aryl linkage through a new disconnection, thus offering a new way to access such structurally interesting motifs.