Characterizing ion mobility and collision cross section of fatty acids using electrospray ion mobility mass spectrometry

This study investigated the ion mobility (IM) and the collision cross section (CCS) of fatty acids (FAs) using electrospray IM MS. The IM analysis of 18 FA ions showed intriguing differences among the saturated FAs, monounsaturated FAs, multi‐unsaturated FAs, and cis‐isomer/trans‐isomer with respect to the aliphatic tail chains. The length of aliphatic tail chain present in the ion structures had a strong influence on the differentiation of drift, while the number of double bond showed a weaker influence. The tiny drift differences between cis‐isomer and trans‐isomer were also observed. In the CCS measurements, two internal standards were involved in the mobility calibration and accuracy estimation. It insured our empirical CCS values were of high experimental precision (±0.35% or better) and accuracy (±0.25% or better). Moreover, the mass‐to‐charge ratio (m/z) – mobility plots obtained by ion mobility spectrometry with mass spectrometry analysis of FAs – was used to investigate the structural relationship between the molecules. Each series of FAs sharing a similar structure was aligned in the linear plot. Finally, the developed procedure was applied to the determination of FAs in rat adipose tissues, and it allowed the presence of 13 FAs to be confirmed with their exact masses and CCS values. These studies reveal the direct relationship between the behaviors in IM and the molecular structures and thus may provide further validations to the FA identification process. Copyright © 2015 John Wiley & Sons, Ltd.     

Revised structure and synthesis of piperolein acids,guineensine and wisanine from Piper guineense

The structures of piperolein acids guineensine and wisanine have been confirmed by synthesis, UV irradiation of trans piperolein B acid ester gave the cis-isomer reported in the literature as the trans-isomer. The trans-2, trans-4 ethylenic bonds in guineensine and wisanine were introduced by reacting piperolein B aldehyde and 2-methoxy piperonal with the appropriate Wittig or Reformatsky reagent.     

Solvent dependent photo-isomerization of 4-dimethylaminoazobenzene carboxylic acid

We have observed reversible trans–cis photo-isomerization behaviors of 4-dimethylaminoazobenzene carboxylic acid (4DAzC) in ethyl acetate by alternating irradiations at 370 and 430 nm. The photo-isomerization from trans- to cis-isomer was found to be strongly solvent dependent and not to occur efficiently in water and ethanol. Also photo-isomerization from cis- to trans-isomer was occurred upon 370 nm illumination or via thermal relaxation. The activation energy for the thermal isomerization from cis to trans-isomer was estimated to be 49.2 kJ/mol in ethyl acetate from the temperature-dependent kinetic absorption measurements.     

CHARACTERIZATION OF CIS- AND TRANS-DINITROBIS-(l-CYCLOHEXANEDIAMINE)-COBALT(III) CHLORIDE1

Abstract

Two geometrical isomers of [Co(l-chxn)₂(No₂)₂]Cl have been isolated. The trans-isomer is eluted first from a cellulose ion exchange column as a single isomer. The cis-isomer corresponds to the complex previously reported as the trans-isomer. The cis-isomer with the same CD sign pattern as for the trans-isomer is stereoselectively favored, but a small amount of the second cis-isomer separates using Cellex CM ion exchange cellulose. The CD spectra of the cis- and trans- isomers are similar to those of the corresponding isomers of the l-pn complex.     

Identification of cis/trans isomers of methyl ester and oxazoline derivatives of unsaturated fatty acids using GC–FTIR–MS

Identification of cis/trans isomers of unsaturated fatty acids cannot usually be achieved by GC-MS (gas chromatography-mass spectrometry) without reference substances. In this study a GC-FTIR-MS system (gas chromatography-Fourier transform-mass spectrometry) was used to identify fatty acid methyl esters (FAMEs) and differentiate between the cis/trans isomers. Besides methyl esters, 2-alkenyl-4,4-dimethyloxazoline derivatives (DMOX), which have been used to locate double bond positions of unsaturated fatty acids, were examined with respect to their suitability for cis/trans differentiation. A combined GC-FTIR-MS system with a wide band (4000–550 cm^?1) mercury cadmium telluride (MCT) detector was used in series and parallel to identify 31 reference unsaturated fatty acids, including 7 pairs of cis/trans isomers. Serum samples of healthy persons and commercially available fish oil were analyzed as examples of complex mixtures. Using splitless injection the detection limit for the less sensitive IR detector was 25 ng/μl in case of the weak cis and trans bands. In the FTIR spectra cis/trans isomers were identified by analysis of bands arising from C? H out-of-plane (oop) bending: for both the FAME and DMOX derivatives cis-1,2-disubstituted double bonds give a strong band near 720 cm^?1 and the corresponding trans isomers near 967 cm^?1. cis Isomers could be identified further by a band at 3012 cm^?1. With the combined data of the GC-FTIR-MS system it is now possible to identify polyunsaturated fatty acids with regard to the discrimination of cis/trans isomers.     

Acid‐based approach for separation of peptide epimers using IM‐MS

Chiral molecules frequently remain undistinguishable using ion mobility mass spectrometry (IM‐MS), due to insufficient differences of their collision cross sections at the available mobility resolution of the ion mobility drift tubes. The influence of the complexation with organic acids on the ion mobility separation of peptide epimers is evaluated using traveling‐wave ion mobility (TWIMS). The examined epimeric tripeptides containing Arg residue with the sequence: Ac‐Phe‐Arg‐Trp‐NH₂ formed stable complexes in the gas phase, and under the increased pressure in ion mobility drift tube, noncovalent associates formed with carboxylic or sulfonic monoacids and diacids with chiral variation of certain acids. Overall, the complexation with an acid leads to the improvement in stereodifferentiation among epimeric peptides, in comparison to the analysis of pure epimers. Detailed characterization of peptide epimer‐acid associates obtained for dibenzoyl‐D‐tartaric acid by theoretical calculations and collisional dissociation studies revealed that the presence of multiple hydrogen bonding interactions between carboxylate anions and hydrogens from N―H of both the guanidinium group of arginine and the indole of tryptophan, as well as the amide backbone hydrogens in the peptide, is responsible for stability of acid‐peptide complexes and for their differentiation in the ion mobility drift tube. The specificity of complex formation toward Arg was determined in terms of complex stability. Based on the reported results, we present general conclusions regarding the utility of the acid‐based complexation in the separation of peptide isomers.     

Ion mobility-mass spectrometry separation of steroid structural isomers and epimers

Drift tube ion mobility spectrometry (DTIMS) coupled with mass spectrometry was evaluated for its capabilities in rapid separation of endogenous isomeric steroids. These compounds, which included eight isomer groups, were investigated as protonated and sodiated species and collision cross sections were measured for all ionization species of each steroid. Pregnenolone (CCS_N2 176.7 Å²) and 5α-dihydroprogesterone (CCS_N2 191.4 Å²) could be separated as protonated species, and aldosterone (CCS_N2 197.7 Å²) and cortisone (CCS_N2 211.7 Å²) could be separated as sodiated monomers. However, the sodiated dimers of the remaining isomers yielded increased separation, resulting in baseline resolution. Specific structural differences including ring conformation and the chirality of hydroxyl groups were compared to evaluate their relative effects on collision cross section in isomers. These results indicated that C5 ring conformation isomers androsterone and etiocholanolone, which both contain a C3 α-hydroxyl group, yielded similar dimer CCS. Yet these compounds were well resolved from their respective β-hydroxyl epimers, trans-androsterone and epietiocholanolone. Alternative drift gases were evaluated, and carbon dioxide drift gas offered slight improvement in isomer resolution well, including allowing separation of testosterone (CCS_CO2 330.0 Å²), dehydroepiandrosterone (CCS_CO2 312.6 Å²), and epitestosterone (CCS_CO2 305.6 Å²). Finally, different metal cation adducts, including alkali, alkaline earth, and first row transition metal adducts were analyzed, and several of these species provided improved resolution between steroid epimers. Overall, this study shows that drift tube ion mobility is a promising tool for improved separation of isomeric steroids.     

trans-chloro(N,N-dimethyl-d-phenylglycine)-(3-methyl-1-phenylpent-1-ene)platinum(II) complexes. HPLC separation and identification of all the diastereomers

The diastereomeric trans-chloro(N,N-dimethyl-d-phenylglycine)(3-methyl-1-phenylpent-1-ene)platinum(II) complexes, derived by coordination of the enantiomeric and geometric isomers of 3-methyl-1-phenylpent-1-ene (2), were separated by HPLC. Four trans- and two cis-olefin complexes were recognized in the chromatogram. The configuration of all chiral centers of the olefin in the six complexes were assigned. Under the conditions of preparation, the pairs of diastereomers 1R,2R,3S/1S,2S,3S and 1S,2S,3R/1R,2R,3R were formed in a ratio > 1 for the trans-isomer, whereas the cis-isomer gave the 1R,2S,3S and 1S,2R,3R epimers only. The complexes do not epimerize on standing at room temperature in solution; similar behaviour of the corresponding complexes of trans-stilbene (4C) indicates that the conjugated aromatic double bond is coordinated more strongly than those aliphatic and cycloaliphatic olefins.The efficient HPLC separation of the diasteromeric complexes 2C, permits the enantiomeric analysis of 2, as well as the preparative resolution of the olefin.     

Two Minute Separation of the cis- and trans-Isomers of Vitamin K1 without Heptane, Chlorinated Solvents, or Acetonitrile

Resolution of the cis-, trans-isomers of vitamin K₁ (phylloquinone) is important in nutritional analysis since only the trans-isomer is biologically active, while artificial vitamin K₁ may contain significant amounts of the inactive cis-isomer. The cis-, trans-isomers of vitamin K₁ were separated, with a resolution of 3.4, using pure carbon dioxide (CO₂) as the mobile phase, with a run time ≈6 min, on a 4.6 × 150 mm, 3.5 μm RX-Sil bare silica column, using supercritical fluid chromatography (SFC). With 2.5 % ethyl acetate in CO₂, R_s = 2.77, with a run time <4 min. On a 3 × 100 mm, 1.8 μm RX-Sil column R_s remained at 2.69, with a run time just over 2 min. This is the first report on the apparent separation of these isomers by SFC, and is up to 3–5 times faster than separations using high performance liquid chromatography (HPLC) in the literature. Unlike most HPLC separations, no dichloromethane, acetonitrile, or hexane/heptane was used. The CO₂ was beverage grade, at 1/20th to 1/50th the cost of the replaced organics, is recycled, and is considered “green”.     

Porphyrines synthètiques porteuses de chaines laterales peptidiques - II : Synthèse et etude comparée des cis et trans (mésotétraphénylporphyrinyl)-3-propénamides

The synthesis and structural properties are reported for mesotetraphenylporphyrin cis and trans 3-propenamide, obtained by condensation of amines or C-protected amino-acids with corresponding carboxylic acids by means of the BOP reagent. The mesotetraphenylporphyrin cis 3-propenoic acid yields cis endo and cis exo atropoisomers. These structural attributions were based on their spectral properties (NMR and circular dichroism). Cis endo and cis exo isomers may be equilibrated in refluxing toluene. The trans 3- propenoic mesotetraphenylporphyrin acid yields only one isomer.     

Potential Stereoselective Binding of Trans-(±)-Kusunokinin and Cis-(±)-Kusunokinin Isomers to CSF1R

Breast cancer cell proliferation and migration are inhibited by naturally extracted trans-(−)-kusunokinin. However, three additional enantiomers of kusunokinin have yet to be investigated: trans-(+)-kusunokinin, cis-(−)-isomer and cis-(+)-isomer. According to the results of molecular docking studies of kusunokinin isomers on 60 breast cancer-related proteins, trans-(−)-kusunokinin was the most preferable and active component of the trans-racemic mixture. Trans-(−)-kusunokinin targeted proteins involved in cell growth and proliferation, whereas the cis-(+)-isomer targeted proteins involved in metastasis. Trans-(−)-kusunokinin targeted CSF1R specifically, whereas trans-(+)-kusunokinin and both cis-isomers may have bound AKR1B1. Interestingly, the compound’s stereoisomeric effect may influence protein selectivity. CSF1R preferred trans-(−)-kusunokinin over trans-(+)-kusunokinin because the binding pocket required a ligand planar arrangement to form a π-π interaction with a selective Trp550. Because of its large binding pocket, EGFR exhibited no stereoselectivity. MD simulation revealed that trans-(−)-kusunokinin, trans-(+)-kusunokinin and pexidartinib bound CSF1R differently. Pexidartinib had the highest binding affinity, followed by trans-(−)-kusunokinin and trans-(+)-kusunokinin, respectively. The trans-(−)-kusunokinin-CSF1R complex was found to be stable, whereas trans-(+)-kusunokinin was not. Trans-(±)-kusunokinin, a potential racemic compound, could be developed as a selective CSF1R inhibitor when combined.     

Complete separation of the geometical isomers of linolenic acid by high performance liquid chromatography with a silver ion column

A method has been developed for separation of linolenic acid and its seven isomers by HPLC on a silver-ion-loaded column. The standard 18:3 isomers, isolated from a heated linseed oil or prepared by isomerization of linolenic acid, were converted into phenacyl esters and detected by UV at 238 nm. The use of low temperature (10 °C) combined with a gradient of dichloromethane and methanol enabled separation of all the cis/trans isomers. The peaks were identified by comparison of ECL values with those of a standard mixture, by chromatographing collected HPLC fractions on a polar GC column. HPLC quantification was compared with GC analysis. There was satisfactory agreement between the tow methods. This method could be used for seperation, collection and quantification of 18:3 fatty acids with trans double bonds in different oils and foods.     

Synthesis and reactions of a monosubstituted dithiirane 1-oxide, 3-(9-triptycyl)dithiirane 1-oxide

A 3-monosubstituted dithiirane 1-oxide, 3-(9-triptycyl)dithiirane 1-oxide, was prepared for the first time, by the reaction of (9-triptycyl)diazomethane and S₈O. The dithiirane 1-oxide was obtained as cis- and trans-isomers, and the structure of the trans-isomer was verified by X-ray crystallography. The cis-isomer isomerized gradually to the trans-isomer in solution. The divalent sulfur atom of the cis- and trans-dithiirane 1-oxides were removed on treatment with triphenylphosphine to give the corresponding Z- and E-sulfines, respectively. The reaction of the trans-dithiirane 1-oxide with (Ph₃P)₂Pt(C₂H₄) provided the (sulfenato-thiolato)Pt^II complex, and that with Lawesson's reagent yielded the 1,3,4,2-trithiaphospholane and 1,2,4,5,3-tetrathiaphosphorinane derivatives.     

Stereochemical effects in the chemical ionization mass spectra of cyclic diols

The chemical ionization mass spectra of configurational isomers of many cyclic diols give substantial differences which are characteristic of their stereochemistry. For the cis-isomer of 1,3- and 1,4-cyclohexanediols, formation of a stable intramolecular proton bridge involving the OH groups gives rise to dominant MH⁺ peaks, suppressing the (M-H)⁺ peaks found in the spectra of the trans-isomers and monoalcohols. The stability of the proton bridge in cis-1,3-cyclohexanediol structures is decreased by a sterically interfering cis-5-methyl substituent, but increased by a cis-5-OH group due to additional proton solvation. cis-Stereochemistry also gives increased formation of the dimeric M₂H⁺ ions, but decreased formation of trimers, at higher diol concentrations, for the 1,3- and 1,4-diols. The similarity of the CI spectra of cis- and trans-1,2-cyclohexanediol are explicable in terms of the similarities of the most stable proton-bridged conformers; the reduced ring flexibility in cis- and trans-1,2-cyclopentanediols makes such similar structures unfavorable, as shown by the substantial differences between their CI spectra. The substantial, but expected, variations in behavior with temperature and reagent gas are useful for maximizing stereochemical effects on CI spectra; conditions of lowest energy are usually, but not always, the most useful.     

Molecular species in liquid carboxylic acids

Measurements of dielectric permittivity and electric conductance are presented for mixtures of carboxylic acids — formic, trifluoroacetic, acetic and propionic — and non-polar liquids. For the dielectric and associative behavior of carboxylic acids a knowledge of the cis—trans conformational equilibria of the monomeric acid molecules seems to be essential. Therefore the cis and trans conformations of these molecules have been calculated by the CNDO/2 and PCILO methods. Appreciable rotational barriers for their interconversion have been obtained.     

Electrochemical studies and photoconversion of cis-and trans-6,6′-diethoxythioindigo

The reduction of cis- and trans-6,6′-diethoxythioindigo (DETI) at a platinum electrode in N,N-dimethylformamide (DMF) solution was studied by cyclic voltammetry and controlled potential coulometry. The cis-form, produced by photoisomerization of the trans-form, is reduced at less negative potentials than the trans-. The trans-isomer produces a fairly stable radical anion upon one-electron reduction; the cis-radical anion isomerizes rapidly to the trans-form and also dimerizes much more rapidly than the trans-isomer. A photogalvanic cell based on this system was devised but showed low efficiency for conversion of radiant energy to electricity.     

The molecular structure of trans- and cis-bicyclo-[4.3.0]nonane in the gas phase,studied by electron diffraction and molecular mechanics

The structure and conformations of trans- and of cis-bicyclo[4.3.0]nonane have been studied in the gas phase. Molecular mechanics calculations applying the force field of Ermer and Lifson were used to obtain geometrical constraints, vibrational amplitudes and perpendicular vibrational corrections. The vibrational parameters were corrected for the large amplitude motion of the five-membered ring. The refinement for the trans-isomer confirms completely the predictions of the force field calculations. Although a stable solution could not be obtained for the cis-compound there is no contradiction between experiment and model calculations. The cyclohexane ring in both isomers is found to have a distorted chair conformation. In the cis-isomer it is flattened along the junction and more twisted in the other part. For the trans-compound the reverse is true.The following structural parameters r_g, r_α-structure) are put forward, (a) trans-compound: C₂-symmetry, _r(C-C)_av = 1.536 Å. Average bond angle and average torsion angle in the cyclohexane ring are 110.2° and 58.1°, respectively. The connection angle, defined as the angle between the planes bisecting C6-C1-C5-C9 and C2-C1-C5-C4, is 180°. (b) cis-compound: no symmetry, r(C-C)_av = 1.536 Å. Average bond and torsion angles in the cyclohexane ring are 112.2° and 52.3°, respectively. The connection angle is 124.8°.A comparison is made with structures of related compounds.     

Phenylene vinylene oligomers studied by theoretical methods: Joint analysis of computational and x-ray results of the configurational isomers of 1,4-bis[2-(3,4,5-trimethoxyphenyl)ethenyl]benzene

The configurational isomers of 1,4-bis[2-(3,4,5-trimethoxyphenyl)ethenyl]benzene have been investigated by ab initio and MOPAC-AM1 semiempirical methods. The calculations were guided by and compared with single crystal X-ray results of the trans, trans-isomer (taken from the literature) and of the cis,cis-isomer (reported here). Using 4-21G-based ab initio calculations, free state geometries, deviations from coplanarity, and barriers to rotation of the central and peripheral rings were evaluated. Such barriers were also enumerated for the solid state of the cis,cis- and trans,trans-isomers. A single-molecule cluster surrounded by point charges sufficed to rationalize observed solid state properties in the trans,trans-isomer, including the quasi-free rotation of the central ring. A multimolecule cluster, however, was required to rationalize the restricted rotation of the rings in the cis,cis-isomer. MOPAC-AM1 methods were used to calculate geometries and energies of rotameric forms on the singlet photoisomerization path cis,cis → cis,trans → trans,trans. Finally, UV absorption wavelengths and oscillator strengths were calculated and the electronic structure of the states discussed. © 1996 by John Wiley & Sons, Inc.