Stereochemical effects in mass spectrometry

Supramolecular assemblies that are formed between amines and trifluoroacetic acid were studied using electrospray ionization mass spectrometry. Distinctive association behavior of primary, secondary, and tertiary amines with trifluoroacetic acid upon identical experimental conditions is observed and indicates that steric effects dominate in the formation of these protonated clusters. Extraordinary complexation behavior is observed in the case of RϪ(ϩ)-␣-methylbenzylamine and 4-tert-butyl-cyclohexylamine that form high-order clusters. The strong relation between stereochemistry and assembly results in the specific association characteristics of trans 4-tert-butyl-1-phenylcyclohexylamine when compared with the cis isomer. The cis isomer gives rise to a highly abundant [M 4

Section: Resultsmentioning

confidence: 99%

Remarkable amine-TFA self assembly

Denekamp

Egbaria

2004

“…Moreover, position around the functionalized site at the C (11) position (C ring) seems to contribute to the anchorage of the hormone within this pocket of the receptor [7][8][9][10][11][12][13], suggesting that steric effects at this position are important for binding affinity. Accordingly, we may consider that the proton donor character efficiency could be reinforced through electrostatic effects mediated by the nature and the stereochemistry of substituent in position 11 [14].Mass spectrometry is widely used to characterize diastereoisomeric compound through stereochemical effects [15,16]. Many reviews have described stereochemistry differentiation of the hydroxyl group in gas phase on rigid rings [17][18][19][20][21][22].…”

mentioning

confidence: 99%

“…Many reviews have described stereochemistry differentiation of the hydroxyl group in gas phase on rigid rings [17][18][19][20][21][22]. The stereochemical effects could provide evidence that the chemical pathways for ion-molecule reaction as well as the dissociation mechanisms promoted by negative charge from stereoisomeric ion species prepared in chemical ionization and electrospray [23].…”

mentioning

confidence: 99%

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Stereochemical effects during [M-H]⁻ dissociations of epimeric 11-OH-17β-estradiols and distant electronic effects of substituents at C₍₁₁₎ position on gas phase acidity

Bourgoin-Voillard

Zins

Fournier

et al. 2009

The affinity of estradiol derivatives for the estrogen receptor (ER) depends strongly on nature and stereochemistry of substituents in C (11) position of the 17␤-estradiol (I). In this work, the stereochemistry effects of the 11␣-OH-17␤-estradiol (III ␣ ) and 11␤-OH-17␤-estradiol (III ␤ ) were investigated using CID experiments and gas-phase acidity (⌬H°a cid ) determination. The CID experiments showed that the steroids decompose via different pathways involving competitive dissociations with rate constants depending upon the ␣/␤ C (11) stereochemistry. It was shown that the fragmentations of both deprotonated [III ␣ -H] Ϫ and [III ␤ -H] Ϫ epimers were initiated by the deprotonation of the most acidic site, i.e. the phenolic hydroxyl at C (3) . This view was confirmed by H/D exchange and double resonance experiments. Furthermore, the ⌬H°a cid of both epimers (III ␣ and III ␤ ), 17␤-estradiol (I), and 17-desoxyestradiol (II) was determined using the extended Cooks' kinetic method. The resulting values allowed us to classify steroids as a function of their gas-phase acidity as follows:Interestingly, the ␣/␤ C (11) stereochemistry appeared to influence strongly the gas-phase acidity. This phenomenon could be explained through stereospecific proton interaction with -orbital cloud of A ring, which was confirmed by theoretical calculation. . The E 2 /ER␣ complex is stabilized by hydrogen contacts occurring between, on the one hand, the hydroxyl group of phenolic A ring (E 2 ) and Glu-353 as well as Arg-394 of the hormone binding pocket (HBP), and on the other hand, between the 17␤-hydroxyl of D-ring and His-524 (Scheme 1a) [5][6][7]. Moreover, position around the functionalized site at the C (11) position (C ring) seems to contribute to the anchorage of the hormone within this pocket of the receptor [7][8][9][10][11][12][13], suggesting that steric effects at this position are important for binding affinity. Accordingly, we may consider that the proton donor character efficiency could be reinforced through electrostatic effects mediated by the nature and the stereochemistry of substituent in position 11 [14].Mass spectrometry is widely used to characterize diastereoisomeric compound through stereochemical effects [15,16]. Many reviews have described stereochemistry differentiation of the hydroxyl group in gas phase on rigid rings [17][18][19][20][21][22]. The stereochemical effects could provide evidence that the chemical pathways for ion-molecule reaction as well as the dissociation mechanisms promoted by negative charge from stereoisomeric ion species prepared in chemical ionization and electrospray [23]. For instance, the differentiation of alkoxides of trans and cis-cyclohexanediols has been widely described in negative chemical ionization [24 -26]. This technique turned out to be also appropriate to distinguish more complex polycyclic molecules, such as mono-or polyhydroxyl norborneols, saccharides, and steroids [27][28][29][30]. The origin of stereochemical effects in these systems has been described in terms of...

“…MS offers several advantages over other techniques: speed of analysis, high sensitivity at low picomol level, possibility to carry out gas phase reactions, etc. A large number of investigations concerning stereochemical effects on gas phase reactions occurring in mass spectrometry experiments has been reported recently [8,9]. Different mass spectrometry techniques, such as chemical ionization [10 -12] and self-ionization (SI) [13][14][15][16], can be successfully used.…”

mentioning

confidence: 99%

Application of self-ionization for enhancing stereochemical and positional effects from arylglycosides under electron ionization conditions in an ion trap mass spectrometer

Silva

Perlat

Tabet

et al. 2003

Ion trap mass spectrometry has been used to structurally characterize and differentiate positional and stereo isomers of arylglycosides having potential antioxidant properties. The use of the self-ionization (SI) technique has allowed to evidence a strong reactivity of fragment ions produced from dissociations of the molecular ion towards the molecules introduced into the trap. Specific structural effects due to positional isomers and anomers have been also envisaged through the occurrence of bimolecular processes inside the ion trap analyzer. Under self-ionization conditions, even-electron ions are produced. The charge is retained on the sugar moiety, in agreement with its proton affinity higher than that of the substituted phenol moiety. Most of the fragmentation pathways involve elimination of acetic acid that protects the hydroxylic groups of the glycoside. SI also produces adduct ions, likely as covalent species, having higher m/z values than the molecular ion. The reaction site is mainly the double bond present in the pyranosidic ring. Even if some fragment ions have lost the initial stereochemistry, their formation can be related to the structure of the parent neutrals introduced into the cell. Collision-induced dissociation (CID) experiments, carried out on ions formed by ionmolecule reactions, have allowed to obtain further information on gas phase ion structures. The study of mass-selected ion-molecule reactions and their kinetics have evidenced a spectacularly different reactivity of the ion at m/z 111 towards the two anomers 2␣ and 2␤, with the latter showing a much more pronounced reactivity. The approach developed in this work revealed to be an useful tool in structural characterization, as well as in stereo and regiochemical differentiation of arylglycosides. A lot of different organic compounds can exist as isomers, such as regio, stereochemical, and positional isomers. Owing to the specific features of a given isomer, such as reactivity and biological properties, its structural characterization and differentiation is of particular importance. Different chemicophysical methods, such as nuclear magnetic resonance, circular dichroism, X-ray crystallography, and other spectroscopic methods can give useful and complementary information. One of these methods is represented by mass spectrometry (MS) [1,2] that has found more and more applications in isomer characterization and differentiation [3,4], some of them developed in our research groups [5][6][7]. MS offers several advantages over other techniques: speed of analysis, high sensitivity at low picomol level, possibility to carry out gas phase reactions, etc. A large number of investigations concerning stereochemical effects on gas phase reactions occurring in mass spectrometry experiments has been reported recently [8,9]. Different mass spectrometry techniques, such as chemical ionization [10 -12] and self-ionization (SI) [13][14][15][16], can be successfully used. In particular, the SI mode is a suitable approach for obtaining gas phase ion spec...