Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups.

ABSTRACT: A substrate has been prepared having two triarylmethanol centers and four pyridine-type substituent groups. Upon ionization in the Brønsted superacid CF₃SO₃H, the substrate undergoes two types of reactions. In the presence of only the superacid, the highly ionized intermediate(s) provide a double cyclization product having two pyrido[1,2-a]indole rings. With added benzene, an arylation product is obtained. A mechanism is proposed involving tetra-, penta-, or hexacationic species.

SUBMITTER: Kennedy SH

PROVIDER: S-EPMC6633208 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups.

Kennedy Sean H SH Gasonoo Makafui M Klumpp Douglas A DA

Beilstein journal of organic chemistry 20190709

A substrate has been prepared having two triarylmethanol centers and four pyridine-type substituent groups. Upon ionization in the Brønsted superacid CF3SO3H, the substrate undergoes two types of reactions. In the presence of only the superacid, the highly ionized intermediate(s) provide a double cyclization product having two pyrido[1,2-a]indole rings. With added benzene, an arylation product is obtained. A mechanism is proposed involving tetra-, penta-, or hexacati ...[more]

PMID: 31354869

Similar Datasets

Preparation of Aryl-Susbstituted 2-Oxyindoles by Superelectrophilic Chemistry.

Project description:A series of pyridyl-substituted 3-hydroxy-2-oxyindoles have been prepared and reacted with arenes in superacid promoted Friedel-Crafts reactions. The product aryl-substituted 2-oxyindoles are formed in generally good yields. With substituted arenes such as toluene, bromobenzene, or ethyl salicylate, the Friedel-Crafts reactions occur with excellent regioselectivity. A mechanism is proposed involving dicationic, superelectrophilic species leading to the electrophilic aromatic substitution chemistry.

| S-EPMC3775391 | biostudies-literature

Developing hybrid approaches to predict pKa values of ionizable groups.

Project description:Accurate predictions of pKa values of titratable groups require taking into account all relevant processes associated with the ionization/deionization. Frequently, however, the ionization does not involve significant structural changes and the dominating effects are purely electrostatic in origin allowing accurate predictions to be made based on the electrostatic energy difference between ionized and neutral forms alone using a static structure and the subtle structural changes be accounted by using dielectric constant larger than two. On another hand, if the change of the charge state is accompanied by a large structural reorganization of the target protein, then the relevant conformational changes have to be explicitly taken into account in the pKa calculations. Here we report a hybrid approach that first predicts the titratable groups whose ionization is expected to cause large conformational changes, termed "problematic" residues, and then applies a special protocol on them, while the rest of the pK(a)s are predicted with rigid backbone approach as implemented in multi-conformation continuum electrostatics (MCCE) method. The backbone representative conformations for "problematic" groups are generated with either molecular dynamics simulations with charged and uncharged amino acid or with ab-initio local segment modeling. The corresponding ensembles are then used to calculate the titration curves of the "problematic" residues and then the results are averaged to obtain the corresponding pKa.

| S-EPMC3220190 | biostudies-literature

Vinyl Carbocations Generated under Basic Conditions and Their Intramolecular C-H Insertion Reactions.

Project description:Here we report the surprising discovery that high-energy vinyl carbocations can be generated under strongly basic conditions, and that they engage in intramolecular sp3 C-H insertion reactions through the catalysis of weakly coordinating anion salts. This approach relies on the unconventional combination of lithium hexamethyldisilazide base and the commercially available catalyst, triphenylmethylium tetrakis(pentafluorophenyl)borate. These reagents form a catalytically active lithium species that enables the application of vinyl cation C-H insertion reactions to heteroatom-containing substrates.

| S-EPMC6608570 | biostudies-literature

Regulation of Ras Paralog Thermostability by Networks of Buried Ionizable Groups.

Project description:Protein folding is governed by a variety of molecular forces including hydrophobic and ionic interactions. Less is known about the molecular determinants of protein stability. Here we used a recently developed computer algorithm (pHinder) to investigate the relationship between buried charge and thermostability. Our analysis revealed that charge networks in the protein core are generally smaller in thermophilic organisms as compared to mesophilic organisms. To experimentally test whether core network size influences protein thermostability, we purified 18 paralogous Ras superfamily GTPases from yeast and determined their melting temperatures (Tm, or temperature at which 50% of the protein is unfolded). This analysis revealed a wide range of Tm values (35-63 °C) that correlated significantly (R = 0.87) with core network size. These results suggest that thermostability depends in part on the arrangement of ionizable side chains within a protein core. An improved capacity to predict protein thermostability may be useful for selecting the best candidates for protein crystallography, the development of protein-based therapeutics, as well as for industrial enzyme applications.

| S-EPMC5574170 | biostudies-literature

Involvement of ionizable groups in catalysis of human liver glycolate oxidase.

Project description:Glycolate oxidase is a flavin-dependent, peroxisomal enzyme that oxidizes alpha-hydroxy acids to the corresponding alpha-keto acids, with reduction of oxygen to H(2)O(2). In plants, the enzyme participates in photorespiration. In humans, it is a potential drug target for treatment of primary hyperoxaluria, a genetic disorder where overproduction of oxalate results in the formation of kidney stones. In this study, steady-state and pre-steady-state kinetic approaches have been used to determine how pH affects the kinetic steps of the catalytic mechanism of human glycolate oxidase. The enzyme showed a Ping-Pong Bi-Bi kinetic mechanism between pH 6.0 and 10.0. Both the overall turnover of the enzyme (k(cat)) and the rate constant for anaerobic substrate reduction of the flavin were pH-independent at pH values above 7.0 and decreased slightly at lower pH, suggesting the involvement of an unprotonated group acting as a base in the chemical step of glycolate oxidation. The second-order rate constant for capture of glycolate (k(cat)/K(glycolate)) and the K(d)((app)) for the formation of the enzyme-substrate complex suggested the presence of a protonated group with apparent pK(a) of 8.5 participating in substrate binding. The k(cat)/K(oxygen) values were an order of magnitude faster when a group with pK(a) of 6.8 was unprotonated. These results are discussed in the context of the available three-dimensional structure of GOX.

| S-EPMC2781520 | biostudies-literature

PKAD: a database of experimentally measured pKa values of ionizable groups in proteins.

Project description:Ionizable residues play key roles in many biological phenomena including protein folding, enzyme catalysis and binding. We present PKAD, a database of experimentally measured pKas of protein residues reported in the literature or taken from existing databases. The database contains pKa data for 1350 residues in 157 wild-type proteins and for 232 residues in 45 mutant proteins. Most of these values are for Asp, Glu, His and Lys amino acids. The database is available as downloadable file as well as a web server (http://compbio.clemson.edu/pkad). The PKAD database can be used as a benchmarking source for development and improvement of pKa's prediction methods. The web server provides additional information taken from the corresponding structures and amino acid sequences, which allows for easy search and grouping of the experimental pKas according to various biophysical characteristics, amino acid type and others.

| S-EPMC6389863 | biostudies-literature

Protein ionizable groups: pK values and their contribution to protein stability and solubility.

Project description:The structure, stability, solubility, and function of proteins depend on their net charge and on the ionization state of the individual residues. Consequently, biochemists are interested in the pK values of the ionizable groups in proteins and how these pK values depend on their environment. We review what has been learned about pK values of ionizable groups in proteins from experimental studies and discuss the important contributions they make to protein stability and solubility.

| S-EPMC2679426 | biostudies-literature

Experimental pKa Value Determination of All Ionizable Groups of a Hyperstable Protein.

Project description:Electrostatic interactions significantly contribute to the stability and function of proteins. The stabilizing or destabilizing effect of local charge is reflected in the perturbation of the pKa value of an ionizable group from the intrinsic pKa value. Herein, the charge network of a hyperstable dimeric protein (ribbon-helix-helix (rhh) protein from plasmid pRN1 from Sulfolobus islandicus) is studied through experimental determination of the pKa values of all ionizable groups. Transitions were monitored by multiple NMR signals per ionizable group between pH 0 and 12.5, prior to a global analysis, which accounted for the effects of neighboring residues. It is found that for several residues involved in salt bridges (four Asp and one Lys) the pKa values are shifted in favor of the charged state. Furthermore, the pKa values of residues C40 and Y47, both located in the hydrophobic dimer interface, are shifted beyond 13.7. The necessary energy for such a shift is about two-thirds of the total stability of the protein, which confirms the importance of the hydrophobic core to the overall stability of the rhh protein.

| S-EPMC6619245 | biostudies-literature

Protons migrate along interfacial water without significant contributions from jumps between ionizable groups on the membrane surface.

Project description:Proton diffusion along membrane surfaces is thought to be essential for many cellular processes such as energy transduction. Commonly, it is treated as a succession of jumps between membrane-anchored proton-binding sites. Our experiments provide evidence for an alternative model. We released membrane-bound caged protons by UV flashes and monitored their arrival at distant sites by fluorescence measurements. The kinetics of the arrival is probed as a function of distance for different membranes and for different water isotopes. We found that proton diffusion along the membrane is fast even in the absence of ionizable groups in the membrane, and it decreases strongly in D(2)O as compared to H(2)O. We conclude that the fast proton transport along the membrane is dominated by diffusion via interfacial water, and not via ionizable lipid moieties.

| S-EPMC3167506 | biostudies-literature

Crystallographic study of hydration of an internal cavity in engineered proteins with buried polar or ionizable groups.

Project description:Although internal water molecules are essential for the structure and function of many proteins, the structural and physical factors that govern internal hydration are poorly understood. We have examined the molecular determinants of internal hydration systematically, by solving the crystal structures of variants of staphylococcal nuclease with Gln-66, Asn-66, and Tyr-66 at cryo (100 K) and room (298 K) temperatures, and comparing them with existing cryo and room temperature structures of variants with Glu-66, Asp-66, Lys-66, Glu-92 or Lys-92 obtained under conditions of pH where the internal ionizable groups are in the neutral state. At cryogenic temperatures the polar moieties of all these internal side chains are hydrated except in the cases of Lys-66 and Lys-92. At room temperature the internal water molecules were observed only in variants with Glu-66 and Tyr-66; water molecules in the other variants are probably present but they are disordered and therefore undetectable crystallographically. Each internal water molecule establishes between 3 and 5 hydrogen bonds with the protein or with other internal water molecules. The strength of interactions between internal polar side chains and water molecules seems to decrease from carboxylic acids to amides to amines. Low temperature, low cavity volume, and the presence of oxygen atoms in the cavity increase the positional stability of internal water molecules. This set of structures and the physical insight they contribute into internal hydration will be useful for the development and benchmarking of computational methods for artificial hydration of pockets, cavities, and active sites in proteins.

| S-EPMC2275713 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data