Ab initio study of (13)C(alpha) chemical shift anisotropy tensors in peptides

This study reports magnitudes and the orientation of the (13)C(alpha) chemical shift anisotropy (CSA) tensors of peptides obtained using quantum chemical calculations. The dependency of the CSA tensor parameters on the energy optimization of hydrogen atom positions and hydrogen bonding effects and the use of zwitterionic peptides in the calculations are examined. Our results indicate that the energy optimization of the hydrogen atom positions in crystal structures is necessary to obtain accurate CSA tensors. The inclusion of intermolecular effects such as hydrogen bonding in the calculations provided better agreement between the calculated and experimental values; however, the use of zwitterionic peptides in calculations, with or without the inclusion of hydrogen bonding, did not improve the results. In addition, our calculated values are in good agreement with tensor values obtained from solid-state NMR experiments on glycine-containing tripeptides. In the case of peptides containing an aromatic residue, calculations on an isolated peptide yielded more accurate isotropic shift values than the calculations on extended structures of the peptide. The calculations also suggested that the presence of an aromatic ring in the extended crystal peptide structure influences the magnitude of the delta(22) which the present level of ab initio calculations are unable to reproduce.     

Determination of 13C chemical shift anisotropy tensors and molecular order of 4-hexyloxybenzoic acid

4-Alkoxy benzoic acids belong to an important class of thermotropic liquid crystals that are structurally simple and often used as starting materials for many novel mesogens. 4-Hexyloxybenzoic acid (HBA) is a homologue of the same series and exhibits an enantiotropic nematic phase. As this molecule could serve as an ideal model compound, high resolution (13)C NMR studies of HBA in solution, solid, and liquid crystalline phases have been undertaken. In the solid state, two-dimensional separation of undistorted powder patterns by effortless recoupling (2D SUPER) experiments have been carried out to estimate the magnitude of the components of the chemical shift anisotropy (CSA) tensor of all the aromatic carbons. These values have been used subsequently for calculating the orientational order parameters in the liquid crystalline phase. The CSA values computed by density functional theory (DFT) calculations showed good agreement with the 2D SUPER values. Additionally, (13)C-(1)H dipolar couplings in the nematic phase have been determined by separated local field (SLF) spectroscopy at various temperatures and were used for computing the order parameters, which compared well with those calculated by using the chemical shifts. It is anticipated that the CSA values determined for HBA would be useful for the assignment of carbon chemical shifts and for the study of order and dynamics of structurally similar novel mesogens in their nematic phases.     

Determination of chemical shift anisotropy tensors of carbonyl nuclei in proteins through cross-correlated relaxation in NMR.

The principal components and orientations of the chemical shift anisotropy (CSA) tensors of nearly all 13C carbonyl nuclei in a small protein have been determined in isotropic solution by a combination of three complementary cross-correlation measurements.     

萜类化合物13C NMR化学位移的定量构谱相关研究

利用原子电性作用矢量(Atomic electro-negativity interaction vector,AEIV)和原子杂化状态指数(Atomic hybridization state index,AHSI)对萜类化合物中的C原子进行结构表征并与其核磁共振碳谱(13C NMR)建立了优良的定量构谱相关(QSSR)模型.其中29个单萜类化合物中的290个C原子建模的计算值经留一法(Leave-one-out,LOO)交互校验(Cross-validation,CV)预测值的复相关系数(R)分别为0.9900和0.9867,进一步使用倍半萜、二萜、三萜化合物分子中65个C原子的13C NMR化学位移值来检测该模型的稳定性,模型预测值和观测值间复相关系数(R)为0.9777,取得了令人满意的结果.     

13C and (15)N chemical shift tensors in adenosine,guanosine dihydrate, 2'-deoxythymidine,and cytidine

The (13)C and (15)N chemical shift tensor principal values for adenosine, guanosine dihydrate, 2'-deoxythymidine, and cytidine are measured on natural abundance samples. Additionally, the (13)C and (15)N chemical shielding tensor principal values in these four nucleosides are calculated utilizing various theoretical approaches. Embedded ion method (EIM) calculations improve significantly the precision with which the experimental principal values are reproduced over calculations on the corresponding isolated molecules with proton-optimized geometries. The (13)C and (15)N chemical shift tensor orientations are reliably assigned in the molecular frames of the nucleosides based upon chemical shielding tensor calculations employing the EIM. The differences between principal values obtained in EIM calculations and in calculations on isolated molecules with proton positions optimized inside a point charge array are used to estimate the contributions to chemical shielding arising from intermolecular interactions. Moreover, the (13)C and (15)N chemical shift tensor orientations and principal values correlate with the molecular structure and the crystallographic environment for the nucleosides and agree with data obtained previously for related compounds. The effects of variations in certain EIM parameters on the accuracy of the shielding tensor calculations are investigated.     

Carbon-13 chemical shift anisotropy in DNA bases from field dependence of solution NMR relaxation rates

Knowledge of (13)C chemical shift anisotropy (CSA) in nucleotide bases is important for the interpretation of solution-state NMR relaxation data in terms of local dynamic properties of DNA and RNA. Accurate knowledge of the CSA becomes particularly important at high magnetic fields, prerequisite for adequate spectral resolution in larger oligonucleotides. Measurement of (13)C relaxation rates of protonated carbons in the bases of the so-called Dickerson dodecamer, d(CGCGAATTCGCG)(2), at 500 and 800 MHz (1)H frequency, together with the previously characterized structure and diffusion tensor yields CSA values for C5 in C, C6 in C and T, C8 in A and G, and C2 in A that are closest to values previously reported on the basis of solid-state FIREMAT NMR measurements, and mostly larger than values obtained by in vacuo DFT calculations. Owing to the noncollinearity of dipolar and CSA interactions, interpretation of the NMR relaxation rates is particularly sensitive to anisotropy of rotational diffusion, and use of isotropic diffusion models can result in considerable errors.     

Revisiting the calculation of (13)C chemical shift tensors in cadmium acetate dihydrate with EIM and EIM/cluster methods

The chemical shift tensors of the acetate anions in cadmium acetate dihydrate are calculated using a cluster approach, the embedded ion method (EIM), and a combination of the two in the EIM/cluster method. The results of these calculations are compared with those completed on the isolated acetate anion and show the need for the inclusion of intermolecular interactions. The RMS difference between experiment and theory improves from over 60 ppm when the calculation is completed on an isolated anion, to below 10 ppm when interactions to nearby atoms are included. The best cluster model includes three cadmium acetate dihydrate and gives an RMS result of 4.4 ppm. The EIM method, which uses point charges to account for the intermolecular effects, achieves an RMS of 7.7 ppm on individual anions alone. A combination of the two, the EIM/cluster method, shows that the only necessary atom to explicitly add is the nearest cadmium; this addition results in an RMS of 4.1 ppm. These results are also discussed in terms of the computational cost of the different calculations.     

Site-specific 13C chemical shift anisotropy measurements in a uniformly 15N,13C-labeled microcrystalline protein by 3D magic-angle spinning NMR spectroscopy

In this Communication, we introduce a 3D magic-angle spinning recoupling experiment that correlates chemical shift anisotropy (CSA) powder line shapes with two dimensions of site-resolved isotropic chemical shifts. The principal tensor elements from 127 ROCSA line shapes are reported, constraining 102 unique backbone and side-chain 13C sites in a microcrystalline protein (the 56 residue beta1 immunoglobulin binding domain of protein G). The tensor elements, determined by fitting to numerical simulations, agree well with quantum chemical predictions. The experiments, therefore, validate calculations of CSAs in a protein of known structure. The data will be useful for the development of side-chain CSA quantum calculations and will aid in the design and interpretation of solution NMR experiments that utilize CSA-dipole cross-correlation to constrain torsion angles or to enhance resolution and sensitivity (such as in TROSY). Furthermore, the methodology described here will enable databases of CSA data to be generated with higher efficiency, for purposes of direct protein structure refinement.     

Acetylenic carbon-13 chemical shift tensors for diphenylacetylene and (eta2-Diphenylacetylene)Pt(PPh3)2: a solid-state NMR and theoretical study

The structure of (eta2-diphenylacetylene)Pt(PPh3) (2), as well as those of its dichloromethane and benzene solvates, is determined via X-ray crystallography. An investigation of the chemical shift (CS) tensors of the 13C-labeled carbons in Ph13C13CPh and (eta2-Ph13C13CPh)Pt(PPh3)2.(C6H6) is carried out via analysis of 13C NMR spectra from stationary solid samples. The principal components of the CS tensors as well as their orientations with respect to the 13C,13C internuclear vector are determined. DFT calculations of these CS tensors are in close agreement with the experimental values. For diphenylacetylene (tolane), the orientations and principal-component magnitudes of the alkynyl carbon CS tensors are comparable to those for other alkynyl carbons, although the CS tensor is not axially symmetric in this case. Coordination to platinum causes a change in the CS tensor orientation and a net increase in the isotropic chemical shift, resulting from a significant increase in two principal components (delta11 and delta33) while the third (delta22) decreases only slightly. The measured carbon CS tensors in the platinum complex bear a striking similarity to those of the alkenyl carbons in trans-Ph(H)C=C(H)Ph, and a short theoretical discussion of these observations is presented.     

Solid-state 13C NMR studies on organic-inorganic hybrid zeolites

A novel type of organic-inorganic hybrid zeolite with organic lattice (ZOL) is studied in detail by solid-state (13)C magic angle spinning nuclear magnetic resonance (MAS NMR). The (13)C MAS NMR measurements employing several pulse sequences quantitatively demonstrate that methylene groups are really incorporated in the framework, although they are partially cleaved into methyl groups. The organic species in ZOL materials are open for adsorbates, which is evidenced by the (13)C MAS NMR measurements for an n-hexane-adsorbing ZOL material. This finding strongly suggests that organic moieties are incorporated as a zeolite framework, indicating that ZOL is not a physical mixture of a carbon-containing amorphous aggregate and a conventional zeolite but a true organic-inorganic hybrid zeolite.     

Experimental and theoretical investigation of the 13C and 15N chemical shift tensors in melanostatin-exploring the chemical shift tensor as a structural probe

The determination of backbone conformations in powdered peptides using 13C and 15N shift tensor information is explored. The 13C and 15N principal shift values in natural abundance 13C and 15N melanostatin (L-Pro-L-Leu-Gly amide) are measured using the FIREMAT technique. Furthermore, the orientation of the C-N bond in the 13C shift principal axis system for the backbone carbons is obtained from the presence of the 13C-14N dipolar coupling. The Ramachandran angles for the title compound are obtained from solid-state NMR data by comparing the experimentally determined shift tensor information to systematic theoretical shielding calculations on N-formyl-L-amino acid-amide models. The effects of geometry optimization and neglect of intermolecular interactions on the theoretical shielding values in the model compounds are investigated. The sets of NMR derived Ramachandran angles are assembled in a set of test structures that are compared to the available single-crystal X-ray structure. Shift tensor calculations on the test structures and the X-ray structure are used to further assess the importance of intermolecular interactions when the shift tensor is used as a structural probe in powdered peptides.     

Validation of structural proposals by substructure analysis and 13C NMR chemical shift prediction

The 2D NMR-guided computer program COCON can be extremely valuable for the constitutional analysis of unknown compounds, if its results are evaluated by neural network-assisted 13C NMR chemical shift and substructure analyses. As instructive examples, data sets of four differently complex marine natural products were thoroughly investigated. As a significant step towards a true automated structure elucidation, it is shown that the primary COCON output can be safely diminished to less than 1% of its original size without losing the correct structural proposal.     

Carbon-13 chemical shift tensors of disaccharides: measurement, computation and assignment

A recently developed chemical shift anisotropy amplification solid-state nuclear magnetic resonance (NMR) experiment is applied to the measurement of the chemical shift tensors in three disaccharides: sucrose, maltose, and trehalose. The measured tensor principal values are compared with those calculated from first principles using density functional theory within the planewave-pseudopotential approach. In addition, a method of assigning poorly dispersed NMR spectra, based on comparing experimental and calculated shift anisotropies as well as isotropic shifts, is demonstrated.     

(39)K NMR of solid potassium salts at 21 T: effect of quadrupolar and chemical shift tensors

39K Solid State NMR spectra (static and magic angle spinning (MAS)) on a set of potassium salts measured at 21.14 T show that the chemical shift range for K(+) ions in diamagnetic salts is well in excess of 100 ppm contrary to previous assumptions that it was quite small. Inequivalent potassium sites in crystals can be resolved through differences in chemical shifts, with chemically similar sites showing differences of over 10 ppm. The quadrupolar coupling constants obtained from MAS and solid echo experiments on powders cover the range from zero for potassium in cubic environments in halides to over 3 MHz for the highly asymmetric sites in K2CO3. Although the quadrupolar effects generally dominate the 39K spectra, in several instances, we have observed subtle but significant contributions of chemical shift anisotropy with values up to 45 ppm, a first such observation. Careful analysis of static and MAS spectra allows the observation of the various chemical shift and quadrupole coupling tensor components as well as their relative orientations, thereby demonstrating that high-field 39K NMR spectroscopy in the solid state has a substantial sensitivity to the local environment with parameters that will be of considerable value in materials characterization and electronic structure studies.     

13C NMR chemical shifts of carbonyl groups in substituted benzaldehydes and acetophenones: substituent chemical shift increments

13C NMR Substituent chemical shift (SCS) increments have been determined for the carbonyl carbon of a variety of substituted benzaldehydes and acetophenones. The 13C NMR chemical shift of the carbonyl carbon can be predicted for many di- and trisubstituted benzaldehydes and acetophenones through simple additivity of the SCS increments. The magnitude and sign of the SCS increments have been explored using Hartree-Fock 6-31G* calculations to determine the natural atomic charges of the carbonyl carbon. When a substituent capable of intermolecular hydrogen bonding is present, deviations from additivity on the order of 2 ppm are observed in dilution experiments; deviations of up to 6 ppm can result from intramolecular hydrogen bonding.     

Measurement of ribose carbon chemical shift tensors for A-form RNA by liquid crystal NMR spectroscopy

Incomplete motional averaging of chemical shift anisotropy upon weak alignment of nucleic acids and proteins in a magnetic field results in small changes in chemical shift. Knowledge of nucleus-specific chemical shift (CS) tensor magnitudes and orientations is necessary to take full advantage of these measurements in biomolecular structure determination. We report the determination by liquid crystal NMR of the CS tensors for all ribose carbons in A-form helical RNA, using a series of novel 3D NMR pulse sequences for accurate and resolved measurement of the ribose (13)C chemical shifts. The orientation of the riboses relative to the rhombic alignment tensor of the molecule studied, a stem-loop sequence corresponding to helix-35 of 23S rRNA, is known from an extensive set of residual dipolar couplings (RDC), previously used to refine its structure. Singular-value-decomposition fits of the chemical shift changes to this structure, or alternatively to a database of helical RNA X-ray structures, provide the CS tensor for each type of carbon. Quantum chemical calculations complement the experimental results and confirm that the most shielded tensor component lies approximately along the local carbon-oxygen bond axis in all cases and that shielding anisotropy for C3' and C4' is much larger than for C1' and C2', with C5' being intermediate.     

Automatic assignment of 13C NMR spectra based on the chemical shift/charge density relationship

An approach for the automatic assignment of ¹³C spectra, based on the chemical shift/charge density relationship, is suggested. All permutations of spectral signals are computer-generated, and for every permutation a least squares adjustment is carried out. The permutation presenting the highest correlation coefficient, or the lowest Hamilton's agreement factor, is considered to be correct. The application is exemplified by the ¹³C chemical shifts of a series of aromatic compounds. It is shown that more reliable assignment is achieved if the considered permutations are restricted by taking intoaccount the signal multiplicity.     

Ring current effects in crystals. Evidence from 13C chemical shift tensors for intermolecular shielding in 4,7-di-t-butylacenaphthene versus 4,7-di-t-butylacenaphthylene

13C chemical shift tensor data from 2D FIREMAT spectra are reported for 4,7-di-t-butylacenaphthene and 4,7-di-t-butylacenaphthylene. In addition, calculations of the chemical shielding tensors were completed at the B3LYP/6-311G** level of theory. While the experimental tensor data on 4,7-di-t-butylacenaphthylene are in agreement with theory and with previous data on polycyclic aromatic hydrocarbons, the experimental and theoretical data on 4,7-di-t-butylacenaphthene lack agreement. Instead, larger than usual differences are observed between the experimental chemical shift components and the chemical shielding tensor components calculated on a single molecule of 4,7-di-t-butylacenaphthene, with a root mean square (rms) error of +/-7.0 ppm. The greatest deviation is concentrated in the component perpendicular to the aromatic plane, with the largest value being a 23 ppm difference between experiment and theory for the 13CH2 carbon delta11 component. These differences are attributed to an intermolecular chemical shift that arises from the graphitelike, stacked arrangement of molecules found in the crystal structure of 4,7-di-t-butylacenaphthene. This conclusion is supported by a calculation on a trimer of molecules, which improves the agreement between experiment and theory for this component by 14 ppm and reduces the overall rms error between experiment and theory to 4.0 ppm. This intermolecular effect may be modeled with the use of nuclei independent chemical shieldings (NICS) calculations and is also observed in the isotropic 1H chemical shift of the CH2 protons as a 4.2 ppm difference between the solution value and the solid-state chemical shift measured via a 13C-1H heteronuclear correlation experiment.     

Solid-state 93Nb and 13C NMR investigations of half-sandwich niobium(I) and niobium(V) cyclopentadienyl complexes

Solid-state 93Nb and 13C NMR experiments, in combination with theoretical calculations of NMR tensors, and single-crystal and powder X-ray diffraction experiments, are applied for the comprehensive characterization of structure and dynamics in a series of organometallic niobium complexes. Half-sandwich niobium metallocenes of the forms Cp'Nb(I)(CO)4 and CpNb(V)Cl4 are investigated, where Cp = C5H5- and Cp' = C5H4R- with R = COMe, CO2Me, CO2Et, and COCH2Ph. Anisotropic quadrupolar and chemical shielding (CS) parameters are extracted from 93Nb MAS and static NMR spectra for seven different complexes. It is demonstrated that 93Nb NMR parameters are sensitive to changes in temperature and Cp' ring substitution in the Cp'Nb(I)(CO)4 complexes. There are dramatic differences in the 93Nb quadrupolar coupling constants (C(Q)) between the Nb(I) and Nb(V) complexes, with C(Q) between 1.0 and 12.0 MHz for Cp'Nb(CO)4 and C(Q) = 54.5 MHz for CpNbCl4. The quadrupolar Carr-Purcell Meiboom-Gill (QCPMG) pulse sequence is applied to rapidly acquire, in a piecewise fashion, a high signal-to-noise ultra-wide-line 93Nb NMR spectrum of CpNbCl4, which has a breadth of ca. 400 kHz. Solid-state 93Nb and 13C NMR spectra and powder XRD data are used to identify a new metallocene adduct coordinated at the axial position of the metal site by a THF molecule: CpNb(V)Cl4.THF. 13C MAS and CP/MAS NMR experiments are used to assess the purity of samples, as well as for measuring carbon CS tensors and the rare instance of one-bond 93Nb, 13C J-coupling, 1J(93Nb,13C). Theoretically calculated CS and electric field gradient (EFG) tensors are utilized to determine relationships between tensor orientations, the principal components, and molecular structures.