Vicinal Proton Coupling Constants Research Articles

Conformations of Flavan-3-ols in Water: Analysis Using Density Functional Theory.

To elucidate the conformations and their relative stabilities of flavan-3-ols in water, the optimized structures and energies were calculated by density functional theory, in which M06-2X, ωB97X-D, B3LYP, and CAM-B3LYP were examined as exchange-correlation functionals. The results were evaluated by comparing calculated spin-spin coupling constants of vicinal protons with the corresponding values observed in experimental 1H NMR spectra in D2O. The M06-2X and ωB97X-D results showed good agreement with the experimental NMR data and revealed that the B-ring (pseudoequatorial)/3-O (pseudoaxial) conformers were more stable [5.4-8.7 kJ/mol (1.3-2.1 kcal/mol)] than the B-ring (pseudoaxial)/3-O (pseudoequatorial) conformers in the 2,3-cis-flavan-3-ols, while the B-ring (pseudoequatorial)/3-O (pseudoequatorial) conformers and the B-ring (pseudoaxial)/3-O (pseudoaxial) conformers had similar stabilities in the 2,3-trans-flavan-3-ols.

The Use of Coupled HSQC Spectra to Aid in Stereochemical Assignments of Molecules with Severe Proton Spectral Overlap

A simple glycoside with only 13 carbons exhibited extensive overlapping of four of the glycosidic protons, causing extreme difficulty in the determination of the stereochemistry of the pyranose unit. However, acquisition of a high-resolution coupled heteronuclear single-quantum coherence (HSQC) spectrum overcame this problem. This spectrum provides a useful method for determining vicinal proton coupling constants between strongly coupled protons. To show the potential of high-resolution coupled HSQC spectra in overcoming spectral overlap. The sample was obtained by methanol extraction, followed by fractionation and column chromatography of the dried leaves of Montrichardia arborescens (Araceae). NMR spectra were obtained on 1.5 mg of sample dissolved in 120 μL of CD₃OD containing 0.1% trimethylsilyl (TMS) as internal standard. A gradient-selected HSQC spectrum was obtained using standard Varian library pulse sequences in phase sensitive mode. The high-resolution coupled HSQC spectrum focused on the saccharide region with a 1025 Hz ¹H spectral window, a 6300 Hz ¹³C spectral window, 1024 data points, a 0.3 Hz relaxation delay, 384 time increments (linear predicted to 4096), and 80 scans per time increment. The use of a high-resolution coupled HSQC spectrum allowed determination of the coupling patterns of the various pyranose protons with sufficient accuracy. This enabled completion of the assignments and identification of the pyranose unit as glucose. The study has shown the effectiveness of the use of a high-resolution coupled HSQC spectrum in the assignment of molecules with severe spectral overlap.

Theoretical prediction and assignment of vicinal 1H–1H coupling constants of diastereomeric 3‐alkoxy‐6,7‐epoxy‐2‐oxabicyclo[3.3.0]octanes

Spin-spin coupling constants between nuclei in NMR spectroscopy reflect their spatial arrangement. A number of calculation methods, applying different levels of theory, have been developed to support the stereochemical assignment of novel compounds. Nevertheless, revisions of the assignment of structures in the literature are not rare. In the present work, the reliability of the calculation methods amenable for a theoretical prediction of spin-spin coupling constants of vicinal protons to support correct stereochemical assignment of substitution at five-membered rings of 3-alkoxy-6,7-epoxy-2-oxabicyclo[3.3.0]octanes was studied. Experimental (3)J(H,H) coupling constants were compared with the coupling constants calculated for all possible diastereomers. The fully quantum chemical approach provided theoretical (3)J(H,H) coupling constants with an absolute deviation of no more than 1.1 Hz for 91% of the experimentally studied coupled spins, whereas the methods without quantum chemical geometry optimization resulted in completely unreliable predictions. Consequently, for a reliable stereochemical assignment of small and medium size molecules, the protocol for calculating the coupling constants based on the results of the quantum chemical geometry optimization is recommended.

Structure of the O-polysaccharide of Erwinia carotovora ssp. atroseptica GSPB 9205 containing a new higher branched monosaccharide

An O-polysaccharide was prepared by mild acid hydrolysis of a lipopolysaccharide of Erwinia carotovora ssp. atroseptica GSPB 9205 and was found to contain a new higher branched monosaccharide, viz., 3,6,8-trideoxy-4-C-(R-1-hydroxyethyl)-D-gulo-octose, which we called erwiniose. The structure of the pentasaccharide repeating unit of the O-polysaccharide was established by monosaccharide analysis, including the determination of absolute configurations, methylation analysis, O-deacetylation, Smith degradation, and one- and two-dimensional NMR spectroscopy. The configuration of erwiniose was determined based on the coupling constants of vicinal protons combined with the nuclear Overhauser effect data and the results of periodate oxidation of the polysaccharide followed by reduction of the resultant 4-keto sugar (the C(1)-C(4)-C(1′)-C(2′) fragment) to give 3,6-dideoxy-D-ribo-hexose(paratose) and oxidation of 3-hydroxybutyraldehyde (the C(5)-C(8) fragment) to give R-3-hydroxybutyric acid.

Insights into the dynamic nature of DNA duplex structure via analysis of nuclear Overhauser effect intensities.

Sequence-dependent structures of DNA duplexes in solution can be reliably determined using NMR data if care is taken to determine restraint bounds accurately. This entails use of complete relaxation matrix methods to analyze nuclear Overhauser effect (NOE) spectroscopic cross-peak intensities, yielding accurate distance restraints. NMR studies of various DNA duplexes have suggested that there may be some limited internal motions. First, it is typically not possible to reconcile all vicinal proton coupling constants in deoxyribose rings with a single conformer. In addition, with the increased accuracy of interproton distance measurements afforded by the complete relaxation matrix algorithm MARDIGRAS, we find inconsistencies in certain distances which can most readily be ascribed to limited conformational flexibility, since conformational averaging is nonlinear. As base-sugar interproton distances depend on both sugar pucker and glycosidic torsion angle chi, motion involving these structural variables should be reflected by experimental data. Possible motional models have been considered to account for all of the data for three DNA duplexes. Analysis of intraresidue base-sugar interproton NOE bounds patterns suggests a motional model with individual sugars in equilibrium between S (2'-endo) and N (3'-endo) conformations, with S being preferred. As sugar repuckering is correlated with changes in glycosidic torsion angle chi, different sugar conformers imply different values for chi, but this is insufficient to account for all data. A two-state jump between anti and syn glycosidic conformers was considered, but it was incapable of accounting for all data. However, a model with restricted diffusion (rocking) about the glycosidic bond in addition to sugar repuckering was capable of accommodating all experimental data. This motional model is in qualitative agreement with experimental 13C relaxation-derived order parameter values in a DNA duplex.

Conformation of kainic acid in solution from molecular modelling and NMR spectra

Conformational behaviour of kainic acid in aqueous solution was elucidated by molecular mechanics and dynamics. The pucker of the five-membered ring in kainic acid was examined and compared with that of model compounds. In cyclopentane there is no barrier to pseudorotation, so that all puckered states coexist. In pyrrolidinium, the presence of a hetero-atom in the ring introduces a small barrier (about 0.6 kcal mol−1) to pseudorotation, separating two stable regions, A and B, which are equivalent by symmetry. In proline, the presence of the carboxylate group on C2 removes the symmetry but two stable conformational minima, A and B, remain. In kainic acid, the presence of side-chains on C3 and C4 introduces complications resulting in additional sub-minima in both regions, A and B. In solution, kainic acid is a complex mixture of conformers with comparable energies, because of the combination of several stable states of the pyrrolidinium ring with the torsional degrees of freedom arising from the two side-chains. The individual geometries, energies, and estimates of relative populations of these conformers were obtained from molecular dynamics simulations. The calculations were validated by a comparison of predicted inter-proton distances and vicinal proton coupling constants with the experimental quantities derived from NMR spectra. Copyright © 1998 John Wiley & Sons, Ltd.

Conformation of kainic acid in solution from molecular modelling and NMR spectra

Conformational behaviour of kainic acid in aqueous solution was elucidated by molecular mechanics and dynamics. The pucker of the five-membered ring in kainic acid was examined and compared with that of model compounds. In cyclopentane there is no barrier to pseudorotation, so that all puckered states coexist. In pyrrolidinium, the presence of a hetero-atom in the ring introduces a small barrier (about 0.6 kcal mol(-1)) to pseudorotation, separating two stable regions, A and B, which are equivalent by symmetry. In proline, the presence of the carboxylate group on C2 removes the symmetry but two stable conformational minima, A and B, remain. In kainic acid, the presence of side-chains on C3 and C4 introduces complications resulting in additional sub-minima in both regions, A and B. In solution, kainic acid is a complex mixture of conformers with comparable energies, because of the combination of several stable states of the pyrrolidinium ring with the torsional degrees of freedom arising from the two side-chains. The individual geometries, energies, and estimates of relative populations of these conformers were obtained from molecular dynamics simulations. The calculations were validated by a comparison of predicted inter-proton distances and vicinal proton coupling constants with the experimental quantities derived from NMR spectra.

Two Highly Populated Conformations at Room Temperature of Monterine and Granjine, Antitumor Bisbenzylisoquinoline Alkaloids: Origin and Tridimensional Structures.

Monterine 1 as well as granjine 3, 1R,1'S configured biphenylic bisbenzylisoquinoline alkaloids, generate two highly populated conformers. The interconversion of two forms was detected by saturation tranfer in (1)H NMR NOEs experiments. Tridimensional structure of the conformers was determined on the basis of (1)H NMR analysis of anisotropic shielding protons, by NOEs measurements and vicinal proton coupling constants of CH1-CH(2)alpha and CH1'-CH(2)alpha'. The structures established from NMR data were further refined to observe the mobility of 3D conformations by molecular dynamics simulation in vacuo. The highly populated conformers, monterine 1a and 1b, as well as granjine 3a and 3b, are interconvertible by rotation about the C1'-Calpha', Calpha'-C9', and C11'-C11 bonds and inversion of the benzyl D ring by reference to CH(2)alpha'. The slow exchange system was investigated by dynamic NMR spectroscopy: DeltaG()(c) 77.9 KJ/mol and k(c) 200 s(-)(1) for monterine 1; DeltaG()(c) 77.7 KJ/mol and k(c) 211 s(-)(1) for granjine 3. Natural and synthetic biphenylic bisbenzylisoquinolines displayed, in vitro, cytotoxic activities against human prostate and breast cancer cell lines.

Solution structures of 13 2-methoxychlorophyll a epimers

The absolute configurations at C-13 2 of 13 2-methoxychlorophyll a (13 2-MeO-Chl a) epimers, synthetic derivatives of Chl a, were determined by the 2D ROESY NMR technique. The ROESY spectra and the vicinal coupling of the C-17 and C-18 protons also provided information on the conformation of ring D which was found to be more distorted in both MeO-Chl a epimers compared with 13 2( R)-Chl a due to increased steric crowding between the C-13 2 and C-17 substituents. This conclusion was supported by the conformational analysis of the C-17 propionic ester side-chain. The populations of the side-chain rotamers were calculated from vicinal proton coupling constants, obtained from spectral simulations of the 17 1- and 17 2-CH 2 proton multiplets. For the R and S epimers of 13 2-MeO-Chl a, the most populated conformers were found to be: ap 1a (populations 0.7 ( R), 0.5 ( S)) and g + 1b (0.3 ( R), 0.5 ( S)) of the C 17 1 C 17 bond rotamers, and ap 2a (0.88 ( R), 0.82 ( S)) of the C 17 2 C 17 1 bond rotamers (Fig. 5). In comparison, for 13 2( R)-pheophytin a, the previously found most populated conformers are: ap 1a (0.7) and g + 1b (0.3) of the C 17 1 C 17 bond rotamers, and ap 2a (0.63) of the C 17 2 C 17 1 bond rotamers. The conformers of the ester fragment and the front part of the phytyl chain in the Chl derivatives are discussed.

Konformation und Bromierung von Bicyclo[3.3.1]nonan‐2,6‐dion sowie Dehydrobromierung der Bromketone. – Verbesserte Synthese von Bicyclo[3.3.1]nona‐3,7‐dien‐2,6‐dion

Conformation and Bromination of Bicyclo[3.3.1]nonane‐2,6‐dione and Dehydrobromination of the Bromo Ketones. – Improved Synthesis of Bicyclo[3.3.1]nona‐3,7‐diene‐2,6‐dioneBromination by copper(II) bromide of bicyclo[3.3.1]nonane‐2,6‐dione (1) affords the epimeric α‐bromo diketones exo‐and endo‐5 and, eventually, the α, α′‐dibromo diketones exo‐ and endo‐7 (3:7) in high yield. Dehydrobromination of the mixtures of bromo diketones by calcium carbonate in dimethylacetamide yields the unsaturated diketones 6 (30%) and 2 (72%), respectively. Bromination of 1 by molecular bromine is less selective and furnishes mixtures of brominated diketones consisting of exo‐ and endo‐7, 8 and the tetrabromo diketone 10. An excess of bromine yields pure 10. – The ethylene acetal 12 is brominated by pyridinium perbromide to produce the α,α′‐dibromo acetal 13 which is very reluctant towards 1,2‐dehydrobromination by potassium tert‐butoxide. Thus, with an excess of potassium tert‐butoxide in tetrahydrofuran, 1,2‐dehydrobromination is achieved only on one side to afford 14. In contrast, potassium tert‐butoxide in dimethyl sulphoxide induces a transannular dehydrobromination leading to the diacetal 15 of 3‐bromonoradamantane‐2,6‐dione. – The conformations of 1,10, and 13 in the solid state are determined by X‐ray diffraction analyses. From torsional angles, vicinal proton coupling constants are calculated with the aid of the Karplus equation and compared to those determined from solutions by high‐field NMR spectroscopy. The reasonable agreement provides the basis for the assessment of the configuration and conformation for exo‐ and endo‐7. magnified image

Solution structure of a conserved DNA sequence from the HIV-1 genome: restrained molecular dynamics simulation with distance and torsion angle restraints derived from two-dimensional NMR spectra.

The three-dimensional solution structure of a trisdecamer DNA duplex sequence, d(AGCTTGCCTTGAG).d(CTCAAGGCAAGCT), from a conserved region of HIV-1 genome's long terminal repeat, has been investigated using NMR spectroscopy and restrained molecular dynamics calculations. Interproton distances derived from two-dimensional nuclear Overhauser enhancement (2D NOE) experiments, using the iterative complete relaxation matrix algorithm MARDIGRAS, and torsion angles for sugar rings, estimated from stimulated fitting of double-quantum-filtered correlation (2QF-COSY) spectra, were obtained [Mujeeb, A., Kerwin, S. M., Egan, W. M., Kenyon, G. L., & James, T. L. (1992) Biochemistry 31, 9325-38]. These structural restraints have now been employed as the basis for structure refinement using restrained molecular dynamics (rMD) to search conformational space for structures consistent with the experimental restraints. Specifically, upper and lower bounds on the restraints were incorporated into the AMBER (version 4.0) total potential energy function of the system, the bounds being used to define the width of a flat-well penalty term in the AMBER force field. Confidence in the time-averaged structure obtained is engendered by convergence to essentially the same structure (root-mean-square deviation approximately 0.9 A) when two quite different DNA models, A-DNA and B-DNA (RMSD approximately 6.5 A), were employed as starting structures and when various initial trajectories were used for the rMD runs. The derived structure is further supported by the total energy calculated, the restraint violation energy, the restraint deviations, and the fit with experimental data. For the latter, the sixth-root residual index indicated a good fit of the determined structure with experimental 2D NOE spectral intensities (R1x < 0.07), and the RMS difference between vicinal proton coupling constants calculated for the derived structure and experimental coupling constants were also in reasonable agreement (JRMS = 0.9 Hz). While the structure of the trisdecamer is basically in the B-DNA family, some structural parameters manifest interesting local variations. The helix parameters indicate that, compared with classical B-DNA, the structure is longitudinally more compressed. Local structural variations at the two TG steps in particular together create bending into the major groove of the duplex. Comparison of the two-CTTG-tetrads in the duplex reveals that they have similar structures, with the TT moieties being almost identical; however, the -CTTG-pur sequence has a larger roll and slide for the -TG- step than for the -CTTG-pyr sequence, in accord with published X-ray crystallographic conclusions.

MM2 conformational analysis of diastereoisomers with phenyl groups on neighbouring carbon atoms and intramolecular hydrogen bonding

The conformations of a set of compounds containing phenyl groups on neighbouring carbon atoms and substituents with the potentiality for formation of an intramolecular hydrogen bond (diols, diamines and amino-alcohols) have been studied with the MM2 force field, enhanced with the addition of electrostatic corrections to the aromatic force field; as proposed by Allinger and Lii (dipole-dipole interactions), and the special MM2 hydrogen bonding parameters for the van der Waals function. The molecular mechanics results are in satisfactory agreement with experimental conformational data (mainly NMR and IR). An average deviation of 1.0 Hz was obtained between 20 observed vicinal proton coupling constants and those estimated with the Haasnoot-Altona equation. Previous indications regarding the electrostatic corrections for modelling phenyl-phenyl interactions and the parameters for the C sp 2 C sp 3 C sp 3 C sp 2 torsional potential are further supported. The molecular mechanics results for the low-energy conformations of six compounds have been supplemented with AM1, PM3 and MM-EHMO estimates of their conformational energies. The results are encouraging for attempting a complete SE-MO conformational analysis of such systems.

Metropolis Monte Carlo calculations of DNA structure using internal coordinates and NMR distance restraints: an alternative method for generating a high-resolution solution structure.

A new method, a restrained Monte Carlo (rMC) calculation, is demonstrated for generating high-resolution structures of DNA oligonucleotides in solution from interproton distance restraints and bounds derived from complete relaxation matrix analysis of two-dimensional nuclear Overhauser effect (NOE) spectral peak intensities. As in the case of restrained molecular dynamics (rMD) refinement of structures, the experimental distance restraints and bounds are incorporated as a pseudo-energy term (or penalty function) into the mathematical expression for the molecular energy. However, the use of generalized helical parameters, rather than Cartesian coordinates, to define DNA conformation increases efficiency by decreasing by an order of magnitude the number of parameters needed to describe a conformation and by simplifying the potential energy profile. The Metropolis Monte Carlo method is employed to simulate an annealing process. The rMC method was applied to experimental 2D NOE data from the octamer duplex d(GTATAATG).d(CATTATAC). Using starting structures from different locations in conformational space (e.g. A-DNA and B-DNA), the rMC calculations readily converged, with a root-mean-square deviation (RMSD) of < 0.3 A between structures generated using different protocols and starting structures. Theoretical 2D NOE peak intensities were calculated for the rMC-generated structures using the complete relaxation matrix program CORMA, enabling a comparison with experimental intensities via residual indices. Simulation of the vicinal proton coupling constants was carried out for the structures generated, enabling a comparison with the experimental deoxyribose ring coupling constants, which were not utilized in the structure determination in the case of the rMC simulations. Agreement with experimental 2D NOE and scalar coupling data was good in all cases. The rMC structures are quite similar to that refined by a traditional restrained MD approach (RMSD < 0.5 A) despite the different force fields used and despite the fact that MD refinement was conducted with additional restraints imposed on the endocyclic torsion angles of deoxyriboses. The computational time required for the rMC and rMD calculations is about the same. A comparison of structural parameters is made and some limitations of both methods are discussed with regard to the average nature of the experimental restraints used in the refinement.

Synthese und Struktur Phenyl‐substituierter Bicyclo[3.3.1]nonene

Synthesis and Structure of Phenyl‐Substituted Bicyclo[3.3.1]nonenesAddition of one mole of phenyllithium to bicyclo[3.3.1]nonane‐2,6‐dione (5) affords the hydroxy ketone 6 besides small amounts of the known diol 7. Dehydration of this mixture by sulfuric acid in acetic acid yields the unsaturated ketone 8 and the diene 1 which are separated by chromatography. Wolff‐Kishner reduction of 8 furnished the hydrocarbon 2. In the same way, the known ketones exo‐ and endo‐10 are converted into 4. The preferential formation of the less stable endo‐10 is interpreted in terms of the relative stability of the conformations required in the intramolecular aldol reaction of diketone 9. The conformations of 4, 8, exo‐ and endo‐10 are determined by X‐ray diffraction analyses. Vicinal proton coupling constants are calculated from torsional angles and compared to those determined in solutions by high‐field NMR spectroscopy.

2,6‐Dicyan‐4,8‐diphenylbarbaralan

2,6‐Dicyano‐4,8‐diphenylbarbaralane[1]Conjugate addition of the phenylcuprate reagent, obtained from phenyllithium, copper(I) cyanide, and boron trifluoride–diethylether, to the bicyclo[3.3.1]nonadienedione 3 affords the diphenylbicyclo[3.3.1]nonanedione 4 in high yield. Catalyzed by the potassium cyanide/18‐crown‐6 complex, addition of trimethylsilyl cyanide produces a mixture of the diastereomeric bis[O‐(trimethylsilyl)cyanohydrins] exo,exo‐, exo,endo‐ and endo,endo‐5. The hydrogen fluoride – pyridine complex in phosphorus oxychloride as solvent and, subsequently, an excess of pyridine convert the diastereomers 5 into the unsaturated γ,γ′1‐diphenyldinirile 6. This is brominated by N1‐bromosuccinimide to yield the γ,γ′1‐dibromodinitriles exo‐ and endo‐ 7 (6:1). The predominant diastereomer exo‐7 is debrominated by the zinc‐copper couple to afford the orange‐red title compound 2 in 78% yield. More conveniently, the unsaturated dinitrile 6 is converted to 2 in a single step by treatment with hexachloroethane and concentrated aqueous sodium hydroxide in the presence of tetrabutylammonium hydroxide as phase‐transfer catalyst. Surprisingly, low yields of 2 are also obtained when the bis[O‐(trimethylsilyl)cyanohydrins] 5 or the unsaturated dinitrile 6 are treated with phosphorus oxychloride in boiling pyridine. – The structures of the new compounds are based on spectroscopic evidence and X‐ray diffraction analyses of 2, 4, and endo,endo‐5. The conformations of 4 and endo,endo‐5 in solution are inferred on the basis of vicinal proton coupling constants and a comparison with coupling constants calculated with the aid of the Karplus equation and torsional angles obtained by X‐ray diffraction analyses. – While the barbaralane 2 exists as a pair of very rapidly rearranging degenerate valence tautomers in solution, the degeneracy is lifted in the crystal lattice. As a result, the crystal consists of two rapidly rearranging but non‐equivalent valence tautomers in a ratio of 9:1 as estimated from the apparent atomic distance C2–C8 of 2 and the C2–C8 bond length of non‐rearranging barbaralanes. – The colour of 2 in the crystal and in solution results from a maximum at 436 nm which increases on heating of the solution to 450 K. Cooling to 77 K results in reversible fading and the disappearance of the maximum. Thus, 2 is a barbaralane like 1 which exhibits colour though it is lacking a classical long‐wavelength chromophore.

2,4,6,8‐Tetraphenylbarbaralan – ein orangeroter, thermochromer Kohlenwasserstoff ohne Chromophor[1,2]

2,4,6,8‐Tetraphenylbarbaralane – an Orange‐Red, Thermochromic Hydrocarbon Devoid of a Chromophore[1,2]The diphenylbicyclo[3.3.1]nonanedione 6 adds phenylcerium‐(III) dichloride to afford a high yield of the triphenyl‐2‐oxa‐twistanol 8. In contrast, phenyllithium yields a mixture of tri‐phenylhydroxyketone exo‐7, tetraphenylbicyclo[3.3.1]nona‐nediol 9, and 8. The latter is dehydrated by sulfuric acid in acetic acid to produce the triphenylbicyclo[3.3.1]nonenone 10 in almost quantitative yield. Addition of phenylcerium(III) dichloride to 10 affords a 3:2 mixture of the tetraphenylbicy‐clo[3.3.1]nonenols exo‐ and endo‐11 which may be separated by chromatography. Dehydration of the mixture yields quantitatively the tetraphenyldiene 12. On treatment with an excess of butylpotassium in pentane, 12 is converted to the deep violet, crystalline dipotassium salt 17 which may be purified by reprecipitation from its tetrahydrofuran solution with pentane. When the solution of 17 in tetrahydrofuran is slowly added to an excess of 1,2‐dibromoethane at –60°C, the dianion is immediately oxidized to produce the tetraphenylbarbara‐lane 4 which is isolated in 30% yield as orange‐red crystals after chromatography. – The structures of the new compounds are based on spectroscopic evidence and X‐ray diffraction analyses of 4, 8, exo‐11, and 12. The conformations in solution are inferred on the basis of vicinal proton coupling constants and a comparison with coupling constants calculated with the aid of the Karplus equation from torsional angles obtained by X‐ray diffraction analyses. The conformation of exo‐11 in solution closely resembles that present in the crystal. – While the barbaralane 4 exists as a pair of very rapidly rearranging degenerate valence tautomers in solution, the degeneracy is lifted in the crystal lattice. As a result, the crystal consists of two rapidly rearranging but non‐equivalent valence tautomers in a ratio of 9:1 as estimated from the apparent atomic distance C2–C8 of 4 and the C2–C8 bond length of the model barbaralane 18. – The orange‐red colour of 4 in the crystal and in solution results from a pronounced shoulder in the UV/Vis spectrum at 430 nm, the intensity of which strongly depends on the temperature. Thus, 4 is the first barbaralane which exhibits colour though it is lacking a classical long‐wavelength chromophore.

Proton NMR studies of syn‐ and anti‐tricyclo [5.1.0.03,5]octanes and their dichloromethyl derivatives

AbstractThe carbon and proton NMR spectra of syn‐ and anti‐tricyclo[5.1.0.03,5]octanes and their dichlorocarbene CH bond insertion products were determined by conventional 1D and 2D methods. Partially relaxed proton spectroscopy was carried out in some instances to aid in the separation of badly overlapped multiplets. A detailed analysis of the spectra was carried out with the aid of a new equation relating both the torsion angles and the CCH angles to the vicinal proton coupling constants. These values were combined with molecular modeling to draw conclusions regarding the conformational preferences for these molecules.

The solution structure of a cyclic endothelin antagonist, BQ-123, based on 1H1H and 13H1H three bond oupling constants

A cyclic pentapeptide endothelin antagonist, cyclo(dTrp-dAsp-Pro-dVal-Leu), recently reported (K. Ishikawa et al., 13th Am. Pept. Symp., Cambridge MA, 1991) has been studied by NMR spectroscopy and molecular modeling. A stable structure has been determined without the use of nuclear Overhauser effects and is based primarily on homonuclear and heteronuclear three bond coupling constants. The 13C-edited TOCSY experiment is demonstrated at natural abundance and ∼30 mM peptide concentrations. Three bond 13C1H coupling constants obtained by this method are shown to reduce the ambiguity in φ angle determination which exists when only interproton coupling constants are used. Three out of four φ angles were determined uniquely by this method and the fourth was reduced to two possible values. The proline φ angle was determined to be −78° based on the 3JHzHα and 3JHzHβ coupling constants. Comparison of amide proton temperature dependence, chemical shifts and vicinal proton coupling constants in a 20% acetonitrile/80% water solvent mixture and in (CD3)2SO indicates that the structure is similar in both solvents.

The structure of gramicidin A in dimethylsulfoxide/acetone

It has been demonstrated by two-dimensional NMR cross-relaxation spectroscopy that gramicidin A exists in dimethylsulfoxide/acetone solution in random coil form. This contradicts earlier conclusions by Hawkes et al. [Hawkes, G. E., Lian, L. Y., Randall, E. W., Sales, K. D. & Curzon, E. H. (1987) Eur. J. Biochem. 166, 437-445] that were based on the interpretation of vicinal proton coupling constants.

Towards understanding 13C-N.M.R. chemical shifts of carbohydrates in the solid state. The spectra of d-mannitol polymorphs and of dl-mannitol

The cross-polarization, magic-angle spinning 13C-n.m.r. spectra of solid dl-mannitol and of three polymorphs of d-mannitol have been recorded and assigned. Recrystallization of d-mannitol from several solvents under different conditions gave either one of the three known pure polymorphs or mixtures containing two or more of these polymorphs. The 13C-chemical shifts from the four species in the solid state were all less than the solution values. Conformations in deuterium oxide and di( 2H 3)methyl sulfoxide solutions were obtained from the vicinal proton coupling constants that resulted from analysis of the 1H-n.m.r. spectra. The major cause of the differences between solid-state and solution chemical shifts is that there are significant populations of one of the gauche rotamers and the anti O-C-C-C rotamer about the terminal C-C bonds in solution. Other effects on solid-state 13C-chemical shifts are discussed.