Terminal Methyl Carbon Research Articles

Methylated tetra-amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST.

Paramagnetic agents that utilize two mechanisms to provide physiological information by magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) are described. MRI with chemical exchange saturation transfer (CEST) takes advantage of the agent's exchangeable protons (e.g., -OH or -NHx , where 2 ≥ x ≥ 1) to create pH contrast. The agent's incorporation of non-exchangeable protons (e.g., -CHy , where 3 ≥ y ≥ 1) makes it possible to map tissue temperature and/or pH using an MRSI method called biosensor imaging of redundant deviation in shifts (BIRDS). Hybrid probes based upon 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelate (DOTA4- ) and its methylated analog (1,4,7,10-tetraazacyclododecane-α, α', α″, α‴-tetramethyl-1,4,7,10-tetraacetate, DOTMA4- ) were synthesized, and modified to create new tetra-amide chelates. Addition of several methyl groups per pendent arm of the symmetrical chelates, positioned proximally and distally to thulium ions (Tm3+ ), gave rise to favorable BIRDS properties (i.e., high signal-to-noise ratio (SNR) from non-exchangeable methyl proton peaks) and CEST responsiveness (i.e., from amide exchangeable protons). Structures of the Tm3+ probes elucidate the influence of methyl group placement on sensor performance. An eight-coordinate geometry with high symmetry was observed for the complexes: Tm-L1 was based on DOTA4- , whereas Tm-L2 and Tm-L3 were based on DOTMA4- , where the latter contained an additional carboxylate at the distal end of each arm. The distance of Tm3+ from terminal methyl carbons is a key determinant for sustaining BIRDS temperature sensitivity without compromising CEST pH contrast; however, water solubility was influenced by introduction of hydrophobic methyl groups and hydrophilic carboxylate. Combined BIRDS and CEST detection of Tm-L2, which features two high-SNR methyl peaks and a strong amide CEST peak, should enable simultaneous temperature and pH measurements for high-resolution molecular imaging in vivo.

Localization of Double Bonds in Bacterial Glycerophospholipids Using 193 nm Ultraviolet Photodissociation in the Negative Mode.

The need for detailed structural characterization of glycerophospholipids (GPLs) for many types of biologically motivated applications has led to the development of novel mass spectrometry-based methodologies that utilize alternative ion activation methods. Ultraviolet photodissociation (UVPD) has shown great utility for localizing sites of unsaturation within acyl chains and to date has predominantly been used for positive mode analysis of GPLs. In the present work, UVPD is used to localize sites of unsaturation in GPL anions. Similar to UVPD mass spectra of GPL cations, UVPD of deprotonated or formate-adducted GPLs yields diagnostic fragment ions spaced 24 Da apart. This method was integrated into a liquid chromatography workflow and used to evaluate profiles of sites of unsaturation of lipids in Escherichia coli (E. coli) and Acinetobacter baumannii (A. baumannii). When assigning sites of unsaturation, E. coli was found to contain all unsaturation elements at the same position relative to the terminal methyl carbon of the acyl chain; the first carbon participating in a site of unsaturation was consistently seven carbons along the acyl chain when counting carbons from the terminal methyl carbon. GPLs from A. baumannii exhibited more variability in locations of unsaturation. For GPLs containing sites of unsaturation in both acyl chains, an MS3 method was devised to assign sites to specific acyl chains.

Molecular dynamics study of nanoscale organization and hydrogen bonding in binary mixtures of butylammonium nitrate ionic liquid and primary alcohols.

Molecular dynamics simulations are utilized here to explore the nanoscale morphology and the nature of hydrogen bonding in the equimolar mixtures of butylammonium nitrate protic ionic liquid with ethanol, propanol, and butanol. The X-ray scattering experimental study of Greaves et al. [Phys. Chem. Chem. Phys. 13, 13 501 (2011)] has evidenced that alkylammonium nitrate plus alcohol mixtures possess nanoscale structural order which becomes more pronounced as the chain length of the alcohol increases. Our analysis carried out using simulated total and partial X-ray scattering structure functions quantifies the basis of these observations. The partial structure functions highlight the off-phase density correlations of alcohol with both cation and anion in the low-q region. We demonstrate that the chain lengthening of alcohols offers significant variation in the structuring of the polar and apolar moieties in the mixtures. The inspection based on radial distribution functions manifests the non-linear hydrogen bonds of cations with nitrate anions as well as alcohol molecules. The alcohol's hydroxyl group prefers to form linear hydrogen bonds with anions and with other alcohol molecules. Incremented chain length of alcohol improves the extent of hydrogen bonding but does not alter their geometry. Spatial distribution functions delineate similar preferences. It shows stronger directional preferences of the hydroxyl group of alcohols than cation in the vicinity of an anion. Enhanced pair correlations associated with the terminal methyl carbons suggest aggregation of butanol chains in apolar domains. Triplet correlation functions (TCFs) are also used to evaluate the orientational preferences of the present polar moieties in the mixtures. Information based on TCFs for distribution of polar head group of cations and anions unveils the dominance of equilateral configurations over the less frequent isosceles configurations in all the three mixtures.

Study of conformation and dynamic of surfactant molecules in graphite oxide via NMR

The conformation and dynamic of surfactant in graphite oxide (GO) was investigated by solid-state 13C magic-angle-spinning NMR and 1H–13C cross-polarization/magic-angle-spinning NMR spectra. The conformation ordering of the alkyl chains in the confined system shows strong dependence on its orientation. While the alkyl chains parallel to the GO layer in lateral monolayer arrangement are in gauche conformation in addition to a small amount of all-trans conformation, those with orientation radiating away from the GO in paraffin bilayer arrangement is in all-trans conformation in addition to some gauche conformation even though high-order diffraction peaks appears. NMR results suggest that the least mobile segment is located at the GO-surfactant interface corresponding to the N-methylene group. Further from it, the mobility of the alkyl chain increases. The terminal methyl and N-methyl carbon groups have the highest mobile. The chains in all-trans conformational state are characterized as more rigid than chains with gauche conformation; each segment of the confined alkyl chains with the lateral monolayer arrangement exhibits less mobility as compared to that with the paraffin bilayer arrangement.

Measurement of position-specific 13C isotopic composition of propane at the nanomole level

We have developed a novel method for analyzing intramolecular carbon isotopic distribution of propane as a potential new tracer of its origin. The method is based on on-line pyrolysis of propane followed by analysis of carbon isotope ratios of the pyrolytic products methane, ethylene and ethane. Using propane samples spiked with 13C at the terminal methyl carbon, we characterize the origin of the pyrolytic fragments. We show that the exchange between C-atoms during the pyrolytic process is negligible, and thus that relative intramolecular isotope composition can be calculated. Preliminary data from 3 samples show that site-preference (SP) values, defined as the difference of δ13C values between terminal and sub-terminal C-atom positions of propane, range from −1.8‰ to −12.9‰. In addition, SP value obtained using our method for a thermogenic natural gas sample is consistent with that expected from theoretical models of thermal cracking, suggesting that the isotope fractionation associated with propane pyrolysis is negligible. The method will provide novel insights into the characterization of the origin of propane and will help better understand the biogeochemistry of natural gas deposits.

NMR study on relationships between reorientational dynamics and phase behaviour of room-temperature ionic liquids: 1-alkyl-3-methylimidazolium cations

We measured longitudinal and transverse relaxation times (T(1) and T(2)) for (1)H, (13)C-T(1) and (13)C spectra for room-temperature ionic liquids of 1-alkyl-3-methylimidazolium bromide [C(n)mim]Br (n = 2, 3, 4) as a function of temperature. Their values and spectra reveal close relationships between their unique phase behaviours and the dynamics of carbons constituting the cations. Carbons in these cations are classified into groups according to their dynamics, namely imidazolium carbons, an N-methyl carbon, a terminal methyl carbon of the alkyl group and others of the alkyl group. The temperature dependences of T(1) values for these groups differ greatly, resulting in a variation in the characteristic thermal behaviours of the salts. Values of (1)H-T(1) and (13)C-T(1) suggest that some carbons continue to move even in the crystalline and/or solid states. Using (13)C-T(1) data, we also estimated the temperature dependences of the correlation times for the segmental motions of carbons in the liquid states.

Liquid structure of N-butyl- N-methylpyrrolidinium bis-(trifluoromethanesulfonyl) amide ionic liquid studied by large angle X-ray scattering and molecular dynamics simulations

Large angle X-ray scattering of the N-butyl- N-methylpyrrolidinium bis-(trifluoromethanesulfony) amide (P 14 +TFSA −) ionic liquid was measured at 298 K. The total interference function i LAXS( s) and the total pair correlation function G LAXS( r) were successfully obtained. The i LAXS( s) was analyzed in terms of the intra-molecular geometries of the conformational isomers of the P 14 + and TFSA − ions based on the crystal structures, the inter-molecular correlation function G inter LAXS( r) and the inter-molecular radial distribution function as the form D inter LAXS( r) − 4 πr 2 ρ 0 were evaluated. With D inter LAXS( r) − 4 πr 2 ρ 0, the inter-molecular correlation peaks at 3.5, 4.5 and 5–6 Å evidently appeared as the short range interaction, while considerable long range interactions were found as the broad peaks at 10 and 15 Å. Molecular dynamics simulations of the ionic liquid based on the effective pairwise potentials were carried out. The X-ray total interference function derived from the MD simulations i MD( s) was in agreement with the experimental one. According to the inter-molecular partial atom–atom correlation functions from MD simulations, the observed peaks at 3.5, 4.5 and 5–6 Å can be predominantly ascribed to the closest atom–atom correlations between the P 14 + and TFSA – ions such as C···O and C···F. In the inter-molecular partial atom–atom correlation function between terminal methyl carbons of the butyl chain in the P 14 + ion, a peak at 4.0 Å was found as the inter-molecular correlation, suggesting that the ionic liquid shows an alkyl chain aggregation, which is similar to that observed for 1-alkyl-3-methylmidazolium ionic liquids.

The Influence of Polytypic Structures on the Solid-state 13C NMR Spectra of n-Alkanes

Abstract Two polytypes for the monoclinic (M011) modification of n-hexatriacontane (n-C36H74), single-layered structure Mon and double-layered structure Orth II, were studied by means of the solid-state CP/MAS 13C NMR spectroscopy. The terminal methyl carbon showed clear differences in the chemical shift as well as spin-lattice relaxation time (T1) between Mon and Orth II, in contrast to no marked difference for the other carbons.

Supercritical Water Cracking and Washing of Used Polymer.

A rubber polymer (EPDM, ethylene-propylene-diene-terpolymer) and its vulcanized rubber were cracked to paraffin oil (PO) in NaOH-containing supercrtitical water (SCW) at 420°C and 30 MPa. PO recovered as a hexane-soluble cracking component could be recycled as the rubber softener because sulfurs added to the rubber for the elasticity were washed out in SCW. The SCW polymer cracking is not oxidative but reductive. The 13C-NMR analysis of PO obtained by SCW D2O cracking demonstrates that the terminal methyl carbons are deuterated as a clear indication of hydrogen supply by SCW.

Low Temperature Studies of Amorphous, Interfacial, and Crystalline Phases in Asphalts Using Solid-State 13C Nuclear Magnetic Resonance

The road performance behavior of an asphalt depends upon its susceptibility to changes in its rheological properties with time and temperature. One important fundamental molecular property of an asphalt, which dictates its temperature-dependent performance, is the nature of the molecular motions associated with the asphalt molecular components. Changes in the rotational motions of the methyl carbons and the segmental motions of the methylene carbons in the 1- to 10-kHz frequency range were studied (via changes in spin-spin dipolar-dephasing relaxation times) as a function of temperature for three Strategic Highway Research Program asphalts using carbon-13 dipolar-dephasing cross polarization with magic angle spinning nuclear magnetic resonance. The data indicate that the rotational motion of the terminal methyl carbons of n-alkanes in the amorphous phase is nearly independent of decreasing temperature until the glass-transition region is reached. Below the Tg, the rotational motion of the methyl carbons decreases slowly with decrease in temperature for asphalts AAA-1 and AAB-1. However, the methyl rotation in asphalt AAM-1 decreases more rapidly. The segmental motions of the methylene carbons in the mobile-amorphous phase for the different asphalts decrease rapidly with decreasing temperature from 20 to – 20°C. At temperatures below — 20°C, the segmental motions have essentially ceased. The slow, low-frequency motions of the methylene carbons in the inter-facial (rigid-amorphous) and crystalline phases were found to be independent of temperature above and below Tg. It is suggested that the methyl rotation and segmental motions of the methylene carbons in the amorphous phase extensively influence the low-temperature rheological properties of asphalts.

13C-NMR Evidence for Hydrogen Supply by Water for Polymer Cracking in Supercritical Water

Abstract A rubber polymer (EPDM, ethylene-propylene-diene-terpolymer) vulcanized was cracked to paraffinic oil (PO) in NaOH-containing supercritical water (SCW) at 420 °C and 30 MPa. The SCW polymer cracking in not oxidative but reductive. The 13C-NMR analysis of PO obtained by SCW D2O cracking demonstrates that the terminal methyl carbons are deuterated as a clear indication of hydrogen supply by SCW in the cracking.

Monoacylglycerols alter the lipid composition and molecular mobility of phosphatidylcholine bilayers: 13C NMR evidence of dynamic lipid remodeling

The physical effects of monoacylglycerols (MAG) in small unilamellar vesicles composed of phosphatidyl-choline (PC), triolein, cholesterol, and varying amounts of monopalmitin and monoolein were studied by 13C-NMR. The signal to noise ratio of the carbonyls of PC and triolein were enhanced by the addition of 1,2-di-[1-13C]palmitoylphosphatidylcholine and tri-[1-13C]oleoylglycerol. The linewidths of the carbonyl-13C, choline methyl, olefinic carbon, and terminal methyl resonances were measured digitally from vesicles with 0 to 42 mol % of MAG. Significant increases in the linewidth of carbonyl (P < 0.05), olefinic and terminal methyl carbons (P < 0.01) of vesicles containing 42 mol % monopalmitin indicated that these groups experienced restricted molecular mobility at high monopalmitin concentrations. However, more striking was the apparent displacement of triolein from the surface environment of PC bilayers to an oil-like environment in systems containing only 8 mol % monopalmitin. Displacement of triolein from the surface by monoolein occurred only above 15 mol %. Thus, saturated and monounsaturated monoacylglycerols, natural products of lipoprotein metabolism, dynamically alter both the lipid composition and molecular mobility of lipoprotein surfaces in distinct ways.

脱ミネラルしたオイルシェールケロージェンの構造解析

The average unit structures of Thai, Colorado and Condor oil shale kerogens were estimated from the results of elementary analysis, and the contents of aromatic, aromatic quaternary, aliphatic and terminal methyl carbons determinedby means of solid state 13C CP/MAS NMR and Dipolar Dephasing NMR (DD) techniques.The average unin structures of these kerogens consisted of 1-2 aromatic and 2-5 naphthenic rings, which were conjuncted only 2 carbons, and 2-3 side chains. The structure of the fused rings was very similar to those of steroids or trierpenoids, which were found in oil shale kerogen as biomarkers. Thai kerogen had longer side chain than the others. Condor kerogen was thought to contain more naphthenic rings than the others.

Biosynthesis of the dialkylmaleic anhydride-containing antibiotics, tautomycin and tautomycetin

The biosynthetic origins of tautomycin and tautomycetin produced by Streptomyces spiroverticillatus and Streptomyces griseochromogenus, respectively, have been studied by feeding experiments with 13C labelled precursors. The left half of tautomycin and tautomycetin are synthesized from one propionate and a C-5 unit. The latter is formed from three acetate units with decarboxylation. The labelling pattern from 13C-acetates indicated that α-keto glutarate or an equivalent may be a precursor. The results of a feeding experiment of [1,2-13C2]glutamate afforded the direct proof for this idea. The right half of tautomycin is biosynthesized by a polyketide pathway which starts with isobutyrate followed by introduction of a glycolate, five acetate and five propionate units. The terminal methyl carbon originates from an acetate-methyl probably formed by decarboxylation of the intermediate terminal β-keto carboxylate anion. The right half of tautomycetin is formed via a polyketide pathway which starts with acetate followed by introduction of three acetate and four propionate units and one butyrate unit.

Dynamic description of the oxidation of n-butane on various faces of (VO) 2P 2O 7 in terms of the crystallochemical model of active sites

(VO) 2P 2O 7 is known to be a very good industrial catalyst for the selective, direct oxidation of n-butane to maleic anhydride, provided that the catalyst is prepared by ways which lead to the predominant exposure of the {100} crystal face. In a former paper ( J. Catal., 122 (1990) 126) we analyzed the geometry and energetics of the {100} face in terms of the crystallochemical model of active sites (CMAS), along with all possible butane-surface interactions and elementary steps. We indicated the structure and performance of the active cluster site for the discussed reaction and its energetically most favourable pathway. Analogous analysis is done in this work for other faces which (according to the electron microscopy studies) are exposed by (VO) 2P 2O 7 crystals: {001}, {010}, {021} and {012}, including the crystallographically non-equivalent sections. It is shown that n-butane reacting on these faces encounters various geometric and energetic “troubles”, much more important than those on {100}. They consist either in an non-convenient arrangement of active, undersaturated oxygens around the possible adsorption sites (hindering a bifurcated activation or bridging of the terminal methyl carbons), or in very high energy barriers for some elementary steps (especially for evolution of water and insertion or surface transfer of oxygen). These hindrances are responsible for the lower activity and selectivity of faces other than {100}. Consequently the catalytic anisotropy shown by (VO) 2P 2O 7 in oxidation of butane is explained by CMAS. Based on the surface energy calculations and Curie-Wulff plot, it is also shown that in the state close to equilibrium, the area of the {100} face comprises only about 30% of the total external grain area. Therefore any method of preparation which contributes to the development of the {100} face enhances strongly the activity and selectivity of the catalyst.

Synthesis of carbon‐13 labeled ibuprofen

AbstractThis report describes the synthesis of ibuprofen of labeled with carbon‐13 either at the terminal methyl carbons, or at the methine carbon of the isobutyl side chain. The synthetic route involves the removal of the isopropyl group in the isobut I side‐chain of ibuprofen via 2‐[4‐(2‐methyl‐1‐propenyl)phenyl] propionic acid followed by restoration of the isopropyl group with a Wittig reaction, using appropriate carbon‐1 3 labeled acetone as the precursor of the isopropyl group. Interesting NMR coupling data attributable to phosphorous and carbon‐13 are presented in the experimental section.

Solid-state 13C nuclear magnetic resonance spectroscopy of simultaneously metabolized acetate and phenol in a soil Pseudomonas sp.

We investigated concentration-dependent primary and secondary substrate relationships in the simultaneous metabolism of the ubiquitous pollutant phenol and the naturally occurring substrate acetate by a Pseudomonas sp. soil isolate capable of utilizing either substance as a sole source of carbon and energy. In addition to conventional analytical techniques, solid-state 13C nuclear magnetic resonance spectroscopy was used to follow the cellular distribution of [1-13C]acetate in the presence of unlabeled phenol. With 5 mM acetate as the primary substrate, Pseudomonas sp. 9S8D2 removed 1 mM phenol (secondary substrate) at a rate of 2 nmol/mg of total cell protein. Although extensive acetate metabolism was indicated by a significant redistribution of the carboxyl label, this redistribution was not affected by the presence of phenol as a secondary substrate. When the primary and secondary substrate roles were reversed, however, the presence of 1 mM phenol altered the metabolism of 0.1 mM acetate, as evidenced by both the two- to fourfold increases in carboxyl label that appeared in terminal methyl and acyl chain methylene carbon resonances and the decrease in label that occurred in the carbohydrate spectral region. These results suggest that, when phenol is present as the primary substrate, acetate is preferentially shuttled into fatty acyl chain synthesis, whereas phenol carbon is funnelled into the tricarboxylic acid cycle. Thus, simultaneous use of a xenobiotic compound and a natural substrate apparently does occur, and the relative concentrations of the two substrates do influence the rate and manner in which the compounds are utilized.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions of myristic acid with bovine serum albumin: a 13C NMR study.

Interactions of myristic acid with bovine serum albumin were studied by 13C NMR spectroscopy at 50.3 MHz using 90% isotopically substituted [1-13C]-, [3-13C]-, and [14-13C]myristic acids, either individually or in a combination of all three with albumin. At pH 7.4, two or more resonances of different intensities were observed for each 13C-enriched myristic acid. Carboxyl and methylene C-3 resonances corresponding to the major myristic acid environment(s) exhibited pH-dependent chemical shift changes indicative of protonation below pH 6.7; in contrast, carboxyl groups in minor environments were resistant to protonation. 13C NMR spectra obtained as a function of the molar ratio of [3-13C]- and [14-13C]myristic acid to bovine serum albumin (from 0.7 to 5.6) revealed at least two narrow resonances for each carbon at all molar ratios. Thus, bovine serum albumin binding sites for myristic acid are heterogeneous with respect to titration behavior and with respect to the local magnetic environment at both the polar and the nonpolar ends of the fatty acid. The narrow resonances observed for the methylene and methyl carbons are inconsistent with complete immobilization of the protein-bound acid molecules. Together with spin- lattice relaxation times and nuclear Overhauser enhancements, the linewidth results indicate that bound myristic acid has internal motions that are rapid compared with overall protein tumbling and that the C-3 methylene carbon is more restricted than the terminal methyl carbon.

Geometry of muscarinic agonists.

In order to account for a common geometric character of the skeleton of known muscarinic agonist molecules in the drug-receptor interaction, common key atoms, terminal methyl carbon, two oxygen, and ammonium nitrogen atoms were remarked which were shown by computer calculation to be concentrated at definite points in space and to be arranged nearly in a plane. Comparison of overlapped patterns of potent agonists and weak-acting or inactive analogues drew a conclusion that the complemental receptor site have a relatively flat shape.

Intramolecular interactions and spin–lattice relaxation times of methyl groups

AbstractThe carbon T1 values of the alkyl substituents of various compounds have been measured. The salient observation is that the terminal methyl carbon of the n‐propyl or a three‐carbon chain bonded to an electronegative atom X(or an electron‐donating group) has a reduced T1 value. A net attractive interaction between the methyl hydrogen atoms and X in the gauche conformation is invoked to account for the observed result. In chains longer than three carbons that are not firmly anchored at one end, the γ steric interaction is suggested to be the main steric interaction that causes the reduced T1 value observed for the terminal methyl carbon.