Spatial structure of heptapeptide Aβ16–22 (beta‐amyloid Aβ1–40 active fragment) in solution and in complex with a biological membrane model

The spatial structure of an active fragment of beta‐amyloid Aβ_1–40 heptapeptide Aβ_16–22 (Lys‐Leu‐Val‐Phe‐Phe‐Ala‐Glu) in aqueous buffer solution and in complex with sodium dodecyl sulfate micelles as a model membrane system was investigated by ¹H NMR spectroscopy and two‐dimensional NMR (TOCSY, HSQC‐HECADE (Heteronuclear Couplings from ASSCI‐domain experiments with E.COSY‐type crosspeaks), NOESY) spectroscopy. Complex formation was confirmed by the chemical shift changes of the heptapeptide's ¹H NMR spectra, as well as by the signs and values of the NOE effects in different environments. We compared the spatial structure of the heptapeptide in borate buffer solution and in complex with a model of the cell surface membrane. Copyright © 2012 John Wiley & Sons, Ltd.     

Homonuclear Selective One-Dimensional Gradient NMR Experiments in the Structure Determination of Natural Diterpene Derivatives

Summary.  The solution structure of two natural diterpene derivatives, the secondary metabolites esulatin-A and esulatin-B of Euphorbia esula, was investigated by homonuclear NMR experiments. Since the spectral dispersion of the ¹H NMR spectra at 500 MHz was sufficient to separate several skeletal protons of the title compounds, they were selectively excited with a double pulsed field gradient spin-echo (DPFGSE) sequence using 180°Gaussian pulses sandwiched between sine shaped gradients. With the use of selective excitation, scalar as well as dipolar interactions of the selected spins were monitored through one-dimensional (1D) COSY, TOCSY, and NOESY experiments. The chemical shifts of the coupling partners could be accurately extracted from the 1D COSY and TOCSY spectra recorded with high digital resolution. The selective TOCSY experiment provided an excellent opportunity to identify spins belonging to the same scalarly coupled spin system. The solution state conformation was investigated by selective gradient enhanced NOESY experiments. Proton–proton distances were evaluated from the cross-relaxation rates obtained from a quantitative analysis of the NOESY spectra recorded with different mixing times. The NMR derived distances were compared to the results of solid state X-ray diffraction measurements. Corresponding author. E-mail: pforgo@chem.u-szeged.hu Received November 21, 2001. Accepted (revised) January 9, 2002     

NMR analysis of a series of imidazobenzoxazines

The complete ¹H and ¹³C NMR assignment of a series of imidazobenzoxazines by a combination of one‐ and two‐dimensional experiments (COSY, HSQC and HMBC) is studied. Moreover, 2D NOESY and 1D selective NOESY are reported. This procedure allows the identification of the regioisomers obtained. Copyright © 2010 John Wiley & Sons, Ltd.     

Tanacetamide D: A New Ceramide from Tanacetum artemisioides

One new ceramide (=long‐chain base linked to a fatty acid via an amide bond), tanacetamide D ( 1 ), was isolated from Tanacetum artemisioides. Besides this, the two known constituents 5‐demethylnobiletin ( 2 ) and 5‐hydroxy‐3,6,7,8,3′,4′‐hexamethoxyflavone ( 3 ) were isolated for the first time from this species. The structure elucidation of the isolated compounds were based primarily on 2D‐NMR techniques including correlation spectroscopy (COSY), heteronuclear multiple‐quantum coherence (HMQC), heteronuclear multiple‐bond correlation (HMBC), and nuclear Overhauser effect spectroscopy (NOESY) experiments.     

USING TWO DIMENSIONAL NMR TECHNIQUES TO ASSIGN PROTON AND CARBON SPECTRA FOR COBALT(III) COMPLEXES DERIVED FROM LINEAR QUINQUEDENTATE LIGANDS CONTAINING NITROGEN AND SULFUR DONOR ATOMS

Abstract

High resolution NMR spectroscopy was used to study the structure of a cobalt(III) complex derived from the linear quinquedentate ligand, 7-methyl-4, 10-dithia-l, 7, 13-tria-zatridecane, NH₂-CH₂CH₂-S-CH₂CH₂-N(CH₃)-CH₂CH₂-S-CH₂CH₂-NH₂. The flexibility of this ligand allows it theoretically to form four distinct structural isomers with metal ions. The one dimensional proton spectrum exhibited by [Co(NSNSN)Cl]Cl₂, is complicated and does not provide structural insight. A combined utilization of proton, carbon, DEPT, COSY, NOESY and HETCOR spectra was employed to establish geometric structure type, make individual proton assignments, identify proton-proton connectivities that result from scalar coupling, and distinguish interactions occurring as a result of through-space interactions. Information about the five-membered chelate ring orientations was also obtained. Two groups of signals were shown to correlate with each carbon signal, exhibiting a definite nonequivalence between geminal protons. Geminal protons were found to have coupling constants of 14 Hz. In contrast, the vicinal protons were found to have coupling constants of 5-7 Hz.     

Stereoisomeric N-(p-Nitrobenzoyl)-5-aminomethylbicyclo[2.2.1]hept-2-enes. Synthesis,Epoxidation, 1H and 13C NMR Spectra

Preparation is described of stereoisomeric (p-nitrobenzoyl)-5-aminomethylbicyclo[2.2.1]hept-2-enes and their epoxidation by peracetic acid. By an example of one of amides was demonstrated a possibility of selective reduction of separated fragments in the polyfunctional compound using sulfur in alkaline medium, hydrazine hydrate in the presence of a nickel catalyst, and lithium aluminum hydride. By reaction with electrophilic reagents from the amines synthesized, (p-aminobenzoyl)-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene and (p-aminobenzoyl)-endo-2-aminomethylbicyclo[2.2.1]hept-2-ene, were obtained new bicyclic compounds containing alongside the amide group also sulfonamide, carboxamide, urea, and thiourea moieties. The structure of compounds obtained was confirmed by ^1Hand ^13C NMR spectroscopy, by two-dimensional spectra measured along COSY and NOESY procedures.     

1H and 13C NMR assignments for two new steroids from the coral Chromonephthea sp.

Two new steroids isolated from EtOH extracts of the South China Sea soft coral Chromonephthea sp. were identified. One‐dimensional (1D) and two‐dimensional (2D) NMR experiments including COSY, HSQC, HMBC and NOESY were used for the determination of their structure. Copyright © 2008 John Wiley & Sons, Ltd.     

Complete NMR analysis of oxytocin in phosphate buffer

Complete NMR analysis of oxytocin (OXT) in phosphate buffer was elucidated by one‐dimensional (1D)‐ and two‐dimensional (2D)‐NMR techniques, which involve the assignment of peptide amide NH protons and carbamoyl NH₂ protons. The ¹H? ¹⁵N correlation of seven amide NH protons and three carbamoyl NH₂ protons were also shown by HSQC NMR of OXT without ¹⁵N enrichment. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of condensed pregnano[17,16-<Emphasis Type="Italic">d</Emphasis>]triazolines under high pressure

Condensed pregnano[17,16-d]triazolines were produced in 1,3-dipolar cycloaddition of 16-dehydropregnenolone acetate with organic azides at 10 kbar. The structure of the synthesized compounds was determined by using two-dimensional NMR spectroscopy (¹H—¹H COSY, NOESY, HSQC, and HMBC).     

Coupling NMR to NOM

This work itemizes and critically assesses several 1D and multi-dimensional nuclear magnetic resonance (NMR) techniques, in both the liquid (solvent suppression, APT, DEPT, INEPT, COSY, TOCSY, HSQC, HMQC, HMBC, NOESY, ROESY and others) and solid states (DP, SACP, RAMP-CP, CP-TOSS, MQ-DEPT, 2D ¹H–¹³C HETCOR and others), which are relevant to the characterization of natural organic matter (NOM). The pros and cons of many of the discussed techniques are compared in an effort to provide guidance to the most beneficial utilization of these NMR instrumental techniques for researchers interested in gaining insight into various aspects of NOM.Abbreviations 1D One dimensional - 2D Two dimensional - APT Attached proton test - BIRD Bilinear rotation decoupling - CP Cross polarization - COSY Correlation spectroscopy - CSA Chemical shift anisotropy - DEPT Distortionless enhancement by polarization transfer - DMSO Dimethyl sulfoxide - DOSY Diffusion ordered spectroscopy - DP Direct polarization - DQ Double quantum - FID Free induced decay - FT Fourier transform - FT-ICR-MS Fourier transform-ion cyclotron resonance-mass spectroscopy - HETCOR Heteronuclear correlation - HH Hartmann–Hahn - HMBC Heteronuclear multiple bond correlation - HMQC Heteronuclear multiple quantum coherence - HSQC Heteronuclear single quantum coherence - INEPT Insensitive nuclei enhanced by polarization transfer - LR-COSY Long-range COSY - MAS Magic-angle spinning - MQ Multiple quantum - MS Mass spectroscopy - NMR Nuclear magnetic resonance - NOE Nuclear Overhauser enhancement - NOESY Nuclear Overhauser enhanced spectroscopy - NOM Natural organic matter - PASS Phase adjustment of spinning sidebands - RAMP Ramped amplitude - RESTORE Restoration of spectra via T _CH and T one rho (T _1H) editing - r.f. Radio frequency - ROESY Rotating frame Overhauser enhancement spectroscopy - SACP Single amplitude cross polarization - SOM Soil organic matter - SS Spinning sideband - TMS Tetramethylsilane - TOCSY Total correlation spectroscopy - TOSS Total suppression of sidebands - TPPM Two-pulse phase modulation - VCT Variable contact time - VSL Variable spin lock - WATERGATE Water suppression by gradient tailored excitation     

Isolation and Structural Characterization of New,Highly Functionalized Diterpenes from Euphorbia serrulata

Five new diterpene polyesters, 1 – 5 , with jatrophane skeletons were isolated from the fresh whole plants of Euphorbia serrulata. The structure elucidation was performed by means of UV/VIS spectroscopy, HR‐ESI‐MS, and advanced two‐dimensional NMR methods, including ¹H‐NMR, JMOD, ¹H,¹H‐COSY, NOESY, HMQC, and HMBC experiments. The relative configurations of 1 – 5 and their conformations in solution were analyzed on the basis of NOESY measurements. As a result of detailed NMR studies, complete ¹H and ¹³C chemical‐shift assignments of the compounds were possible. The isolated compounds differ stereochemically and do not comprise a uniform series regarding the configurations at C(2), C(6), and C(13). Compound 5 possesses the new structural feature of a double bond with (Z)‐configuration in the macrocyclic ring of the jatrophane skeleton, while compound 2 has a C?C bond in the five‐membered ring, this being the first observation of this structural feature in the type of macrocyclic Euphorbiaceae diterpenes.     

A novel pimara-8(9) ,15-diene from lycopus europaeus

Identification of a novel trioxygenated Δ^8(9),15_ pimaric acid methyl ester from plant species Lycopus europaeus by means of two-dimensional ¹H NMR spectroscopy (COSY and NOESY) is reported.     

Study of the addition of diazoles to vinylsilanes

The reaction of trimethoxy(vinyl)silane with diazoles in the presence of metal lithium was studied. The structure of the reaction products was assigned by NMR spectroscopy (¹H, ¹³C, ²⁹Si, COSY, NOESY, HMBC, and HSQC). An explanation for the different reactivities of reagents (aliphatic amines, diazoles, allylalkylsilanes, vinylalkylsilanes, and vinylalkoxysilanes) was provided.     

The two-dimensional NMR spectroscopy of macromolecules

Two-dimensional (2D) NMR is a versatile technique which exists in many versions. Two broad classes of 2D techniques are (1) correlated spectroscopy and (2) J-resolved spectroscopy. The first of these may be divided into two further subdivisions: COSY, which permits correlations of resonances via J-coupling, and NOESY, which allows direct measurement of intenuclear (usually interproton) distances by the nuclear Overhauser effect. COSY greatly facilitates the interpretation of complex spectra and spectral interpretation in terms of stereochemical sequences is placed on a firmer foundation. NOESY provides direct information concerning the local conformations of polymers in solution. By use of J-resolved 2D NMR, we can separate J-couplings and chemical shifts on different axes and thus achieve a degree of resolution of both these parameters far beyond what is attainable in the 1D spectrum. Finally, we may combine correlated and J-resolved spectroscopy and achieve the benefits of both in 3D NMR, in which the 2D cross peaks exhibit J-coupling fine structure. These techniques are illustrated for a variety of polymers including poly(methyl methacrylate), poly(vinyl fluoride), poly-y-benzyl L-glutamate, and poly(propylene oxide).     

Spatial Structure of a DNA Duplex d(CGTTTATT)p-Net:d(AATAAACG) with an Unusual Localization of a Covalently Bound Netropsin (Net) Analog According to Two-Dimensional NMR Spectroscopy

Two-dimensional ¹H NMR (NOESY, COSY) spectroscopy was used to study the spatial structure of a DNA complex CGTTTATTp-Net:AATAAACG with a netropsin analog bound at the terminal 3-phosphate group in aqueous solution. The positions of the proton NMR signals of the duplex are compared with those for the unmodified duplex and the free ligand. A mean conformation of the duplex is constructed by the molecular mechanics technique using the obtained NMR limitations on the interproton distances. The data obtained indicate that the aromatic pyrrole rings of the netropsin analog are involved in a stacking interaction with the terminal AT base pair of the duplex; this is generally not typical of ordinary minor-groove netropsin type ligands.     

Isolation and Structure Determination of New Jatrophane Diterpenoids from Euphorbia platyphyllos L.

Three new, highly functionalized jatrophane diterpenes ( 1 – 3 ) have been isolated from the whole, dried plants of Euphorbia platyphyllos L., together with one known jatrophane polyester ( 4 ). The structures were established by UV/VIS spectroscopy, HR‐ESI‐MS, and advanced two‐dimensional NMR, including ¹H‐NMR, JMOD, ¹H,¹H‐COSY, HMQC, and HMBC experiments. Stereochemical studies and conformational analyses were performed by means of NOESY experiments. Interestingly, compounds 1 – 4 do not represent a stereochemically uniform series because they differ in the orientations of the Me groups at C(2), C(6), and C(13). A similar observation was reported earlier for Euphorbia serrulata, whose diterpenes are related to the compounds obtained from E. platyphyllos. This chemical relationship is of taxonomic importance and supports the botanical similarity of the two species.     

NMR studies on 1,2‐dihydro‐2‐(4‐aminophenyl)‐4‐[4‐(4‐aminophenoxy)‐4‐phenyl]‐(2H)phthalazin‐1‐one

An unsymmetrical heterocyclic diamine, 1,2‐dihydro‐2‐(4‐aminophenyl)‐4‐[4‐(4‐aminophenoxy)‐4‐phenyl]‐(2H)phthalazin‐1‐one, was synthesized. Its ¹H and ¹³C NMR spectra were completely assigned by utilizing the two‐dimensional heteronuclear ¹³C–¹H multiple‐bond coherence (HMBC) spectroscopy, and heteronuclear ¹³C–¹H one‐bond correlation spectroscopy, homonuclear shift correlation spectroscopy (H,H‐COSY) and rotating frame Overhauser enhancement spectroscopy (ROESY). The structure of the compound was shown to be the phthalazinone rather than the phthalazine ether from cross peaks and chemical shifts of the protons. Copyright © 2002 John Wiley & Sons, Ltd.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-(2,3-epoxypropyl)arenesulfonamides with (bicyclo[2.2.1]hept-5-en-<Emphasis Type="Italic">endo</Emphasis>-2-yl)methanamine

Reactions of bicyclo[2.2.1]hept-5-en-endo-2-ylmethanamine with N-(2,3-epoxypropyl)arenesulfonamides gave amino alcohols having a norbornene fragment and sulfonamide group. The major products were formed via opening of the oxirane ring according to the Krasuskii rule. The product structure was determined by ¹H and ¹³C NMR spectroscopy using DEPT and two-dimensional COSY, NOESY, HMQC, and HMBC techniques.     

Direct Self‐Assembly of a 2D and 3D Star of David

Two‐ and three‐dimensional metallosupramolecules shaped like a Star of David were synthesized by the self‐assembly of a tetratopic pyridyl ligand with a 180° diplatinum(II) motif and Pd^II ions, respectively. In contrast to other strategies, such as template‐directed synthesis and stepwise self‐assembly, this design enables the formation of 2D and 3D structures in one step and high yield. The structures were characterized by both one‐dimensional (¹H, ¹³C, ³¹P) and two‐dimensional (COSY, NOESY, DOSY) NMR spectroscopy, ESI‐MS, ion‐mobility mass spectrometry (IM–MS), AFM, and TEM. The stabilities of the 2D and 3D structures were measured and compared by gradient tandem mass spectrometry (gMS²). The high stability of the 3D Star of David was correlated to its high density of coordination sites (DOCS).     

Chemoselectivity and Conformational Analysis of the Reaction of 2‐Acetylcycloalkanones with Benzohydrazide: Synthesis and Reduction of 1‐Aroylcycloalkapyrazole Derivatives

From the reaction of 2‐acetylcyclopentanone and 2‐acetyl‐2‐methylcyclopentanone with benzohydrazide, the 1‐benzoyl‐6a‐hydroxycyclopentapyrazole derivatives 2a and 2b were obtained as the only reaction products, whereas from the reaction of 2‐acetylcyclohexanone an epimeric cis/trans mixture of the 2‐benzoyl‐3‐hydroxy‐2H‐indazole derivative 3c was formed. The dehydration of the isolated compounds 2a and 3c , as well as the NaBH₄ and NaBH₃CN reduction products of 2a were studied. The structural assignments of the compounds derived were established by analysis of their NMR spectra (¹H, ¹³C, DEPT, COSY, NOESY, HETCOR C? H, and COLOC C? H). The chemoselectivity of the reactions of 1a and 1c with benzohydrazide was studied by conformational analysis with MM2 and semiempirical (AM1 and PM3) MO calculations.