Modified Spectral Editing Methods for C CP/MAS Experiments in Solids

The spectral editing approach of Zilm and coworkers utilizes polarization, polarization inversion, and spin depolarization methods for enhancing or suppressing NMR spectral lines in solids. The proposed pulse sequences allow nonprotonated C, CH, CH₂, and CH₃ types of carbon resonances to be separated from one another and identified accordingly. The former method tentatively separates the nonprotonated C and CH₃ peaks with a cutoff shift of 35 ppm. This shift is a reasonable demarcation shift for a preponderance of organic molecules, but exceptions do exist that could constitute a serious drawback in a few instances. The new approach separates the nonprotonated C and CH₃ carbon peaks unequivocally using modified pulse sequences similar to those of Zilm. Further, both the CH only and CH₂ only spectra, respectively, can be acquired directly from combining so called (+) and (−) sequences using different spectral delay periods and pulse parameters. The (+) and the (−) pulse sequences produce signals for the nonprotonated and methyl carbons that have essentially the same amplitude but opposite phases. These spectra, combined with the previously reported CH₃ and nonprontonated C only spectra, offer a complete spectral editing technique for solid samples. Examples of these spectral editing methods are provided for 3-methylglutaric acid, fumaric acid monoethyl ester, and two complex natural products: methyl o-methylpodocarpate and 10-deacetylbaccatin III.     

13C NMR Chemical Shifts of Heterocycles: Empirical Substituent Effects in 5-Halomethylisoxazoles

Evaluation by empirically derived equations for the Substituent effect (α, β, γ, δ) on the ¹³C NMR chemical shifts for C-3, C-4. C-5 and halomethyl-substituent carbon (C-6) in isoxazoles 1-5 [where C-3 substituent (R¹) = H, alkyl or phenyl, C-4 Substituent (R²) = H, alkyl, and C-5 substituent (R³) = di-or trihalomethyl, methyl and H], taking as reference the compound la, is reported. From the calculated values for the α, β, γ, δ effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1–5. The ¹³ C chemical shifts of the C-3, C-4, C-5, C-6 of these compounds, can be estimated with good precision: 94% of the calculated chemical shifts are found to be within ±1.0ppm, and 100% are found to be within ±1.5ppm.     

13C-NMR Assignments for Methyls and Quaternary Carbons of the Limonoid Obacunone

The high field ¹H and ¹³C resonances of obacunone were established by a series of I D and 2D NMR experiments. The ¹³C-NMR signals of the five tertiary methyl groups and all quatenary carbons were unambiguously assigned. The results confirm the stereochemical assignments at all stereogenic centres.     

Isocoumarines: Structural Study by NMR and by AM1 Semi-Empirical Method

Study of a serie of isocoumarins by ¹³C and ¹⁷O NMR spectrometry and AM1 method is reported. These methods gave valuable informations on electronic effect and the structure of isocoumarins.     

Identification and Quantitative Determination of Dipropylene Glycol in Terpene Mixtures Using 13C NMR Spectroscopy

A method that allows direct identification and quantitative determination of dipropylene glycol (DPG) using ¹³C NMR spectroscopy was developed. The quantitative procedure was checked and validated with commercially available DPG, controlled with two DPG-added essential oils, and then applied to commercial “Extraits de parfum” (perfume extracts).     

13C- and 1H-NMR Relaxation Investigation of a Polyciclic Nitrogen Compound: 3,3-Dimethyl-1,5-diphenyl-9-hydroxy-bispidinium Iodide

The rigid polycyclic nitrogen compound was considered as a test for the reliability of internuclear distances calculated by ¹H-NMR spin-lattice relaxation rates. The ‘isotropic’ motional correlation time was calculated from ¹³C relaxation rates (τ_C = 0.11 ns at 298 K). Dipolar cross-relaxation rates were calculated by measuring non-, mono- and double-selective proton spin-lattice relaxation rates. All the experimental relaxation rates were thoroughly accounted for by dipolar pairwise interactions. Only at high temperatures a certain contribution from the spin rotational mechanism was apparent.     

Separate Quantification of Doubly and SinglyC-Labeled Metabolites by HSQC-FilteredJSpectroscopy

NMR detection of multiply labeled compounds in biological samples is often used to follow metabolic pathways. Detection of protons bound to¹³C atoms offers a more sensitive approach than direct¹³C detection, but generally results in the loss of carbon–carbon coupling information. We have modified an HSQC sequence to refocus the carbon chemical shifts in order to obtain a proton-correlated¹³C homonuclearJspectrum, which allows us to measure singly and doubly labeled compounds in the same spectrum.     

Assignments of 1H and 13C NMR Spectral Data for Benzoylecgonine,a Cocaine Metabolite

The complete assignment of the ¹H and ¹³C NMR spectra of benzoylecgonine, a cocaine metabolite, was performed, with the aid of some 2D experiments such as gCOSY and gHSQC.     

Carbon-13 NMR Spectrum of Bilirubin

The structure of bilirubin and of bilirubin derivatives has been studied by various physical techniques, including optical spectroscopy^(1,2), optical rotatory dispersion,⁽⁴⁾ isotope exchange⁽⁵⁾ and proton magnetic resonance spectroscopy^(2,3,5). A good deal of chemical information on bilirubin is also available^(6). The interpretation of most of the experimental results, however, have been inconclusive and different possible structures of the molecule could be shown to accommodate the experimental data.     

Isotope-Filtered Affinity NMR

A double-editing pulse sequence has been developed that allows the direct observation of protein binding ligand(s) from a mixture of compounds. This technique should aid the discovery of lead pharmaceutical compounds. The proton NMR signals from protein and the nonbinding ligands are simultaneously eliminated using¹³C isotope editing and PFG diffusion-edited NMR. This new experiment is demonstrated using¹³C/¹⁵N-labeled stromelysin catalytic domain (SCD).     

Complete Analysis of the 1H and 13C NMR Spectra of 5-Isopropylsulfonyl-2-Norbornenes Through the Application of Two-Dimensional NMR Techniques

Total assignment of ¹³C and ¹H NMR spectra of the 5-isopropylsulfonyl-2-norbornenes 2 was achieved using the concerted application of two-dimensional homonuclear and heteronuclear chemical shift correlations. The stereochemistry of both the diastereoisomers endo 2a and exo 2b have been established using the magnitude of the proton coupling constants.     

Structural and 14N EFG Information on Solid Imidazole by 13C CP/MAS NMR Data

Residual dipolar coupling between carbons and ¹⁴N nuclei in the ¹³C CPMAS NMR spectrum of solid imidazole is studied. Calculations of expected splittings with a previously reported equation leads to the complete assignment of the solid state carbon chemical shifts. Additionally, information is provided on the location of ¹⁴N electric field gradient axes at the N-H site.     

13C NMR Chemical Shift of β-Alkoxyvinylketones: II. Empirical Substituent Effects in β-Aryl-β-Methoxyvinyltrihalomethylketones

Evaluation by empirically derived equations for the substituent effect (α,β,γ,δ) on the ¹³C NMR chemical shifts for C-1, C-2, C-3 and C-4 in β-aryl-β-methoxyvinylhalomethylketones 1a-g to 2a-g [R³C(O)-CH=C(Ar)-OMe, where R³ = CCl₃, CF₃ and Ar = p-YC₆H₄ (Y = H, Me, MeO, F, Cl, Br, NO₂)], taking as reference the β-ethoxyvinyltrichloromethylketone (3), is reported. From the calculated values for the α,β,γ,δ effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1,2. The ¹³C chemical shifts of the C-1, C-2, C-3, C-4 of these compounds, can be estimated with good to rasoable precision: 84% of the calculated chemical shifts are found to be within ±1.0ppm, and 100% are found to be within ±1.5ppm. The Y-Effects on C-3 and C-4 are compared with carbon charge densities (qr).     

Determination of the Stereochemistry of Substituted 5-Methylenehydantoins and Thiohydantoins by 13C NMR and Homonuclear NOE Experiments

Basically the aim of this work is to define the accurate configuration of the exocyclic double bond of substituted 5-methylenehydantoins and thiohydantoins which have been conceived as potential Aldose Reductase inhibitors. A previsional survey based upon the chemical shifts analysis from ¹H and decoupled ¹³C NMR spectra discloses, for a part of the family of compounds, the assignment of the Zconfiguration for unsubstituted (2,3) and N-3 substituted (6,7,9) derivatives, and the E-configuration for the N-1 substituted (8,11) ones. The qualitative study with Homonuclear NOE (8,11) and the coupling constant measuring ^{3 J}C4-C=C-H6 from coupled ¹³C NMR (1–11), lead to the assignment of the accurate configuration of the whole family's compounds in agreement with the previsional study.     

Structural Assignment of Isomeric S‐ and S,N‐1‐Alkoxycarbonylalkylated 6‐Amino‐2‐thiouracil Derivatives by Means of 1H and 13C NMR Spectroscopy

Abstract

The structures of new isomeric 2‐alkoxycarbonylalkylthio‐ and 2‐alkoxy‐ carbonylalkylthio‐1‐alkoxycarbonylalkyl‐6‐aminouracils (1–21) have been established on the basis of the ¹H NMR and ¹³C NMR spectroscopic data. The ¹H NMR and ¹³C NMR spectra of 1–21 have been fully assigned by a combination of two‐dimensional experiments [heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC)]. The ¹³C NMR spectra have been shown to be able to differentiate between isomers.     

2D CP/MASC Isotropic Chemical Shift Correlation Established byH Spin Diffusion

A new 2D solid-state CP/MAS¹³C NMR exchange experiment for through-space isotropic chemical shift correlation is proposed and demonstrated. Through-space correlation is established via a second cross polarization from¹³C to¹H and subsequent¹H spin diffusion. A third cross polarization results in the final¹³C–¹³C isotropic chemical shift correlation. The¹H spin diffusion time is a variable parameter allowing different mean square magnetization displacements to be probed. Experimental results on mixtures of differently¹³C-labeled alanine and polyethylene indicate that this site-selective 2D technique can be used to characterize domain sizes and proximities over a wide range of length scales (1–200 nm) in solids such as polymers or biological materials.     

13C NMR Chemical Shifts of β-Alkoxyvinyl Ketones: III✠-Empirical Substituent Effects in 1-Alkylamino-6-Ethoxy-1,5-Hexadien-3,4-Diones and 1,6-bis(Alkylamino)-1,5-Hexadien-3,4-diones

Evaluation by empirically derived equations for the substituent effect (E_Xn and E_Yn, n = 1 to 6) on the ¹³C NMR chemical shifts for C-1, C-2, C-3, C-4, C-5 and C-6 in 1-alkylamino-6-ethoxy-1,5-hexadien-3,4-diones 1a-f and 1,6-bis(alkylamino)-1,5-hexadien-3,4-diones 2a-f [XCH=CHC(O)-C(O)CH=CHY, where X, Y = OEt, NH₂, PhCH₂NH, n-BuNH, i-PrNH, cyclo-C₆H₁₁NH, t-BuNH], taking as reference the 1,6-diethoxy-1,5-hexadien-3,4-dione (3), is reported. From the calculated values for the E_Xn and E_Yn effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1,2 with excellent precision: 100% of the calculated chemical shifts are found to be within ±0.5ppm. The carbon-13 chemical shifts of C-1, C-2 and C-3 of compounds 1a,2a,3 led a good correlation with carbon charge densities (qr).     

Assignment of the 1H and 13C Spectra of 5-Methylthio-4H-1-(p-R1-phenyl)-3a-(p-R2-phenyl)-3a,4-dihydro (1,2,4) oxadiazolo(4,5-a), 1,5-benzodiazepines using 2D NMR Spectroscopy.

The ¹H NMR spectra of the title benzodiazepines derivatives is highly congested because all the protons are in aromatic enviroment so many proton signals remain overlap even 300 MHz or higher fields. With this in mind, the assignment of the ¹H and ¹³C spectra of these compounds obtained using COSY, NOESY, HMQC and HMBC experiments is reported.