Beata Jasiewicz

Mass spectrometry of bis-quinolizidine alkaloids: 2- and 17-alkyl-substituted derivatives of sparteine and lupanine

The mass spectral fragmentations of 2-methylsparteine (1), 2, 17-dimethylsparteine (2), 2-methyl-17-isopropylsparteine (3), 2-methyl-17-oxosparteine (4), 2-oxo-17-methylsparteine (17-methyllupanine) (5) and 2-oxo-17-isopropylsparteine (17-isopropyllupanine) (6) were investigated. Fragmentation pathways, whose identification was assisted by accurate mass measurements and a correlation between the abundances of the M(+.) and selected fragment ions of the investigated compounds, are discussed. The data obtained create the basis for distinguishing the structural isomers and metamers.

Synthesis and haemolytic activity of novel salts made of nicotine alkaloids and bile acids

A series of novel salts made of nicotine alkaloids and bile acids were synthesized and their haemolytic activity was examined in vitro using human erythrocytes. All compounds were characterized by spectroscopic methods. The novel salts show membrane-perturbing properties inducing the erythrocyte shape alterations and haemolysis in dose-dependent manner. Nicotine decreases the membrane interacting potential of bile acids in the novel compounds. The presence of sulfur or selenium atom in the nicotine molecule affects the haemolytic activity of its novel salts depending on the hydrophobicity of bile acids.

Conformation of some sparteine N-16 oxides revisited

Sparteine N-16 oxides were thought to occur in all chair conformations with cis fusion between their C and D rings. NMR spectral analysis made possible indication of the chair – chair – boat– chair form with cis fussion of C, D rings for sparteine, 2phenyl- and 2-methylsparteine N-16 oxides. Molecular energy found by means of DFT, Hartree– Fock, AM1, PM3 methods supported this new shape of bisquinolizidine skeleton. q 2002 Elsevier Science B.V. All rights reserved.

Antioxidant properties of thio-caffeine derivatives: Identification of the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine as antioxidant and highly potent cytoprotective agent

A series of nine thio-caffeine analogues were synthesized and characterised by NMR, FT-IR and MS spectroscopic methods. Molecular structures of four of them were determined using single crystal X-ray diffraction methods. The antioxidant properties of all compounds, at concentration ranges from 0.025 to 0.1mg/mL, were evaluated by various chemical- and cell-based antioxidant assays. Human erythrocytes were used to examine in vitro haemolytic activity of all compounds and their protective effect against oxidative haemolysis induced by AAPH, one of the commonly used free radical generator. All compounds studied showed no effect on the human erythrocytes membrane structure and permeability with the exception of 8-(phenylsulfanyl)caffeine. Among the nine caffeine thio-analogues tested, the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine possessed exceptionally high antioxidant properties. Moreover, it protects human erythrocytes against AAPH-induced oxidative damage as efficiently as the standard antioxidant Trolox. Therefore, 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine may have a significant cytoprotective potential caused by its antioxidant activity.

Mass Spectrometry of Bis-quinolizidine Alkaloids: Differentiation of Stereoisomers and Metamers Using ESI and FAB Mass Spectrometry

ABSTRACT The ESI and FAB mass spectral fragmentations of seven bis-quinolizidine alkaloids were investigated. Fragmentation pathways, elucidation of which was assisted by FAB/CID mass spectra measurements, are discussed. The data create the basis for distinguishing stereoisomers and metamers.

Synthesis, spectroscopy, theoretical and biological studies of new gramine-steroids salts and conjugates

New gramine connections with bile acids (lithocholic, deoxycholic, cholic) and sterols (cholesterol, cholestanol) were synthesized. The structures of products were confirmed by spectral (NMR, FT-IR) analysis, mass spectrometry (ESI-MS) as well as PM5 semiempirical methods. Unexpectedly, the products of the reaction of gramine with cholesterol and cholestanol were symmetrical compounds consisting of two molecules of sterols connected by N(CH3)2 group. All new synthesized compounds interact in vitro with the human erythrocyte membrane and alter discoid erythrocyte shape inducing stomatocytosis or echinocytosis. Increase in the incorporation of the fluorescent dye merocyanine 540 (MC540) into the erythrocyte membrane indicates that new compounds at sublytic concentrations are capable of disturbing membrane phospholipids asymmetry and loosening the molecular packing of phospholipids in the bilayer. Gramine significantly decreases the membrane partitioning properties as well as haemolytic activity of lithocholic acid in its new salt. Moreover, both deoxycholic and cholic acids completely lost their membrane perturbing activities in the gramine salts. On the other hand, the capacity of new gramine-sterols connections to alter the erythrocyte membrane structure and its permeability is much higher in comparison with sterols alone. The dual effect of gramine on the bile acid and sterols cell membrane partitioning activity observed in our study should not be neglected in vivo.

Chalcogen analogues of nicotine lactam studied by NMR, FTIR, DFT and X-ray methods.

The selenoanalogue of nicotine has been synthesized and characterized by spectroscopic and X-ray diffraction methods. The crystals of selenonicotine are isomorphic with the thionicotine homologue and consist of molecules engaged in columnar π⋯π stacking interactions between antiparallely arranged pyridine moieties. These interactions, absent in other crystals containing nicotine fragments, seem to be induced by the presence of a lactam group. The molecular structures in the vacuum of the oxo-, thio- and selenonicotine homologues have been calculated by the DFT method and compared with the available X-ray data. The delocalized structure of thionicotine is stabilized by intramolecular C-H⋯S hydrogen bond, which becomes weaker in the partial zwitterionic resonance structure of selenonicotine in favor of multiple C-H⋯Se intermolecular hydrogen-bonds. The calculated data allow a complete assignment of vibration modes in the solid state FTIR spectra. The (1)H and (13)C NMR chemical shifts were calculated by the GIAO method with B3LYP/6-311G(3df) level. A comparison between experimental and calculated theoretical results indicates that the density functional B3LYP method provided satisfactory results for predicting FTIR, (1)H, (13)C NMR spectra properties.

Mass spectrometry of metal complexes of bis-quinolizidine alkaloids: electron ionization and fast atom bombardment mass spectral study of copper(II) (–)-sparteine and (–)-α-isosparteine complexes

The electron ionization (EI) and fast atom bombardment (FAB) mass spectral fragmentations of ten copper(II) dichloride (dibromide, diformate, diacetate and dithiocyanate) complexes of (–)-sparteine and (–)-α-isosparteine were investigated. Fragmentation pathways, elucidation of which was assisted by accurate mass measurements and metastable transitions (EI-MS), as well as FAB/collision-induced dissociation (CID) mass spectral measurements are discussed. The data obtained create the basis for the differentiation of the ligand (sparteine or α-isosparteine) in the investigated complexes. The comparison of the results with those obtained previously for corresponding zinc(II) complexes forms the basis for the differentiation of metals in these compounds. The results show that both EI-MS and FAB-MS are very useful tools for the differentiation of ligands, as well as metals in the series of Zn(II) and Cu(II) dichloride (dibromide, diacetate, diformate, dithioacetate) complexes of (–)-sparteine and (–)-α-isosparteine.

Electron ionization and fast atom bombardment mass spectral study for differentiation of ligand of zinc(II) (–)-sparteine and (–)-α-isosparteine complexes

The (–)-sparteine bis-quinolizidine alkaloid produced by lupine species has generated much interest due to its pharmacological properties, and its application in asymmetric synthesis. The basic bis-quinolizidine system of (–)sparteine consists of four rings, two of which (A/B) form a double-chair system of trans-quinolizidine, which is relatively resistant (for thermodynamic reasons) to conformationalconfigurational changes. The second system of rings (C/D) is much more susceptible to inversion at the N16 nitrogen atom and it can occur in either the trans boat-chair or the cis double-chair conformation. According to Haasnoot, sparteine adopts exclusively the C-boat conformer. Theoretical calculations have confirmed that the free base of sparteine has one predominant conformer with a chair-

N16-oxides of sparteine, 2-methylsparteine and 2-phenylsparteine as ligands; spectroscopic and DFT studies of complexes with ZnX2 (X=Cl, Br)

Six new ZnX2 (X=Cl, Br) complexes with N16-oxides of sparteine, 2-methylsparteine and 2-phenylsparteine as ligands have been synthesized and characterized by MS, IR, NMR and DFT methods. All complexes have 1 : 1 stoichiometry. Complexation with N16-oxides involves inversion of the configuration at N16, converting ring C from a boat into a chair with the oxygen engaged in coordination. All complexes investigated are of composition [(L–H)+(ZnX3)−] (where L is N-oxide). The structures of the complexes obtained have been compared with those of the monoperchlorate salts of the N-oxides.