Application of the Atoms in Molecules Theory and Computational

ARTICLE pubs.acs.org/JPCA

Application of the Atoms in Molecules Theory and Computational Chemistry in Mass Spectrometry Analysis of 1,4-Naphthoquinone Derivatives Ricardo Vessecchi,†,‡ Jos
e N. C. Lopes,§ Norberto P. Lopes,‡ and S
ergio E. Galembeck*,† †

Departamento de Química, Faculdade de Filosofia, Ci^encias e Letras de Ribeir~ao Preto, Universidade de S~ao Paulo, 14040-901 Ribeir~ao Preto - SP, Brazil ‡ Departamento de Física e Química, Faculdade de Ci^encias Farmac^euticas de Ribeir~ao Preto, Universidade de S~ao Paulo, 14040-901 Ribeir~ao Preto - SP, Brazil § Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Av. dos Bandeirantes 3900, Incubadora Supera - Campus da USP, 14040-903 Ribeir~ao Preto - SP, Brazil

bS Supporting Information ABSTRACT: Mass spectrometry analysis of 2-(acylamino)-1,4-naphthoquinone derivatives was carried out using electrospray ionization ion source in combination with tandem mass spectrometry. Protonated molecules were dissociated by application of the collision-induced dissociation (CID), and the protonation sites were suggested on the basis of the HOMO, molecular electrostatic potential map (MEP), proton affinity, and Fukui functions calculated by B3LYP/6-31+G(d,p). The main fragmentation mechanisms undergone by the protonated ions were elucidated on the basis of energy, geometry, and topology analysis of equilibrium geometries. Compounds exhibiting only aliphatic hydrogens at the lateral chain undergo interesting ketene elimination. On the other hand, only the benzoylium ion formation is detected for 2-benzoylamino-1,4-naphthoquinone. The bonds geometric and atoms in molecules parameters give evidence that acidic hydrogen atoms play an important role in the fragmentation pathways.

’ INTRODUCTION Over the last decades, the development of gas-phase chemistry has been accelerated by two crucial factors: increased computational power1 and design of new mass spectrometry techniques.1
6 These advances have also contributed to improving several chemistry areas.3 Gas-phase chemistry is interesting for mass spectrometry analysis because it allows comparison of the intensity of pattern ions and their fragments and aids understanding of the structure of various species observed in the mass spectra.7
9 Many experimental methods can be employed to obtain thermochemical parameters, which, in turn, can be related to mass spectrometry studies.10
14 Thermochemical parameters, such as gas-phase basicity, proton affinity, and ionization energy, can be achieved for one molecule only, and variation of these parameters due to the substituent effect can be estimated, which is important for studies on derivatives and homologues series.10
12 However, experimental measurements can be a disadvantage when physicalchemical factors pose difficulties to their attainment.15 In this sense, the theoretical approach has been applied for determination of thermochemical parameters, mainly when the accomplishment of experimental measurements is not possible.16
19 Application of the computational quantum chemistry to mass spectrometry studies has been the theme of countless papers.16
21 r 2011 American Chemical Society

Chart 1. Structure of the 2-(Acylamino)-1,4-naphthoquinone Derivativesa

a

Q1, 2-acetylamino; Q2, 2-propyonylamino; Q3, 2-butyrylamino; and Q4, 2-benzoylamino-1,4-naphthoquinone. The labeled atoms at the Q1 structure indicate the atom numbers.

Special Issue: Richard F. W. Bader Festschrift Received: April 27, 2011 Revised: June 13, 2011 Published: June 30, 2011 12780

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Quantum chemistry models may furnish accurate results for thermochemical parameters, as well as other parameters, that are interesting for mass spectrometry analysis.16,17,19 For instance, reactive sites can be analyzed by means of molecular electrostatic potential map, atomic charges, frontier orbitals, and Fukui functions

Figure 1. (A) Molecular electrostatic potential map (MEP) plotted at 0.25/a3 for 2-propyonilamino-1,4-naphthoquinone. (B) HOMO for Q2.

Table 1. Electrophilic Fukui Functions, f
atom

Q1

Q2

Q3

Q4

O(1)

0.003

0.003

0.003

0.003

O(2)

0.039

0.041

0.063

0.061

O(3)

0.057

0.052

0.092

0.050

N(1)

0.240

0.247

0.244

0.231

’ MATERIAL AND METHODS

Table 2. Proton Affinities (PA) and Gas-Phase Basicities (GB), kcal mol
1, Obtained for 1,4-Naphthoquinone and Its Derivatives by Using the B3LYP/6-31+G(d,p) Model molecules

PA

GB

1,4-naphthoquinone

200.5

193.1

Q1

186.7

175.5

Q2

189.1

176.4

Q3

189.6

177.7

Q4

195.5

188.8

among others.16,17 Nevertheless, geometric and topologic changes can be employed to understand alterations in chemical bonds strength after a chemical event, such as protonation, which is an inherent phenomenon in the case of electrospray ionization.17 In addition, the energy profile can contribute to better comprehension of the dissociation channels obtained by collisional activation and tandem mass spectrometry studies.20
22 Research groups have been devoted to many works involving mass spectrometry in combination with computational chemistry.7,16
20 Although the latter technique has been widely applied to gas-phase chemistry, topological analysis of the electron density by the atoms in molecules (AIM) method has been rarely used for elucidation of fragmentation mechanism.23,24 Thus, application of parameters generated by AIM shall aid analysis of the results regarding the fragmentation mechanism. AIM analysis25 in combination with computational thermochemistry can also be used to gain insight into protonated molecules fragmentation mechanism. AIM parameters such as electron density (Fb) and its Laplacian (r2Fb), among others, can be employed, so that the reactivity for different isomers can be better interpreted.26 Early studies on 2-(acylamino)-1,4-naphthoquinones (Chart 1) have suggested that the lateral chain plays an important role in the fragmentation of the protonated species generated by electrospray ionization.27 These investigations were based on the low resolution analysis conducted on a triple quadrupole analyzer, where three possible mechanisms were suggested to take place. However, the potential energy surface has not yet been exploited. Thus, in this work, high resolution mass spectrometry analysis was accomplished for protonated 1,4-naphthoquinone derivatives by electrospray ionization. The interesting in studying these molecules stems from the fact that they have been shown to display moluscicidal and larvicidal activities28,29 and, more recently, they have emerged as anticancer agents.30 Herein, fragmentation mechanisms are proposed and compared to quantum chemistry energy calculations. Moreover, the AIM theory has been employed, to understand the influence of the lateral chain on protonation and dissociation channels during these experiments.

Chemical and Mass Spectrometry. The 2-(acetylamino)(Q1), 2-(propyonylamino)- (Q2), 2-(butyrylamino)- (Q3), and 2-(benzoylamino)-1,4-naphthoquinones (Q4) were obtained from 1-naphthol, as previously reported28,29 (Chart 1). All the compounds were recrystallized in acetonitrile HPLC grade, and stock solutions were prepared from 0.2 mg mL of each compound in ACN/H2O (1:1). These stock solutions were then diluted 10 times in the same solvent system. Deionized water was used throughout the study. High resolution ESI-MS analyses were performed on an Ultro-TOF-Q Bruker Daltonics, fitted with an electrospray ion source operating in the negative ion mode. Samples were directly infused into the ionization source at a 10 μL.min
1 flow rate.

Table 3. Ionic Species, u, Observed in the ESI-MS Spectra of 1,4-Naphthoquinone Derivatives Q1 ion

Q2

Q3

Q4

accurate mass

exact mass

accurate mass

exact mass

accurate mass

exact mass

accurate mass

exact mass

+

[M + H] [M + Na+]

216.0671 238.0472

216.06552 238.04746

230.0817 252.0634

230.08117 252.06311

244.0983 266.0812

244.09682 266.07876

278.0822 300.0638

278.08117 300.06311

[M + K]+

254.0212

254.0214

268.0372

268.03705

282.0561

282.0527

316.0398

316.03705

12781

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Figure 2. ESI-MS (A) and ESI-MS/MS (B) spectra for compound Q2.

The accuracy masses were achieved by using TFA
Na+ (sodiated trifluoroacetic acid) as internal standard. The source block and desolvation temperature was 150 °C. The optimum energy applied at the capillary emitter was tested, so that a higher intensity of protonated and cationized molecule would be obtained. The protonated molecule (precursor ion) was selected and fragmented by CID, using N2 as the collision gas. The variation at Elab was determined, to construct the energy-resolved curves.31 The MS/MS experiments were conducted at different Elab, and the energy-resolved fragmentation curves were achieved by varying the Elab (0
40 eV). Computational Methods. To obtain thermochemical, geometric, and electronic structure parameters for the carbonyl compound, several computational models were tested. We have tested the G2, G2MP2, B3LYP/6-31+G(d,p), B3LYP/6-31+ +G(d,p), and CBS-Q to obtain thermochemical parameters for 1,4-benzoquinone. These results are available as Supporting

Information. The lowest errors were observed by using of DFT methods, and it is possible to conclude that the B3LYP/6-31 +G(d,p) model is the most adequate to obtain Gibbs energies and enthalpies.32,33 The proton affinity (PA) and gas-phase basicity (GB) parameters achieved for 1,4-benzoquinone were compared to values available in the NIST34 Web site, and the errors were
0.2 and +0.8 kcal mol
1, respectively. In recent studies, larger basis sets were tested for this compound and the stability of computed energies was observed.33 Thus, these results indicate that B3LYP/6-31+G(d,p) is a useful model for the calculation of thermochemical parameters for this class of compound (Table S1, Supporting Information). For this reason, all subsystems were optimized by means of the B3LYP/6-31+G(d,p) model,35,36 using Gaussian 03 suite programs.37 The vibrational frequencies evidenced that all the 12782

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Figure 3. Elab plot for protonated 1,4-naphthoquinone derivatives: (A) Q1H+; (B) Q4H+. For others compounds, the results were the same as those of (A).

structures are minima in the potential energy surface. All the structures were visualized with the Molekel 4.3 software.38 Protonation sites were indicated on the basis of HOMO analysis, natural charges, and the relative Gibbs energies between several protonated forms (gas-phase basicity) and Fukui functions, as described by Contreras et al.39 The Gibbs energy for each molecule was calculated by subtracting the thermally corrected Gibbs energy of the acid from the sum of the thermally corrected Gibbs energies of the anion and proton. The GB values were determined according to the equation: Q + H+ f QH+, where the Gibbs energy of the proton was considered to be equal to
6.28 kcal mol
1.40 PA values were also obtained by considering the enthalpies variation for the same equation. This way, the most stable ions and the fragmentation pathways suggested by Gibbs energies and enthalpies calculations carried out at 298.15 K were proposed. The products and the corresponding transition state (TS) energies

Table 4. Ionic Masses Obtained in the ESI-MS/MS Spectra of 2-(Acylamino)-1,4-naphthoquinone Derivativesa compound

[M + H]+

C10H8NO2+

C9H8NO+

C7H5O+

174.05495b

146.06004

105.03349

Q1

216.0672 (15.1) 174.0565 (100) 146.0596 (6.7) 105.0341 (11.8)

Q2

230.0782 (35.4) 174.0523 (100) 146.0563 (15.0) 105.0283 (54.9)

Q3

244.0975 (28.6) 174.0544 (100) 146.0573 (14.3) 105.0298 (32.1)

Q4

278.0792 (28.6)

b

b

105.0283 (100)

a

Relative intensities at Elab = 20 eV are between parentheses. All values are in u. b Not observed.

were obtained and reported relative to their respective precursors. A standard approach was utilized for TS characterization, by employing the Synchronous Transit Guided Quasi-Newton method developed by Schlegel and co-workers,41 and TS with only one imaginary vibrational frequency was found. In some cases, the 12783

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Figure 4. Equilibrium geometries for 2-(acetylamino)-1,4-naphthoquinone: (A) neutral; (B) protonated.

connectivity between TS, precursor, and product ions was achieved by performing intrinsic reaction coordinate (IRC) calculations.42 It is noteworthy that the Gibbs energies were used with caution, because the thermal equilibrium cannot be reached under CID conditions.43 The AIM25 analysis was accomplished by using of the AIM 2000 program,44 to understand the changes in bond strength after protonation.

’ RESULTS 1,4-Naphthoquinone Derivatives Protonation Site. The first step toward understanding electrospray ionization mass spectrometry analysis is indicating the protonation site on the target compounds.16 For this purpose, the HOMO and the molecular electrostatic potential map (MEP) plots were obtained, as depicted in Figure 1. For all the molecules, the results were the same as those described in Figure 1 (Figure S1, Supporting Information). The MEP indicates that the most basic region, which can accommodate the proton, is located near the nitrogen atom of the lateral chain (Figure 1A). HOMO analysis suggest that protonation may occur at the nitrogen or oxygen (2) and (3) atoms. To confirm these results, the electrophilic Fukui functions,

which govern the electrophilic attack, were computed, and the most favorable site for protonation was found to be the nitrogen atom (Table 1). PA and GB values were also calculated, and data agreed with those described above; i.e., the most stable protonated species occurs by proton attachment at the nitrogen atom. PA follows an additivity rule with the number of carbon atoms present at the lateral chain for Q1
Q4, as illustrated in Table 2 and Figure S2 (Supporting Information). Gas-Phase Chemistry and Mass Spectrometry Analysis. High-resolution mass spectrometry analyses were accomplished, and the results are listed in Table 3. The protonated species have accurate mass with error lower than 5 ppm. All the ESI-MS spectra display signals relative to the protonated and cationized species, similarly to Figure 2A (Figures S3, S4, S6, and S8, Supporting Information). Protonated species were selected and dissociated by CID conditions, by variation of Elab, and the resolved-energy plots were thus obtained (Figure 3). All the molecules containing an R-carbonyl hydrogen atom at the lateral chain exhibit m/z 174 as the most intense fragment ion (Figure 2B and Table 4, Figures S5 and S7, Supporting Information) followed by m/z 146 and m/z 105. As for Q4, m/z 105 is the only ion observed in its ESI-MS/ 12784

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Figure 5. Molecular graphs for Q1 and Q1H+, Q2 and Q2H+, Q3 and Q3H+, and Q4 are similar. For Q4H+, only one HB is observed (Figure S1, Supporting Information).

MS spectrum (Figure 3B and Table 4, Figure S9, Supporting Information). The MS/MS spectra for m/z 174 ions were registered, and the m/z 146 and m/z 105 ions were observed (Figure S10, Supporting Information). Therefore, it is possible to conclude that the appearance of the m/z 146 and m/z 105 ions depends on m/z 174 formation. These results show that the R-hydrogen plays an important role in the fragmentation mechanism of these compounds. Thus, to understand the influence of the lateral chain on 1,4-naphthoquinone derivatives fragmentation pathways, energy, geometry, and AIM analyses were carried out, and they corroborated the experimental data. Previous studies have suggested that m/z 174 formation is triggered by torsion of the lateral chain, where protonation occurs at the N atom.15 Geometry analysis demonstrated that N atom protonation augments the p character of the amide bond, and the N
C atoms assume a tetrahedral conformation (Figure 4). The proximity of the N
H bond with the O(1) atom implies possible hydrogen bond (HB) formation. The N
C(O) bond length increases after protonation, revealing weakening of this bond, Figure 4. For Q4, lengthening of this bond is to a larger extent compared to those for Q1, Q2, and Q3 (Table S2, Supporting

Information), evidencing that the N
CO bond breaks more easily in the case of Q4H+ than in the other studied compounds. On the basis of ESI-MS/MS data (Table 4) and previous reports, two alternative pathways can be suggested for 1, 4-naphthoquinone derivatives fragmentation: (i) elimination of the lateral chain as a ketene, to form the m/z 174 ion; (ii) elimination of the quinonoid moiety, to produce an acylium ion. The occurrence of the HB on protonated and neutral 1, 4-naphthoquinone derivatives is indicated by the presence of the bond critical point (BCP) between N
H
O(1), as evidenced in Figure 5 and Figure S12 (Supporting Information). Some AIM parameters,45 such as the positive Fb and rFb2 values (Table 5) also suggest the presence of a typical HB. The protonated molecules containing an R-hydrogen contain one BCP between this hydrogen atom and the carbonyl oxygen, which implies that interaction takes place between these atoms. This bond path (BP) may be due to a CR
H
O(1) HB or to a steric interaction between these atoms.45 To confirm that the CR
H
O(1) is an HB, Fb, r2Fb, and Hb (total energy density) values were analyzed. The negative values obtained for Hb are evidence that these interactions have partial covalent character (Tables S4 and S5, Supporting Information). 12785

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Protonation enhances electron density in the rings, which can be verified by Fb analyses at ring critical points (RCPs). The Fb values are larger for almost all BCPs, except for BCPs (3), (14), and (17), for which lower Fb values were achieved (Table 5 and Figure 6). For BCP (17), the amide bond, Fb reduction was more pronounced compared to those of other BCPs. This can be attributed to bond length increase, as discussed above. Weakening for this chemical bond can suggest that fragmentation occurs Table 5. AIM Parameters, au, for BCPs of Q1 and Q1H+au Q1H+

Q1 bond

BCPs

Fb

r2Fb

ε

Fb

r2Fb

ε

C(1)
C(2)

(1)

0.266
0.663 0.100 0.274
0.700 0.113

C(2)
C(3)

(2)

0.332
0.954 0.298 0.364
1.150 0.321

C(3)
C(4)

(3)

0.280
0.723 0.110 0.265
0.660 0.062

C(4)-C(4a)

(4)

0.267
0.662 0.083 0.275
0.701 0.100

C(5)
-C(4a) C(5)
C(6)

(5) (6)

0.312
0.852 0.179 0.325
0.925 0.181 0.313
0.859 0.186 0.319
0.898 0.166

C(6)
C(7)

(7)

0.311
0.850 0.187 0.323
0.925 0.176

C(7)
C(8)

(8)

0.314
0.863 0.193 0.320
0.904 0.176

C(8)
C(8a)

(9)

0.310
0.838 0.180 0.322
0.910 0.178

C(1)
C(10)

(10)

0.275
0.702 0.100 0.285
0.751 0.117

C(8a)
C(10)

(11)

0.306
0.817 0.176 0.312
0.851 0.174

C(1)
O(1)

(12)

0.394

C(4)
O(2) C(2)
N(1)

(13) (14)

0.396 0.074 0.053 0.414 0.273 0.075 0.306
0.929 0.060 0.245
0.637 0.013

N(1)
H

(15)

0.340
1.838 0.043 0.332
1.822 0.005

O(1)
H

(16)

0.023

N(1)
C(1)0

(17)

0.306
0.954 0.094 0.212
0.401 0.037

0.100 0.035 0.402

0.089 0.407 0.029

C(1)0
O(3)

(18)

0.406
0.001 0.102 0.441

C(1)0
CR

(19)

0.256

at this point. For all compounds studied, the variations of AIM parameters, after protonation, are similar to those described in Table 5 and Figure 6 (Tables S7
S9 and Figures S12
S14, Supporting Information). These results are important when it comes to understanding the fragmentation mechanism previously proposed for this group of compounds.27 m/z 174 formation has been suggested to occur via cyclization of the lateral chain, to form a seven-membered ring (Scheme 1). The distance between O(1) and HR and the intramolecular HB, from AIM analysis, characterize the seven-membered ring formation, which is not possible for Q4H+ (Figure S11, Supporting Information). Thus, AIM analysis in combination with geometric parameters can explain the occurrence of m/z 174, 146, and 105 ions for Q1H+, Q2H+, and Q3H+ (Scheme 1, Figures 4 and 5). Scheme 1. Fragmentation Mechanism for Protonated 1,4Naphthoquinones, Adapted from Reference 15 and Based on High Resolution Analyses (Table 2)

0.151 0.036

0.098 0.228 0.498 0.127

1.912 0.068 0.264
0.671 0.059

CR
H

(20)

0.278
0.954 0.008 0.286
1.041 0.015

CR
H C(3)
H(3)

(200 ) (21)

0.278
0.954 0.008 0.291
1.120 0.018

O(3)
H(3)

(22)

0.016

0.058 0.139

Figure 6. Fb plotting for BCPs of neutral and protonated Q1 1,4-naphthoquinone. 12786

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Scheme 2. Energy Profile of [Q + H]+ Fragmentationa

a All values are relative enthalpies at 298 K and are given in kcal mol
1. Absolute energies for (a1), (a2), and transitions states are available in the Supporting Information, Table S6.

Relative Gibbs energies and enthalpies at 298 K were calculated to explain formation of m/z 174, m/z 146, and m/z 105 from [Q + H]+. All possible TS for each step of the dissociation reactions were obtained, and the most stable pathway can be exploited by analyzing Scheme 2. The critical energy necessary for m/z 146 formation can be the reason for this ion’s lower intensity at the lowest Elab (Figure 2). For Q1, Q2, and Q3 the maximum energy transferred during collision (ECM) by considering only simple collisions at Elab of 35 eV is 92 kcal mol
1, approximately. This result can account for the difficult of m/z 174 fragmentation, because this value is close to those computed for the critical energy for this reaction: 101 kcal mol
1, approximately. It is worth mentioning that the electron density can sustain changes during analysis and, the classical phenomena should be considered with caution. Thus, Scheme 2 can be used to explain the occurrence of above-mentioned ions. The formation of the m/z 105 ion for Q4H+ was suggested on the basis of geometric analysis, which indicates increased N
CO bond length. N
CO lengthening is the largest observed for naphthoquinones (Table S3, Supporting Information). In the same way, Fb reduction for Q4H+ is more marked compared to those for other naphthoquinones (Figures S12
S14 and Tables S7
S9, Supporting Information). From these results, the m/z 105 formation was assumed on the basis of benzoylium ion formation through the carbonyl amide lone pair migration, Scheme 3. The relative enthalpies calculated for this reaction indicate that for Q4H+ this process occurs more easily, compared to other 1,4-naphthoquinone derivatives, Table 6. The absence of R
CO+ formation during Q1H+, Q2H+, and Q3H+ fragmentation can be attributed to the higher energies necessary for acylium ion formation as compared to m/z 174 formation. The ECM for Q4H+ at an Elab of 7.5 eV (see energy-resolved plot) was determined as being 15.86 kcal mol
1. This value is very close to the computationally

Scheme 3. Fragmentation Proposed for [Q + H]+ a

a

R =
CH3,
CH2CH3,
CH2CH2CH3,
Ph.

Table 6. Enthalpies (ΔH298), kcal mol
1, for the R
CO+ Ion Formation at the B3LYP/6-31+G(d,p) Level molecule

ΔH298

Q1 Q2

26.53 23.29

Q3

20.97

Q4

16.02

obtained ones (16.02 kcal mol
1). These results in combination with AIM results can be used to explain the fragmentation processes of 2-(acylamino)-1,4-naphthoquinones derivatives.

’ CONCLUSIONS In the present case, computational chemistry was essential to understand the influence of protonation and lateral chain reactivity on quinonoid compounds fragmentation pathways during ESI-MS/ MS analysis. The occurrence of a specific fragmentation mechanism for molecules displaying an R-hydrogen at the lateral chain is indicative of different fragmentation pathways for protonated 1,4naphthoquinone derivatives. The m/z 174 formation suggests that 12787

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The Journal of Physical Chemistry A the fragmentation pathway takes place through an interesting rearrangement that can be explained by the high critical energy necessary for fragmentation of this ion. Indeed, this suggestion was supported by the higher intensity of this ion at different Elab conditions. The fragmentation mechanism can be interpreted by using the atoms in molecules theory, where parameters such as electron density and its Laplacian are a useful tool for comprehension of the bond weakening/strengthening phenomena occurring after activation. The diminished electron density detected after protonation at the amide bond indicates that this is the initial point of the fragmentation mechanism.

’ ASSOCIATED CONTENT

bS

Supporting Information. Critical tests to perform the best computational model to obtain the thermochemical parameters for quinonoid compounds are available as Table S1. All geometries and energies and a HOMO plot. All ESI-MS and ESIMS/MS spectra and molecular graphs. AIM parameters and plots for Q2, Q3, Q4, and protonated species. This information is available free of charge via the Internet at http://pubs.acs.org.

’ AUTHOR INFORMATION Corresponding Author

*Phone: +55 16 3602 - 3765. E-mail: [email protected].

’ ACKNOWLEDGMENT We thank Brazilian foundations FAPESP and CNPq for financial support. R.V. thanks FAPESP for Ph.D. and Post-Doc financial support (Grants 05/01572-1 and 09/08281-3, respectively). N.P.L. and S.E.G. thank FAPESP for research support. ’ REFERENCES (1) Borkar, S.; Chien, A. A. Commun. ACM 2011, 54, 67–77. (2) Feen, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Science 1989, 246, 64–71. (3) Ifa, D.; Wu, C. P.; Ouyang, Z.; Cooks, R. G. Analyst 2010, 135, 669–681. (4) McLuckey, S. A.; Wells, J. M. Chem. Rev. 2001, 101, 571–606. (5) Vestal, M. L. Chem. Rev. 2001, 101, 361–375. (6) (a) Cacace, F Pure Appl. Chem. 1997, 69, 227–229. (b) Somorjai, G. A.; Levine, R. D. J. Phys. Chem. B 2005, 109, 9853–9854. (7) Xavier, L. A.; Morgon, N. H.; Menegon, J. J.; Riveros, J. M. Int. J. Mass Spectrom. 2002, 219, 485–495. (8) Sanz, P.; Ya~nez, M.; M
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