A note on additive convex processes

We deal with the category $\text{P}$ the objects of which are finite-dimensional, real spaces and the morphisms of which are polyhedral convex processes introduced by R. T. Rockafellar [6]. We give some characterizations of additive processes, and we study superpositions of epimorphisms and monomorphisms in the category $\text{P}$.     

A synthesis of 17-epi-calcidiol

The first synthetic approach to 17-epi-calcidiol 4 and congeners is presented. Key steps of the synthesis involve Pd-catalyzed reaction of the androst-16-ene derivative 6 with alkyl diazoacetates producing the respective cyclopropane derivatives 5, and lithium in liquid ammonia reduction of 5 leading to 17α-pregnane-20-carboxylic acid derivatives 9. The side chain was attached to ester 19 in a known manner.     

Substrate binding favors enhanced NO binding to P450cam

Ferric cytochrome P450cam from Pseudomonas putida (P450cam) in buffer solution at physiological pH 7.4 reversibly binds NO to yield the nitrosyl complex P450cam(NO). The presence of 1R-camphor affects the dynamics of NO binding to P450cam and enhances the association and dissociation rate constants significantly. In the case of the substrate-free form of P450cam, subconformers are evident and the NO binding kinetics are much slower than in the presence of the substrate. The association and dissociation processes were investigated by both laser flash photolysis and stopped-flow techniques at ambient and high pressure. Large and positive values of S and V observed for NO binding to and release from the substrate-free P450cam complex are consistent with the operation of a limiting dissociative ligand substitution mechanism, where the lability of coordinated water dominates the reactivity of the iron(III)-heme center with NO. In contrast, NO binding to P450cam in the presence of camphor displays negative activation entropy and activation volume values that support a mechanism dominated by a bond formation process. Volume profiles for the binding of NO appear to be a valuable approach to explain the differences observed for P450cam in the absence and presence of the substrate and enable the clarification of the underlying reaction mechanisms at a molecular level. Changes in spin state of the iron center during the binding/release of NO contribute significantly to the observed volume effects. The results are discussed in terms of relevance for the biological function of cytochrome P450 and in context to other investigations of the related reactions between NO and imidazole- and thiolate-ligated iron(III) hemoproteins.     

Synthesis and biological activity of novel benzoazoles,benzoazines and other analogs functionalized by 2,4-dihydroxyphenyl moiety

Research on Chemical Intermediates - Novel benzoazoles, benzoazines, benzothiazoles, benzothiazines and other related compounds possessing a 2,4-dihydroxyphenyl moiety were prepared. The compounds...     

TLC and HPLC Analysis of the Flavonoid Glycosides in the Aerial Parts of Peucedanum tauricum Bieb.

JPC – Journal of Planar Chromatography – Modern TLC - Flavonoid glycosides from the aerial parts (leaves, flowers, and fruits) of Peucedanum tauricum Bieb. (Apiaceae) have been analyzed...     

Covalent cucurbit[7]uril–dye conjugates for sensing in aqueous saline media and biofluids

Non-covalent chemosensing ensembles of cucurbit[n]urils (CBn) have been widely used in proof-of-concept sensing applications, but they are prone to disintegrate in saline media, e.g. biological fluids. We show here that covalent cucurbit[7]uril–indicator dye conjugates are buffer- (10× PBS buffer) and saline-stable (up to 1.4 M NaCl) and allow for selective sensing of Parkinson''s drug amantadine in human urine and saliva, where the analogous non-covalent CB7⊃dye complex is dysfunctional. The in-depth analysis of the covalent host–dye conjugates in the gas-phase, and deionized versus saline aqueous media revealed interesting structural, thermodynamic and kinetic effects that are of general interest for the design of CBn-based supramolecular chemosensors and systems. This work also introduces a novel high-affinity indicator dye for CB7 through which fundamental limitations of indicator displacement assays (IDA) were exposed, namely an impractical slow equilibration time. Unlike non-covalent CBn⊃dye reporter pairs, the conjugate chemosensors can also operate through a S_N2-type guest–dye exchange mechanism, which shortens assay times and opens new avenues for tailoring analyte-selectivity.

Unimolecular chemosensor shows superior stability and detection capabilities in biofluids compared to bimolecular reporter pairs.     

2,6‐Dimethoxy‐7,9‐dimethylpurinium iodide hemihydrate

In the title compound, C₉H₁₃N₄O₂⁺·I⁻·0.5H₂O, the non‐H atoms of the ionic components lie on a mirror plane in Cmca, with the O atom of the partial water molecule lying on a twofold rotation axis. Whereas one of the methoxy methyl groups is directed away from the adjacent N‐methyl group, the other methoxy methyl group is directed towards its adjacent N‐methyl group. The conformation of the methoxy methyl groups provides an explanation for the outcomes of intramolecular thermal rearrangements of 2,6‐dialkoxy‐7,9‐dimethylpurinium salts.     

Drug Metabolism by Cytochrome P450 Enzymes: What Distinguishes the Pathways Leading to Substrate Hydroxylation Over Desaturation?

Cytochrome P450 enzymes are highly versatile biological catalysts in our body that react with a broad range of substrates. Key functions in the liver include the metabolism of drugs and xenobiotics. One particular metabolic pathway that is poorly understood relates to the P450 activation of aliphatic groups leading to either hydroxylation or desaturation pathways. A DFT and QM/MM study has been carried out on the factors that determine the regioselectivity of aliphatic hydroxylation over desaturation of compounds by P450 isozymes. The calculations establish multistate reactivity patterns, whereby the product distributions differ on each of the spin‐state surfaces; hence spin‐selective product formation was found. The electronic and thermochemical factors that determine the bifurcation pathways were analysed and a model that predicts the regioselectivity of aliphatic hydroxylation over desaturation pathways was established from valence bond and molecular orbital theories. Thus, the difference in energy of the O?H versus the O?C bond formed and the π‐conjugation energy determines the degree of desaturation products. In addition, environmental effects of the substrate binding pocket that affect the regioselectivities were identified. These studies imply that bioengineering P450 isozymes for desaturation reactions will have to include modifications in the substrate binding pocket to restrict the hydroxylation rebound reaction.     

Spectroscopic Studies of Fluorescence Effects in Bioactive 4-(5-Heptyl-1,3,4-Thiadiazol-2-yl)Benzene-1,3-Diol and 4-(5-Methyl-1,3,4-Thiadiazol-2-yl)Benzene-1,3-Diol Molecules Induced by pH Changes in Aqueous Solutions

This paper presents the results of stationary fluorescence spectroscopy and time-resolved spectroscopy analyses of two 1,3,4-thiadiazole analogues, i.e. 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C1) and 4-(5-heptyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C7) in an aqueous medium containing different concentrations of hydrogen ions. An interesting dual florescence effect was observed when both compounds were dissolved in aqueous solutions at pH below 7 for C1 and 7.5 for C7. In turn, for C1 and C7 dissolved in water at pH higher than the physiological value (mentioned above), single fluorescence was only noted. Based on previous results of investigations of the selected 1,3,4-thiadiazole compounds, it was noted that the presented effects were associated with both conformational changes in the analysed molecules and charge transfer (CT) effects, which were influenced by the aggregation factor. However, in the case of C1 and C7, the dual fluorescence effects were visible in a higher energetic region (different than that observed in the 1,3,4-thiadiazoles studied previously). Measurements of the fluorescence lifetimes in a medium characterised by different concentrations of hydrogen ions revealed clear lengthening of the excited-state lifetime in a pH range at which dual fluorescence effects can be observed. An important finding of the investigations presented in this article is the fact that the spectroscopic effects observed not only are interesting from the cognitive point of view but also can help in development of an appropriate theoretical model of molecular interactions responsible for the dual fluorescence effects in the analysed 1,3,4-thiadiazoles. Furthermore, the study will clarify a broad range of biological and pharmaceutical applications of these compounds, which are more frequently used in clinical therapies.

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Graphical Abstract Upper left corner – C7 molecule at high pH, right upper corner - fluorescence emission spectrum for C7 dissolved in H₂O at high pH (7–12) - single fluorescence. Bottom left corner – C7 molecule at low pH (1–7), lower right corner - fluorescence emission spectrum for C7 dissolved in water at low pH – two fluorescence emissions. The circles indicate the group related to dissociation of molecules at low and high pH and the additional long circles indicate C1 or a molecule with a shorter acyl chain.