Combining [Arene–Ru] with Azocarboxamide to Generate a Complex with Cytotoxic Properties

Azocarboxamide (azcH) has been combined for the first time with [Ru–Cym] to generate metal complexes with N,N‐ and N,O‐coordination mode, [(Cym)Ru(azc)Cl] and [(Cym)Ru(azcH)Cl]⁺[PF₆]^?. Geometric and electronic structures of the complexes are reported along with their in vitro activities against different tumour cell lines and preliminary results on solution chemistry. Compound [(Cym)Ru(azc)Cl] exhibited remarkable cytotoxic properties. It was cell‐type specific and had comparable IC₅₀ values towards both cancer cells and their drug‐resistant subline. A tenfold increase in the sensitivity towards [(Cym)Ru(azc)Cl] was noted for the tumour cells with depleted intracellular glutathione (GSH) level, suggesting the essential role of GSH in cell response to this compound.     

An Isolated Nitridyl Radical‐Bridged {Rh(N.)Rh} Complex

Photochemical activation of [(PNNH)Rh(N₃)] (PNNH=6‐di‐(tert‐butyl)phosphinomethyl‐2,2′‐bipyridine) complex 2 produced the paramagnetic (S=1/2), [(PNN)Rh?N^.‐Rh(PNN)] complex 3 (PNN^?=methylene‐deprotonated PNNH), which could be crystallographically characterized. Spectroscopic investigation of 3 indicates a predominant nitridyl radical (^.N^2?) character, which was confirmed computationally. Complex 3 reacts selectively with CO, producing two equivalents of [(PNN)Rh^I(CO)] complex 4 , presumably by nitridyl radical N,N‐coupling.     

On resin synthesis of sulfated oligosaccharides

Sulfated glycans are involved in many biological processes, making well-defined sulfated oligosaccharides highly sought molecular probes. These compounds are a considerable synthetic challenge, with each oligosaccharide target requiring specific synthetic protocols and extensive purifications steps. Here, we describe a general on resin approach that simplifies the synthesis of sulfated glycans. The oligosaccharide backbone, obtained by Automated Glycan Assembly (AGA), is subjected to regioselective sulfation and hydrolysis of protecting groups. The protocol is compatible with several monosaccharides and allows for multi-sulfation of linear and branched glycans. Seven diverse, biologically relevant sulfated glycans were prepared in good to excellent overall yield.

Well-defined sulfated oligosaccharides are important synthetic targets. We present an on resin approach for the synthesis of sulfated glycans with a broad reaction scope that overcomes previous limitations associated with on resin synthesis.     

Effects of Regioisomerism on the Antiproliferative Activity of Hydroxystearic Acids on Human Cancer Cell Lines

A series of regioisomers of the hydroxystearic acid (HSA) was prepared, and the effect of the position of the hydroxyl group along the chain on a panel of human cancer cell lines was investigated. Among the various regioisomers, those carrying the hydroxyl at positions 5, 7, and 9 had growth inhibitor activity against various human tumor cell lines, including CaCo-2, HT29, HeLa, MCF7, PC3, and NLF cells. 10-HSA and 11-HSA showed a very weak effect. 8-HSA did not show inhibitory activity in all cell lines. The biological role of 7-HSA and 9-HSA is widely recognized, while little is known about the effects of 5-HSA. Therefore, the biological effects of 5-HSA in HeLa, HT29, MCF7, and NLF cell lines were investigated using the Livecyte’s ptychography technology, which allows correlating changes in proliferation, motility, and morphology as a function of treatment at the same time. 5-HSA not only reduces cell proliferation but also induces changes in cell displacement, directionality, and speed. It is important to characterize the biological effects of 5-HSA, this molecule being an important component of fatty acyl esters of hydroxy fatty acids (FAHFA), a class of endogenous mammalian lipids with noticeable anti-diabetic and anti-inflammatory effects.