Ionization processes in matrix‐assisted laser desorption/ionization mass spectrometry: Matrix‐dependent formation of [M + H]<sup>+</sup> vs [M + Na]<sup>+</sup> ions of small peptides and some mechanistic comments

The sodium cation affinities of six commonly used MALDI matrices are determined here using guided ion beam tandem mass spectrometry techniques. The collision-induced dissociation behavior of six sodium cationized MALDI matrices, Na + (MALDI), with Xe is studied as a function of kinetic energy. The MALDI matrices examined here include: nicotinic acid, quinoline, 3-aminoquinoline, 4-nitroaniline, picolinic acid, and 3-hydroxypicolinic acid. In all cases, the primary dissociation pathway corresponds to endothermic loss of the intact MALDI matrix. The cross section thresholds are interpreted to yield zero and 298 K Na + −MALDI bond dissociation energies (BDEs), or sodium cation affinities, after accounting for the effects of multiple ionneutral collisions, the kinetic and internal energy distributions of the reactants, and dissociation lifetimes. Density functional theory calculations at the B3LYP/6-311+G(2d,2p)//B3LYP/6-31G* and MP2(full)/6-311+G(2d,2p)//B3LYP/6-31G* levels of theory are used to characterized the structures and energetics for these systems. The calculated BDEs exhibit very good agreement with the measured values for most systems. The experimental and theoretical Na + −MALDI BDEs determined here are compared with those previously measured by cation transfer equilibrium methods.

Section: Introductionmentioning

confidence: 99%

Sodium Cation Affinities of Commonly Used MALDI Matrices Determined by Guided Ion Beam Tandem Mass Spectrometry

Chinthaka¹,

Rodgers²

2012

“…This photo/ thermal ionization model was analyzed more in detail by Allwood et al [10]. Different authors proposed the possibility of energy pooling processes of two neighboring (localized) excited molecules (multicenter ionization model) [8,11,12] with higher ionization efficiency than resonant two-step absorption processes. This model was further extended by Setz et al proposing mobile matrix excitations [13].…”

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confidence: 99%

Using fluorescence dyes as a tool for analyzing the MALDI process

Jaskolla

Karas

2008

In a recent paper (Setz, P. D.; Knochenmuss, R. Phys. Chem. A 2005, 109, 4030 -4037) energy-transfer from excited matrix molecules to fluorescent traps was used to study the role of pooling reactions for the ionization processes in matrix-assisted laser desorption ionization (MALDI) using 2,5-dihydroxybenzoic acid as matrix. Exciton trapping was shown to interfere with matrix ionization. These investigations were extended to analyze the influence of fluorescent traps on both matrix and analyte ions for ␣-cyano-4-hydroxycinnamic acid and further matrices. A strong influence of the fluorescent traps on both matrix and analyte ionization was revealed, depending on the matrix:trap ratio, and manifested itself differently for low and high mass analytes. (MALDI) has become an enabling technology for the fields of protein mass spectrometry (MS) and proteomics. Despite its widespread use, e.g., for protein identification via peptide mass fingerprinting [4], a comprehensive model for the generation of free gasphase ions has not yet been developed [5,6]. All matrices in use today have been found empirically and stem from the early days of MALDI, such as ␣-cyano-4-hydroxycinnamic acid (CHCA) [7]. With regard to analyte ionization, the essential role of protonated matrix species was already discussed in the early MALDI papers proposing that the central reaction of analyte ionization in the positive ion mode is a proton transfer from protonated matrix species to analyte molecules. A so-called "photochemical" ionization model was proposed by Ehring et al. [8]; energy pooling processes and resonant two-step absorption were assumed to occur and to facilitate the generation of the primary radical cation matrix species for which more than one UV photon is needed. Karbach et al. experimentally determined the ionization potential of 2,5-DHB to be higher than the energy content of two 337 nm UV photons [9]. Resonant two-step absorption is only possible taking into consideration that the missing energy is contributed by the thermal energy of the matrix system. This photo/ thermal ionization model was analyzed more in detail by Allwood et al. [10]. Different authors proposed the possibility of energy pooling processes of two neighboring (localized) excited molecules (multicenter ionization model) [8,11,12] with higher ionization efficiency than resonant two-step absorption processes. This model was further extended by Setz et al. proposing mobile matrix excitations [13].Laser excitation also induces the MALDI ablation and evaporation process above a distinct threshold fluence. Theoretical investigations of the MALDI process on the basis of the breathing sphere model predict two desorption mechanisms: thermal vaporization of single molecules up to small clusters (four molecules or less) and ablation of large clusters at higher laser fluences [14 -16]. The mechanistic discussions and considerations have been carefully reviewed by Dreisewerd [17]. Moreover, it is included in the considerations that the diverging initial velocities as m...

“…MALDI has been successfully applied for the analysis of peptides and proteins [5][6][7][8][9][10][11], oligonucleotides and nucleic acids [12,13], carbohydrates [14 -16], and synthetic polymers [17][18][19][20][21]. Despite its wide range of applications and many fundamental studies [22][23][24][25][26][27][28][29][30], there is a need for better understanding of the MALDI process, to improve ion yields, to gain access to new classes of compounds, and to provide rational guidelines for matrix selection, which play crucial roles in sample analysis. In the discussions of the ionization mechanism, proton-transfer reactions have a very prominent role.…”

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confidence: 99%

Estimation of the proton affinity values of fifteen matrix-assisted laser desorption/ionization matrices under electrospray ionization conditions using the kinetic method

Mirza

Raju

Vairamani

2004

The kinetic method, which is known to be simple, fast and precise, is used for the measurement of proton affinity values of fifteen selected matrix-assisted laser desorption/ionization matrices under electrospray ionization conditions. The stabilization of [ T he most exciting innovations in the last decade for the analysis of non-volatile, high molecular weight compounds is the development of new mass spectral techniques like matrix-assisted laser desorption/ionization (MALDI) [1][2][3] and electrospray ionization (ESI) [4]. MALDI has been successfully applied for the analysis of peptides and proteins [5][6][7][8][9][10][11], oligonucleotides and nucleic acids [12,13], carbohydrates [14 -16], and synthetic polymers [17][18][19][20][21]. Despite its wide range of applications and many fundamental studies [22][23][24][25][26][27][28][29][30], there is a need for better understanding of the MALDI process, to improve ion yields, to gain access to new classes of compounds, and to provide rational guidelines for matrix selection, which play crucial roles in sample analysis. In the discussions of the ionization mechanism, proton-transfer reactions have a very prominent role. The protonated analyte is presumably produced by gas-phase reactions between matrix ions and analyte molecules. Thermochemical data like gas phase basicities (GB) and proton affinities (PA) of the matrices may contribute to better understanding of the MALDI processes.To date, very few studies have been carried out for the measurement of GB and PA of MALDI matrices [31][32][33][34]. The PA values that have been reported for MALDI matrices are inconsistent with one another because of intrinsic errors in the different methods, due to sampling of ions of different internal energy, and because of the use of different ionization techniques in these studies. So far, ESI has not been used for the estimation of PA values of MALDI matrices. In the present study, we estimated PA values of fifteen MALDI matrices under electrospray ionization conditions, which is easier and more broadly applicable than fast atom bombardment or chemical ionization techniques, using the kinetic method [35,36].Estimation of PA values by the kinetic method involves measurement of peak height ratios of the protonated monomers of the compound with unknown PA and that of the reference base with known PA values, generated from the collision induced dissociation of the corresponding proton-bound heterodimers. According to the kinetic method, the ratio of rate constants (k A and k B ) for the competitive dissociation of a cluster ion comprised of the compound of interest and a reference compound, eq 1, can be expressed as eq 2 [37, 38].(1) Experimental MaterialsThe MALDI matrices, 4-hydroxy-␣-cyanocinnamic acid (4HCCA), 2,5-dihydroxy benzoic acid (gentisic acid, GA), 5-methoxysalicylic acid (MSA), trans-3, 5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid, SA), 1,8,9-anthracenetriol (dithranol, DT), 2,4,6-trihydroxyacetophenone (THAP), trans-3-indoleacrylic acid (IAA), 3-hydroxypicoli...