Chemical Profiles and Antibacterial Activity of Essential Oils from Rhizomes of Aspidistra phanluongii

Chemistry of Natural Compounds -     

Redox-sensitive membrane-electrode based on the organic free radical octachlorophenothiazinyl

An electrode based on an organic free radical and sensitive to redox systems is described.     

Neue Molekülverbindungen des β-1,2,3,4,5,6-Hexachlorcyclohexans

Eight new molecular compounds between -1,2,3,4,5,6-hexachlorocyclohexane (-HCH) and some heterocyclic salts (hydrochlorides of - and -picoline, 2,4,6-collidine, ,-bipyridine, isoquinoline, acridine, 9-phenylacridine, and 2,4,6-triphenylpyrylium perchlorate), with the molecular ratio 12, were synthesised and described by means of spectroscopic (IR, UV, NMR) and X-ray-diffraction methods. Some of the molecular compounds may be used for quantitative separation of the heterocyclic salts from complex mixtures.

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Lehrstuhl für Mineralogie.     

The unanticipated loss of SO2 from sulfonamides in collision-induced dissociation

A potent and selective sulfonamide beta3 agonist with an excellent pharmacokinetic profile has recently been synthesized. During the analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS) of metabolites of the sulfonamide N-[4-[2-(2-hydroxy-2-pyridin-3-ylethylamino)ethyl]phenyl]-4-[4-(4-trifluoromethylphenyl)thiazol-2-yl]benzulfonamide (compound A), we observed loss of 64 Da for a few of the metabolites in the negative ion mode. Accurate mass measurements performed with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and quadrupole time-of-flight (Q-TOF) mass spectrometry suggested that the loss of 64 Da corresponded to the loss of SO(2). The same phenomenon was observed for a group of structurally related and commercially available compounds that also contain a sulfonamide moiety. MS/MS analysis of the fragment ions that had lost SO(2) in the ion source suggested that these ions were covalently bound rather than ion-molecule complexes. The neutral loss involving the cleavage of two bonds was unanticipated and suggested a complex rearrangement process. A mechanism for the loss of SO(2) has been proposed.     

Comparison of metabolic soft spot predictions of CYP3A4, CYP2C9 and CYP2D6 substrates using MetaSite and StarDrop

Metabolite identification study plays an important role in determining the sites of metabolic liability of new chemical entities (NCEs) in drug discovery for lead optimization. Here we compare the two predictive software, MetaSite and StarDrop, available for this purpose. They work very differently but are used to predict the site of oxidation by major human cytochrome P450 (CYP) isoforms. Neither software can predict non-CYP catalyzed metabolism nor the rates of metabolism. For the purpose of comparing the two software packages, we tested known probe substrate for these enzymes, which included 12 substrates of CYP3A4 and 18 substrates of CYP2C9 and CYP2D6 were analyzed by each software and the results were compared. It is possible that these known substrates were part of the training set but we are not aware of it. To assess the performance of each software we assigned a point system for each correct prediction. The total points assigned for each CYP isoform experimentally were compared as a percentage of the total points assigned theoretically for the first choice prediction for all substrates for each isoform. Our results show that MetaSite and StarDrop are similar in predicting the correct site of metabolism by CYP3A4 (78% vs 83%, respectively). StarDrop appears to do slightly better in predicting the correct site of metabolism by CYP2C9 and CYP2D6 metabolism (89% and 93%, respectively) compared to MetaSite (63% and 70%, respectively). The sites of metabolism (SOM) from 34 in-house NCEs incubated in human liver microsomes or human hepatocytes were also evaluated using two prediction software packages and the results showed comparable SOM predictions. What makes this comparison challenging is that the contribution of each isoform to the intrinsic clearance (Clint) is not known. Overall the software were comparable except for MetaSite performing better for CYP2D6 and that MetaSite has a liver model that is absent in StarDrop that predicted with 82% accuracy.     

Protonation of Ferrocene in the Gas Phase

Hydrogen-deuterium exchange, proton and deuteron transfer, and collision-induced dissociation experiments involving protonated ferrocene, [Fe(cC₅H₅)₂]H⁺, and isotopically labeled analogues have been carried out using a Fourier transform ion cyclotron resonance (FTICR) spectrometer and a double-focusing mass spectrometer of reversed geometry. These experiments reveal that the structure in which the added proton is bound to one of the cyclopentadienyl rings, possibly via agostic interaction with the iron atom, plays an important role in the gas-phase behavior of protonated ferrocene. It is demonstrated that extensive hydrogen atom scrambling occurs in the cyclopentadiene ring and that the extra hydrogen can also switch from one ring to the other, probably via the iron atom. An interpretation is presented which implicates slow thermal unimolecular rearrangement on the FKR time scale from a metal-protonated form to a ring-protonated form which is higher in energy. This interpretation successfully rationalizes the current data as well as previous gas-phase measurements and is found to be in good agreement with solution and matrix isolation studies.     

Transformation of neutral rhenium compounds during electrospray ionization mass spectrometry

Four neutral rhenium compounds were examined by electrospray ionization mass spectrometry. Acetonitrile solutions of (Ind)Re(CO)₃ (Ind = indenyl) and (Cp)Re(CO)₃ (Cp = cyclopentadienyl) gave rise to [Re(CO)₃(CH₃CN)₃]⁺ ions. This is indicative of a reaction with the solvent, although these compounds do not react with acetonitrile under regular laboratory conditions. In contrast, (Ind)Re(CO)₂(butyne) and (Cp)Re(CO)₂(butyne) did not lose their aromatic hydrocarbon ligand upon ionization; the predominant product ions generated upon electrospray ionization were [(Ind)Re(CO)(CH₃CN)(butyne)]⁺ and [(Cp)Re(CO)(CH₃CN)(butyne)]⁺, respectively.