Baseline resolution of isomers by traveling wave ion mobility mass spectrometry: investigating the effects of polarizable drift gases and ionic charge distribution.

We have studied the behavior of isomers and analogues by traveling wave ion mobility mass spectrometry (TWIM-MS) using drift-gases with varying masses and polarizabilities. Despite the reduced length of the cell (18 cm), a pair of constitutional isomers, N-butylaniline and para-butylaniline, with theoretical collision cross-section values in helium (ΩHe ) differing by as little as 1.2 Å(2) (1.5%) but possessing contrasting charge distribution, showed baseline peak-to-peak resolution (Rp-p ) for their protonated molecules, using carbon dioxide (CO2), nitrous oxide (N2O) and ethene (C2H4 ) as the TWIM drift-gas. Near baseline Rp-p was also obtained in CO2 for a group of protonated haloanilines (para-chloroaniline, para-bromoaniline and para-iodoaniline) which display contrasting masses and theoretical ΩHe , which differ by as much as 15.7 Å(2) (19.5%) but similar charge distributions. The deprotonated isomeric pair of trans-oleic acid and cis-oleic acid possessing nearly identical theoretical ΩHe and ΩN2 as well as similar charge distributions, remained unresolved. Interestingly, an inversion of drift-times were observed for the 1,3-dialkylimidazolium ions when comparing He, N2 and N2O. Using density functional theory as a means of examining the ions electronic structure, and He and N2-based trajectory method algorithm, we discuss the effect of the long-range charge induced dipole attractive and short-range Van der Waals forces involved in the TWIM separation in drift-gases of differing polarizabilities. We therefore propose that examining the electronic structure of the ions under investigation may potentially indicate whether the use of more polarizable drift-gases could improve separation and the overall success of TWIM-MS analysis.

Exploring the intrinsic polar [4+2(+)] cycloaddition reactivity of gaseous carbosulfonium and carboxonium ions.

Gas-phase reactions of model carbosulfonium ions (CH(3)-S(+)=CH(2;) CH(3)CH(2)-S(+)=CH(2) and Ph-S(+)=CH(2)) and an O-analogue carboxonium ion (CH(3)-O(+)=CH(2)) with acyclic (isoprene, 1,3-butadiene, methyl vinyl ketone) and cyclic (1,3-cyclohexadiene, thiophene, furan) conjugated dienes were systematically investigated by pentaquadrupole mass spectrometry. As corroborated by B3LYP/6-311 G(d,p) calculations, the carbosulfonium ions first react at large extents with the dienes forming adducts via simple addition. The nascent adducts, depending on their stability and internal energy, react further via two competitive channels: (1) in reactions with acyclic dienes via cyclization that yields formally [4+2(+)] cycloadducts, or (2) in reactions with the cyclic dienes via dissociation by HSR loss that yields methylenation (net CH(+) transfer) products. In great contrast to its S-analogues, CH(3)-O(+)=CH(2) (as well as C(2)H(5)-O(+)=CH(2) and Ph-O(+)=CH(2) in reactions with isoprene) forms little or no adduct and proton transfer is the dominant reaction channel. Isomerization to more acidic protonated aldehydes in the course of reaction seems to be the most plausible cause of the contrasting reactivity of carboxonium ions. The CH(2)=CH-O(+)=CH(2) ion forms an abundant [4+2(+)] cycloadduct with isoprene, but similar to the behavior of such α,ß-unsaturated carboxonium ions in solution, seems to occur across the C=C bond.

Intrinsic mobility of gaseous cationic and anionic aggregates of ionic liquids.

Travelling-wave ion mobility mass spectrometry was used to measure the intrinsic mobility of a series of gaseous supra-cation and supra-anion aggregates of several ionic liquids. Close mobilities were observed in a T-wave cell filled with helium at ca. 0.8 mbar for [(DAI)(n+1)(X)(n)](+) (DAI is the 1,3-dialkylimidazolium cation and X is the anion) as compared to the respective anions [(DAI)(n)(X)(n+1)](-) for n=0 to 9. The anomalous behavior reported before in the condensed phase seems therefore to be related to the unique structural organization of pure ionic liquids that provides both polar and non-polar regions with directionality in which the anionic species are more retained than the cationic species in the salt network.

Fast screening and secure confirmation of milk powder adulteration with maltodextrin via electrospray ionization-mass spectrometry [ESI(+)-MS] and selective enzymatic hydrolysis.

Direct-infusion electrospray ionization-mass spectrometry [ESI(+)-MS] of several milk powder samples, confiscated by the Brazilian Federal Police, showed ions accounting for sodiated and potassiated molecules of disaccharides (m/z 365 and 381) as well as trisaccharides (m/z 527 and 543), whereas monosaccharide ions were not detected. The trisaccharide ions were not detected in samples of genuine milk powder, raising the suspicion that their presence indicates adulteration by the addition of maltodextrin. In control samples, maltose and maltotriose were hydrolyzed by alpha-glucosidase and not beta-galactosidase, whereas lactose was resistant to alpha-glucosidase but was hydrolyzed with beta-galactosidase. Samples suspected of being adulterated behaved in the same fashion, confirming the presence of maltose and maltotriose or maltodextrin. Direct-infusion ESI-MS is shown therefore to provide rapid screening of milk powder for adulteration with maltodextrin, whereas its combination with selective enzymatic hydrolysis provides highly reliable confirmation for unambiguous results.

Sesquiterpene lactones from Vernonia scorpioides and their in vitro cytotoxicity.

Fresh leaves of Vernonia scorpioides are widely used in Brazil to treat a variety of skin disorders. Previous in vivo studies with extracts of this species had also demonstrated a high antitumor potential. This paper reports isolation of four sesquiterpene lactones (hirsutinolides and glaucolides), together with diacetylpiptocarphol, 8-acetyl-13-etoxypiptocarphol, luteolin, apigenin, and ethyl caffeate from fresh leaves and flowers of Vernonia scorpioides. The hypothesis that hirsutinolide 3 is formed during extraction was verified theoretically using Density Functional Theory. The effects of isolated compounds on in vitro tumor cells were investigated, as well as their genotoxicity by means of an in vitro comet assay. The results indicate that glaucolide 2 and hirsutinolide 4 are toxic to HeLa cells. These compounds were genotoxic in vitro, a property that appears to be related to the presence of their epoxy groups, which has been a more reliable indication of toxicity than substitution on C-13 or the presence of alpha,beta-unsaturated keto-groups. These results need to be replicated in vivo in order to ascertain their toxicity.

Intrinsic acidity and electrophilicity of gaseous propargyl/allenyl carbocations.

The ion/molecule chemistry of four representative propagyl/allenyl cations 1-4 of the general formula R(1)CH(+)-C[triple bond]C-R (a) <--> R(1)CH=C=C(+)-R (b), that is, the reactive C(3)H(3)(+) ions of m/z 39 from EI of propargyl chloride (H(2)C(+)-C[triple bond]C-H, 1a), isomeric C(4)H(5)(+) ions of m/z 53 from EI of 3-butyne-2-ol (2a, H(2)C(+)-C[triple bond]C-CH(3)) and 2-butyne-1-ol (CH(3)-CH(+)-C[triple bond]C-H, 3a), and Ph-C(3)H(2)(+) ions of m/z 115 from 3-phenyl-2-propyn-1-ol (H(2)C(+)-C[triple bond]C-Ph, 4a) was studied via pentaquadrupole mass spectrometry. With pyridine, proton transfer was observed as the predominant process for 1 and the sole reaction channel for the isomeric 2 and 3, whereas 4 reacted preferentially by adduct formation. These outcomes were rationalized using DFT calculations from isodesmic proton transfer reactions. Similar reaction tendencies were observed with acetonitrile and acrylonitrile, with adduct formation appearing again as a minor pathway for 1, 2 and 4, and as a major reaction channel for 4. With 1,3-dioxolane, hydride abstraction was a dominant reaction, with proton transfer and adduct formation competing as side reactions. With 2,2-dimethyl-1,3-dioxolane, an interplay of reactions including methyl anion abstraction, proton transfer, hydride abstraction and adduct formation were observed depending on the ion structure, with 4 reacting again mainly by adduct formation. Proton transfer was also observed as a dominant process in reactions with ethanol for 1, 2 and 3, with 4 being nearly unreactive whereas no adduct formation was observed for any of the carbocations studied. Limited reactivity was exhibited by these ions in cycloaddition reaction with isoprene.

Petroleomics by EASI(+/-) FT-ICR MS.

An ambient ionization/desorption technique, namely, easy ambient sonic-spray ionization mass spectrometry (EASI), has been applied to crude oil samples. From a single droplet of the sample placed on an inert surface, EASI(+/-) is shown to promote efficient desorption and ionization of a myriad of polar components via the action of its cloud of very minute supersonic bipolar charged droplets. The gaseous [M + H](+) and [M - H](-) ions concurrently formed by EASI(+/-) were analyzed by Fourier transform mass spectrometry (FT-ICR MS), and a total of approximately 6000 acidic and basic components have been attributed. EASI(+/-) FT-ICR MS of crude oils is show to be almost as fast as ESI(+)/ESI(-) FT-ICR MS, providing similar compositional information of polar components and spectral quality comparable to that of a commercial nonochip-based robotic ESI device. EASI(+/-) requires no sample workup thus eliminating risks of contamination during sample manipulation and memory effects because of carry over in pumping ESI lines. More importantly, EASI(+/-) is a voltage-free ionization technique therefore eliminating risks of redox processes or duality of ionization mechanisms that can be observed in voltage-assisted processes. Data visualization via typical petroleomic plots confirms the similarity of the compositional information provided by EASI(+/-) compared to ESI(+)/ESI(-). The ambient EASI(+/-) FT-ICR MS method requires no voltage switching in changing the ion polarity mode, offering a workup, heating and voltage-free protocol for petroleomic studies performed at open atmosphere directly on the undisturbed crude oil sample.

From monomers to geometry-constrained molecules: one step further toward cyanide bridged wires.

We report on the synthesis and properties of a family of linear cyanide bridged mixed-valence heptanuclear complexes with the formula: trans-[L(4)Ru(II){(mu-NC)Fe(III)(NC)(4)(mu-CN)Ru(II)L'(4)(mu-NC)Fe(III)(CN)(5)}(2)](6-) (with L and L' a para substituted pyridine). We also report on the properties of a related pentanuclear complex. These oligomers were purified by size exclusion chromatography, characterized by electrospray ionization (ESI) mass spectrometry and elemental analysis, and their linear shape was confirmed by scanning tunneling microscopy (STM). These complexes present a rich electrochemistry associated with the seven redox active centers. The redox potential split of identical fragments indicates that there is considerable communication along the cyanide bridged backbone of the compounds, even for centers more than 3 nm apart. This small attenuation of the interaction at long distances make these cyanide bridged compounds good candidates for molecular wires. Interestingly, the extent of the communication depends on the relative energy of the fragments, as evaluated by their redox potentials, providing a guide for improvement of this interesting property.

Recognition and resolution of isomeric alkyl anilines by mass spectrometry.

Two MS techniques have been used to recognize and resolve a representative isomeric pair of N-alkyl and ring-alkyl substituted anilines. The first technique (1) uses MS/MS to perform ion/molecule reactions of structurally-diagnostic fragment ions (SDFI) whereas the second (2) uses traveling wave ion mobility spectrometry (TWIMS) of the pair of protonated molecules followed by on-line collision-induced dissociation (CID), that is, MS/TWIMS-CID/MS. Isomeric C(7)H(7)N(+) ions of m/z 106 (1' from 4-butylaniline and 2 from N-butylaniline) are formed as abundant fragments by 70 eV EI of the anilines, and found to function as suitable SDFI. Ions 1' and 2 display nearly identical unimolecular dissociation chemistry, but contrasting bimolecular reactivity with ethyl vinyl ether, isoprene, acrolein, and 2-methyl-1,3-dioxolane. Ion 2 forms adducts to a large extent whereas 1' is nearly inert towards all reactants tested. The intact protonated anilines are readily resolved and recognized by MS/TWIMS-CID/MS in a SYNAPT mass spectrometer (Waters Corporation, Manchester, UK). The protonated N-butyl aniline (the more compact isomer) displays shorter drift time and higher lability towards CID than its 4-butyl isomer. The general application of SDFI 1' and 2 and other homologous and analogous ions and MS/TWIMS-CID/MS for absolute recognition and resolution of isomeric families of N-alkyl and ring-alkyl mono-substituted anilines and analogues is discussed.

Recognizing alpha-, beta- or gamma-substitution in pyridines by mass spectrometry.

A general mass spectrometric method able to recognize the site of substitution of monosubstituted pyridines is described. The method requires that the molecule under investigation forms, upon ionization and dissociation, the respective alpha-, beta- or gamma- pyridinium ion of m/z 78. Pyridinium ions are stable and common fragments of ionized and protonated pyridines and are found to function as appropriate structurally diagnostic fragment ions. They can be identified by their characteristic and nearly identical collision-induced dissociation behavior and distinguished by the combined use of two structurally diagnostic ion/molecule reactions with acetonitrile and 2-methyl-1,3-dioxolane. alpha-, beta- or gamma-substitution in pyridines can, therefore, be securely recognized via an MS-only method based on structurally diagnostic ions and by the inspection of a single molecule (no need for intracomparisons within the whole set of isomers).