Nucleoside Cation Radicals: Generation, Radical-Induced Hydrogen Atom Migrations, and Ribose Ring Cleavage in the Gas Phase.

Nucleoside ions that were furnished on ribose with a 2'--acetyl radical group were generated in the gas phase by multistep collision-induced dissociation of precursor ions tagged with radical initiator groups, and their chemistry was investigated in the gas phase. 2'--Acetyladenosine cation radicals were found to undergo hydrogen transfer to the acetoxyl radical from the ribose ring positions that were elucidated using specific deuterium labeling of 1'-H, 2'-H, and 4'-H and in the N-H and O-H exchangeable positions, favoring 4'-H transfer. Ion structures and transition-state energies were calculated by a combination of Born-Oppenheimer molecular dynamics and density functional theory and used to obtain unimolecular rate constants for competitive hydrogen transfer and loss of the acetoxyl radical.

Competitive Radical Migrations and Ribose Ring Cleavage in Adenosine and 2'-Deoxyadenosine Cation Radicals.

We report a combined experimental and computational study of adenosine cation radicals that were protonated at adenine and furnished with a radical handle in the form of an acetoxyl radical, CHCOO, that was attached to ribose 5'-O. Radicals were generated by collision-induced dissociation (CID) and characterized by tandem mass spectrometry and UV-vis photodissociation action spectroscopy. The acetoxyl radical was used to probe the kinetics of intramolecular hydrogen transfer from the ribose ring positions that were specifically labeled with deuterium at C1', C2', C3', C4', C5', and in the exchangeable hydroxyl groups.

[Early predictor of bronchial suture failure after pneumonectomy].

Objective: To identify the relationship between serum CRP/albumin and bronchial suture failure after pneumonectomy.

Material And Methods: A retrospective analysis included 100 patients who underwent pneumonectomy with extended lymph node dissection for lung cancer. Patients were divided into 2 groups depending on postoperative complications: group 1 - bronchial stump failure, group 2 - no similar complications.

Tracking Isomerizations of High-Energy Adenine Cation Radicals by UV-Vis Action Spectroscopy and Cyclic Ion Mobility Mass Spectrometry.

We report experimental and computational studies of protonated adenine C-8 σ-radicals that are presumed yet elusive reactive intermediates of oxidative damage to nucleic acids. The radicals were generated in the gas phase by the collision-induced dissociation of C-8-Br and C-8-I bonds in protonated 8-bromo- and 8-iodoadenine as well as by 8-bromo- and 8-iodo-9-methyladenine. Protonation by electrospray of 8-bromo- and 8-iodoadenine was shown by cyclic-ion mobility mass spectrometry (c-IMS) to form the N-1-H, N-9-H and N-3-H, N-7-H protomers in 85:15 and 81:19 ratios, respectively, in accordance with the equilibrium populations of these protomers in water-solvated ions that were calculated by density functional theory (DFT).

Carbene Cross-Linking in Gas-Phase Peptide Ion Scaffolds.

Scaffolds consisting of a peptide, a phthalate linker, and a 4,4-azipentyl group were synthesized and used to study intramolecular peptide-carbene cross-linking in gas-phase cations. Carbene intermediates were generated by UV-laser photodissociation at 355 nm of the diazirine ring in mass-selected ions, and the cross-linked products were detected and quantified by collision-induced dissociation tandem mass spectrometry (CID-MS, = 3-5). Peptide scaffolds containing Ala and Leu residues with a C-terminal Gly gave 21-26% yields of cross-linked products, while the presence of the Pro and His residues decreased the yields.

Thermodynamic and structural characterization of an optimized peptide-based inhibitor of the influenza polymerase PA-PB1 subunit interaction.

Influenza virus causes severe respiratory infection in humans. Current antivirotics target three key proteins in the viral life cycle: neuraminidase, the M2 channel and the endonuclease domain of RNA-dependent-RNA polymerase. Due to the development of novel pandemic strains, additional antiviral drugs targetting different viral proteins are still needed.

Radical Cascade Dissociation Pathways to Unusual Nucleobase Cation Radicals.

We report unusual dissociations of protonated RNA nucleosides tagged with radical initiator groups at ribose 5'-O and furnished with a 2',3'--isopropylidene protecting group. The ions undergo collision-induced radical cascade dissociations starting at the radical initiator that break down the dioxolane ring and trigger the formation of nucleobase cations and cation radicals. The adenine cation radical that was formed by radical cascade dissociations was identified by MS UV-vis photodissociation action spectroscopy to be a higher-energy N-3-H tautomer of the canonical ionized nucleobase.

Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors.

The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including the FDA-approved drug Xofluza. A general feature of endonuclease inhibitors is their ability to chelate Mg or Mn ions located in the enzyme's catalytic site. Previously, we screened a panel of flavonoids for PA inhibition and found luteolin and its C-glucoside orientin to be potent inhibitors.

Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors.

The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity.

How N-(pyridin-4-yl)pyridin-4-amine and its methyl and nitro derivatives are arranged in the interlayer space of zirconium sulfophenylphosphonate: a problem solved by experimental and calculation methods.

Classical molecular simulation methods were used for a description of an arrangement of intercalated molecules N-(pyridin-4-yl)pyridin-4-amine (AH) and its derivatives, 3-methyl-N-(pyridin-4-yl)pyridin-4-amine (AMe), and 3-nitro-N-(pyridin-4-yl)pyridin-4-amine (ANO2) within a layered structure of zirconium 4-sulfophenylphosphonate. The intercalated molecules were placed between SOH groups of the host layers. Their mutual positions and orientations were solved by molecular simulation methods and compared with the presented experimental results.

Exfoliation of layered mixed zirconium 4-sulfophenylphosphonate phenylphosphonates.

Mixed zirconium 4-sulfophenylphosphonate phenylphosphonates with formulae Zr(HO3SC6H4PO3)1.8(C6H5PO3)0.2·2.

Formation of Layered Proton-Conducting Zirconium and Titanium Organophosphonates by Topotactic Reaction: Physicochemical Properties, Proton Dynamics, and Atomic-Resolution Structure.

A series of new zirconium and titanium phosphates-organophosphonates, in which the organophosphonate moiety is functionalized with a sulfo group, was prepared by a topotactic reaction involving the gamma modification of zirconium or titanium hydrogen phosphate with 2-bis(phosphonomethyl)amino-ethan-1-sulfonic acid (HTDP). HTDP represents a new type of functionalizing agent, which can be easily prepared by a Moedritzer-Irani reaction from taurine (2-aminoethanesulfonic acid). The gamma modification of zirconium hydrogen phosphate () with HTDP provides mixed phosphate-organophosphonate compounds with the formula Zr(PO)(HPO)(HTDP)·HO, where = 0.

Interaction of Halictine-Related Antimicrobial Peptides with Membrane Models.

We have investigated structural changes of peptides related to antimicrobial peptide Halictine-1 (HAL-1) induced by interaction with various membrane-mimicking models with the aim to identify a mechanism of the peptide mode of action and to find a correlation between changes of primary/secondary structure and biological activity. Modifications in the HAL-1 amino acid sequence at particular positions, causing an increase of amphipathicity (Arg/Lys exchange), restricted mobility (insertion of Pro) and consequent changes in antimicrobial and hemolytic activity, led to different behavior towards model membranes. Secondary structure changes induced by peptide-membrane interaction were studied by circular dichroism, infrared spectroscopy, and fluorescence spectroscopy.

Layered calcium phenylphosphonate: a hybrid material for a new generation of nanofillers.

The use of nanosheets of layered calcium phenylphosphonate as a filler in a polymeric matrix was investigated. Layered calcium phenylphosphonate (CaPhP), with chemical formula CaCHPO∙2HO, is a hybrid organic-inorganic material that exhibits a hydrophobic character due to the presence of phenyl groups on the surface of the layers. In this paper, various CaPhP synthesis methods were studied with the aim of obtaining a product most suitable for its subsequent exfoliation.

Outerly functionalized and non-functionalized boron clusters intercalated into layered hydroxides with different modes of binding: materials for superacid storage.

Two binary boron hydrides (NH4)2B10H10 and Na2B12H12 and mono- and dicarboxy p- and m-carboranes (namely, 1-(COOH)-closo-1,7-C2B10H11, 1,12-(COOH)2-closo-1,12-C2B10H10 and 1,7-(COOH)2-closo-1,7-C2B10H10) were intercalated into ZnAl-layered double hydroxides (ZnAl-LDH) and into Zn5(OH)8(NO3)2·2H2O. The formed compounds were characterized using elemental analysis, thermogravimetry analysis, X-ray powder diffraction, infrared spectroscopy and solid state NMR. All the intercalated boron compounds are present in the interlayer space of the layered hosts as anions.

Intracellular cavity of sensor domain controls allosteric gating of TRPA1 channel.

Transient receptor potential ankyrin 1 (TRPA1) is a temperature-sensitive ion channel activated by various pungent and irritant compounds that can produce pain in humans. Its activation involves an allosteric mechanism whereby electrophilic agonists evoke interactions within cytosolic domains and open the channel pore through an integrated nexus formed by intracellular membrane proximal regions that are densely packed beneath the lower segment of the S1-S4 sensor domain. Studies indicate that this part of the channel may contain residues that form a water-accessible cavity that undergoes changes in solvation during channel gating.

Alkaline-earth metal phenylphosphonates and their intercalation chemistry.

The intercalation chemistry of layered alkaline-earth metal phenylphosphonates with the general formula MeCHPO·2HO (Ca, Sr, Ba) is reviewed. The preparation of the host materials is described and their behavior in dependence on the relative humidity and pH of the reaction medium is discussed. Mutual relationships between MeCHPO·2HO and Me(CHPOH) were investigated using a method of computer-controlled addition of reagents.

Geometry optimization of zirconium sulfophenylphosphonate layers by molecular simulation methods.

Classical molecular simulation methods were used for a detailed structural description of zirconium 4-sulfophenylphosphonate and zirconium phenylphosphonate 4-sulfophenylphosphonates with general formula Zr(HOSCHPO) (CHPO) ·yHO (x = 0.7-2; y = 0 or 2). First, models describing the structure of zirconium 4-sulfophenylphosphonate (x = 2) were calculated for the hydrated (y = 2) and dehydrated (y = 0) compounds.

Synthesis and characterization of new barium methylphosphonates.

Eight new barium methylphosphonates were prepared and described. In dependence on pH, either barium hydrogen methylphosphonates or barium methylphosphonates can be formed. In the case of barium methylphosphonates, BaCHPO·3HO crystallizes from the solution at room temperature and BaCHPO·HO at a temperature above 65 °C.

The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel.

Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works.

Influence of 1,2-alkanediols on the structure of their intercalates with strontium phenylphosphonate solved by molecular simulation and experimental methods.

Strontium phenylphosphonate intercalates with 1,2-diols (from 1,2-ethanediol to 1,2-hexanediol) were synthesized and characterized by X-ray diffraction, thermogravimetry, chemical analysis, and molecular simulation methods. Prepared samples exhibit a very good stability at ambient conditions. Structural arrangement calculated by simulation methods suggested formation of cavities surrounded by six benzene rings.

Prorenin Receptor Homologue VHA-20 is Critical for Intestinal pH Regulation, Ion and Water Management and Larval Development in C. elegans.

The prorenin receptor (ATP6AP2) is a multifunctional transmembrane protein; it is a constituent of proton-translocating V-ATPase, a non-proteolytic activator of renin and an adaptor in the Wnt/β-catenin pathway. Here, we studied vha-20, one of the two prorenin receptor homologues that are identified by sequence similarity in the C. elegans genome.

Intercalation of 1,n-diols into strontium phenylphosphonate: how the shape of the host layers influences arrangement of the guest molecules.

Strontium phenylphosphonate intercalates with 1,n diols (n=2-4, 6-8) having general formula SrC6H5PO3⋅x(HO(CH2)nOH)⋅yH2O were prepared by precipitation from strontium phenylphosphonate solution and the corresponding diols. Prepared compounds exhibit a very good stability at ambient conditions. The intercalates were characterized by X-ray diffraction, thermogravimetry and elemental analysis.