A Maltol-Containing Ruthenium Polypyridyl Complex as a Potential Anticancer Agent

Cancer is one of the main causes of death worldwide. Chemotherapy, despite its severe side effects, is to date one of the leading strategies against cancer. Metal-based drugs present several potential advantages when compared to organic compounds and they have gained trust from the scientific community after the approval on the market of the drug cisplatin. Recently, we reported the ruthenium complex ([Ru(DIP)₂(sq)](PF₆) (where DIP is 4,7-diphenyl-1,10-phenantroline and sq is semiquinonate) with a remarkable potential as chemotherapeutic agent against cancer, both in vitro and in vivo. In this work, we analyse a structurally similar compound, namely [Ru(DIP)₂(mal)](PF₆), carrying the flavour-enhancing agent approved by the FDA, maltol (mal). To possess an FDA approved ligand is crucial for a complex, whose mechanism of action might include ligand exchange. Herein, we describe the synthesis and characterisation of [Ru(DIP)₂(mal)](PF₆), its stability in solutions and under conditions that resemble the physiological ones, and its in-depth biological investigation. Cytotoxicity tests on different cell lines in 2D model and on HeLa MultiCellular Tumour Spheroids (MCTS) demonstrated that our compound has higher activity than cisplatin, inspiring further tests. [Ru(DIP)₂(mal)](PF₆) was efficiently internalised by HeLa cells through a passive transport mechanism and severely affected the mitochondrial metabolism.     

A Covalent Binding Mode of a Pyrazole-Based CD38 Inhibitor

Brain concentrations of nicotinamide adenine dinucleotide (NAD⁺), an important cellular co-factor, tend to decrease with age and in neurodegeneration. As the NADase cluster of differentiation 38 (CD38) significantly contributes to NAD⁺ consumption, we reasoned that CD38 inhibition may be of therapeutic value for CNS disorders. The new pyrazole compound was designed based on a known CD38 inhibitor and showed good inhibitory potency. Several attempts to co-crystallise this pyrazole with CD38 and cyclic adenosine diphosphate ribose (cADPR) culminated in a high-resolution X-ray structure, in which the pyrazolyl group in the new compound formed a covalent bond with one of the ribosyl units of cADPR. This reaction proceeded under retention of configuration and resulted in a neutral ribosyl-pyrazole conjugate that is embedded within the active site of the enzyme. An analysis of this structural complex gave rise to design principles that enabled the preparation of more potent CD38 inhibitors with drug-like properties.     

A New Insight into the Stereoelectronic Control of the Pd0-Catalyzed Allylic Substitution: Application for the Synthesis of Multisubstituted Pyran-2-ones via an Unusual 1,3-Transposition

Pyran-2-ones 3 undergo a novel Pd⁰-catalyzed 1,3-rearrangement to afford isomers 6 . The reaction proceeds via an η²-Pd complex, the pyramidalization of which (confirmed by quantum chemistry calculations) offers a favorable antiperiplanar alignment of the Pd−C and allylic C−O bonds ( C ), thus allowing the formation of an η³-Pd intermediate. Subsequent rotation and rate-limiting recombination with the carboxylate arm then gives isomeric pyran-2-ones 6 . The calculated free energies reproduce the observed kinetics semi-quantitatively.     

Parameters Tied to Treewidth

Treewidth is a graph parameter of fundamental importance to algorithmic and structural graph theory. This article surveys several graph parameters tied to treewidth, including separation number, tangle number, well‐linked number, and Cartesian tree product number. We review many results in the literature showing these parameters are tied to treewidth. In a number of cases we also improve known bounds, provide simpler proofs, and show that the inequalities presented are tight.     

Some Aspects of Intra- and Inter-Molecular Reactions of Siliconium Ions in the Vapor Phase

Intramolecular rearrangement processes in the mass spectra of trimethylsilyl derivatives of hydroxy steroids are discussed in terms of the reaction of a siliconium center and a heteroatom. The reaction is shown to be stereospecific. The reactivity of siliconium cations also results in the occurrence of intermolecular reactions under electron impact ionization conditions. Tetramethylsilane is used as a precursor for the production of siliconium ions and examples of chemical ionization mass spectra employing this reagent are shown.     

Determination of Iprodione,Vinclozolin, and Procymidone as the Heptafluorobutyramides of 3,5-Dichloroaniline

Abstract

A method was developed for the determination of three fungicides in foods based on alkaline degradation to 3,5-dichloroaniline, isolation of the latter by steam distillation and measurement of the heptafluorobutyrate by gas chromatography. Recoveries averaged 91% from several commodities spiked at from 10–80ppb. The minimum detectable limit of 2.6ppb was attainable in grape, with similar limits found in strawberry, tomato and beans. The method was capable of determining degradation products formed as a result of cooking.