Studies of the dissociation mechanisms of deprotonated mononucleotides by energy resolved collision-induced dissociation

100

157

An electrospray ionization (ESI) source developed for use with the guided ion beam tandem mass spectrometer (GIBMS) is described. For accurate determination of thermochemistry using threshold collision-induced dissociation (TCID), it is essential that any source produces ions with four exacting characteristics: (1) high intensity, (2) stable signal, and well-defined energies both (3) kinetic, and (4) internal. To accomplish these objectives, the ions generated by the electrospray are collected using a radio frequency electrodynamic ion funnel and are then transferred into a hexapole ion guide where they are thermalized and subsequently passed into higher-vacuum regions for analysis. The resulting ion intensities using this source can exceed 10 6 ions/s. Stable beams (Ͻ10% variation in signal) can be generated over multiple hours. The kinetic energy distribution of ions emerging from this source has been shown to be well described by a Gaussian distribution with a full width half maximum (FWHM) of about 0.1-0.2 eV in the laboratory frame of reference. Finally, TCID results for ions generated with this source show excellent agreement with previously reported threshold values for ions generated using a variety of sources and experimental methodologies. This confirms that internal energies of the ions are well described by a Maxwell-Boltzmann distribution at room temperature. ( , electrospray ionization (ESI) has become a widely used source for mass spectrometry. The popularity of the ESI can be credited to a number of factors. In addition to its ability to gently transfer large biological molecules into the gas phase in multiple charge states, ESI sources benefit from being simple in design and robust in use. However, despite its widespread acceptance, the ESI source has been used in only a limited number of experiments for quantitative determination of thermochemical information [2][3][4][5][6]. This is unfortunate, given the ability of the ESI to easily produce a large number of interesting gas-phase biological ions [7][8][9], charged transition metals [10 -12], and alkali metal/ligand complexes [12][13][14]. The scarcity of thermochemical data originating from the ESI most likely lies in the difficulty of producing an ion beam that is suitable for rigorous thermochemical analysis. These prior ESI studies [2][3][4][5][6], where simpler ESI sources have been used to generate ions, have not thoroughly demonstrated whether such conditions (outlined below) have been reached.Threshold collision-induced dissociation (TCID) experiments represent a well-established means of obtaining accurate thermochemical data for a diverse range of gas-phase ions [15][16][17][18][19][20]. Essentially, TCID consists of systematically varying the kinetic energy of a mass selected ion beam and then colliding the ions with a stationary non-reactive gas such as xenon. With increasing collision energy, the parent ion begins to fragment into products that are then collected as a function of the collision energy. The resulting data may be mod...

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confidence: 99%

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confidence: 99%

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confidence: 99%

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An electrospray ionization source for thermochemical investigation with the guided ion beam mass spectrometer

Moision

Armentrout

2007

100

157

“…This differentiation is based upon both the precursor and product ion relative abundance evolutions. Both, the latter parameters (i.e., curvature at the beginning and slope at V 1/2 ) reflect different properties of transition-state (i.e., loose over tight configuration) as well as entropic effects [61,62]. It results from these effects a V 1/2 shift toward the higher energy range.…”

Section: Cid Mass Spectra and Erms Investigations With Ion Trapmentioning

confidence: 99%

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...

“…Briefly, the proposed mechanisms involve either the loss of the nucleobase in its deprotonated form, followed by proton abstraction from the ODN such that the base is ultimately lost as a neutral, or the loss of the nucleobase in its neutral form, which requires proton transfer either before or in concert with cleavage of the N-glycosidic linkage. It has been suggested that these two general mechanisms might be distinguished based on a correlation between the dissociation energetics of the different nucleobases and their proton affinity (PA), if the base is protonated prior to cleavage of the glycosidic bond [11,[13][14][15], or their gas phase deprotonation enthalpy (⌬H acid ) [2,10,16,17], if the base is lost in its deprotonated form. To date, however, there are few energetic data available for the loss of nucleobases from ODN anions with which to compare the thermodynamic acid/base properties.…”

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confidence: 99%

Arrhenius activation parameters for the loss of neutral nucleobases from deprotonated oligonucleotide anions in the gas phase

Daneshfar

Klassen

2004

Arrhenius activation parameters (E a and A) for the loss of neutral nucleobase from a series of doubly deprotonated oligodexoynucleotide 10-mers of the type XT 9 , T 9 X, and T 5 XT 4 , where X ϭ A, C, and G, have been determined using the blackbody infrared radiative dissociation technique. At temperatures of 120 to 190°C, the anions dissociate exclusively by the loss of a neutral nucleobase (XH), followed by cleavage of the sugar 3Ј C™O bond leading to (a-XH) and w type ions or, in the case of the T 9 X 2Ϫ ions, the loss of H 2 O. The dissociation kinetics and energetics are sensitive to the nature and position of X. Over the temperature range investigated, the kinetics for the loss of AH and GH were similar, but ϳ100 times faster than for the loss of CH. For the loss of AH and GH, the values of E a are sensitive to the position of the base. The order of the E a s for the loss of XH from the 5Ј and 3Ј termini is: C Ͼ G Ͼ A; while for T 5 XT 4 the order is: C Ͼ A Ͼ G. The trends in the values of E a do not parallel the trend in deprotonation enthalpies or proton affinities of the nucleobases in the gas phase, indicating that the energetic differences do not simply reflect differences in their gas phase acidity or basicity. The pre-exponential factors (A) vary from 10 10 to 10 15 s Ϫ1 , depending on the nature and position of X. These results suggest that the reactivity of individual nucleobases is influenced by stabilizing intramolecular interactions. M ass spectrometry (MS), combined with soft ionization techniques such as electrospray (ES) and matrix assisted laser desorption/ ionization (MALDI), has become an indispensable tool for identifying the primary structure (sequence) of biopolymers: peptides, oligosaccharides, and oligonucleotides. The mass spectrometry-based sequencing approach typically involves isolating the biopolymer ion of interest in the gas phase, dissociating it to produce sequence specific fragment ions and accurately determining the mass of the ions. Sequence information is extracted from the mass differences of the sequential fragment ions of the same general structure. The MSbased sequencing approach has many attractive features, most notably its inherent speed and sensitivity and its ability to sequence biopolymers containing unnatural or unusual modifications. Despite its widespread use in the sequencing of biopolymers, fundamental questions regarding the gas phase dissociation mechanisms remain. Elucidating these mechanisms is of practical importance, since it will facilitate the rational development of MS-based techniques for sequencing. In addition, the dissociation of biomolecules in the gas phase reflects their intrinsic properties, which are of fundamental interest.For oligodeoxynucleotides (ODNs), sequence information can be obtained from the fragmentation behaviour of either the protonated or deprotonated gaseous ions and the dissociation behaviour of both forms has been extensively investigated [1][2][3][4][5][6][7][8][9][10]. The dissociation of deprotonated ODNs, the focus ...