The 15N and 13C solid state NMR study of intramolecular hydrogen bond in some Schiff's bases

A series of 11 Schiff's bases derived from substituted salicylaldehyde and aliphatic amines has been studied in the solid state by ¹⁵N and ¹³C cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR). ¹⁵N CPMAS is especially useful for investigation of the tautomerism in the compounds considered, owing to the large difference in the nitrogen chemical shifts of OH and NH tautomers. In the solid state, three of the compounds examined were shown by ¹⁵N NMR to exist as OH tautomeric forms, and the remaining eight as the corresponding NH forms. This was confirmed by ¹³C CPMAS. The results reported were compared with those obtained in CDCl₃ solutions.     

Assignment of 13C Resonances in the Phencyclone-Norbornadiene Adduct Via 2D NMR. 13C Evidence for Hindered Rotation of Unsubstituted Bridgehead Phenyl Rings

¹³C NMR chemical shift assignments were obtained for the Diels-Alder adduct of phencyclone with norbornadiene in CD₂Cl₂ and in CDCl₃ solution. The ¹³C spectrum at 50.3 MHz, as well as the ¹H spectrum at 200.1 MHz, show evidence for hindered rotation of the two unsubstituted bridgehead phenyl rings of the adduct at ambient temperatures. In CD₂Cl₂ solution, all 19 of the unique ¹³C nuclei of this molecule give rise to individual ¹³C resonances. The ¹H assignments which were made earlier, together with one-bond and long-range 2D heteronuclear correlation experiments, allowed the assignment of all ¹³C chemical shifts in the molecule.     

Discrimination of C NMR signals in solid material with liquid-like behavior presenting residual dipolar proton–proton homonuclear interactions: application on seeds

In this communication, we propose, a modified spin echo fourier transform (SEFT) experiment run under magic angle spinning (MAS) to obtain structural informations of the liquid-like domains inside complex organic materials. It includes a proton-proton dipolar decoupling such as BLEW12 or Lee-Goldburg sequence just after the 180 degrees 13C refocusing pulse and short echo delays are used in order to overcome T(2) relaxation. This very easy implemented sequence allows a clear discrimination among fast relaxing 13C signals between those with a pure liquid-like behavior and those presenting residual proton-proton dipolar coupling. The interests of the sequence, combined with other classical NMR experiments, are illustrated on whole vegetable seeds that represent an example of a complex material.     

Sensitivity enhancement in (13)C solid-state NMR of protein microcrystals by use of paramagnetic metal ions for optimizing (1)H T(1) relaxation

We discuss a simple approach to enhance sensitivity for (13)C high-resolution solid-state NMR for proteins in microcrystals by reducing (1)H T(1) relaxation times with paramagnetic relaxation reagents. It was shown that (1)H T(1) values can be reduced from 0.4-0.8s to 60-70 ms for ubiquitin and lysozyme in D(2)O in the presence of 10 mM Cu(II)Na(2)EDTA without substantial degradation of the resolution in (13)C CPMAS spectra. Faster signal accumulation using the shorter (1)H T(1) attained by paramagnetic doping provided sensitivity enhancements of 1.4-2.9 for these proteins, reducing the experimental time for a given signal-to-noise ratio by a factor of 2.0-8.4. This approach presented here is likely to be applicable to various other proteins in order to enhance sensitivity in (13)C high-resolution solid-state NMR spectroscopy.     

Conformational Analysis of Baclofen Analogues by 1H and 13C NMR: Phaclofen,Saclofen, and Hydroxy-Saclofen. Influence of the Anionic Moiety

The conformations of three analogues of baclofen 1: phaclofen, saclofen, and hydroxy-saclofen 2–4, potent GABA_B antagonists, in solution (D₂O) are estimated from high-resolution (300 MHz) H NMR coupling data. Conformations and populations of conformers are calculated by means of a modified Karplus-like relationship for the vicinal coupling constants. H NMR spectral analysis evidences how 1–3 keep in solution the preferred a conformation around C3-C4 bond. A partial rotation is set up around C2–C3 bond (the conformations about C2–C3 are all highly populated in solution) particularly for 2 and 3 while 1 shows a relative preferred a conformation. This evidences the influence of the anionic moiety.     

13C NMR Assignments of the Antimalarials,Chloroquine, 4-Methylprimaquine, 5-Methoxy-4-methylprimaquine and 5-Methoxyprimaquine

The ¹³C nmr assignments for the antimalarial drugs chloroquine, 4-methyl primaquine, 5-methoxy-4-methylprimaquine and 5-methoxyprimaquine were established. These assignments were based on comparison with those of primaquine, proton-coupled data, and selective long-range proton decoupling.     

The Prediction of the 13C NMR Signal Positions in Substituted Naphthalenes,Part 2: The Use of Statistical Substituent Chemical Shift (SSCS) Values

The prediction of the ¹³C NMR signals for derivatives of naphthalene has been investigated using statistical Substituent Chemical Shift (SSCS) values. For α-derivatives the model had a correlation coefficient of observed versus predicted line positions of r=.98 with an standard deviation of 2.1ppm while in the β case r=.98 with the standard deviation being 2.0ppm. Prediction of the 9 and 10 positions had an r=.93 with the standard deviation being 1.5ppm. The data base consisted of 5250 signals from 525 naphthalene derivatives.     

GC(Retention Indices), GC-MS,and 13C NMR of Two Citral-Rich Cymbopogon Leaf Oils: C. Flexuosus and C. tortilis

Leaf oils of Cymbopogon flexuosus and Cymbopogon tortilis were submitted to combined analysis by CG(retention indices), Gas Chromatography Mass Spectrometry (GC-MS), and ¹³C Nuclear Magnetic Resonance (NMR). The composition was dominated by geranial (39.2% and 32.0%) and neral (24.1% and 19.1%). Cis- and trans-7-hydroxy-3,7-dimethyl-3,6-oxyoctanal (synonym: cis- and trans-tetrahydro-5-(1-hydroxy-1-methylethyl)-2-methyl-2-furanacetaldehyde) were identified by ¹³C NMR by comparison with literature data.     

Structure Elucidation and Assignment of 1H and 13C Spectra of the New Fused Cyclobutane-Naphthofuran Derivative by Two-Dimensional NMR in Different Solvents

One of the major product from the photodimerization of 2-[2-(2-methyl-phenyl)ethenyl)]naphtho[2. 1-b]furan (1) is a new fused cyclobutane-naphthofuran derivative, 6-(2-methylphenyl)-1-[2-(2-methylphenyl)ethenyl]-7-(2-naphtho-[2,1-b]furyl)-3-[2,1]naphtho-2-oxabicyclo[3.2.0]hept-3-ene (2). Its ¹H and ¹³C NMR spectra were fully assigned by the application of COSY, LR COSY, NOESY, APT and HETCOR experiments in deuterated chloroform, acetone and benzene solutions.     

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 environment 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.     

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.     

Effect of the frequency of intramolecular motions on the NMR relaxation in liquid state temperature regime

Equations for the spectral densities of complex motion of a spin pair undergoing internal motion and isotropic/anisotropic overall rotation have been considered. The fluctuations of the interproton distances, caused by internal motion, have been taken into account in the theoretical equations. A method allowing a distinction between the isotropic and the anisotropic overall rotation of molecules has been proposed. The effect of the activation parameters of internal motions (known from the solid state study) on the measured T ₁ relaxation of the ¹³C and ¹H–¹H cross-relaxation rates has been analysed for methyl-β-D-galactopyranoside in DMSO-d6 solution. The conformational trans-gauche jumps of the methylene group are not fast enough to affect the T ₁ value of carbon C6 in the liquid state temperatures regime. Only the methyl group rotation is a very fast internal motion. This motion influences the carbon C7 relaxation and methyl protons–anomeric proton cross-relaxation. The values of interatomic distances between anomeric H(C1) and H(C5) as well as the three methyl protons H(C7) have been calculated from the cross-relaxation rates. The distance H(C1)–H(C7) fluctuates due to the rotation of methyl group. The application of the ‘model-free approach’ to study molecular dynamics in solutions is discussed.     

Theoretical and experimental investigation of (13)C relayed (2)H-(2)H-COSY 2D experiments: application to the analysis of weakly aligned solutes

We describe new NMR 2D experiments denoted DECADENCY for DEuterium CArbon DEuterium Nuclear Correlation spectroscopY dedicated to the analysis of anisotropic deuterium spectra. They belong to the class of X-relayed Y,Y-COSY 2D experiments that was initially explored in the case of a (1)H-X-(1)H fragment (I(X)=1/2) in isotropic medium. DECADENCY 2D experiments permit to correlate the quadrupolar doublets associated with two inequivalent deuterium nuclei in an oriented CD(2) fragment through heteronuclear polarization transfers. Two kinds of pulse sequences are described here using either a double INEPT-type or DEPT-type process. DECADENCY 2D experiments provide an interesting alternative to (2)H-(2)H COSY experiments when the geminal (2)H-(2)H total coupling (scalar and dipolar) is null or too small to provide visible cross-correlation peaks. Such a situation is typically observed for geminal deuteriums in prochiral or chiral molecules dissolved in chiral liquid crystals. The efficiency of these techniques is illustrated using dideuterated prochiral molecules, the phenyl[(2)H(2)]methanol and the 1-chloro[1-(2)H(2)]nonane, both dissolved in organic solutions of poly-gamma-benzyl-l-glutamate. The advantages of each sequence are presented and discussed. It is shown that the relative sign of the quadrupolar doublets can be determined.     

13C NMR and 2D (H,H and H,C COSY) Spectra of Triazolo-triazino-indole Derivatives and the Conformational Analysis of the Respective C-Nucleoside Analogues

¹³C NMR and 2D (H,H and H,C COSY) spectra of selected examples of sugar (5H-1,2,4-triazino[5,6-b]-indol-3-yl) hydrazones, peracetylated sugar-1-acetyl -1- (5-acetyl-1,2,4-triazino[5,6-b]indol-3-yl)hydrazones, and 10-acetyl-3-(per-0-acetylalditol-1-yl)-1,2,4-triazolo[4′, 3′:2,3][1,2,4]triazino[5,6-b]indole have been reported. The conformation of the latter C-nucleoside analogues have been determined by analysis of their ¹H NMR spectra. The D-galacto, D-manno and L-arabino isomers are preponderantly existing in the planar zigzag arrangement of carbon atoms.     

The 2D {P} Spin-Echo-Difference Constant-Time [C, H]-HMQC Experiment for Simultaneous Determination of JH3′P and JC4′P in C-Labeled Nucleic Acids and Their Protein Complexes

A two-dimensional {³¹P} spin-echo-difference constant-time [¹³C, ¹H]-HMQC experiment (2D {³¹P}-sedct-[¹³C, ¹H]-HMQC) is introduced for measurements of ³J_C4′P and ³J_H3′P scalar couplings in large ¹³C-labeled nucleic acids and in DNA–protein complexes. This experiment makes use of the fact that ¹H–¹³C multiple-quantum coherences in macromolecules relax more slowly than the corresponding ¹³C single-quantum coherences. ³J_C4′P and ³J_H3′P are related via Karplus-type functions with the phosphodiester torsion angles β and ε, respectively, and their experimental assessment therefore contributes to further improved quality of NMR solution structures. Data are presented for a uniformly ¹³C, ¹⁵N-labeled 14-base-pair DNA duplex, both free in solution and in a 17-kDa protein–DNA complex.     

1H and 13C NMR Determination of the Enantiomeric Purity of Substituted 4-Amino-3- (thien-2-Yl)-Butyric Acids and 4-Amino-3-(Benzo[b]Furan-2-yl)-Butyric Acids,Ligands of the GabaB Receptor.

The enantiomeric composition and absolute configuration of 4-Amino-3-(benzo[b]furan-2-yl)-Butanoic Acids and of 4-Amino-3-(thien-2-yl)-Butanoic Acids 1 may be accurately determined by ¹H and ¹³C nuclear magnetic resonance analysis of the corresponding derivatives 3 prepared by reaction with chiral reagents. Correlation with HPLC is signaled.