Calcium-43 chemical shift tensors as probes of calcium binding environments. Insight into the structure of the vaterite CaCO3 polymorph by 43Ca solid-state NMR spectroscopy

Natural-abundance (43)Ca solid-state NMR spectroscopy at 21.1 T and gauge-including projector-augmented-wave (GIPAW) DFT calculations are developed as tools to provide insight into calcium binding environments, with special emphasis on the calcium chemical shift (CS) tensor. The first complete analysis of a (43)Ca solid-state NMR spectrum, including the relative orientation of the CS and electric field gradient (EFG) tensors, is reported for calcite. GIPAW calculations of the (43)Ca CS and EFG tensors for a series of small molecules are shown to reproduce experimental trends; for example, the trend in available solid-state chemical shifts is reproduced with a correlation coefficient of 0.983. The results strongly suggest the utility of the calcium CS tensor as a novel probe of calcium binding environments in a range of calcium-containing materials. For example, for three polymorphs of CaCO3 the CS tensor span ranges from 8 to 70 ppm and the symmetry around calcium is manifested differently in the CS tensor as compared with the EFG tensor. The advantages of characterizing the CS tensor are particularly evident in very high magnetic fields where the effect of calcium CS anisotropy is augmented in hertz while the effect of second-order quadrupolar broadening is often obscured for (43)Ca because of its small quadrupole moment. Finally, as an application of the combined experimental-theoretical approach, the solid-state structure of the vaterite polymorph of calcium carbonate is probed and we conclude that the hexagonal P6(3)/mmc space group provides a better representation of the structure than does the orthorhombic Pbnm space group, thereby demonstrating the utility of (43)Ca solid-state NMR as a complementary tool to X-ray crystallographic methods.     

An NMR crystallography investigation of furosemide

This paper presents an NMR crystallography study of three polymorphs of furosemide. Experimental magic-angle spinning (MAS) solid-state NMR spectra are reported for form I of furosemide, and these are assigned using density-functional theory (DFT)-based gauge-including projector augmented wave (GIPAW) calculations. Focusing on the three known polymorphs, we examine the changes to the NMR parameters due to crystal packing effects. We use a recently developed formalism to visualise which regions are responsible for the chemical shielding of particular sites and hence understand the variation in NMR parameters between the three polymorphs.     

Scaling factors for carbon NMR chemical shifts obtained from DFT B3LYP calculations

A linear scaling of the calculated chemical shifts is used in order to improve the accuracy of the DFT predicted ¹³C NMR chemical shifts. The widely applied method of GIAO B3LYP/6-311+G(2d,p) using the B3LYP/6-31G(d) optimized geometries is chosen, which allows cost-effective calculations of the ¹³C chemical shifts in the molecular systems with 100 and more atoms. A set of 27 ¹³C NMR chemical shifts determined experimentally for 22 simple molecules with various functional groups is used in order to determine scaling factors for reproducing experimentally measured values of ¹³C chemical shifts. The results show that the use of a simple relationship (δ_scalc = 0.95 δ_calc + 0.30, where δ_calc and δ_scalc are the calculated and the linearly scaled values of the ¹³C chemical shifts, respectively) allows to achieve a three-fold improvement in mean absolute deviations for 27 chemical shifts considered. To test the universal applicability of the scaling factors derived, we have used complex organic molecules such as taxol and a steroid to demonstrate the significantly improved accuracy of the DFT predicted chemical shifts. This approach also outperforms the recently recommended usage of the Hartree-Fock optimized geometries for the GIAO B3LYP/6-311+G(2d,p) calculations of the ¹³C chemical shifts.     

Theoretical and experimental NMR study of protopine hydrochloride isomers

The 1H and 13C NMR chemical shifts of cis- and trans-protopinium salts were measured and calculated. The calculations of the chemical shifts consisted of conformational analysis, geometry optimization (RHF/6-31G** method) and shielding constants calculations (B3LYP/6-31G** method). Based on the results of the quantum chemical calculations, two sets of experimental chemical shifts were assigned to the particular isomers. According to the experimental results, the trans-isomer is more stable and its population is approximately 68%.     

Spectroscopic, electronic structure and natural bond orbital analysis of o-fluoronitrobenzene and p-fluoronitrobenzene: a comparative study

Experimental FTIR, FT-Raman and FT-NMR spectroscopic studies of o-fluoronitrobenzene and p-fluoronitrobenzene have been carried out. A detailed quantum chemical calculations have been performed using DFT/B3LYP method with 6-311++G** and 6-31G** basis sets. Complete vibrational analyses of the compounds were performed. The temperature dependence of thermodynamic properties has been analysed. The atomic charges, electronic exchange interaction and charge delocalisation of the molecule have been performed by natural bond orbital (NBO) analysis. Molecular electrostatic surface potential (MESP), total electron density distribution and frontier molecular orbitals (FMOs) are constructed at B3LYP/6-311++G** level to understand the electronic properties. The charge density distribution and site of chemical reactivity of the molecules have been obtained by mapping electron density isosurface with electrostatic potential surfaces (ESP). The electronic properties, HOMO and LUMO energies were measured by time-dependent TD-DFT approach. (1)H and (13)C NMR spectra were recorded and (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were calculated. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecules in chloroform solvent and in gas phase were calculated by using the Gauge-Independent Atomic Orbital (GIAO) method and are found to be in good agreement with experimental values. The theoretical parameters obtained at B3LYP levels have been compared with the experimental values.     

Solvation and crystal effects in bilirubin studied by NMR spectroscopy and density functional theory

The open-chain tetrapyrrole compound bilirubin was investigated in chloroform and dimethyl sulfoxide solutions by liquid-state NMR and as solid by (1)H, (13)C, and (15)N magic-angle spinning (MAS) solid-state NMR spectroscopy. Density functional theory (DFT) calculations were performed to interpret the data, using the B3LYP exchange-correlation functional to optimize geometries and to compute NMR chemical shieldings by the gauge-including atomic orbital method. The dependence of geometries and chemical shieldings on the size of the basis sets was investigated for the reference molecules tetramethylsilane, NH(3), and H(2)O, and for bilirubin as a monomer and in clusters consisting of up to six molecules. In order to assess the intrinsic errors of the B3LYP approximation in calculating NMR shieldings, complete basis set estimates were obtained for the nuclear shielding values of the reference molecules. The experimental liquid-state NMR data of bilirubin are well reproduced by a monomeric bilirubin molecule using the 6-311+G(2d,p) basis set for geometry optimization and for calculating chemical shieldings. To simulate the bilirubin crystal, a hexameric model was required. It was constructed from geometry-optimized monomers using information from the X-ray structure of bilirubin to fix the monomeric entities in space and refined by partial optimization. Combining experimental (1)H-(13)C and (1)H-(15)N NMR correlation spectroscopy and density functional theory, almost complete sets of (1)H, (13)C, and (15)N chemical shift assignments were obtained for both liquid and solid states. It is shown that monomeric bilirubin in chloroform solution is formed by 3-vinyl anti conformers, while bilirubin crystals are formed by 3-vinyl syn conformers. This conformational change leads to characteristic differences between the liquid- and solid-state NMR resonances.     

Structural and solvent effects on the 13C and 15N NMR chemical shifts of indoloquinoline alkaloids: experimental and DFT study

Indoloquinoline alkaloids represent an important class of antimalarial, antibacterial and antiviral compounds. They have been shown to bind to DNA via intercalation preferentially at GC-rich sequences containing nonalternating CC sites. The stability of complexes formed with biological macromolecules depends on noncovalent binding. In the present study, the ability of indoloquinolines to form intermolecular interactions with solvents was investigated by using NMR spectroscopy and density functional theory (DFT) (B3LYP/6-31G**) calculations. NMR data measured for indoloquinoline bases and the corresponding hydrochlorides are discussed in relation to the structure. DFT calculations of shielding constants in vacuo and in solution allowed the investigation of the influence of the environment on the NMR parameters. Calculations incorporating solvent effects indicated significant changes in the anisotropy of the electron distribution, reflected in the span of the chemical shielding tensor (Omega = sigma11 - sigma33). Solvent effects on the span of the 13C and 15N shielding tensor depended on the type of atom and the data indicated a significant influence of solute-solvent interactions.     

Density functional theory study of 13C NMR chemical shift of chlorinated compounds

The use of the standard density functional theory (DFT) leads to an overestimation of the paramagnetic contribution and underestimation of the shielding constants, especially for chlorinated carbon nuclei. For that reason, the predictions of chlorinated compounds often yield too high chemical shift values. In this study, the WC04 functional is shown to be capable of reducing the overestimation of the chemical shift of Cl‐bonded carbons in standard DFT functionals and to show a good performance in the prediction of ¹³C NMR chemical shifts of chlorinated organic compounds. The capability is attributed to the minimization of the contributions that intensively increase the chemical shift in the WC04. Extensive computations and analyses were performed to search for the optimal procedure for WC04. The B3LYP and mPW1PW91 standard functionals were also used to evaluate the performance. Through detailed comparisons between the basis set effects and the solvent effects on the results, the gas‐phase GIAO/WC04/6‐311+G(2d,p)//B3LYP/6‐31+G(d,p) was found to be specifically suitable for the prediction of ¹³C NMR chemical shifts of chlorides in both chlorinated and non‐chlorinated carbons. Further tests with eight molecules in the probe set sufficiently confirmed that WC04 was undoubtedly effective for accurately predicting ¹³C NMR chemical shifts of chlorinated organic compounds. Copyright © 2012 John Wiley & Sons, Ltd.     

NMR spectra, GIAO and charge density calculations of five-membered aromatic heterocycles

The B3LYP/6-31+G(d) molecular geometry optimized structures of 17 five-membered heterocycles were employed together with the gauge including atomic orbitals (GIAO) density functional theory (DFT) method at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p) and B3LYP/6-311+G(2d,p) levels of theory for the calculation of proton and carbon chemicals shifts and coupling constants. The method of geometry optimization for pyrrole (1), N-methylpyrrole (2) and thiophene (7) using the larger 6-311++G(d,p) basis sets at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p), B3LYP/6-31+G(2d,p) and B3LYP/cc-pVTZ levels of theory gave little difference between calculated and experimental values of coupling constants. In general, the (1)H and 13C chemical shifts for all compounds are in good agreement with theoretical calculations using the smaller 6-31 basis set. The values of nJHH(n=3, 4, 5) and rmnJ(CH)(n=1, 2, 3, 4) were predicted well using the larger 6-31+G(d,p) and 6-311++G(d,p) basis sets and at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p), B3LYP/6-31+G(2d,2p) levels of theory. The computed atomic charges [Mülliken; Natural Bond Orbital Analysis (NBO); Merz-Kollman (MK); CHELP and CHELPG] for the B3LYP/6-311++G(d,p) geometry optimized structures of 1-17 were used to explore correlations with the experimental proton and carbon chemical shifts.     

Investigation of structure, vibrational and NMR spectra of oxycodone and naltrexone: a combined experimental and theoretical study

In this work, two important opioid antagonists, naltrexone and oxycodone, were prepared from thebaine and were characterized by IR, (1)H NMR and (13)C NMR spectroscopy. Moreover, computational NMR and IR parameters were obtained using density functional theory (DFT) at B3LYP/6-311++G** level of theory. Complete NMR and vibrational assignment were carried out using the observed and calculated spectra. The IR frequencies and NMR chemical shifts, determined experimentally, were compared with those obtained theoretically from DFT calculations, showed good agreements. The RMS errors observed between experimental and calculated data for the IR absorptions are 85 and 105 cm(-1), for the (1)H NMR peaks are 0.87 and 0.17 ppm and for those of (13)C NMR are 5.6 and 5.3 ppm, respectively for naltrexone and oxycodone.     

Spectroscopic investigation (IR and NMR) and HOMO-LUMO analysis of aromatic imines using theoretical approach

In this work, the theoretical studies on the structure, FT-IR, NMR, and UV–Vis spectroscopy of (E)-N-benzylidenebenzenamine (A1) and (E)-N-(2, 4′-dichlorobenzylidene) propan-1-amine (A2) are presented. The optimized structure of the molecules, NMR and UV–Vis spectra analysis were determined by the Density Functional Theory (DFT) method using B3LYP/6-311G (d, p) basis set. For FT-IR analysis, both the HF and DFT methods were used in order to determine their accuracy and reliability in theoretical calculations. The computed result of DFT calculations in comparison with the experimental results showed that the DFT method gives a more accurate prediction. The infrared (IR) spectra for the imine molecules have been recorded in the region of 500–4000 cm^?1. The gauge-independent atomic orbital (GIAO) method has been used to evaluate the ¹³C and ¹H nuclear magnetic resonance (NMR) chemical shifts of the molecules. The computed results of NMR spectra of the molecules was found to be in good agreement with the experimental data. The UV–Vis spectra of the molecules were computed to determine the HOMO-LUMO energies in order to gain insight into their electronic properties. Mulliken population analysis on atomic charges of the molecules was also calculated using the HF (Hartree-Fock) and B3LYP method. All the computed results indicated that the B3LYP method provides satisfactory results and, therefore, can be employed to support experimental data. It also demonstrated a reliable approach towards characterization of molecules in chemical science.     

Prediction of the 13C NMR Chemical Shifts of Fluorenone Analogues by the GIAO Method

After the geometry optimization at B3LYP/6-31+G(d,p) level,the NMR calcula-tions of a series of fluorenone analogues have been carried out by GIAO method at HF/6-31+G(d) level and B3LYP/6-311G+(2d,p) level,respectively.The 13C NMR chemical shifts calculated at HF/6-31+G(d) level show better agreement with the observed values.By a series of linear correction equations (δpred=a + bδcalc),accurate prediction of 13C chemical shifts was achieved for the new fluorenone compound.The linear correlation of δpred with δexptl is excellent,and the square of correlation coefficient,r2,is up to 0.994.The maximum absolute difference between δpred and δexptl,Δδ,is 4.6 ppm,and the root-mean-square error between δpred and δexptl is only 2.6 ppm.     

Beta-silyl-substituted silaadamantyl,silabicyclo[2.2.2]octyl,silanorbornyl, and 1-silacyclohexyl cations. A theoretical (DFT and GIAO NMR) study

Parent 1-silaadamant-1-yl (1+) and a series of mono-beta-silyl-substituted- (2-Me+, 2-F+, 2-Cl+, 2-Br+), bis-beta-silyl-substituted- (3-Me+), and tris-beta-silyl-substituted (4-Me+)-1-silaadamant-1-yl cations were studied by the DFT method at the B3LYP/6-31G(d,p) level and by GIAO NMR at the B3LYP/ 6-31G(d,p)//B3LYP/6-31G(d,p) level. The geometries, relative energies, NMR chemical shifts, and charge distribution in the bridgehead silylium ions are discussed and compared. The magnitude of the beta-silyl effect (the Si-C-Si+ hyperconjugation) is gauged as a function of structure. Related model studies on the silabicyclo[2.2.2]octyl (5+, 6+, 5a+, and 6a+), silanorbornyl (7+ and 8+), and silacyclohexyl cations (9+ and 10+) were carried out in which the effect of beta-silyl substitution on geometry, stability, and NMR chemical shifts was probed. The acyclic model Me3Si-CH2-Si+(Me)2 (11+) was used to gauge the influence of the twist angle between the p-orbital at Si+ and the C-Si bond on relative stability and on the changes in the 29Si NMR chemical shifts. Finally, interaction of 1+ with H2O and MeOH and 2-Me+ with H2O was also examined. The resulting optimized structures (12+, 13+, and 14+) and the computed NMR chemical shifts are most compatible with the formation of silaoxonium ions.     

Characterization of covalent linkages in organically functionalized MCM-41 mesoporous materials by solid-state NMR and theoretical calculations

The covalent linkages formed during functionalization of MCM-41 mesoporous molecular sieves with five chloroalkylsilanes ((EtO)3Si(CH2Cl), (MeO)3Si(CH2CH2CH2Cl), Cl3Si(CH2CH2CH3), Cl2Si(CH3)(CH2Cl) and Cl2Si(CH3)2) have been investigated using high-resolution solid-state NMR spectroscopy and DFT calculations. Structural information was obtained from 1H-13C and 1H-29Si heteronuclear (HETCOR) NMR spectra, in which high resolution in the 1H dimension was obtained by using fast MAS. The 1H-13C HETCOR results provided the assignments of 1H and 13C resonances associated with the surface functional groups. Sensitivity-enhanced 1H-29Si HETCOR spectra, acquired using Carr-Purcell-Meiboom-Gill refocusing during data acquisition, revealed the identity of 29Si sites (Qn, Tn, and Dn) and the location of functional groups relative to these sites. Optimal geometries of local environments representing the Qn, Tn and Dn resonances were calculated using molecular mechanics and ab initio methods. Subsequently, DFT calculations of 29Si, 13C, and 1H chemical shifts were performed using Gaussian 03 at the B3LYP/6-311++G(2d,2p) level. The theoretical calculations are in excellent accord with the experimental chemical shifts. This work illustrates that state-of-the-art spectroscopic and theoretical tools can be used jointly to refine the complex structures of inorganic-organic hybrid materials.     

Anisotropic and hydrogen bonding effects in phenylglyoxamides and mandelamides: theoretical and NMR conformational evaluation

Interesting anisotropic effects were observed for phenylglyoxamides and their respective mandelamides. Such effects were observed in experimental (1)H and (13)C NMR (in CDCl(3), CD(3)OD, and DMSO-d(6) solvents) and in some cases with good correlation to theoretical (1)H and (13)C NMR DFT-GIAO (B3LYP/6-311++G**//B3LYP/6-31G*) calculations. A systematic conformational analysis of these compounds was performed in a two-step methodology, using PM3 and DFT (B3LYP/6-31G*) calculations; with good accomplishment and computational time economy. It was observed that intramolecular hydrogen bonding plays a significant role in the conformation of such compounds. Finally, a geminal nonequivalence of an N-CH(2) moiety, in one of the alkyl side chain (R1 = R2), was found for the tertiary mandelamides studied.     

Structure and tautomerism of 4-substituted 3(5)-aminopyrazoles in solution and in the solid state: NMR study and Ab initio calculations

Annular tautomerism of 3(5)-aminopyrazoles containing a cyano, thiocyanato, or aryl substituent in the 4-position has been studied by ¹H and ¹³C NMR in solution, cross-polarization and magic-angle spinning ¹³C NMR in the solid state, and ab initio quantum chemical calculations (B3LYP/6-31G**). The title compounds in the solid state exist as 3-amino tautomers. A rare case of slow (on the NMR time scale) annular prototropic tautomerism has been observed in DMSO-d ₆: signals of particular tautomers (3- and 5-aminopyrazoles) have been detected in the NMR spectra. 4-Cyano and 4-thiocyanato derivatives exist preferentially as 5-amino tautomers, whereas 4-methoxy analog is represented mainly by the 3-amino tautomers. Ab initio calculations (B3LYP/6-31G**) for the gas phase and DMSO solution (in terms of the polarizable continuum model) have shown increase of the relative stability of more polar 5-amino tautomer in going to DMSO.     

Complete 1H, 13C and 15N NMR assignment of tirapazamine and related 1,2,4-benzotriazine N-oxides

1H, 13C and 15N NMR measurements (1D and 2D including 1H--15N gs-HMBC) have been carried out on 3-amino-1, 2,4-benzotriazine and a series of N-oxides and complete assignments established. N-Oxidation at any position resulted in large upfield shifts of the corresponding N-1 and N-2 resonances and downfield shifts for N-4 with the exception of the 3-amino-1,2,4-benzotriazine 1-oxide in which a small upfield shift of N-4 was observed. Density functional GIAO calculations of the 15N and 13C chemical shifts [B3LYP/6-31G(d)//B3LYP/6-311+G(2d,p)] gave good agreement with experimental values confirming the assignments. The combination of 13C and 15N NMR provides an unambiguous method for assigning the 1H and 13C resonances of N-oxides of 1,2,4-benzotriazines.     

Ab initio study of 2,4-substituted azolidines. II. Amino-imino tautomerism of 2-aminothiazolidine-4-one and 4-aminothiazolidine-2-one in water solution

The relative stabilities of the tautomers of 2-aminothiazolidine-4-one and 4-aminothiazolidine-2-one were calculated at the MP2/6-31+G(d,p) level by considering their mono- and trihydrated complexes. Single-point calculations at the MP4/6-31+G(d,p)//MP2/6-31+G(d,p) level of theory were performed to obtain more accurate energies. The values of proton transfer barriers in the isolated, mono- and trihydrated tautomers of 2-aminothiazolidine-4-one (2AT) and 4-aminothiazolidine-2-one (4AT) were calculated for two different mechanisms of tautomerisation. In the absence of water, the process of proton transfer should not occur. Addition of water molecules decreases the barrier making the process faster, as the participation of two water molecules in a proton transfer reaction is more favorable than the participation of only one water molecule. To estimate the effect of the medium (water) on the relative stabilities of the tautomers of the studied compounds we applied the polarizable continuum model (PCM). (13)C NMR chemical shieldings were calculated using the GIAO approach at MP2/6-31+G(d,p) optimized geometries. HF and the DFT B3LYP functional with 6-31+G(d,p) basis set were employed. The quantum chemical results for the chemical shifts in gas phase and in polar solvents (water and DMSO) were compared with experimental data. TD DFT B3LYP/aug-cc-pVTZ calculations were performed to predict the absorption maxima of tautomers A and B of 2AT and 4AT.     

1H and 13C NMR spectra, structure and physicochemical features of phenyl acridine-9-carboxylates and 10-methyl-9-(phenoxycarbonyl)acridinium trifluoromethanesulphonates--alkyl substituted in the phenyl fragment

The 1H and 13C NMR spectra of twelve phenyl acridine-9-carboxylates--alkyl-substituted in the phenyl fragment--and their 10-methyl-9-(phenoxycarbonyl)acridinium salts dissolved in CD3CN, CD3OD, CDCl3 and DMSO-d6 were recorded in order to examine the influence of the structure of these compounds and the properties of the solvents on chemical shifts and 1H-(1)H coupling constants. Experimental data were compared with 1H and 13C chemical shifts predicted at the GIAO/DFT level of theory for DFT(B3LYP)/6-31G** optimised geometries of molecules, as well as with values of 1H chemical shifts and 1H-(1)H coupling constants, estimated using ACD/HNMR database software to ensure that the assignment was correct. To investigate the relations between chemical shifts and selected structural or physicochemical characteristics of the target compounds, the values of several of these parameters were determined at the DFT or HF levels of theory. The HOMO and LUMO energies obtained at the HF level yielded the ionisation potentials and electron affinities of molecules. The DFT method provided atomic partial charges, dipole moments, LCAO coefficients of pz LUMO of selected C atoms, and angles reflecting characteristic structural features of the compounds. It was found that the experimentally determined 1H and 13C chemical shifts of certain atoms relate to the predicted dipole moments, the angles between the acridine and phenyl moieties, and the LCAO coefficients of the pz LUMO of the C atoms believed to participate in the initial step of the oxidation of the target compounds. The spectral and physicochemical characteristics of the target compounds were investigated in the context of their chemiluminogenic ability.