13C Nuclear Magnetic Resonance Chemical Shifts Research Articles

Protonation of Carbon Single-Walled Nanotubes Studied Using 13C and 1H−13C Cross Polarization Nuclear Magnetic Resonance and Raman Spectroscopies

The reversible protonation of carbon single-walled nanotubes (SWNTs) in sulfuric acid and Nafion was investigated using solid-state nuclear magnetic resonance (NMR) and Raman spectroscopies. Magic-angle spinning (MAS) was used to obtain high-resolution 13C and 1H-13C cross polarization (CP) NMR spectra. The 13C NMR chemical shifts are reported for bulk SWNTs, H2SO4-treated SWNTs, SWNT-Nafion polymer composites, SWNT-AQ55 polymer composites, and SWNTs in contact with water. Protonation occurs without irreversible oxidation of the nanotube substrate via a charge-transfer process. This is the first report of a chemically induced change in a SWNT 13C resonance brought about by a reversible interaction with an acidic proton, providing additional evidence that carbon nanotubes behave as weak bases. Cross polarization was found to be a powerful technique for providing an additional contrast mechanism for studying nanotubes in contact with other chemical species. The CP studies confirmed polarization transfer from nearby protons to nanotube carbon atoms. The CP technique was also applied to investigate water adsorbed on carbon nanotube surfaces. Finally, the degree of bundling of the SWNTs in Nafion films was probed with the 1H-13C CP-MAS technique.

Whole‐Molecule Calculation of Log P Based on Molar Volume, Hydrogen Bonds, and Simulated 13C NMR Spectra.

The prediction of Log P is usually accomplished using either substructure or whole-molecule approaches. However, these methods are complicated, and previous whole-molecule approaches have not been successful for the prediction of Log P in very complex molecules. The observed chemical shifts in nuclear magnetic resonance (NMR) spectroscopy are related to the electrostatics at the nucleus, which are influenced by solute−solvent interactions. The different solvation effects on a molecule by either water or methanol have a strong effect on the NMR chemical shift value. Therefore, the chemical shift values observed in an aqueous and organic solvent should correlate to Log P. This paper develops a rapid, objective model of Log P based on molar volume, hydrogen bonds, and differences in calculated 13C NMR chemical shifts for a diverse set of compounds. A partial least squares (PLS) model of Log P built on the sum of carbon chemical shift differences in water and methanol, molar volume, number of hydrogen bond do...

Whole-Molecule Calculation of Log P Based on Molar Volume, Hydrogen Bonds, and Simulated13C NMR Spectra

The prediction of Log P is usually accomplished using either substructure or whole-molecule approaches. However, these methods are complicated, and previous whole-molecule approaches have not been successful for the prediction of Log P in very complex molecules. The observed chemical shifts in nuclear magnetic resonance (NMR) spectroscopy are related to the electrostatics at the nucleus, which are influenced by solute-solvent interactions. The different solvation effects on a molecule by either water or methanol have a strong effect on the NMR chemical shift value. Therefore, the chemical shift values observed in an aqueous and organic solvent should correlate to Log P. This paper develops a rapid, objective model of Log P based on molar volume, hydrogen bonds, and differences in calculated 13C NMR chemical shifts for a diverse set of compounds. A partial least squares (PLS) model of Log P built on the sum of carbon chemical shift differences in water and methanol, molar volume, number of hydrogen bond donors and acceptors in 162 diverse compounds gave an r2 value of 0.88. The average r2 for 10 training models of Log P made from 90% of the data was 0.87+/-0.01. The average q2 for 10 leave-10%-out cross-validation test sets was 0.87+/-0.05.

Crystalline diamond polymorphs analyzed with first‐principles 13C NMR chemical shift calculations

AbstractWe present the fully periodic calculation of nuclear magnetic resonance (NMR) chemical shifts in crystalline diamond polymorphs within density functional theory. The carbon atoms in these systems have identical fourfold coordination, their topology up to their first neighbors is completely the same. The differences occur only with respect to their second neighbors, which are oriented differently in the considered crystals. We focus on the 2H, 4H, 6H, and 15R polymorphs and compare their computed 13C NMR chemical shift spectra to that of cubic diamond. The results show that it should be possible to discriminate between the only slightly different topologies of the diamond polymorphs by means of magic‐angle‐spinning solid‐state NMR experiments. The predicted variations in the solid‐state NMR spectrum are strong enough to allow for a quantitative experimental analysis of such systems. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005

Multimodal Inclusion Complexes Between Barbiturates and 2‐Hydroxypropyl‐β‐Cyclodextrin in Aqueous Solution: Isothermal Titration Microcalorimetry, 13C NMR Spectrometry, and Molecular Dynamics Simulation

Multiple types (structures) of inclusion complexes between barbiturates and 2‐hydroxypropyl‐β‐cyclodextrin (HPCD) were evaluated by isothermal titration microcalorimetry and 13C NMR spectroscopy. The geometries of the inclusion complexes were suggested by molecular dynamics simulation. Barbituric acid (BA), barbital (B), amobarbital (AB), pentobarbital (PB), secobarbital (SB), cyclobarbital (CB), and phenobarbital (PHB) were used as barbiturates with different substituents on the barbituric acid ring and compared for inclusion types in aqueous solution. The association constants (K), stoichiometries, and thermodynamic parameters change in free energy (ΔG) change in enthalpy (ΔH), and change in entropy [ΔS] for each type of complex were determined from the calorimetric data. The inclusion complexation was largely entropy driven because of hydrophobic interactions. The values of K increased in the order BA<B<AB<PB<SB<CB<PHB. Barbiturates, except B and BA, form two types of inclusion complex with a 1:1 stoichiometry in the un‐ionized forms. The first type of inclusion complex with high affinity (K1) was characterized by small negative values of ΔH1 and large positive ΔS1, where the substituent R2 of the barbiturate was initially inserted into the cavity of HPCD through hydrophobic interactions. There was a good relationship between ΔG1 obtained from the calorimetric data for the first type of inclusion complex and ΔGR2 calculated from the changes in 13C Nuclear Magnetic Resonance (NMR) chemical shifts for the substituent R2 of barbiturates. These types were very stable in aqueous solution at various pHs. The second type of complex, with low affinity (K2), was characterized by large negative values of ΔH2 and small positive ΔS2, reflecting van der Waals' interactions in the un‐ionized forms of barbiturates at pH values less than pKa. The values of K2 were markedly decreased to <103 M−1 as the barbiturates were ionized over pH 8. Thus, in the second type, the barbituric acid ring contributed to forming the complexes. The geometries were stabilized by hydrogen bond formation between the hetero atoms in the barbituric acid ring and the secondary hydroxyl groups on the rim of the cyclodextrin. The 13C NMR chemical shifts of C4 and C6 carbons in the barbituric acid ring were moved upfield significantly by the inclusion complexation. On the other hand, B and BA could form only one type of complex, the lid‐type supramolecular complex with small association constants. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1186–1197, 2001

13C NMR and Electron Ionization Mass Spectrometric Data-Activity Relationship Model of Estrogen Receptor Binding

Two Spectroscopic Data-Activity Relationship (SDAR) models based on 13C nuclear magnetic resonance (NMR) and electron ionization mass spectra (EI MS) data were developed for 108 compounds whose relative binding affinities (RBA) to the estrogen receptor are known. The 13C NMR and EI MS data were used as spectrometric digital fingerprints to reflect the electronic and structural characteristics of the compounds. Both SDAR models segregated the 108 compounds into 20 strong, 15 medium, and 73 weak relative binding classifications. The first SDAR model, based on 13C NMR data alone, gave a leave-one-out (LOO) cross-validation of 75.0%. The second SDAR model, based on a composite of 13C NMR and EI MS data, gave a LOO cross-validation of 82.4%. Many of the misidentifications from the cross-validations were between medium and weak classifications, where there were fewer specific spectrometric characteristics to identify the relationship of spectra to estrogen receptor binding. Real and predicted 13C NMR chemical shifts were used to test the predictive behavior of both SDAR models. The ease of use and speed of SDAR modeling may facilitate their use with other toxicological endpoints.

Mechanisms for the enhanced thermal stability of a mutant of transcription factor 1 as explained by 1H, 15N and 13C NMR chemical shifts and secondary structure analysis

A variant of the bacteriophage SPO1-encoded transcription factor 1 (TF1) with two site-specific mutations (E15G and T32I) was shown to be more thermally stable and bind DNA more tightly compared to the wild-type protein. In order to understand the biochemical mechanisms underlying these properties, we are engaged in determining the solution structures of this mutant alone and in complex with DNA using nuclear magnetic resonance (NMR) spectroscopy. The first phase of this project is reported here, as we have completed most of the backbone and sidechain sequential NMR assignments of the mutant protein, TF1-G15/I32. Insights derived from the 1H, 15N and 13C chemical shifts and from the secondary structure analysis provide us with an explanation for the noted increase in thermal stability of TF1-G15/I32. Compared to the structure of the wild-type protein, the β-sheet and the C-terminal helix remain largely unaffected whereas the mutations cause great changes in the first two helices and their enclosed loop. Specifically, we have found that the second helix is extended by one residue at its N-terminus and rotated in a way that allows Ala-37 to interact with Tyr-94 of the C-terminal helix. The loop has been found to become more rigid as a result of hydrophobic interactions between the flanking second and first helices and also between the second helix and the loop itself. Furthermore, the T32I mutation allows tighter packing between the second helix and the β-sheet. Collectively, these changes contribute to a more tightly associated dimer and hence, to a greater thermal stability.

Acyl positional distribution of glycerol tri-esters in vegetable oils: a 13C NMR study

It has recently been shown that high-resolution 13C nuclear magnetic resonance (NMR) spectroscopy is a technique which can provide valuable information about the acyl distribution and acyl positional distribution (1,3-acyl and 2-acyl) of glycerol tri-esters of different vegetable oils. It has also been observed that many of the carbon atoms of α- and β- acyl chains in tri-acyl-glycerol show different 13C NMR chemical shifts. However, previous assignments of 13C NMR spectra are either tentative or incomplete. Thus, through a series of INADEQUATE experiments, we made a full assignment of all 13C resonances of glycerol tri-esters. We also noticed a strong concentration dependence of the shifts of all resonances. Thus, in vegetable oils, the full assignment of 13C resonances must be made by progressive addition of known glycerol tri-esters. Following this method, we report a full assignment of the 13C spectra of seed and olive oils obtaining an accurate analysis of the acyl positional distribution (1,3-acyl and 2-acyl) of glycerol tri-esters. From the knowledge of the acyl positional distribution (1,3-acyl and 2-acyl) of glycerol tri-esters interesting biochemical information can be achieved.

An Experimental and Quantum Chemical Investigation of CO Binding to Heme Proteins and Model Systems: A Unified Model Based on13C,17O, and57Fe Nuclear Magnetic Resonance and57Fe Mössbauer and Infrared Spectroscopies

We have investigated the question of how CO ligands bind to iron in metalloporphyrins and metalloproteins by using a combination of nuclear magnetic resonance (NMR), 57Fe Mössbauer, and infrared spectroscopic techniques, combined with density functional theoretical calculations to analyze the spectroscopic results. The results of 13C NMR isotropic chemical shift, 13C NMR chemical shift anisotropy, 17O NMR isotropic chemical shift, 17O nuclear quadrupole coupling constant, 57Fe NMR isotropic chemical shift, 57Fe Mössbauer quadrupolar splitting, and infrared measurements indicate that CO binds to Fe in a close to linear fashion in all conformational substates. The 13C-isotropic shift and shift anisotropy for an Ao substate model compound: Fe(5,10,15,20-tetraphenylporphyrin)(CO)(N-methylimidazole), as well as the 17O chemical shift, and the 17O nuclear quadrupole coupling constant (NQCC) are virtually the same as those found in the Ao substate of Physeter catodon CO myoglobin and lead to most probable ligand tilt (τ) and bend (β) angles of 0° and 1° when using a Bayesian probability or Z surface method for structure determination. The infrared νCO for the model compound of 1969 cm-1 is also that found for Ao proteins. Results for the A1 substate (including the 57Fe NMR chemical shift and Mössbauer quadrupole splitting) are also consistent with close to linear and untilted Fe−C−O geometries (τ = 4°, β = 7°), with the small changes in ligand spectroscopic parameters being attributed to electrostatic field effects. When taken together, the 13C shift, 13C shift anisotropy, 17O shift, 17O NQCC, 57Fe shift, 57Fe Mössbauer quadrupole splitting, and νCO all strongly indicate very close to linear and untilted Fe−C−O geometries for all carbonmonoxyheme proteins. These results represent the first detailed quantum chemical analysis of metal−ligand geometries in metalloproteins using up to seven different spectroscopic observables from three types of spectroscopy and suggest a generalized approach to structure determination.

Studies of intramolecular hydrogen bonds in di-Schiff bases of 2-hydroxy-5-methyl isophthaldehyde

Di-Schiff bases obtained by the reaction of 2-hydroxy-5-methyl isophthaldehyde with 4-R-anilines (R = H, CH 3 and OCH 3) were synthesized and studied by ultraviolet-visible (UV-vis) spectrophotometry and 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The UV-vis spectra of di-Schiff bases 1–3 and their protonated and deprotonated analogues in acetonitrile are discussed. Isotope effects on the 13C NMR chemical shifts resulting from deuteration of the OH groups were determined. Inequivalence of the two 4-R-phenyl-imino methyl groups at low temperatures was evidenced.

Structure-Carcinogenicity Studies for Benz[a]Anthracenes by13C NMR Spectroscopy and Molecular Orbital Calculation

Abstract Structure-carcinogenicity studies of polycyclic aromatic hydrocarbons (PAHs) were performed on the basis of average 13C nuclear magnetic resonance (NMR) chemical shifts (δavs). The δav values of carcinogenic compounds were found to concentrate in a certain range. To clarify the chemical significance of the correlation, we investigated the relationship of the individual 13C NMR chemical shifts (δs) and carcinogenicity for three benz[a]anthracenes whose carcinogenicities vary largely. The δ values at the C1, C2, and C6 positions differ significantly between the carcinogenic and noncarcinogenic compounds. Molecular orbital calculations revealed that the carcinogens have higher electron densities at C1 and C6 positions than dose the noncarcinogen.

Heavy metal binding to heparin disaccharides. II. First evidence for zinc chelation.

To map out the heavy metal binding sites of iduronic acid containing oligosaccharides isolated from human kidneys, we studied Zn(II) binding by nuclear magnetic resonance (NMR) and molecular modeling to two disaccharides isolated after nitrous acid depolymerization of heparin and two synthetic disaccharides representative of the heparin structure, namely, IdopA2S (alpha 1,4)AnManOH, 1 alpha, IdopA2S (alpha 1,4)AnManOH6S, 1b, IdopA2S-(alpha 1,4)GlcNS alpha Me, 2a, and IdopA2S (alpha 1,4)GlcNS6S alpha Me, 2b (see previous article in this series). A conformational analysis of the metal free and metal bound solutions was made by comparing calculated [(NOE)]s, [T1]s, and [J]s to experimental values. The 1C4, 4C1, and 2S0 conformations of the L-idopyranosiduronate ring and the 4E and 4T3 of the anhydro-D-mannitol ring are evaluated as are rotations about the C5-C6 hydroxymethylene of the AnManOH(6S) or GlcNS (6S) residues. The NOE between IdopA2S H1 and H3 and the known NOE between H2 and H5, as well as the T1 of IdopA2S H3, are introduced as NMR observables sensitive to the IdopA2S ring conformation. Similarly, a NOE between IdopA2S H5 and AnManOH(6S) or GlcNS(6S) H3 was observed that directly restricts the allowed interglycosidic conformational space. For all disaccharides, the Zn(II) bound spectral data are consistent with models in which these motions are partially "frozen" such that the 1C4 conformation of the IdopA2S is stabilized along with the 4T3 conformation of the AnManOH(6S) ring. The interglycosidic conformation is also stabilized in one of two minima. Electrostatic potential energy calculations gave the best overall agreement with experiment and suggest metal binding conformations with the carboxylate and ring oxygen of the IdopA2S residues (1C4 conformation) and either O3 of the GlcNS(6S) residues or the sulfate oxygens of the 6-sulphate for 2b providing additional chelating sites. These chelation models concur with the observation of marked 13C and 1H NMR chemical shifts for the IdopA2S resonances and of GlcNS H3 for 2 alpha and GlcNS6S C6 for 2b. This study of model compounds implicates the IdopA2S(alpha 1,4)GlcNS6S group as part of the heavy metal binding site in biologically important acidic oligosaccharides such as heparin.

Effective bilayer expansion and erythrocyte shape change induced by monopalmitoyl phosphatidylcholine. Quantitative light microscopy and nuclear magnetic resonance spectroscopy measurements

When human erythrocytes are treated with exogenous monopalmitoyl phosphatidylcholine (MPPC), the normal biconcave disk shape red blood cells (RBC) become spiculate echinocytes. The present study examines the quantitative aspect of the relationship between effective bilayer expansion and erythrocyte shape change by a newly developed method. This method is based on the combination of direct surface area measurement of micropipette and relative bilayer expansion measurement of 13C crosspolarization/magic angle spinning nuclear magnetic resonance (NMR). Assuming that 13C NMR chemical shift of fatty acyl chain can be used as an indicator of lateral packing of membrane bilayers, it is possible for us to estimate the surface area expansion of red cell membrane induced by MPPC from that induced by ethanol. Partitions of lipid molecules into cell membrane were determined by studies of shape change potency as a function of MPPC and red cell concentration. It is found that 8(+/- 0.5) x 10(6) molecules of MPPC per cell will effectively induce stage three echinocytes and yield 3.2(+/- 0.2)% expansion of outer monolayer surface area. Surface area of normal cells determined by direct measurements from fixed geometry of red cells aspirated by micropipette was 118.7 +/- 8.5 microns2. The effective cross-sectional area of MPPC molecules in the cell membrane therefore was determined to be 48(+/- 4) A2, which is in agreement with those determined by x-ray from model membranes and crystals of lysophospholipids. We concluded that surface area expansion of RBC can be explained by a simple consideration of cross-sectional area of added molecules and that erythrocyte shape changes correspond quantitatively to the incorporated lipid molecules.

NMR in medicine

Nuclear magnetic resonance (NMR) offers a powerful new probe of the body's internal anatomy and function. The technique utilizes a combination of static and radio frequency (RF) magnetic fields to excite a weak resonant magnetic field emission from various selected naturally abundant nuclei in the body such as hydrogen ( 1H), phosphorus ( 31P) and carbon ( 13C). The emissions can be spatially encoded by application of magnetic field gradients, to enable the generation of high resolution anatomical images which reflect the nuclear density distribution, and/or spatial variations in the molecular level and chemical environments of the nuclei as measured by the NMR relaxation times and chemical shifts. 1H NMR relaxation time images are proving useful for the detection of a wide spectrum of disorders, whilst spatially localized 31P and 13C NMR chemical shift spectra measure directly the metabolic status of living tissue. A qualitative explanation of NMR, NMR imaging, relaxation times, and chemical shifts is presented, and the historical development, future of the technology, and its range of applications explored.

Determination of Distribution of O-Acetyl Group in Trihydric Alcohol Units of Cellulose Acetate by Carbon-13 Nuclear Magnetic Resonance Analysis

The total degree of substitution, DS(≡‹‹F››), the distribution of DS and the distribution of the substituent group in a glucopyranose unit ‹‹fk›› (the suffix k means the carbon position in the C1 chain conformation) are accurately defined for cellulose derivatives. ‹‹fk›› of cellulose acetate (CA) was evaluated from the 1H nuclear magnetic resonance (NMR) chemical shift of the O-acetyl protons and the 13C NMR chemical shift of the O-acetyl carbons. 1H NMR method is applicable only to completely substituted cellulose acetate, but the 13C NMR method is proved applicable for the entire range of the DS (0—3). CA (DS=2.92)–trichloromethane, CA (DS=2.46)–acetone, and CA (DS=0.49)–dimethyl sulfoxide systems are employed successfully. ‹‹F›› values determined by 13C NMR spectrum are in good agreement with those by the chemical analysis. The reactivity of the O-acetyl groups during the hydrolysis reaction process using hydrochloric acid as a catalyst decreases in the following order: C2>C6>C3.

Nuclear magnetic resonance of the filamentous bacteriophage fd

The filamentous bacteriophage fd and its major coat protein are being studied by nuclear magnetic resonance (NMR) spectroscopy. 31P NMR shows that the chemical shielding tensor of the DNA phosphates of fd in solution is only slightly reduced in magnitude by motional averaging, indicating that DNA-protein interactions substantially immobilize the DNA packaged in the virus. There is no evidence of chemical interactions between the DNA backbone and the coat protein, since experiments on solid virus show the 31P resonances to have the same principle elements of its chemical shielding tensor as DNA. 1H and 13C NMR spectra of fd virus in solution indicate that the coat proteins are held rigidly in the structure except for some aliphatic side chains that undergo relatively rapid rotations. The presence of limited mobility in the viral coat proteins is substantiated by finding large quadrupole splittings in 2H NMR of deuterium labeled virions. The structure of the coat protein in a lipid environment differs significantly from that found for the assembled virus. Data from 1H and 13C NMR chemical shifts, amide proton exchange rates, and 13C relaxation measurements show that the coat protein in sodium dodecyl sulfate micelles has a native folded structure that varies from that of a typical globular protein or the coat protein in the virus by having a partially flexible backbone and some rapidly rotating aromatic rings.

On the reaction of dialkyl acylphosphonate with 2-methyl-1,3,4-thiadiazolium salts.

Dialkyl acylphosphonate acted as an acylating agent for the 2-methyl group in 1, 3, 4-thiadiazolium salts, as well as 2-methylthiazolium and thiazolinium salts, to give 2-acylidenethiadiazoline derivatives. The reaction of diethyl benzoylphosphonate (1) with 5-amino-2, 3-dimethyl-1, 3, 4-thiadiazolium iodide (2c) gave the N-monobenzoate inner salt (6), C-monobenzoate (7), C, N-dibenzoate (8) and 5-benzoylamido-2-styryl-thiadiazolium hydroxide inner salt (9) ; the extent of N-acylation was greater than that of C-acylation. The structures of the inner salt products (6 and 9) were confirmed by an alternative synthesis. A proposed mechanism for the acylphosphonate reaction with 2-methyl-1, 3, 4-thiadiazolium salts is presented, and is consistent with the 13C-nuclear magnetic resonance chemical shifts of the 2-methyl groups of the 1, 3-azolium salts.