Multiply charged ions in the mass spectra of aromatics

The prominence of multiply charged molecular and fragment ions upon electron-impact in the mass spectrometer is proposed as an experimental, empirical indication of aromatic character. The effects of electron withdrawing and donating substituents on the production of multiply charged ions are considered and appearance potentials are noted for several species.     

New designs for inhibitors of the NF-κB: DNA binding

We present a series of new inhibitors of the association between nuclear factor kappa B (NF-B) and the corresponding B site in DNA. They were designed using the lead compound 15-deoxy-^12,14 -prostaglandin J₂ (PGJ2), which is a natural product with demonstrated inhibitory efficiency for this system. First, the binding mode of PGJ2 to NF-B was unraveled by GOLD docking calculation. Subsequently, substitutions were made to PGJ2 to optimize its association with NF-B. Care was taken not to strongly increase the reactivity of the new compounds, and to keep the overall shape, size and hydrophilicity of the lead compound, which should render them a similar bioavailability. Molecular mechanics calculations were performed to decide on the suitability of the substitutions, and to evaluate the energies of association with NF-B. Density functional theory calculations were performed also to study the overall reactivity of the substituted drugs towards NF-B. Important general conclusions were obtained, concerning the improvement of these natural inhibitors; namely, a set of rational methodologies were deduced to improve the association between the PGJ2 derivatives and NF-B, and their efficiency demonstrated by generating a set of substituted complexes, some of them with a very much increased affinity for NF-B, opening new doors to enlarge the therapeutic capabilities of this class of drugs.     

Coupled liquid chromatography-gas chromatography for the rapid analysis of gamma-oryzanol in rice lipids

An approach based on on-line coupled liquid chromatography-gas chromatography (LC-GC) was developed for the rapid analysis of gamma-oryzanol in rice. Total lipids were extracted from rice and subjected to LC-GC without any prior purification. gamma-Oryzanol was pre-separated by HPLC from rice lipids and transferred on-line to GC analysis in order to separate its major constituents. 24-methylenecycloartanyl ferulate, cycloartenyl ferulate, campesteryl ferulate, beta-sitosteryl ferulate and campestanyl ferulate. The identities of the compounds were confirmed by off-line GC-MS analysis. Total gamma-oryzanol content could be quantified by HPLC-UV detection and the distribution of gamma-oryzanol constituents could be determined by on-line coupled GC analysis. The proposed methodology paves the way for high-throughput investigations providing information on natural variations in gamma-oryzanol content and its composition in different rice varieties.     

Kinetics of formation and dissociation of lanthanide(III) complexes with the 13-membered macrocyclic ligand TRITA4-

The tetraazamacrocyclic ligand TRITA(4-) is intermediate in size between the widely studied and medically used 12-membered DOTA(4-) and the 14-membered TETA(4-). The kinetic inertness of GdTRITA(-) was characterized by the rates of exchange reactions with Zn(2+) and Eu(3+). In the Zn(2+) exchange, a second order [H(+)] dependence was found for the pseudo-first-order rate constant (k(0)=(4.2 +/- 0.5) x 10(-7) s(-1); k'=(3.5 +/- 0.3) x 10(-1) M(-1)s(-1), k" =(1.4 +/- 0.4) x 10(3) M(-2)s(-1)). In the Eu(3+) exchange, at pH <5 the rate decreases with increasing concentration of the exchanging ion, which can be accounted for by the transitional formation of dinuclear GdTRITAEu(2+) species. At physiological pH, the kinetic inertness of GdTRITA(-) is considerably lower than that of GdDOTA(-)(t(1/2)= 444 h (25 degrees C) vs. 3.8 x 10(5) h (37 degrees C), respectively). However, GdTRITA(-) is still kinetically more inert than GdDTPA(2-), the most commonly used MRI contrast agent (t(1/2)= 127 h). The formation reactions of LnTRITA(-) complexes (Ln = Ce, Gd and Yb) proceed via the rapid formation of a diprotonated intermediate and its subsequent deprotonation and rearrangement in a slow, OH(-) catalyzed process. The stability of the LnH(2)TRITA* intermediates (log K(LnH2L*)= 3.1-3.9) is lower than that of the DOTA-analogues. The rate constants of the OH(-) catalyzed step increase with decreasing lanthanide ion size, and are about twice as high as for DOTA-complexes.     

A facile approach to architecturally defined nanoparticles via intramolecular chain collapse

A novel approach is presented for the controlled intramolecular collapse of linear polymer chains to give well-defined single-molecule nanoparticles whose structure is directly related to the original linear polymer. By employing a combination of living free radical polymerization and benzocyclobutene (BCB) chemistry, nanoparticles can be routinely prepared in multigram quantities with the size being accurately controlled by either the initial degree of polymerization of the linear chain or the level of incorporation of the BCB coupling groups. The latter also allows the cross-link density of the final nanoparticles to be manipulated. In analogy with dendritic macromolecules, a significant reduction of up to 75% in the hydrodynamic volume is observed on going from the starting random coil linear chains to the corresponding nanoparticles. The facile nature of the living free radical process also permits wide variation in monomer selection and functional group incorporation and allows novel macromolecular architectures to be prepared. Furthermore, the use of block copolymers functionalized with benzocyclobutene groups in only one of the blocks gives, after intramolecular collapse, a hybrid architecture in which a single linear polymer chain is attached to the globular nanoparticle.     

Muffin-tin orbital Wannier-like functions for insulators and metals.

Herein, we outline a method that is able to generate truly minimal basis sets that accurately describe either a group of bands, a band, or even just the occupied part of a band. These basis sets are the so-called NMTOs, muffin-tin orbitals of order N. For an isolated set of bands, symmetrical orthonormalization of the NMTOs yields a set of Wannier functions that are atom-centered and localized by construction. They are not necessarily maximally localized, but may be transformed into those Wannier functions. For bands that overlap others, Wannier-like functions can be generated. It is shown that NMTOs give a chemical understanding of an extended system. In particular, orbitals for the pi and sigma bands in an insulator, boron nitride, and a semimetal, graphite, will be considered. In addition, we illustrate that it is possible to obtain Wannier-like functions for only the occupied states in a metallic system by generating NMTOs for cesium. Finally, we visualize the pressure-induced s-->d transition.     

Synthesis,characterization, and curing of hyperbranched allyl ether–maleate functional ester resins

A model two-step synthesis of a saturated hyperbranched hydroxyl-terminated ester has been developed to show a synthesis route. Three different series of hyperbranched esters with different terminations have been synthesized to relate some of their properties to their structures. This route has then been used to synthesize three different allyl ethermaleate functional hyperbranched ester resins in a two-step procedure. The resins have been characterized with respect to rheology, structure, and properties, and the differences are discussed. The allyl ether-maleate functional resins have also been studied with respect to curing performance and final film properties. © 1993 John Wiley & Sons, Inc.     

PHOTOSENSITIZING PROPERTIES OF BACTERIOCHLOROPHYLLIN a and BACTERIOCHLORIN a, TWO DERIVATIVES OF BACTERIOCHLOROPHYLL a

Abstract The photosensitizing properties of two water soluble derivatives of bacteriochlorophyll a , bacteriochlorophyllin a and bacteriochlorin a (lacking the central Mg-ion) were investigated and compared to those of hematoporphyrin derivatives. At physiological pH the oxygen consumption rate of histidine, tryptophan, dithiothreitol and guanosine upon illumination was 3 to 4 times higher when bacteriochlorin a was used as photosensitizer than when hematoporphyrin derivatives were used. Especially bacteriochlorin a proved to be an effective sensitizer for the killing of L929 cells. Because bacteriochlorin a has an absorption maximum at 765 nm in phosphate buffered saline (allowing a light penetration in tissue about ten times larger than at 630 nm) and a high molar absorption coefficient (32 000 M cm⁻¹) it has promising possibilities for the application in photodynamic therapy.     

Comparison of reversed-phase liquid chromatography and hydrophilic interaction/cation-exchange chromatography for the separation of amphipathic alpha-helical peptides with L- and D-amino acid substitutions in the hydrophilic face

Mixed-mode hydrophilic interaction/cation-exchange chromatography (HILIC/CEX) is a novel high-performance technique which has excellent potential for peptide separations. Separations by HILIX/CEX are carried out by subjecting peptides to linear increasing salt gradients in the presence of high levels of acetonitrile, which promotes hydrophilic interactions overlaid on ionic interactions with the cation-exchange matrix. In the present study, HILIC/CEX has been compared to reversed-phase liquid chromatography (RP-HPLC) for separation of mixtures of diastereomeric amphipathic alpha-helical peptide analogues, where L- and D-amino acid substitutions were made in the centre of the hydrophilic face of the amphipathic alpha-helix. Unlike RP-HPLC, temperature had a substantial effect on HILIC/CEX of the peptides, with a rise in temperature from 25 to 65 degrees C increasing the retention times of the peptides as well as improving resolution. Our results again highlight the potential of HILIC/CEX as a peptide separation mode in its own right as well as an excellent complement to RP-HPLC.