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.     

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.     

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.     

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.     

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.     

Room temperature dehalogenation of (hetero)aryl halides with magnesium/methanol

Magnesium in methanol was found to be an effective and inexpensive reagent for the dehalogenation of (hetero)aryl chlorides, bromides and iodides under mild conditions. The halogen/hydrogen exchange proceeded at room temperature and tolerated functional groups such as esters, nitriles, alcohols, and alkenes.     

The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-l-ene compounds against breast cancer cells

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 oxidative quinone methide formation. We now present a series of analogous amine and acetamide compounds: 2-ferrocenyl-1-(4-aminophenyl)-1-phenyl-but-1-ene (Z+E-2), 2-ferrocenyl-1-(4-N-acetylaminophenyl)-1-phenyl-but-1-ene (Z-3), and their corresponding organic molecules 1-(4-aminophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-4) and 1-(4-N-acetamidophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-5). All of the compounds have adequate relative binding affinity values for the estrogen receptor; between 2.8% and 5.7% for ERα, and between 0.18% and 15.5% for ERβ, as well as exothermic ligand binding in in silico ER docking experiments. Compounds 2 and 3 show dual estrogenic/cytotoxic activity on the MCF-7 cell line; they are proliferative at low concentrations (0.1 μM) and antiproliferative at high concentrations (10 μM). On the MDA-MB-231 cell line, the ferrocenyl complexes 2 and 3 are antiproliferative with IC₅₀ values of 0.8 μM for 2 and 0.65 μM for 3, while the purely organic molecules 4 and 5 show no effect. Electrochemical experiments suggest that both 2 and 3 can be transformed to oxidized quinoid-type species, analogous to what had previously been observed for the ferrocene phenols.