Computation of through-space NMR shielding effects by aromatic ring-cation complexes: substantial synergistic effect of complexation

The HF-GIAO method in Gaussian 03 was employed to calculate the NMR isotropic shielding values of a diatomic hydrogen probe and to predict the through-space proton NMR shielding increment surfaces above benzene complexed with ammonium, lithium, sodium, potassium, magnesium or calcium ion. The sum of the calculated isotropic shielding values for the proximal hydrogen of a diatomic hydrogen probe over benzene and those calculated at appropriate positions relative to cations were subtracted from the isotropic shielding values calculated for the complexes. The result is a shielding increment for complexation. Complexation results in a synergistic effect on NMR shielding. Enhanced shielding was observed over the π electron cloud of benzene upon complexation with the cations, more than the sum of the separate effects of the aromatic ring and the charge. The results are interpreted in terms of polarization of the π cloud of benzene by the cation and its consequences.     

Computation of through-space NMR shielding effects by small-ring aromatic and antiaromatic hydrocarbons

The GIAO-HF method in Gaussian 03 was employed to calculate the isotropic NMR shielding values of a diatomic hydrogen probe above simple small-ring aromatic and antiaromatic hydrocarbons, including neutral and ionic examples. Subtraction of the isotropic shielding of diatomic hydrogen by itself allowed the prediction of through-space proton NMR shielding increment surfaces for these systems. Substantial shielding was observed above the center of aromatic rings, regardless of whether the ring was pi-aromatic or sigma-aromatic, and also regardless of the charge. In sharp contrast, deshielding was observed above the center of antiaromatic rings, regardless of whether the ring was pi-aromatic or sigma-aromatic, and also regardless of the charge. Shielding increment values at 2.5 angstrom above the ring centers were compared to NICS values at the same position. The shielding effects predicted by using diatomic hydrogen as a computational probe are diagnostic of whether a structure possesses aromaticity or antiaromaticity.     

An algorithm for predicting the NMR shielding of protons over substituted benzene rings

In a strong magnetic field, hydrogen nuclei located over an aromatic ring experience a reduced magnetic field as a result of the induced magnetic field associated with circulating pi electrons. We used GIAO-SCF, an ab initio subroutine in Gaussian 94 to calculate isotropic shielding values and to determine the proton nuclear magnetic resonance (NMR) shielding increment for a simple model system: methane held at various positions over a substituted benzene ring. The NMR shielding increments experienced by the proximal protons of methane have been mapped as a function of their position X, Y, and Z relative to the center of aniline and, separately, nitrobenzene. A mathematical function of the same form has been fit to the three-dimensional shielding increment surface at each of five distances from the face of each aromatic ring. In addition, a single mathematical equation has been developed for predicting the shielding caused by either substituted aromatic ring. The chemical shifts predicted by using the results of this equation in conjunction with additive substituent increments are compared to observed values.     

Computation of through-space NMR shielding effects by functional groups common to peptides

The GIAO-HF method in Gaussian 03 was employed to calculate the isotropic shielding values of a covalently bonded hydrogen probe and to predict the through-space proton NMR shielding increment surfaces near models of simple structures containing functional groups common to peptides. The functional groups examined include the carboxylate anion, carboxylic acid, amide, amino, ammonium and guanidinium groups. Our previously developed methodology involving the use of diatomic hydrogen as a probe of through-space shielding effects was employed. Substantial shielding or deshielding effects were observed only in the cases of the charged (ionic) groups, each of which displayed shielding or deshielding effects of greater than 1 ppm at distances comparable to those observed in peptides. Equations for predicting the shielding increments of these groups as a function of the Cartesian coordinate position of the affected proton were determined. The validity of using simple structures as models of shielding by comparable functional groups in peptides was confirmed by computing the shielding effects at selected positions above a model of glycylglycylglycine and its hydrogen-bonded dimer. Knowledge of these through-space shielding effects should aid in the tertiary structure determination of peptides by NMR.     

A comparison of calculated NMR shielding probes

In a strong magnetic field, covalently bonded hydrogen nuclei located over the plane of an anisotropic pi bond-containing functional group experience magnetic shielding (or deshielding) that results from the combined effect of the magnetic anisotropy of the functional group and other nearby covalent bonds plus other intramolecular shielding effects. These effects can now be calculated with reasonable accuracy using ab initio methods. We have investigated several computational probes of the magnetic shielding surface near anisotropic functional groups and compared the results to previous reports of experimental observations in example structures. GIAO-HF in Gaussian 03 was employed to calculate isotropic shielding values and to predict the net NMR shielding increment for several computational probes: methane, diatomic hydrogen, a hydrogen atom, a helium atom, or a ghost atom, each held in various positions over simple test molecules (ethene, ethyne, benzene and HCN) that contain the functional groups studied. Also, the effect of performing single point calculations versus constrained geometry-optimized calculations was examined. In addition, the effect of the angle of the orientation of the probe molecule (in the case of CH(4) and H(2)) relative to the pi bond in the test molecule was studied. Finally, the atomic charges in the molecular probes (CH(4) and H(2)) were computed to investigate the nature of the interaction of the probe with the test molecule. The optimal, most economical computational results were obtained using single point calculations of a diatomic hydrogen probe oriented perpendicular to the surface (or axis) of the test molecule.     

Semiempirical and ab initio conformational analysis of 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane with application of GIAO-SCF methods to NMR spectrum interpretation

The GIAO-SCF method for calculating isotropic nuclear magnetic shielding values has been utilized to explain certain features in the ¹H-NMR spectrum of 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane. Population distributions of the low-energy conformers based on their ab initio energies were used to produce weighting factors for the individual calculated shielding values to calculate the weighted average of the shielding values for a complete set of conformers. The differences in ¹H chemical shifts between the hydrogens of the two methyl groups and between the axial and equatorial hydrogens in 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane were shown to be due to energy differences between the chair and boat orientations of the six-membered ring and contribution from a twist-boat conformation. Results suggest a hypothesis that intramolecular differences in chemical shift might be calculated to a greater degree of accuracy than chemical shifts calculated relative to a standard.     

Semiempirical and ab initio conformational analysis of 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane with application of GIAO-SCF methods to NMR spectrum interpretation

The GIAO-SCF method for calculating isotropic nuclear magnetic shielding values has been utilized to explain certain features in the ¹H-NMR spectrum of 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane. Population distributions of the low-energy conformers based on their ab initio energies were used to produce weighting factors for the individual calculated shielding values to calculate the weighted average of the shielding values for a complete set of conformers. The differences in ¹H chemical shifts between the hydrogens of the two methyl groups and between the axial and equatorial hydrogens in 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane were shown to be due to energy differences between the chair and boat orientations of the six-membered ring and contribution from a twist-boat conformation. Results suggest a hypothesis that intramolecular differences in chemical shift might be calculated to a greater degree of accuracy than chemical shifts calculated relative to a standard.     

Modeling through-space magnetic shielding over ethynyl,cyano, and nitro groups

In a strong magnetic field, covalently bonded hydrogen nuclei located over a pi bonded functional group experience magnetic shielding (or deshielding) that results from the combined effect of the magnetic anisotropy of the pi bond and various other intramolecular shielding effects. Gauge including atomic orbital (GIAO)-HF in Gaussian 98 was employed to calculate isotropic shielding values and to predict the net through-space proton NMR shielding increment for a simple model system: the proximate proton of methane held in various positions over simple molecules that contain a carbon-carbon triple bond, a carbon-nitrogen triple bond, or a nitro group. These net shielding increments of the proximate proton of methane, plotted against their Cartesian coordinates, led to the development of a single empirical equation for predicting the NMR shielding experienced by a covalently bonded proton over each group. The predictive capability of each equation has been validated by calculating shielding increments of protons over the functional group in known structures. These shielding increments are then used to adjust predicted chemical shifts for through-space shielding effects, and the adjusted values are compared to experimentally observed chemical shifts. The algorithms for predicting the shielding increment for a proton over these functional groups can be used in a spreadsheet or incorporated into software that estimates chemical shifts using additive substituent constants or a database of structures. Their use can substantially improve the accuracy of the estimated chemical shift of a proton in the vicinity of these functional groups, and thus assist in spectral assignments and in correct structure determination.     

An algorithm for predicting proton nuclear magnetic resonance deshielding over a carbon-carbon double bond

Hydrogen nuclei located over a carbon-carbon double bond in a strong magnetic field experience NMR shielding effects that result from the magnetic anisotropy of the nearby double bond and various other intramolecular shielding effects. We have used GIAO, a subroutine in Gaussian 98, to calculate isotropic shielding values and to predict the proton NMR shielding increment for a simple model system: methane held in various orientations, positions, and distances over ethene. The average proton NMR shielding increments of several orientations of methane have been plotted versus the Cartesian coordinates of the methane protons relative to the center of ethene. A single empirical equation for predicting the NMR shielding experienced by protons over a carbon-carbon double bond has been developed from these data. The predictive capability of this equation has been validated by comparing the shielding increments for several alkenes calculated using our equation to the experimentally observed shielding increments. This equation predicts the NMR shielding effects more accurately than previous models that were based on fewer geometries of methane over ethene. In fact, deshielding is predicted by this equation for protons over the center and within about 3 A of a carbon-carbon double bond. This result is in sharp contrast to predictions made by the long-held McConnell "shielding cone" model found in nearly every textbook on NMR, but is consistent with experimental observations. The algorithm for predicting the (de)shielding increment for a proton over an alkene can be used in a spreadsheet on a PC or incorporated into software that estimates chemical shifts using additive substituent constants or a database of structures. In either application its use can substantially improve the accuracy of the estimated chemical shift of a proton in the vicinity of a carbon-carbon double bond, and thus assist in spectral assignments and in correct structure determination.     

An NMR shielding model for protons above the plane of a carbonyl group

Covalently bonded hydrogen nuclei located over the plane of a carbonyl group in a strong magnetic field experience magnetic shielding (or deshielding) that results from the combined effect of the magnetic anisotropy of the carbon-oxygen double bond and various other intramolecular shielding effects. GIAO-HF in Gaussian 98 was employed to calculate isotropic shielding values and to predict the net proton NMR shielding increment for a simple model system: the proximate proton of methane held in various positions over formaldehyde. The net shielding increments of the proximate proton of methane, plotted against its Cartesian coordinates relative to the center of the carbon-oxygen double bond, led to the development of a single empirical equation for predicting the NMR shielding experienced by a covalently bonded proton over the plane of a carbonyl group. The predictive capability of this equation has been validated by calculating the shielding increments of protons over the plane of a carbonyl group in known structures, using this as a correction to the chemical shift estimated by subtituent effects and comparing the result to experimentally observed chemical shifts. Shielding is predicted by this equation for protons located in the region from over the center of the carbon-oxygen double bond to beyond the carbon atom; deshielding is predicted for protons located above and beyond the oxygen atom. This prediction differs from those made by the long-held "shielding cone" model found in nearly every textbook on NMR, but is consistent with experimental observations. The algorithm for predicting the shielding increment for a proton over a carbonyl group can be used in a spreadsheet or incorporated into software that estimates chemical shifts using additive substituent constants or a database of structures. Its use can improve the accuracy of the estimated chemical shift of a proton in the vicinity of a carbon-oxygen double bond, and thus assist in spectral assignments and in correct structure determination.     

UNIFAC法估算甲烷在常三柴油中的高压溶解度

为满足富氢气氛下,煤直接液化基础数据的需要,选择大港常三柴油做溶剂,用自建的循环法测定气体高压溶解度试验装置,测定甲烷在柴油中的高压溶解度数据(273.45 K-293.75 K,1.79 MPa-8.06 MPa)。根据柴油特点假设其基团构成,用n-d-M-LP法计算柴油的平均结构。用UNIFAC方程估算同条件下的溶解度值,结果估算值与实验值比较,当芳香环和环烷环上有2个取代基时,平均相对误差为3.36%,满足数据缺乏下的估算要求。     

Density functional calculations of oxygen, nitrogen and hydrogen electric field gradient and chemical shielding tensors to study hydrogen bonding properties of peptide group (O=C-NH) in crystalline acetamide

A density functional theory (DFT) study was carried out to investigate hydrogen bonding (HB) properties of peptide group (O=C-NH) in crystalline acetamide. Since the peptide group in acetamide contributes to N-H...O and C-H...O types of HB interactions, acetamide is considered as the simplest form of peptide linkage in proteins. The evaluated NMR parameters including quadrupole coupling constants and asymmetry parameters from the calculated electric field gradient (EFG) tensors at the sites of O17, N14 and H2 nuclei and isotropic chemical shieldings from the calculated chemical shielding (CS) tensors at the sites of O17, N15 and H1 nuclei reveal the major contribution of O=C-NH group to HB interactions. Although N-H...O type of HB interaction play the major role in the HB properties of peptide group in lattice form of crystalline acetamide, however, the role of weaker C-H...O type of HB interaction cannot be neglected.     

Molecular modeling study of beta-cyclodextrin complexes with (+)-catechin and (-)-epicatechin

The structural aspects for the complexation of (+)-catechin (CA) and (-)-epicatechin (EC) (an enantiomer) to beta-cyclodextrins (CDs) were explored by using a semi-empirical PM3 method. In the beta-CD/CA inclusion complex, the orientation in which the aromatic A-ring of CA projects onto the 2-OH/3-OH face of beta-CD, and the B-ring projects from the 6-OH face is preferred in the binding energy (BE). In contrast, the inclusion of the B-ring of EC from either the secondary hydroxyl group side or the primary hydroxyl group side gives rise to the two most probable complexes. The molecular modeling results are in agreement with the NMR observations and molecular dynamics (MD) simulations. EC forms a more stable complex with beta-CD than the corresponding CA, as judged from the difference in BE. The differential interactions between each enantiomer and the chiral host give rise to the significant structural differences for the corresponding inclusion complexes. Numerous host-guest C-Hcdots, three dots, centeredO interactions, resulting from induced fit of the hosts toward each of the enantiomeric guests, comprise a third significant component besides the O-Hcdots, three dots, centeredO hydrogen bonds and the van der Waals contacts.     

Enhanced stability of a naringenin/2,6-dimethyl β-cyclodextrin inclusion complex: Molecular dynamics and free energy calculations based on MM- and QM-PBSA/GBSA

The structure, dynamic behavior and binding affinity of the inclusion complexes between naringenin and the two cyclodextrins (CDs), β-CD and its 2,6-dimethyl derivative (DM-β-CD), were theoretically studied by multiple molecular dynamics simulations and free energy calculations. Naringenin most likely prefers to bind with CDs through the phenyl ring. Although a lower hydrogen bond formation of naringenin with the 3-hydroxyl group of DM-β-CD (relative to β-CD) was observed, the higher cavity could encapsulate almost the whole naringenin molecule. In contrast for the naringenin/β-CD complex, the phenyl ring feasibly passed through the primary rim resulting in the chromone ring binding inside instead. MM-PBSA/GBSA and QM-PBSA/GBSA binding free energies strongly suggested a greater stability of the naringenin/DM-β-CD inclusion complex. Van der Waals force played an important role as the key guest–host interaction for the complexation between naringenin and each cyclodextrin.     

Combined quantum mechanical and molecular mechanical reaction pathway calculation for aromatic hydroxylation by p-hydroxybenzoate-3-hydroxylase

The reaction pathway for the aromatic 3-hydroxylation of p-hydroxybenzoate by the reactive C4a-hydroperoxyflavin cofactor intermediate in p-hydroxybenzoate hydroxylase (PHBH) has been investigated by a combined quantum mechanical and molecular mechanical (QM/MM) method. A structural model for the C4a-hydroperoxyflavin intermediate in the PHBH reaction cycle was built on the basis of the crystal structure coordinates of the enzyme-substrate complex. A reaction pathway for the subsequent hydroxylation step was calculated by imposing a reaction coordinate that involves cleavage of the peroxide oxygen-oxygen bond and formation of the carbon-oxygen bond between the C3 atom of the substrate and the distal oxygen of the peroxide moiety of the cofactor. The geometric changes and the Mulliken charge distributions along the calculated reaction pathway are in line with an electrophilic aromatic substitution type of mechanism. The energy barrier of the calculated reaction is considerably lower when the substrate hydroxyl moiety is deprotonated, in comparison with the barrier found with a protonated hydroxyl moiety. This effect of the protonation state of the substrate on the calculated energy barrier supports experimental observations that deprotonation is required for hydroxylation of the substrate. A notable event in the calculated reaction pathway is a lengthening of the peroxide oxygen-oxygen bond at an intermediate stage. Further analysis of the reaction pathway indicates that this oxygen-oxygen bond elongation is accompanied by an increase in electrophilic reactivity on the distal oxygen of the peroxide moiety, which may assist the C-O bond formation in the reaction of the C4a-hydroperoxyflavin intermediate with the substrate. Analysis of the effect of individual active site residues on the reaction reveals a specific transition state stabilization by the backbone carbonyl moiety of Pro293. The crystal water 717 appears to drive the hydroxylation step through a stabilizing hydrogen bond interaction to the proximal oxygen of the C4a-hydroperoxyflavin intermediate, which increases in strength as the hydroperoxyflavin cofactor converts to the anionic (deprotonated) hydroxyflavin.     

Intramolecular C-H--O interaction between lactam oxygen and N-alkyl protons.

We report evidence of an unusual C-H--O interaction between an alpha-methylene hydrogen of the alkylamine chain of substituted (N,N-dimethylamino)propyl-azetidinones, substituted (N,N-dimethylamino)propyl-thiazolidinones and substituted (N,N-dimethylamino)propyl-thiazinone and the lactam carbonyl oxygen. NMR analysis results, supported by molecular mechanic predictions, were in agreement with ab initio calculations. The observed interaction shorting the nitrogen-nitrogen distance in the H1-histamine antagonist, 2-(4-methylphenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-one (1) could explain its fitting with the H1-antihistaminic pharmacophoric model and the high antihistaminic activity.     

二氧化碳水合物小晶穴和大晶穴的密度泛函研究

本文通过B3LYP方法,在6-31G(d,p)水平下对结构Ⅰ型二氧化碳水合物的十二面体小晶穴和十四面体大晶穴的结构进行优化,并计算了其振动频率.13C-NMR化学屏蔽常数及电子密度.结果表明,水合物晶穴的氢键键能强于水分子二聚体和冰晶格中的氢键键能.由此可以看出结构Ⅰ型二氧化碳水合物的晶穴是由氢键组成的稳定结构.通过CO2分子与大、小晶穴的范德华能比较,发现C02分子在大晶穴中更稳定.所计算出的C=O键的不对称伸缩振动频率和13C-NMR化学屏蔽常数与文献中的实验值基本一致.通过分析CO2与晶穴的电子密度,其结果与氢键键能计算结果一致,计算结果还表明,CO2在大晶穴中的稳定性较在小晶穴中的稳定性强.     

Automatic detection of the breast border and nipple position on digital mammograms using genetic algorithm for asymmetry approach to detection of microcalcifications

The presence of microcalcifications in breast tissue is one of the most incident signs considered by radiologist for an early diagnosis of breast cancer, which is one of the most common forms of cancer among women. In this paper, the Genetic Algorithm (GA) is proposed for automatic look at commonly prone area the breast border and nipple position to discover the suspicious regions on digital mammograms based on asymmetries between left and right breast image. The basic idea of the asymmetry approach is to scan left and right images are subtracted to extract the suspicious region. The proposed system consists of two steps: First, the mammogram images are enhanced using median filter, normalize the image, at the pectoral muscle region is excluding the border of the mammogram and comparing for both left and right images from the binary image. Further GA is applied to magnify the detected border. The figure of merit is calculated to evaluate whether the detected border is exact or not. And the nipple position is identified using GA. The some comparisons method is adopted for detection of suspected area. Second, using the border points and nipple position as the reference the mammogram images are aligned and subtracted to extract the suspicious region. The algorithms are tested on 114 abnormal digitized mammograms from Mammogram Image Analysis Society database.