PI by NMR: Probing CH–π Interactions in Protein–Ligand Complexes by NMR Spectroscopy

While CH–π interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH–π interactions in drug–protein complexes. Herein, we present a fast and reliable methodology called PI (π interactions) by NMR, which can differentiate the strength of protein–ligand CH–π interactions in solution. By combining selective amino-acid side-chain labeling with ¹H-¹³C NMR, we are able to identify specific protein protons of side-chains engaged in CH–π interactions with aromatic ring systems of a ligand, based solely on ¹H chemical-shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH–π interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual π interactions rather than averaged measures of all interactions.     

γ-ray radiolysis of dihydroxyurea in nitric acid and its radiolytic products

Journal of Radioanalytical and Nuclear Chemistry - Dihydroxyurea (DHU) is a new salt-free reducing agent applied for the separation of Pu and Np from U in spent fuel reprocessing. This paper...     

Investigation of Bis(α-Phenylethylamido)Methylphosphonates by NMR Spectroscopy

Abstract

The influence of the relative location of chiral carbon and phosphorus atoms and the position of the aryl-group on diastereomeric anisochronity in non-racemic mixtures of enantiomers has been examined. The optical isomers of methanephosphonic acid bis(α-phenylethylamide) (I), which contain pro-chiral phosphorus atom, were synthesized by the reaction of methanephosphonic acid dichloride(II) with (+)- or (-) -α-phenylethylamine (III). The extent of chemical shift nonequivalence in ³¹P and ¹H NMR spectra of non-racemic mixtures of RR- and SS-I was negligible. It can be explained by the absence of aryl-amino group, favouring intermolecular association, effect of SCADA¹, and the long distance between the chiral center and pro-chiral phosphorus. Phosphonylation of non-racemic mixtures of (+)- and (-)-III by II proceeds stereospecifically giving mixture of RR-, SS-I, and two meso-compounds analyzed by ³¹P ¹H NMR.     

Sample Preparation and the Detection of α-Aminopropiophenone and Amphetamine in Narcotic Drugs Using IR Spectroscopy

A procedure was developed for the IR-spectroscopic detection of -aminopropiophenone and amphetamine in narcotic drugs prepared from phenylpropanolamine-containing medicines using sample preparation by liquid–liquid extraction. Extraction conditions were selected using the computation of physicochemical parameters of the analytes. The procedure is simple, inexpensive, and can be used in combination with other chemical and physicochemical methods for the expert analysis of narcotic drugs.     

Characterizations of Some N—Substituted—salicylhydrazide in Mixtures by NMR Diffusion Ordered Spectroscopy

1 INTRODUCTION Metallacrown has emerged as inorganic host molecules. There has been considerable interest in metallacrown chemistry owing to its potential applications in chemically modified electrodes, anion-selective separation agents, liquid-crystal precursors and magnetic materials[1]. Multidentate ligands which can bridge two metal ions are used to synthesize metallacrowns. The cyclic repetition of the ligand bridging two metal ions generates the macrocyclic metal cluster. In the c…     

Synthesis and 125Te NMR Spectroscopy of α-Tellurocarbonyl Compounds and Derivatives

The reaction of lithium alkyl-, alkenyl-, alkynyl-, and aryl tellurolates with α-bromocarobonlyl compounds in anhydrous tetrahydrofuan gives the title compounds in yields ranging from 55–92%. The ¹²⁵Te NMR chemical shift range for these compounds is 405–1024 ppm.     

Pathways of Methane Transformation over Copper-Exchanged Mordenite as Revealed by In Situ NMR and IR Spectroscopy

The reaction of methane with copper-exchanged mordenite with two different Si/Al ratios was studied by means of in situ NMR and infrared spectroscopies. The detection of NMR signals was shown to be possible with high sensitivity and resolution, despite the presence of a considerable number of paramagnetic Cu^II species. Several types of surface-bonded compounds were found after reaction, namely molecular methanol, methoxy species, dimethyl ether, mono- and bidentate formates, Cu^I monocarbonyl as well as carbon monoxide and dioxide, which were present in the gas phase. The relative fractions of these species are strongly influenced by the reaction temperature and the structure of the copper sites and is governed by the Si/Al ratio. While methoxy species bonded to Brønsted acid sites, dimethyl ether and bidentate formate species are the main products over copper-exchange mordenite with a Si/Al ratio of 6; molecular methanol and monodentate formate species were observed mainly over the material with a Si/Al ratio of 46. These observations are important for understanding the methane partial oxidation mechanism and for the rational design of the active materials for this reaction.     

Detection of systemic pesticide residues in tea products at trace level based on SERS and verified by GC–MS

Analytical and Bioanalytical Chemistry - Surface-enhanced Raman spectroscopy (SERS) has the potential to detect pesticide residues in agricultural products. However, some systemic pesticides, such...     

Standard enthalpies of formation of γ-aminobutyric acid and the products of its dissociation in aqueous solution

Heat effects of the dissolution of crystalline γ-aminobutyric acid in water and potassium hydroxide solutions are determined by direct colorimetry at 298.15 K. Standard enthalpies of formation of γ-aminobutyric acid and the products of its dissociation in aqueous solution are calculated.     

Standard enthalpies of formation of α-aminobutyric acid and products of its dissociation in an aqueous solution

Heats of solution of crystalline α-aminobutyric acid in water and in aqueous solutions of potassium hydroxide at 298.15 K are measured by means of direct calorimetry. Standard enthalpies of formation of the amino acid and products of its dissociation in an aqueous solution are calculated.     

Mapping the Binding Site of P53 on UBC9 by NMR Spectroscopy

Human UBCP9 is a member of the E2 family of proteins.However,instead of conjugating to ubiquitin,it conjugates to a ubiquitin bomologue SUMO-1(also known as UBL1,GMP1,SMTP3,PICT-1 and sentrin).The SUMO-1 conjugation pathway is very similar to that of ubiquin with regard to the primary sequences of the ubiquitin activating enzymes(E1),the three-dimensional structures of the ubiquitin conjugating enzymes(E2),and the chemistry of the overall conjugation pathway.The interactiov of p53 and UBC9,the E2 of the SUMO-1 pathway,has heen studied by nuclear magnetic resonance spectroscopy.A peptide corresponding to the nuclear localization domain of p53 specifically interacts with UBC9 and this interaction is likely to be important for conjugation of p53 with SUMO-1.The largest chemical shift changes on UBC9 occur at residues94 and 129-135.This region is adjacent to the active site and has slgniflcant dynamic behavior on the μs-ms and ps-ns timescales.Correlation of chemical shift changes and mobility of these residues further suggest the importance of these residues in substrate recognition.     

Enzymatic catalysis of 2,6-dimethoxyphenol by laccases and products characterization in organic solutions

2,6-Dimethoxyphenol (DMP) as a substrate was widely used in determination of laccase activity. It is surprising, however, that its catalyzed oxidation products have not been completely determined until now. Studies were thus conducted on Rhus laccase (RL) and immobilized Rhus laccase (IRL)-catalyzed oxidation reactions of 2,6-dimethoxyphenol in water-organic solvent systems. These reactions pro- ceeded well in water-(im)miscible organic solvent systems pre-saturated with water. Only one product, 3,3′,5,5′-tetramethoxy-1,1′biphenyl-4,4′-diol (TMBP), was produced by RL catalysis, and it was thor- oughly characterized by FT-IR, NMR, GC-MS, etc. A simple enzymatic mechanism of this reaction is proposed.     

Determination of the Chemical Structure of Poly-β (-)-pinene by NMR Spectroscopy

This paper is dedicated to the memory of our friend and colleague Annalaura Segre.

The chemical structure of a series of β (-)-pinene polymers (PBP) obtained by radiation-induced polymerization, free radical initiation, cationic polymerization over a Friedel-Craft catalyst and by coordinative polymerization over a Ziegler-Natta catalyst has been fully elucidated by ¹H and ¹³C-NMR spectroscopy. 2D NMR techniques have been applied in order to assign all the NMR resonances to the structures of the PBP investigated. The NMR spectra show that the most regular PBP structure is obtained by radiation-induced polymerization followed by the free radical initiated polymerization. The most defective structure has been observed in the case of PBP prepared by cationic mechanism over a Friedel-Crafts catalyst. The discussion accounts for different types of defects and cross-links present in the PBPs investigated whose fundamental structure is based on the p-menthene repeating unit.

NMR self-diffusion measurements have been performed to evaluate the molecular weight of all the PBP investigated. The highest molecular weight (2600 Dalton) was found in the case of PBP prepared by Ziegler-Natta catalyst, while the lowest molecular weight was found in the case of PBP prepared by radiation-induced polymerization (about 1000 Dalton).     

1H and 13C NMR Spectroscopy of Stereoisomeric 2′-deoxy-C-Nucleosides

Eleven furanosyl 2′-deoxy-C-nucleosides with β-D-erythro, α-D-erythro and β-D-threo configurations have Been studied by IH and ¹³C NMR spectroscopy recorded in CDC1₃ and/or DMSO-d ₆. Results obtained indicate that each of the three stereoisomeric configurations studied are identifiable by ¹H and ¹³C NMR spectroscopy using a combination of coupling constant and chemical shift criteria.     

Studies on Single-electron Oxidation of N-Alkyl-p-Phenylenediamines and Benzidines in Aqueous Acetonitrile by Cyclovoltammetry and ESR Spectroscopy

It is demonstrated by cyclovoltammetry and ESR spectroscopy that N,N,N,'N,'-tetramethyl; tetraethgl, tetra-n-propyl, tetra-n-butyl-p-phenylenediamine and tetraethyl, tetra-n-propyl-p-benzidine undergo deprotonat ion and two consecutive single electron transfer step CE reaction at electrode in aqueous acetonitrile with the corresponding radical cations as the intermediate. The bivalent cations produced at the electrode react not only with hydroxyl anion in the medium to give quinone but also with the N-alkyl-p-phenylene-diamines or benzidines to produce the corresponding radical cations.     

Solution chemistry in fused monochloroacetic acid—V: Solvolytic reactions of Lewis acids in monochloroacetic acid and the nature of the solvolysed products

Tetrachlorides of tin, titanium, zirconium, thorium and silicon form compounds of composition SnCl₂(CH₂ClCOO)₂, Ti(CH₂ClCOO)₄, Zr(CH₂ClCOO)₄, Th(CH₂ClCOO)₄ and Si₂O(CH₂ClCOO)₆ when refluxed with excess of monochloroacetic acid. From i.r., molecular weight and conductance studies, their structures have been elucidated. Their Lewis acid character is established by isolating and characterising their adducts with organic tertiary bases. Antimony pentachloride, aluminium trichloride and ferric chloride form compounds of composition SbCl₂(CH₂ClCOO)₃, Al(CH₂ClCOO)₃, FeCl(CH₂ClCOO)₂ and Fe(CH₂ClCOO)₃ when refluxed with excess of solvent and these have been characterised by i.r. studies.     

Simultaneous Determination of Magnolol and Honokiol by Synchronous Fluorescence Spectroscopy

MOL and HOL are the useful ingredients of Houpo that has been used in traditional Chinese medicine for the treatment of thrombotic stroke, typhoid fever, and headache. Therefore, it is necessary to determine theirs contents in pharmaceutical dosage. Up to…     

gem-Diol-Type Intermediate in the Activation of a Ketone on Sn-β Zeolite as Studied by Solid-State NMR Spectroscopy

Lewis acid zeolites have found increasing application in the field of biomass conversion, in which the selective transformation of carbonyl-containing molecules is of particular importance due to their relevance in organic synthesis. Mechanistic insight into the activation of carbonyl groups on Lewis acid sites is challenging and critical for the understanding of the catalytic process, which requires the identification of reaction intermediates. Here we report the observation of a stable surface gem-diol-type species in the activation of acetone on Sn-β zeolite. ¹³C, ¹¹⁹Sn, and ¹³C–¹¹⁹Sn double-resonance NMR spectroscopic studies demonstrate that only the open Sn site ((SiO)₃Sn-OH) on Sn-β is responsible for the formation of the surface species. ¹³C MAS NMR experiments together with density functional theory calculations suggest that the gem-diol-type species exhibits high reactivity and can serve as an active intermediate in the Meerwein—Ponndorf–Verley–Oppenauer (MPVO) reaction of acetone with cyclohexanol. The gem-diol-type species offers an energy-preferable pathway for the direct carbon-to-carbon hydrogen transfer between ketone and alcohol. The results provide new insights into the transformation of carbonyl-containing molecules catalyzed by Lewis acid zeolites.     

Conformational Study of 8—C—glucosyl—prunetin by Dynamic NMR Spectroscopy

By means of variable temperature NMR spectra,conformation of 8-C-glucosyl prunetin, isolated from the leaves of Dalbergia hainanensis (Leguminosae), was studied. The restricted rotation around the C(sp^3)-C(sp^2) bond in the C-glucosides isoflavonoid results in two main conformers (syn and anti). With the help of MM calculation, the preferred conformation A has H-1″ gauche to the 7-OCH3. The barrier to rotation was 18.1 kcal/mol. This result agrees with the calculated value 16.2 kcal/mol of free energy of activation for the interconversion between the conformers.