Oxonium Ion Research Articles

Unusual N-glycan Structures Required for Trafficking Toxoplasma gondii GAP50 to the Inner Membrane Complex Regulate Host Cell Entry Through Parasite Motility

Toxoplasma gondii motility, which is essential for host cell entry, migration through host tissues, and invasion, is a unique form of actin-dependent gliding. It is powered by a motor complex mainly composed of myosin heavy chain A, myosin light chain 1, gliding associated proteins GAP45, and GAP50, the only integral membrane anchor so far described. In the present study, we have combined glycomic and proteomic approaches to demonstrate that all three potential N-glycosylated sites of GAP50 are occupied by unusual N-glycan structures that are rarely found on mature mammalian glycoproteins. Using site-directed mutagenesis, we show that N-glycosylation is a prerequisite for GAP50 transport from the endoplasmic reticulum to the Golgi apparatus and for its subsequent delivery into the inner complex membrane. Assembly of key partners into the gliding complex, and parasite motility are severely impaired in the unglycosylated GAP50 mutants. Furthermore, comparative affinity purification using N-glycosylated and unglycosylated GAP50 as bait identified three novel hypothetical proteins including the recently described gliding associated protein GAP40, and we demonstrate that N-glycans are required for efficient binding to gliding partners. Collectively, these results provide the first detailed analyses of T. gondii N-glycosylation functions that are vital for parasite motility and host cell entry.

Stability and hydration structure of model perfluorosulfonic acid compound systems, CF 3SO 3H(H 2O) n ( n = 1–4), and its isotopomer by the direct treatment of H/D nuclear quantum effects

We theoretically analyzed the stability and hydration structures of perfluorosulfonic acid (PFSA) for polymer electrolyte fuel cell (PEFC) by using model compound systems, CF 3SO 3H and its D isotopomer with one to four water molecules (H 2O/D 2O). We applied to the systems the multi-component molecular orbital method that takes into account the quantum effects of H and D nuclei directly. By comparing the results of H/D isotopomers, we clearly demonstrated the geometrical difference in hydrogen bonds due to the difference of H/D quantum behavior. The interaction energy of deuterated hydrogen bonds became small due to the weakness of hydrogen bond by the deuterium substitution. When four water molecules are hydrated, only the proton transfer structure for H compound was obtained due to the drastic change of the potential. We also analyzed the details of geometry and electronic charge of H/D isotopic oxonium ions, H 3O +, H 2DO +, HD 2O +, and D 3O +, in proton transfer structures.

On the mechanism of AuCl 3-catalyzed synthesis of highly substituted furans from 2-(1-alkynyl)-2-alken-1-ones with nucleophiles: A DFT study

The mechanism of AuCl 3-catalyzed synthesis of highly substituted furans from 2-(1-alkynyl)-2-alken-1-ones with nucleophiles have been investigated using density functional theory calculations done at the BHandHLYP/6-31G(d, p) (lanl2dz for Au) level of theory. Our calculations suggest that the first step of the cycle is the cyclization of the carbonyl oxygen onto the triple bond to form a new and stable five-membered resonance structure of an oxonium ion and a carbocation intermediate. Furthermore, the six-membered carbocation intermediate proposed by Larock et al. was found and characterized as a transition structure on the potential energy surface. The attack of the carbonyl oxygen to the gold coordinated alkynes results in the formation of a resonance structure intermediate which upon subsequent trapping with alcohols followed by migration of hydrogen atom results in the formation of the final products and regeneration of the catalyst. Our computational results are in consistent with the experimental observations of Larock et al. for the AuCl 3-catalyzed synthesis of highly substituted furans from 2-(1-alkynyl)-2-alken-1-ones with nucleophiles.

Impact of chemical treatments on the behavior of water in Nafion® NRE-212 by 1H NMR: Self-diffusion measurements and proton quantization

In this article, we have studied by 1H NMR the behavior of water in Nafion under acid, sodium and potassium forms which arises from different chemical treatments with or without EDTA. Self-diffusion coefficients were measured by PGSTE (Pulsed Gradient STimulated Echo) whereas integration of the proton spectrum provides a quantitative information about water content. Examination of the self-diffusion coefficients of water in Nafion shows clearly that: (i) in the acid form, the use of a chelating agent does not affect translational diffusion of water, (ii) regardless of sample conditioning, water within Nafion in acid form diffuses more rapidly than in sodium and potassium forms, in particular at low water content (at λ=3.4, D=5.4×10−7cm2s−1 vs. 7.2×10−8cm2s−1), and (iii) for a given water amount, water diffusion is identical in sodium and potassium forms. Point (ii) is due to the presence of oxonium ions within Nafion in acid form, favoring both vehicle and Grotthuss mechanisms. It is also due to a higher number of protons available for diffusion (we find an average value of 1.19 in acid form vs. 0.91 in sodium form). Our results suggest in the case of Nafion in acid form that, at low water content, diffusion occurs by jumps between different sites. Moreover, plotting self-diffusion coefficients vs. relative humidity leads to a clear differentiation between sodium and potassium cations, related to their respective solvation number.

ChemInform Abstract: Stereoselective C‐Glycosidations with Achiral and Enantioenriched Allenylsilanes.

AbstractThe nucleophile adds exclusively to the α‐face of the oxonium ion intermediate and high diastereoselectivity is observed for all products.

Oxocarbenium Ion Mediated Alkylation and Ring-Closing Metathesis: A General Iterative Approach towards Synthesis of Linearly Fused cis:anti:cis Polycyclic Ethers

A general stereoselective method for the synthesis of cis:anti:cis polycyclic ethers containing six-, seven-, and eight-membered rings from a simple precursor has been reported. The methodology involves oxonium ion mediated intramolecular cyclization, carbon-carbon bond formation and ring-closing metathesis as key features.

S053011 PEFC触媒層のionomer内における酸素拡散に関する分子論的研究([S05301]次世代電池のナノ・マイクロフルイディクス(1))

In the Polymer electrolyte membrane fuel cell (PEFC) cathode catalyst layer, the structure of ionomer with which the catalyst is covered is very important on the point of transferring protons to the catalytic surface and oxygen permeation to the surface. But the mechanism of oxygen permeation through an ionomer was not analyzed in detail because it is too small to research by experiment. Moreover molecular dynamics simulation of the catalyst layer and oxygen permeability has not yet researched. In this research, we constructed the system including PFSA membrane, water, oxonium ion and platinum layers by using molecular dynamics study and researched about the effect of the water content of the ionomer on the structure of the ionomer and the permeability of the oxygen molecule. As the result, we found that PFSA and water molecule gathered on the platinum catalyst surface, the oxygen permeability decreased as water content rate increased in the ionomer.

Self-healing inside a scratch of oxetane-substituted chitosan-polyurethane (OXE-CHI-PUR) networks

These studies elucidate the origin of molecular and macroscopic processes of oxetane-substituted chitosan-polyurethane (OXE-CHI-PUR) crosslinked networks that occur inside a mechanically generated scratch during UV-initiated self-repair. The role of each network component, OXE, CHI, PUR, and dibutyltin dilaurate (DBTDL), inside the scratch of the OXE-CHI-PUR damaged network is determined using chemical and thermo-mechanical imaging probes. These studies show that the presence of controlled acidic environments determines whether self-healing will occur or not. The network remodeling during UV initiated repair involves activation of dormant oxonium ions that react with accessible and reactive macromolecular ends resulting from mechanical damage. Precisely controlled stoichiometry of the individual components giving pH = 6.8 induce cationic OXE ring opening as well as polyurea-to-polyurethane (PUA-to-PUR) conversions driven by a free radical process. This is accompanied by chair-to-boat conformational changes of glycosine units of CHI moieties. These orchestrated events trigger intra- and intermolecular crosslinking reactions resulting in self-repair via –C–O–C– bond formation. Deviations towards higher acidity will have adverse effects, and instead of repair, expansion of the scratch will occur. Upon mechanical damage, the glass transition temperature (Tg) inside the surface of the scratch diminishes, but upon repair a scar is formed, and the Tg is recovered. The scratch recovery during self-repair reactions is initiated at the lowest point of the scratch that exhibits the highest surface energy, thus forcing fragmented network components to flow to the top to form a scar. These studies show that minute localized chemical changes within a network have a tremendous impact on network rearrangements during repair processes.

Intramolecular Bromonium Ion Assisted Epoxide Ring-Opening: Capture of the Oxonium Ion with an Added External Nucleophile

9-Oxabicyclo[6.1.0]non-4-ene (1) undergoes intramolecular bromonium ion-assisted epoxide ring-opening using N-bromosuccinimide via a presumed oxonium ion that is subject to stereospecific, nonregioselective capture with added external nucleophiles producing novel bicyclo[4.2.1] and bicyclo[3.3.1] ethers. Carboxylic acids (as catalyzed by tetramethylguanidine), alcohols, water, and halides can all function as effective nucleophiles. Stereospecific direct opening of the bromonium ion with carboxylic acids was found to be a competing process where high dilution disfavors this pathway. Halogen-induced isotopic (13)C NMR shifts (Δδ CBr 1.3-1.9 ppb; Δδ CCl 8.6-8.7 ppb) were found to be most useful in unambiguously identifying halogen-bearing carbons, and correlation of these (13)C NMR shifts allowed ready assignment of diastereomeric structures. The structure of adducts 6b, 6c, 7b, 7c, 7d, and 8a-d were all elucidated by X-ray crystallography.

Glycosylation analysis of interleukin‐23 receptor: elucidation of glycosylation sites and characterization of attached glycan structures

Interleukin-23 (IL-23) is a heterodimeric cytokine, a central factor in chronic/autoimmune inflammation. It signals through a heterodimeric receptor consisting of IL-23r, which is heavily glycosylated. The structural characterization of IL-23r has not been reported. In this work, glycosylation profiles of soluble recombinant human IL-23r (rhIL-23r) were established using mass spectrometry (MS), which included defining glycosylation sites, degree of glycosylation occupancy of each site and structure of attached oligosaccharides. Specifically, precursor ion scan of oxonium ion protonated N-acetylglucosamine (GlcNAc(+)) (m/z 204) was performed using a triple quadrupole MS instrument to locate the retention time of glycopeptides. Both the glycopeptides and their corresponding deglycosylated forms in each collected HPLC fraction were studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (LTQ-Orbitrap) for glycosylation site profiling. The attached glycan structures were elucidated by collision-induced dissociation (CID) fragmentation of target glycopeptides in combination with accurate mass measurement. Eight glycosylation sites were identified on IL-23r (Asn24, Asn209, Asn239, Asn157, Asn118, Asn250, Asn58 and Asn6). Most of the glycosylation sites were > 95% occupied except Asn250 and Asn6. Those two sites were 88% and 45% occupied by estimation from trypsin digestion and were 55% and 42% occupied from LysC digestion. Multiple glycoforms were observed in IL-23r. Most of them were bi-, tri- or tetra-antennary complex type structures with fucose and sialic acid. High mannose and hybrid type glycans were only observed on Asn157. The structural characterization on IL-23r glycosylation provides useful information for better understanding of the biological function of IL-23r.

Stereoselective C-glycosidations with achiral and enantioenriched allenylsilanes.

Allenylsilanes are used as carbon nucleophiles in highly stereoselective Lewis acid-promoted C-glycosidations, resulting in the introduction of an internal alkyne with an adjacent stereocenter. Both achiral and chiral allenylsilanes form the desired products with high diastereoselectivity, where the nucleophile adds exclusively to the α-face of the intermediate oxonium ion. Reactions with glucal and galactal afford dihydropyran products, while reactions with a ribose derivative yield dihydrofuran products.

ChemInform Abstract: An Isotopic Study (2H and 18O) of the Enzymic Conversion of Linoleic Acid into Colneleic Acid with Carbon Chain Fracture: The Origin of Shorter Chain Aldehydes.

Contrary to earlier reports, the divinyl 9-ether oxygen of colneleic acid is shown by experiment with 18O2 to originate from oxygen, not water. Using [9,10,12,13-2H4]-9(S)-hydroperoxyoctadeca-1O(E), 12(Z)-dienoic acid, made enzymically from synthetic [9,10,12,13-2H4]Iinoleic acid, it is found that the distribution of deuterium as determined by NMR and mass spectrometry in the fractured carbon chain of colneleic acid formed by potato enzyme, is consistent with the intervention of an epoxycarbonium ion intermediate. Though divinyl acids such as colneleic and colnelenic acid give the expected shorter chain aldehydes on treatment with aqueous acid, it is likely that the latter are formed in most plants by trapping of a monovinyl oxonium ion rather than by rehydration of colneleic and colnelenic acid.

Asymmetric Total Synthesis of Trilobacin via Organoselenium-Mediated Oxonium Ion Formation/SiO2-Promoted Fragmentation

An asymmetric total synthesis of trilobacin (1), an annonaceous acetogenin with potent anticancer activities, was accomplished wherein the construction of its erythro-bis(2,2')-tetrahydrofuran core 2 featured a novel organoselenium-mediated oxonium ion formation/SiO(2)-promoted fragmentation of alpha,alpha'-cis-oxocene 3.

ChemInform Abstract: New Synthesis of Isoxazolidines.

A new synthesis of 5-substituted isoxazolidines was developed by direct isoxazolidine ring formation of allylic hydroxylamines under acidic conditions. The cyclization process is an electrophilic SN1 type reaction. The formed carbocation intermediate is stabilized by electron rich groups (i.e., phenyl). A moiety that mediates oxonium ion formation (i.e., para-methoxy) accelerates the rate of product formation.

Conformational properties of 2-methyl-1,3,2-oxazaborinane oxonium and ammonium ions

It is known that 1,3,2-oxazaborinanes are convenient model compounds for the study of the influence of heteroatoms on the conformational and configuration characteristics of the cyclohexane heteroanalogs [1–3]. In this paper using non-empirical quantum-chemical approximation RHF/6-31G(d) within the software HyperChem [4] we studied the influence of protonation of 2-methyl-1,3,2-oxazaborinane (I) at the nitrogen or oxygen atoms (associates II and III, respectively) on the conformational properties of the adducts. As a result of the calculations we found that the formation of exothermic complexes II and III was barrier-free. The energy of formation is higher for associate II than for adduct III: ΔEII = –222.5 kcal mol ; ΔEIII = –209.2 kcal mol. Previously [1] it was shown that the potential energy surface of the ether I contains degenerate energy minima corresponding to the semichair conformers (SC and SC*) that in the NMR time scale rapidly interinverted through the 2,5-twist (2,5-T) transition state. The results of computer modeling of the molecules of associates II and III also indicate an equilibrium between the degenerate by energy SC and SC* conformers.

IR spectra of protonated benzaldehyde clusters, C7H7O+–Ln (L=Ar,N2;n≤2): Ion-ligand binding motifs of the cis and trans oxonium isomers

Infrared photodissociation (IRPD) spectra of mass-selected protonated benzaldehyde (C(7)H(7)O(+),BZH(+)) and its weakly bound clusters with Ar and N(2) produced in an electron impact source are recorded in the C-H and O-H stretch ranges. The experimental results are supported by ab initio and density functional calculations. Analysis of the IRPD spectrum of the BZH(+) monomer is consistent with the presence of the cis and trans isomers of the oxonium ions, which is confirmed by the cluster spectra. No signature of the less stable carbenium ions is detected. Frequency shifts in the IRPD spectra of dimers and trimers provide information about the preferred intermolecular ligand binding site (pi-bonding versus H-bonding) and the corresponding interaction strength. H-bonding to the OH group of the oxonium ions of BZH(+) is found to be favored over pi-bonding to the aromatic ring for both Ar and N(2). There are significant differences in the microsolvation structure and energetics of the cis and trans oxonium isomers of BZH(+) due to the rather different acidities of their OH groups and isomer-dependent effects arising from steric hindrance. The large positive partial charge of the protonated formyl group implies that the cluster growth of the larger clusters continues by further solvation of the protonated substituent rather than the aromatic ring.

Gas-Phase Meerwein Reaction of Epoxides with Protonated Acetonitrile Generated by Atmospheric Pressure Ionizations

Ethylnitrilium ion can be generated by protonation of acetonitrile (when used as the LC-MS mobile phase) under the conditions of atmospheric pressure ionizations, including electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) as well as atmospheric pressure photoionization (APPI). Ethylnitrilium ion (CH(3)-C≡N+H and its canonical form CH(3)-C+=NH) is shown to efficiently undergo the gas-phase Meerwein reaction with epoxides. This reaction proceeds by the initial formation of an oxonium ion followed by three-to-five-membered ring expansion via an intramolecular nucleophilic attack to yield the Meerwein reaction products. The density functional theory (DFT) calculations at the B3LYP/6-311+G(d,p) level show that the gas-phase Meerwein reaction is thermodynamically favorable. Collision-induced dissociation (CID) of the Meerwein reaction products yields the net oxygen-by-nitrogen replacement of epoxides with a characteristic mass shift of 1 Da, providing evidence for the cyclic nature of the gas-phase Meerwein reaction products. The gas-phase Meerwein reaction offers a novel and fast LC-MS approach for the direct analysis of epoxides that might be of genotoxic concern during drug development. Understanding and utilizing this unique gas-phase ion/molecule reaction, the sensitivity and selectivity for quantitation of epoxides can be enhanced.

Differential Solvation Free Energies of Oxonium and Ammonium Ions: Insights from Quantum Chemical Calculations

We have employed computational protocols to determine the differential solvation free energy in water of oxonium and ammonium ions. We have focused our analysis on pairs of onium ions having the same hydrocarbon content and substitutional pattern (HCSP pairs). In agreement with previous suggestions (Taft, R. W.; Wolf. J. F.; Beauchamp, J. L.; Scorrano, G.; Arnett, E. M. J. Am. Chem. Soc. 1978, 100, 1240), we found that cavitation and van der Waals terms do not contribute to the differential solvation free energy. Moreover, we observe that oxonium ions are more strongly solvated than the analogous ammonium ions even though the former ones have fewer H-bond donor sites. The performance of two different continuum solvation models, PCM and SMD, is discussed.

ChemInform Abstract: Using the Pummerer Cyclization-Deprotonation-Cycloaddition Cascade of Imidosulfoxides for Alkaloid Synthesis.

The Pummerer reaction of imidosulfoxides bearing tethered alkenyl groups has been employed for the synthesis of several alkaloids. The required imidosulfoxides necessary for the cascade sequence were easily obtained by heating the appropriate amide with (ethylsulfenyl)acetyl chloride followed by sodium periodate oxidation. The initially formed thionium ion, obtained by treating the imidosulfoxide with acetic anhydride and p-toluenesulfonic acid, reacts with the neighboring imido group, and the resulting oxonium ion undergoes subsequent deprotonation to produce an isomunchnone dipole. This mesoionic betaine intermediate undergoes ready intramolecular dipolar cycloaddition across the neighboring π-bond. Exposure of the resulting cycloadducts to additional acetic anhydride leads to ring opening and formation of a 5-acetoxy-substituted 2(1H)-pyridone. This six-ring heterocyclic system constitutes a valuable building block for the synthesis of a variety of pyridine, quinolizidine, and clavine alkaloids. The cy...

Theoretical evaluation of the geometry and conformational properties of oxonium and ammonium ions of tetra- hydro-1,3-oxazine

Theoretical evaluation of the geometry and conformational properties of oxonium and ammonium ions of tetra- hydro-1,3-oxazine