electrospray ionization tandem mass spectrometric study of salt

JOURNAL OF MASS SPECTROMETRYJ. Mass Spectrom. 2001; 36: 79–96

Electrospray ionization tandem mass spectrometricstudy of salt cluster ions. Part 1 — Investigations ofalkali metal chloride and sodium salt cluster ions

Chunyan Hao, Raymond E. March,∗ Timothy R. Croley, Jeffrey C. Smith andSteven P. Rafferty

Department of Chemistry, Trent University, Peterborough, ON, Canada K9J 7B8

Received 11 May 2000; Accepted 1 November 2000

Salt cluster ions of alkali metal chlorides ACl (A = Li+, Na+, K+, Rb+ and Cs+) and sodium salts NaB (B = I−,HCOO−, CH3COO−, NO2

−, and NO3−), formed by electrospray ionization, were studied systematically

by mass spectrometry. The influences on the total positive ion and negative ion currents of variation ofsolvent, solution concentration, desolvation temperature, solution flow-rate, capillary voltage and conevoltage were investigated. Only cone voltage was found to influence dramatically the distribution of saltcluster ions in the mass spectra observed. Under conditions of normal cone voltage of∼70 V, cluster ionshaving magic numbers of molecules are detected with high relative signal intensity. Under conditions oflow cone voltage of ∼10 V, the distribution of cluster ions detected is characterized by a relatively lowaverage mass/charge ratio due to the presence of multiply charged cluster ions; in addition, there is amarked reduction in cluster ions having a magic number of molecules. Product ion mass spectra obtainedby tandem mass spectrometry of cluster ions are characterized by a base peak having a magic number ofmolecules that is less than and closest to the number of molecules in the precursor ion. Structures havebeen proposed for some dications and some quadruply charged ions.

At pH 3 and 11, the mass spectra of NaCl clusters show the presence of mixed clusters of NaCl withHCl and NaOH, respectively. The effects of ionic radius on 20 distributions of cluster ions for 10 salts wereinvestigated; however, the fine structure of these effects is not readily discerned. Copyright 2001 JohnWiley & Sons, Ltd.

KEYWORDS: electrospray ionization; collision-induced dissociation; salt cluster; singly charged ion; multiply charged ion

INTRODUCTION

Electrospray ionization (ESI),1 – 3 introduced by Dole et al.4

has proved to be of great value in the pursuit of massspectrometry. In the past decade, salt cluster ions havebeen investigated extensively by electrospray ionizationmass spectrometry (ESI-MS) both for practical purposesand to discern the mechanisms of ESI. An ideal masscalibration standard for ESI-MS is one that gives a massspectrum in which the peaks are sufficiently closely spacedto make interpolation errors negligible, but not too closelyspaced to prevent the identification of individual peaks.Such a calibration standard has been proposed by Anacletoet al.5 In their investigation of protonated water clustersand salt clusters of NaF, KF, NaI, KI, RbI, CsI, CsNO3

ŁCorrespondence to: R.E. March, Department of Chemistry, TrentUniversity, Peterborough, ON, Canada K9J 7B8. E-mail:[email protected]/grant sponsor: National Sciences and EngineeringResearch Council Canada.Contract/grant sponsor: Canada Foundation for Innovation.Contract/grant sponsor: Ontario Research and DevelopmentChallenge Fund.

and Cs2CO3, they found that metal salt clusters couldprovide excellent calibration standards in both positive-and negative-ion modes. Later, Moini et al.6 reported thatsodium trifluoroacetate cluster ions could act as a calibrationstandard over a wide mass range of 100–4000 Th.7

Two mechanisms for the ESI process have been pro-posed: the ion evaporation model (IEM) proposed byIribarne and Thomson8,9 and the charge residue model(CRM) originated by Dole et al.4 and developed by Rollgenand co-workers.10,11 In their study of aqueous solutionsof alkali metal chlorides, Kebarle and Peschke12 detectedboth hydrated ions of the form M(H2O)x

C and salt clus-ter ions M(MX)n

C in the low mass/charge ratio region.These observations led to a blurring of the distinctionbetween the IEM and the CRM for small ions. Alkali metalhalide solutions were studied also by Wang and Cole13 andthey regarded their results as evidence in support of theextended CRM.14 – 16 A similar conclusion that is support-ive of the modified CRM was drawn from the observationof sodium salt cluster ions of NaC(NaCl)n, NaC(HCOONa)n

and NaC(HCOONa)n(CH3COONa)m17 although the cluster

ions observed by these two groups13,17 were in the low

Copyright 2001 John Wiley & Sons, Ltd.

80 C. Hao et al.

mass/charge ratio region. In an investigation of the parame-ters that may effect the abundance of salt cluster ions, doublycharged salt cluster ions in ESI-MS were observed by Wangand Cole.18 Cluster ions, NaxC

x (NaCl)n where x D 1� 2,formed under nanospray ionization and ESI conditions wereobserved by Juraschek et al.19 More recently, tandem massspectrometric (MS/MS) results for doubly charged sodiumchloride cluster ions were published by Zhang and Cooks.20

They reported the observation of cluster ions having magicnumbers of molecules, collisional fragmentation channels fordoubly charged cluster ions, and they proposed structures fordoubly charged ions. In addition to mass spectrometers, dif-ferential mobility analyzers were used by Gamero-Castanoand De la Mora21 for the study of cluster ions produced in theESI process. With this technique, data on small cluster ionsand on large particle residues were obtained simultaneously.

However, no multiply charged salt cluster ions, that is,ions bearing three or more charges, have been surveyed untilnow. In addition, the factors that influence the formation ofcluster ions require further investigation and relatively littlework has been done on salt cluster ions using MS/MS.Here, concentrated solutions of alkali metal chlorides andsodium salts were studied systematically; collision-induceddissociation (CID) mass spectra, obtained with triple-stagequadrupole (TSQ) and quadrupole time-of-flight (Q-TOF-2)mass spectrometers, of multiply charged salt clusters arereported for the first time.

EXPERIMENTAL

Alkali metal chlorides ACl (A D LiC, NaC, KC, RbC, and CsC)and sodium salts NaB (B D I�, HCOO�, CH3COO�, NO2

�

and NO3�) were dissolved in deionized water or HPLC-

grade solvent and the solutions were subjected to ESI. Theions produced were studied with a Micromass (Manchester,UK) Quattro LC TSQ mass spectrometer with a hexapolecollision cell and a Micromass Q-TOF-2 mass spectrometer.

Each instrument was equipped with a Z-spray electrosprayinterface. A diagram of this dual orthogonal ‘Z’ samplinginterface is shown in Fig. 1. Ions from the electrosprayaerosol pass perpendicularly through the aperture of thesample cone into a region of partial vacuum located betweenthe sample cone and the extraction cone. Ions are thendirected orthogonally into the second aperture, that is, of theextraction cone, and they are extracted electrostatically intothe mass analyser.

Solutions were introduced by a Harvard Apparatus(Holliston, MA, USA) Model 11 syringe pump at flow-rates of 5–20 µl/min�1. The source temperature was heldat 80–150 °C and the desolvation gas temperature at100–400 °C. The flow-rates of the nebulizer gas and ofthe desolvation gas were 84 and 262 lh�1, respectively.The voltage applied to the capillary was varied from 750to 4500 V and the voltage applied to the sample conewas varied from 0 to 200 V. The voltage applied to theextraction cone was set to zero. UHP argon was usedas collision gas for MS/MS experiments and the outletpressure was set to ¾700 mbar (10 psi). The pressure ofargon collision gas in the collision cell was in the range10�2 � 10�3 mbar when collision gas was on. However,because the collision gas was admitted as a jet to theregion wherein the collision cell was located and this regionwas evacuated (directly and indirectly) by more than onevacuum pump, the pressure of collision gas may not havebeen constant throughout the length of the collision cell.It is believed that there was a pressure gradient alongthe collision cell with a pressure maximum in the centreof the cell, and there was a pressure gradient across thecell. The lengths of the first quadrupole analysers and thehexapole collision cells in the two instruments were 200and 186 mm, respectively. The lengths of the r.f.-only pre-and post-filters were both 20 mm. All ESI mass spectraldata in positive and negative ion modes were acquired withMasslynx NT software (version 3.4).

Figure 1. Diagram of the Z-spray electrospray interface. The schematic is more a notional representation than an exactrepresentation. Reproduced with the permission of Micromass UK limited.

Copyright 2001 John Wiley & Sons, Ltd. J. Mass Spectrom. 2001; 36: 79–96

Colleen Daly

Colleen Daly

ESI/MS/MS Study of Salt Cluster Ions 81

RESULTS AND DISCUSSIONEffects of instrumental conditions and the role ofin-source collisions on the masses and chargestates of cluster ionsAlthough it is expected that instrument parameters will affectthe formation of salt cluster ions, no detailed study of theseparameters has appeared. The influences of instrumentalconditions on salt cluster ions were studied for NaCl and KCland are reported in this paper. The total ion current (TIC)obtained for a full mass scan increases with increases in eachof flow-rate, temperature and capillary voltage. However,the distributions of cluster ions were influenced markedlyonly by the magnitude of the cone voltage.

In Figure 2(a) and (b) are shown positive-ion ESI massspectra of a 0.05 M solution (50% waterC 50% methanol)of NaCl obtained with the Quattro LC at cone voltages of10 and 75 V, respectively. All of the observed NaCl clusterions obtained under normal cone voltage (NCV, 45–80 V)and low cone voltage (LCV, <30 V) conditions are listed inTables 1 and 2, respectively. In each of Tables 1 and 2, thecluster ions are identified by the corresponding values of xand n, where x is the number of charges borne by a clusterand n is the number of salt molecules of which the cluster isformed. Those values of n shown in normal type denote ionsthat were observed under NCV conditions only, where asthose values of n given in italics and marked with an asteriskdenote ions that were observed under LCV conditions only.The values of n shown in bold denote ions that were observedunder both NCV and LCV conditions. Wherever an ellipsis

(Ð Ð Ð) appears in Tables 1–4, this means that ‘the cluster isincreased one salt molecule at a time between the givenlimits of n.’ Positively charged cluster ions of NaCl bearingone to four and six charges were detected and are reported inTable 1. Negatively charged cluster ions of NaCl bearing oneto three charges were observed and are reported in Table 2.

In Fig. 3(a) and (b) are shown positive- and negative-ionESI mass spectra, respectively, of a 0.05 M solution (50%waterC 50% methanol) of KCl obtained with the QuattroLC at an NCV of 75 V. All of the observed positively andnegatively charged KCl cluster ions obtained under LCV andNCV conditions are listed in Tables 3 and 4, respectively.The KCl cluster ion species reported in Tables 3 and 4 areidentified in the same manner as in Tables 1 and 2 for NaClcluster ions. Positively and negatively charged KCl clustersbearing one to three charges were observed.

At NCV, several series of peaks were observed for NaCland KCl in both positive- and negative-ion modes. The mainseries of peaks shown in Figs 2 and 3 correspond to singlycharged salt cluster ions of the form A(ACl)n

C and Cl(ACl)n�,

where A represents a molecule of either NaCl or KCl. Otherminor series of ions are interposed with the singly chargedions. Mass/charge ratio values and MS/MS results (for CIDspectra, see below) support the conclusion that these minorseries of peaks correspond to salt cluster ions of the formAx(ACl)xC

n and Clx(ACl)x�n where x > 1.

The same magic numbers22 of salt molecules in the clusterions, that is, n D 1, 4, 9, 13, 22, 28, 37 and 47, are observedfor KCl as for NaCl, though the cluster of n D 9 is not

Figure 2. Positive-ion ESI mass spectra of a 0.05 M solution (50% waterC 50% methanol) of NaCl obtained with a Quattro LCtriple-stage quadrupole mass spectrometer (TSQMS) at a cone voltage of (a) 10 and (b) 75 V. The numbers above some of the peaksrefer to the number of molecules of NaCl in the cluster ion. The superscript numbers preceding plus signs denote the number ofpositive charges carried by the cluster ion.


82 C. Hao et al.

Table 1. Positively charged NaCl cluster ionsobserved by ESI/MS

Cluster number n of Nax(NaCl)nxC

x D 1 x D 2 x D 3 x D 4 x D 6

1a

2345

11Łb

67 14Ł

15Ł

8 16Ł 32Ł

33Ł

17Ł 34Ł

52Ł

35Ł

53Ł

9 18Ł 27Ł 36Ł

37Ł

28Ł

19Ł 38Ł

29Ł

39Ł

10 20Ł 30Ł 40Ł

41Ł

31Ł

21Ł 42Ł

32Ł

43Ł

11 22Ł 33Ł 44Ł

45Ł

34Ł

23Ł 46Ł

35Ł

47Ł

12 24Ł 36Ł

37Ł

25Ł

38Ł

13 26 39Ł

40Ł

2741Ł

14 28 42Ł

Ð Ð Ð Ð Ð Ð Ð Ð Ð16 32 48Ł

49Ł

3350Ł

17 34 51Ł

52Ł

3553Ł

18 36 54Ł

Ð Ð Ð Ð Ð Ð Ð Ð Ð

Table 1. (Continued)

Cluster number n of Nax(NaCl)nxC

x D 1 x D 2 x D 3 x D 4 x D 6

24 48 72Ł

73Ł

4974Ł

25 50 75Ł

76Ł

5177Ł

26 52 78Ł

79Ł

5380Ł

27 54 81Ł

82Ł

5583Ł

28 56 84Ł

85Ł

5786Ł

29 58 87Ł

88Ł

5989Ł

30 60 90Ł

91Ł

6192Ł

31 62 93Ł

6332 64Ð Ð Ð Ð Ð Ð35 70

7136c 72

7337 74Ð Ð Ð Ð Ð Ð67 128

a Where the cluster number n is given in bold, thecluster ions were observed under NCV and LCVconditions.b Where the cluster number n is given in italics andmarked with an asterik (*), the cluster ions wereobserved under LCV conditions only.c Where the cluster number n is given in normaltype, the cluster ions were observed under NCVconditions only.

apparent for NaCl in the positive-ion full-scan mass spectra.The signal intensities of cluster ions composed of 14, 15, 24and 32 salt molecules are markedly lower (such that thesespecies are almost ‘absent’) in Figs 2(b) and 3, which wereobtained under NCV conditions, than in Fig. 2(a), that wasobtained under LCV conditions.



Table 2. Negatively chargedNaCl cluster ions observed byESI/MS

Cluster number n of Clx(NaCl)nx�

x D 1 x D 2 x D 3

1a

2345

11Łb6 12Ł

13Ł

7 14Ł

15Ł

8 16Ł

17Ł

9 18Ł

19Ł

10 20Ł

31Ł

21Ł

32Ł

11 22Ł 33Ł

34Ł

23Ł

12 24Ł 36Ł

37Ł

2538Ł

13 26 39Ł

40Ł

2741Ł

14 28 42Ł

Ð Ð Ð Ð Ð Ð Ð Ð Ð16 32 48Ł

49Ł

3350Ł

17 34 51Ł

52Ł

3553Ł

18 36 54Ł

Ð Ð Ð Ð Ð Ð Ð Ð Ð24 48 72Ł

73Ł

4974Ł

25 50

51

26c 5279

53


Cluster number n of Clx(NaCl)nx�

x D 1 x D 2 x D 3

8027 54 81

8255

8328 56 84

8557

8629 58 87

5930 60

6131 62 93

9495

32 64 96Ð Ð Ð Ð Ð Ð Ð Ð Ð35 70 105

7136 72

7337 74Ð Ð Ð Ð Ð Ð52 10453545562

a Where the cluster number n isgiven in bold, the cluster ionswere observed under NCV andLCV conditions.b Where the cluster number n isgiven in italics and marked with anasterisk (*), the cluster ions wereobserved under LCV conditionsonly.c Where the cluster number n isgiven in normal type, the clusterions were observed under NCVconditions only.

These ‘magic’23 – 25 and ‘absent’ numbers, which areassumed to correspond to stable and unstable clusters,respectively, can provide key information on the geometryof salt cluster ions. Structures of cluster ions (NaCl)nCl�

(n D 1� 35) have been suggested by Doye and Wales.26

They found that those cluster ions composed of n D 13 and22 molecules and having regular and compact structureswere of greater stability. Barlak et al.23 had proposed‘cubiclike’ structures for n D 13 and 22 that can bedefined simply as 3ð 3ð 3 (corresponding to 13 NaClmolecules plus an ion for a total of 27 ions) and as


84 C. Hao et al.

Figure 3. (a) Positive- and (b) negative-ion ESI mass spectra of a 0.05 M solution (50% waterC 50% methanol) of KCl obtained witha Quattro LC TSQMS at a cone voltage of 75 V. The numbers above some of the peaks refer to the number of molecules of KCl inthe cluster ion. The superscript numbers preceding plus or minus signs denote the number of positive or negative charges,respectively, carried by the cluster ion.

Table 3. Positively charged KClcluster ions observed by ESI/MSa

Cluster number n of Kx(KCl)nxC

x D 1 x D 2 x D 3

12345

11Ł

67

15Ł

8 16Ł

17Ł

9 18Ł

19Ł

10 20Ł

21Ł

11 22Ł

23Ł

35Ł

12 24Ł

25Ł

13 2640Ł

2714 28 42Ł

43Ł

29


Cluster number n of Kx(KCl)nxC

x D 1 x D 2 x D 3

44Ł

15 30 45Ł

3116 32 48Ł

49Ł

3350Ł

17 34 51Ł

Ð Ð Ð Ð Ð Ð Ð Ð Ð22 44 66Ł

67Ł

4568Ł

23 46 69Ł

4724 48

4925 50

5126 52

5327 54

5528 56Ð Ð Ð Ð Ð Ð53 106

a See footnotes to Tables 1 and 2.



Table 4. Negatively charged KCl clusterions observed by ESI/MSa

Cluster number n of Clx(KCl)nx�

x D 1 x D 2 x D 3

12345

11Ł

6 12Ł

13Ł

7 14Ł

15Ł

8 16Ł

17Ł

9 18Ł

19Ł

10 20Ł

21Ł

11 22Ł

23Ł

35Ł

12 24Ł 36Ł

25Ł

13 26 39Ł

40Ł

2714 28 42Ł

43Ł

2944Ł

15 30 45Ł

46Ł

3147Ł

16 32 48Ł

3350Ł

17 34 51Ł

Ð Ð Ð Ð Ð Ð Ð Ð Ð22 44 66Ł

67Ł

4568Ł

23 46 69Ł

4724 48

4925 50

5126 52

5327 54

5528 56Ð Ð Ð Ð Ð Ð53 106

aSee footnotes to Tables 1 and 2.

3ð 3ð 5 (corresponding to 22 NaCl molecules plus an ionfor a total of 45 ions), respectively. However, the enhancedstability of the cluster ions having n D 4 and 9, hence theiridentification as having magic numbers, is not immediately

Figure 4. Comparison of the intensities of singly chargedNaC(NaCl)n ions (n D 1–29) plotted as a function of clusternumber n. The ions were detected at cone voltages of (ž) 10and (°) 75 V.

apparent from the results of Doye and Wales.26 On the otherhand, irregular structures showing particles protruding fromregular structures, such as clusters with n D 14, 15, 24 or 32,may be expected to be of lower stability.

Let us examine the effect of change of cone voltage. UnderNCV conditions, the mass spectra obtained and shown inFigs 2(b) and 3 consist of a wide variety of ions extendingover the entire mass/charge ratio range investigated, thatis, up to m/z 4000. When the cone voltage is decreasedso that the system is operated under LCV conditions, ionsignals as shown in Fig. 2(a) appear predominantly in thelow mass/charge ratio region, that is, of m/z < 1700. Whenthe cone voltage is decreased to LCV (¾10 V), clusters havingmagic numbers of salt molecules are no longer dominant inthe mass spectra observed. When those ions that appear inthe low mass/charge ratio region were subjected to CID, itwas found that many such ions corresponded to multiplycharged clusters. Although dications have been reported,multiply charged salt cluster ions have not been observedpreviously, although such cluster ions have been observedpreviously from an arginine solution.27

Figure 4 shows a comparison of the intensities of singlycharged NaC(NaCl)n ions (n D 1� 29) detected at conevoltages of 10 and 75 V versus cluster number n. Theintensities of singly charged ions used here were obtainedby subtracting the contributions of the overlapping doublycharged ions from the total intensities. It can be seen thatthe signal intensities of cluster ions having a magic number(4, 13, 22, 28) of NaCl molecules are much greater at a conevoltage of 75 V at 10 V. Also shown in Figure 4 are the sumsof the cluster ion signal intensities, that is, 138ð 106 countsat LCV and 220ð 106 counts at NCV, such that the totalion intensity is greater under the latter conditions. The conevoltage serves to focus the ion beam through the samplecone, (see below). Similar results have been obtained alsowith a Q-TOF-2 mass spectrometer.

From a comparison of the results shown in Fig. 4, itwould appear that the number of energetic collisions28 (thatis, collisions that lead to an increase in vibrational energyin the ionic species) suffered by nascent cluster ions in the


86 C. Hao et al.

volume between the sample and extraction cones varieswith the cone voltage magnitude. It should be noted thatthe total number of collisions suffered is independent ofthe cone voltage magnitude. At LCV, wherein the potentialdifference between the sample cone and the extraction coneis decreased to¾10 V, the number of such energetic collisionsis reduced sharply. The relatively low collision energyenvironment at LCV benefits the survival of labile multiplycharged cluster ions that are collisionally cool. At higher conevoltages, wherein the number of energetic collisions (and theprobability of dissociation) is greater, the formation of stablecluster ions having magic numbers of salt molecules and,possibly, some degree of internal excitation is favoured.

Although Kebarle and Peschke12 noted have that theformation of charged salt residues is not precluded by theIEM, these authors favour the CRM for concentrations ofsalt solutions >0.01 M. Thus, on the basis of the resultsreported here, it is assumed that charged droplets composedof salt molecules and solvent molecules with excess cations(in positive-ion mode) or anions (in negative-ion mode)are formed first. Then these droplets undergo solventevaporation and uneven fission continually until the nascentsalt cluster ions are generated. The nascent cluster ions collidewith gas molecules in the volume between the sample andextraction cones. The energies of these collisions determinethe distribution of cluster ions detected. As the cone voltage isreduced, in stages, to near 0 V, the cluster ions detected massspectrometrically reflect the final distribution of dropletsin the vicinity of the sample cone entrance though thedistribution may be modified slightly due to non-uniformion transmission. The ions undergo few, if any, energeticcollisions in the volume between the sample cone and theextraction cone and are detected ultimately. These ions areidentified in Table 1 with an asterisk adjacent to the n valuegiven in italics. For positively charged cluster ions of NaCl, itis seen that the nascent ion ensemble is composed principallyof numerous doubly, triply and quadruply charged speciesand two additional species, corresponding to n D 52 and53, that carry six charges each. Thus, the preponderanceof ions of low mass/charge ratio shown in Fig. 2(a) is dueto nascent ions having relatively high numbers of charges,rather than having low mass and a single charge. Relativelyfew singly charged cluster ions are observed under LCVconditions. Since the relative intensities of cluster ions withn D 13 (a magic number) is so low at LCV, we are confidentthat the nascent ion ensemble suffers few, if any, collisionsthat are sufficiently energetic so as to induce dissociation.Thus, the observation of cluster ions formed by ESI andhaving a magic number of salt molecules indicates that suchcluster ions have been formed predominately as a result ofenergetic collisions suffered by their precursors under NCVconditions. Hence the conditions of the ESI process itselfdo not appear to be conducive to the formation of clustershaving a magic number of salt molecules. At the same time,these conditions are conducive to the formation of clusterions that are thermodynamically less stable.

As the magnitude of the sample cone voltage is increased,so is the fraction of ion–neutral collisions that may be classedas energetic or energy-rich. The ions in the nascent ion

ensemble formed in the ESI source undergo partial charge-transfer reactions and fragmentation (see the next section) asa result of energetic collisions. The secondary ion ensembleis now of higher average mass/charge ratio owing, here,to lower numbers of charges associated with the molecularclusters. Hence the sample cone voltage, that affects theenergies of the in-source collisions, plays a key role indetermining the types of cluster ions that enter the massspectrometer. The magnitude of the cone voltage determinesthe size (or mass) and the charge state of detected cluster ions.

However, as displayed in Fig. 5, which shows thevariation of ion signal intensity due to NaC(NaCl)13 (acluster ion having a magic number of salt molecules) asa function of cone voltage, the ion signal intensity increaseswith increasing cone voltage until ¾55 V and, after thatpoint, the ion signal intensity decreases due to collisionaldissociation and scattering. As stated above, the cone voltageserves to focus the ion beam through the sample cone withthe result that the maximum ion signal intensity is observedat a cone voltage of 55 V. Hence the low total ion signalintensity observed under LCV conditions relative to thatobserved under the NCV condition, and shown in Fig. 4, isdue to poor focusing of the ion beam.

Because the conditions of the ESI process itself do notappear to be conducive to the formation of clusters havinga magic number of salt molecules, the formation of suchclusters during droplet evaporation is not precluded. Itis possible that such clusters are the precursors of themultiply charged cluster ions. Under LCV conditions, themultiply charged cluster ions enter the mass spectrometerand are detected; under NCV conditions, CID leads to there-formation of clusters having a magic number of saltmolecules.

Tandem mass spectrometric study of singly,doubly and multiply charged salt cluster ionsCID is a powerful tool that provides useful information onstructure, fragmentation pathways, and the thermodynamicbehaviour of gas-phase ions. However, the application ofMS/MS to the study of salt cluster ions has receivedlittle attention. An opportunity is taken here to present asystematic discussion of the application of MS/MS to a wide

Figure 5. Variation of the ion signal intensity of NaC(NaCl)13 asa function of cone voltage.



Table 5. Collision-induced dissociation of selected cluster ions of the form Nax(NaCl)xCn

na of parent ion n of fragment ions

xb D 1 x D 2 x D 3 x D 4 x D 6 x D 1 x D 2 x D 3 x D 4

4 1c, 2, 315 1–13–14

8 16 32 1–4–7, 16 32 3253 53 53, 47

9 18 27 36 1–4–8, 18, 27 27, 36 3610 20 1–4–13, 15–19

21 1–13, 15–2013 26 1–9–12, 16–22, 25

27 1–5, 13,16–22–2614 28 42 1–6, 9–13, 21–22–27, 37 27, 41,42

29 1,4,7,13, 20–22, 25–28 26–2815 30 11–13–14, 21, 22, 27–29 27–2916 32 1, 4–13, 22, 25–31 31

50 1–4 46–49–5022 44 1–13–21, 30, 34–37–43 35–43

45 1–4, 28–37–44 33–4451 37, 42–47–49 41–48

37 74 22, 25–36 61, 67–73

a n is the number of salt molecules in a given cluster ion.b x is the number of net charges borne by a cluster ion.c Values of n in bold type signify the base peak of the fragment ion mass spectrum. Data presented in italics wereobtained under conditions of low cone voltage. Data presented in normal type were obtained under conditions ofnormal cone voltage.

variety of salt cluster ions. MS/MS entails the selection orisolation of ions falling within a narrow band (1–2 Da) ofmass/charge ratios, dissociation of the selected or isolatedions by collision(s) and mass analysis of the fragment ionsor product ions formed. The mass spectrum of the fragmentions or product ions is called a product ion mass spectrum, orfragment ion mass spectrum, or simply a CID mass spectrum.

CID mass spectra were obtained for a large number ofsalt cluster ions. On the basis of this not inconsiderable

Table 6. Collision-induced dissociation of selected clusterions of the form Clx(NaCl)nx�a

n of parent ion n of fragment ions

x D 1 x D 2 x D 3 x D 1 x D 2

4 1, 2, 313 1, 4, 7–9, 1215 1–13–14

8 16 1–4–159 1–4–8

13 26 1–9–12, 16,17,19–2240 1, 2, 4, 13, 22, 37 36–39

27 1–13,16–22–26 24–2641 1–13–14, 22–27, 37–39 35–40–41

14 28 42 1–13, 16–22, 27, 37 24–27, 34–41–4217 34 4–9–13–16, 19–22–32 25–3322 44 9–13–21, 37 33–43

aSee footnotes to Table 5.

Table 7. Collision-induced dissociation of selected clusterions of the form Kx(KCl)nxCa


x D 1 x D 2 x D 3 x D 1 x D 2

11 1–4–107 1–4–6

15 1–13–14 13,1413 26 1–9–12, 16, 17, 22

43 1, 9, 37 39–42–4329 1, 22, 25–28 26–28

44 1, 37, 42 41–43–4415 30 45 1–4, 9–13–14, 25–29,37,43 27–29, 41–44–45

33 1–4, 22, 25–28–31 25–27–3122 44 9–13–21, 31, 34–37 33–43


compendium of information, CID data have been tabulatedfor a representative sample of the ion clusters observed.In Tables 5 and 6 are identified the product ions detectedfrom species of (NaCl)nNaxC

x (x D 1� 4, 6) and (NaCl)nClx�x

(x D 1� 3), respectively. In Tables 7 and 8 are identifiedthe product ions detected from (KCl)nKxC

x (x D 1� 3) and(KCl)nClx�

x (x D 1� 3), respectively. The values of n inbold Tables 5–8 designate the peak of greatest ion signalintensity, or base peak in each product ion mass spectrum;it is of particular significance that the base peaks observedcorrespond invariably to clusters having magic numbers ofmolecules for singly and doubly charged parent ions.


88 C. Hao et al.

Table 8. Collision-induced dissociation of selected clusterions of the form Clx(KCl)nx�a


x D 1 x D 2 x D 3 x D 1 x D 2

11 1–4–107 1–4–6

15 1–1313 3–9–12

43 41–42–4329 1, 22, 25–28 26–28

44 42–43–4415 30 45 1, 11–13, 27–29 27–29, 42–44–45

33 1, 22, 26–28–31 27–3222 44 7–21, 31, 37 33–43


From these CID results, it is seen that singly chargedclusters generate smaller singly charged clusters by losingneutral salt molecules under CID conditions. For dicationswith n < 28, only singly charged fragment ions are observedin the product ion mass spectra. It may be assumed that,for dications with n < 28, the internal energy acquired in adissociative collision together with the repulsive energy dueto the two charges exceed the energy required to dissociatethe dication. Furthermore, dications with n < 28 dissociateinvariably by charge separation. For dications with n ½ 28,doubly and singly charged product ions are observed. Thus,for dications with n ½ 28, where the intercharge separationis assumed to be larger than that for dications with n � 27,the charge repulsion is lower than in dications with n � 27.Hence the physical size of the cluster dication with n ½ 28leads to a stable doubly charged product ion.29,30

Let us discuss a possible structure for the NaCl dicationcluster with n D 28. Because the dication is stable, a regularstructure is preferred. However, for structures that areboth regular and compact, the intercharge separation isreduced with a concomitant increase in charge repulsion.Therefore, it is proposed that for dications and, indeed,for multiply charged clusters, a regular flat structure ofthickness equal to the size of a single molecule is preferred.A flat structure will have two faces each with a relativelylarge area and will resemble a rectangular wafer. Forthe NaCl dication cluster with n D 28, the proposedstructure can be defined as 2ð 4ð 7; this is a regular,flat structure composed of 56 positive and negative ionsand where the lengths of the sides are approximatelyequal. The two sodium ions in excess are attached tochloride ions located at opposite corners, diagonally opposedfor maximum intercharge separation. In this case, theintercharge separation is 24.8 A. For charge-separationreactions, the coulombic energy T (eV) is related31 to theintercharge distance R.A) as follows:

T D 14.39R

.1/

Thus the coulombic energy contribution to the dissociation ofa dication is estimated as 0.58 eV. With increasing distance R,

the coulombic contribution becomes less and the doublycharged ion become more stable. The converse is true also inthat with decreasing distance R, the coulombic contributionincreases and the doubly charged ion becomes less stable. Letus pursue further this line of argument. The low mass/chargeratio limits for the direct observation (without CID) of doublycharged cluster ions correspond to the mass/charge ratiosfor A2(ACl)11

2C and Cl2(ACl)112� for both NaCl and KCl.

Hence it can be assumed that the coulombic repulsion foreach of the four cluster ions with n D 11 is just less thanthe dissociation energy for the corresponding cluster ion.For the n D 11 dication, the coulombic repulsion is 0.89 eVassuming an undistorted structure of (2ð 3ð 3/C .2ð 2)plus two diametrically opposed ions.

When the charge borne by a cluster ion is increased, sois the tendency for that cluster ion to undergo partial chargetransfer as a result of collisions. For clusters that carry morethan three charges, partial charge transfer is the dominantcollisional process.

CID mass spectra of singly and doubly charged NaCland KCl clusters, in both positive and negative ion modes,are dominated by product ions having a magic number (1,4, 9, 13, 22, 28, 37, 47, etc.) of salt molecules. In each case,the magic number of the base peak is that which is lowerthan and closest to the cluster number of the parent ion. InCID spectra of triply charged parent ions, (ACl)nA3

3C and(ACl)nCl3

3�, doubly charged fragment ions with n� 1 saltmolecules correspond to the base peak.

Each of the five ion species discussed below exemplifiescomplementarily the variety of fragmentation reactionsobserved when salt cluster ions were subjected to CID.The CID mass spectra of (NaCl)4NaC, (NaCl)21Na2

2C,(NaCl)45Na2

2C, (NaCl)50Na33C and (NaCl)53Na6

6C are shownin Fig. 6(a)–(e), respectively. The dominant product ion of(NaCl)4NaC, m/z 257a, as shown in Fig. 6(a), is (NaCl)NaC

(m/z 81) while (NaCl)2NaC (m/z 139) and (NaCl)3NaC (m/z197) are also observed. It should be noted that m/z 257corresponds to the mass/charge ratio of the [MC 2]C ion,where M is the molecular mass of the isotopomer composedof the lowest isotope masses. The [MC 2]C ion is the ion ofgreatest abundance in the molecular ion cluster. The ions ofgreatest abundance in the molecular ion cluster were selectedfor CID. The sole dissociative process for singly chargedcluster ions is loss of one or more salt molecules. The production mass spectrum of doubly charged (NaCl)21Na2

2C ions(m/z 637), Fig. 6(b), shows all of the possible singly-chargedproduct ions having from 1–20 NaCl molecules, except theion having 14 NaCl molecules. The cluster ion of n D 14 isreported to be unstable26 and was observed in this studywith low abundance under NCV conditions. The clearlydominant fragment ion is (NaCl)13NaC, corresponding to themagic number n D 13. As can be seen in Fig. 6(b), severalproduct ions were observed having a mass/charge ratiogreater than that of the selected precursor. This behaviouris typical of multiply charged ions upon dissociation (eitherby collision or because the ion is metastable) when theloss of charge is proportionately greater than the loss ofmass. The product ion mass spectrum of doubly charged(NaCl)45Na2

2C ions (m/z 1339), Fig. 6(c), shows singly and



Figure 6. Product ion mass spectra of (a) singly charged ions, NaC(NaCl)4, (b) doubly charged ions, Na22C(NaCl)21, (c) doubly

charged ions, Na22C(NaCl)45, (d) triply charged ions, Na3

3C(NaCl)50, and (e) sextuply charged ions, Na66C(NaCl)53, obtained with a

Quattro LC TSQMS under low cone voltage conditions. In each case, the ion species subjected to CID is indicated with a verticalarrow. The energy given in each mass spectrum is the centre-of-mass collision energy.


90 C. Hao et al.

doubly charged fragment ions. Singly charged fragment ionshaving n D 1� 4 and 28� 44 are observed, that of n D 37(a magic number) having the highest signal intensity. Thequestion may arise as to why singly charged fragment ionshaving magic number n D 13 are not observed; this questionis addressed below. Doubly charged product ions havingn D 33� 44 are observed. The four doubly-charged productions of greatest ion signal intensity correspond to the loss of1–4 NaCl molecules from the parent dication.

Triply charged (NaCl)50Na33C ions (m/z 998), when

subjected to CID, produced singly charged ions with 1–4NaCl molecules and the complementary doubly charged ionswith 49–46 NaCl molecules, as shown in Fig. 6(d). The onlyother fragment ion observed was identified as (NaCl)50Na2

2C

formed by loss of NaC; no triply charged fragment ions wereobserved. The fragment ions observed with the greatestsignal intensity were identified as (NaCl)49Na2

2C.The product ion mass spectrum of sextuply charged

(NaCl)53Na66C ions (m/z 539), Fig. 6(e), is strikingly simple.

Only three dissociative channels are observed for parentions: these channels are loss of 3NaC to form (NaCl)53Na3

3C

(m/z 1051), loss of 2NaC to form (NaCl)53Na44C (m/z 795)

and loss of (6NaClC 2NaC) to form (NaCl)47Na44C (m/z

707). The fragment ions of low mass/charge ratio that arecomplementary to those of m/z 1051, 795 and 707 werenot observed, presumably owing to marked scattering fromthe coulombic explosion. It should be noted that n D 47 isdescribed as a magic number; however, the magic nature ofthis number is based on the observation of neutral clustersand of singly charged ions and on calculation. No calculations

have been made concerning the stability of clusters havingfour ions in excess; furthermore, to our knowledge, this is thefirst reported observation of a species such as (NaCl)47Na4

4C

(m/z 707). Because the total number of constituent ions is98, a possible regular structure can be proposed as 2ð 7ð 7,with each of the four sodium ions in excess occupying acorner position on one of the 7ð 7 faces.

Charge states of fragment ions can be identified, inprinciple, by the isotopic spacing of peaks. While such iden-tification was not possible with the triple-stage quadrupoleinstrument used here, the higher resolution of the Q-TOFinstrument did allow the determination of charge states. InFig. 7, a CID mass spectrum obtained with the Q-TOF-2 oftriply charged cluster ions (NaCl)41Cl3

3� (m/z 833) is shown;the mass/charge ratio of the selected ion species is markedwith a vertical arrow. This mass spectrum was obtainedunder LCV conditions. From the specific mass/charge ratiosand the adjacent peak spacing in the enlarged section belowthe mass spectrum, the charge states of the ions can be readilyconcluded. In this case, there are 45 peaks in the molecularion cluster spread over 29 1/3 Th. The CID mass spectrumshows a variety of product ions and the ion signals for someof these product ions have been enlarged for clarity. In orderof increasing mass/charge ratio, the examples of enlargedproduct ion signals are due to (NaCl)Cl�, (NaCl)13Cl� and(NaCl)26Cl2

2�, (NaCl)27Cl22� and (NaCl)41Cl3

3�, (NaCl)14Cl�

and (NaCl)28Cl22�, (NaCl)41Cl2

2�, and (NaCl)22Cl�. Note thatthree of these examples show overlapping cluster ion distri-butions.

Figure 7. High-resolution product ion mass spectra of negative triply charged ions Cl33�(NaCl)41, obtained by Q-TOF-2 under lowcone voltage conditions. The ion species subjected to CID is denoted with a vertical arrow.



Effects of solution conditions (solvent,concentration and pH)It has been pointed out that solution conditions, such asconcentration, solvent and pH, could influence the formationof cluster ions in ESI-MS.27 The failure of earlier attempts toobserve cluster ions of alkali metal halides14 may indicate thatthese cluster ions can only be generated from concentratedsalt solution. In this study, 0.1, 0.05 and 0.01 M aqueoussolutions of NaCl in deionized water containing either 25, 50or 75% of either methanol or acetonitrile were examined. Itwas found that, in the concentration range 0.01–0.1 M, changein concentration or change in solvent slightly affected thedistribution of cluster ions where the total cluster ion current

observed varied apparently with both concentration changeand solvent. The TIC increased with increasing concentrationand with the presence of either methanol or acetonitrile.The solution composed of 25% water C75% methanol gavethe highest ion signal intensities in the positive ion-mode,whereas the solution composed of 75% waterC25% methanolgave the highest ion signal intensities in the negative-ionmode.

It was found that a change of pH, brought about byadding the corresponding acid (HCl) or the correspondingbase (NaOH), could effect changes in the mass spectraobtained from salt solutions. In Fig. 8(a)–(d) are displayedfour ESI mass spectra of a 0.05 M NaCl solution showing

Figure 8. ESI mass spectra of a 0.05 M NaCl solution at pH 3 and 11. NaCl was dissolved in 50% waterC 50% methanol andchange of pH was brought about by adding either 38% HCl or 2 M NaOH. (a) Positive-ion mass spectrum obtained at pH 3;(b) negative-ion mass spectrum obtained at pH 3; (c) positive-ion mass spectrum obtained at pH 11; and (d) negative-ion massspectrum obtained at pH 11.


92 C. Hao et al.

positive and negative ions obtained at each of pH 3 and 11.At pH 3, the mass spectrum of positively charged clusterions of NaCl (Fig. 8(a)) shows that cluster ions containingNaCl and one or two HCl molecules can be observed,starting at (NaCl)17(HCl)2NaC and (NaCl)18(HCl)NaC asshown in the enlarged section. Furthermore, many ionspecies can no longer be observed in the high mass/chargeratio range and there is considerably more noise in thismass/charge ratio region than was observed under pHneutral conditions (Fig. 2(b)). It is probable that the noisein the high mass/charge ratio range may be caused byunresolved cluster ions of the type (NaCl)n(HCl)mNaC

due to the large range of n and m combinations possible.The mass spectrum of negatively charged cluster ions ofNaCl (Fig. 8(b)) obtained at pH 3 is remarkably similarto the negative-ion spectrum obtained under pH neutralconditions; the ions observed at pH 7 are shown in Table 2.

At pH 11, the mass spectrum of positively charged clusterions of NaCl (Fig. 8(c)) and of negatively charged cluster ionsof NaCl (Fig. 8(d)) differ strongly from those obtained underneutral conditions. The absence at pH 11 of large clusterions of NaCl in the high mass/charge ratio range is striking.In addition, peaks are observed at low mass/charge ratiosthat correspond to ions of mixed clusters of NaCl and NaOH.Mixed cluster ions of the form (NaCl)3 – 5(NaOH)1 – 2 with NaC

or Cl� are shown in the enlarged sections of Figs 8(c) and(d), respectively. It is inferred that the above observationsare due to changes of ion pairs in the charged droplets. Thepresence of NaOH molecules in a salt cluster appears toperturb the stability of NaCl clusters (and vice versa) suchthat the large ion clusters of NaCl are no longer sufficientlystable to permit their detection. This instability of the clusterstructure arises from the difference in size of the chlorideand hydroxyl ions, as is discussed below.

Effects of ionic radius on salt cluster ionsAs referred to above, Wang and Cole18 have discussed thefactors that may influence the abundances of salt cluster ionsformed in ESI. They concluded that ionic radii can influencethe abundances of salt clusters by affecting their solvationenergy. Such is the case for small clusters where the clusternumber n < 10. Here, two series of large salt cluster ionsare considered: first, cluster ions from a series of alkali metalchlorides and, second, a series of sodium salts are examined.

Four full-scan ESI mass spectra of 0.05 M solutions (50%waterC 50% methanol) of alkali metal chlorides ACl (whereA D LiC, RbC, CsC) were obtained at a cone voltage of75 V (NCV conditions) and are displayed in Fig. 9(a)–(d).In Figs 9(a) and (b) are shown positive- and negative-ionmass spectra, respectively, obtained from an LiCl solution.The distributions of LiCl cluster ions observed showedapproximately the same ranges of n and x as were observedin the mass spectra obtained from similar solutions of NaCland KCl, as discussed earlier. It should be noted that NaCland KCl showed the most widespread distributions of all thealkali metal chlorides in that the upper limits of n for NaCland KCl cluster ions corresponded to the upper mass/chargeratio limit, m/z 4000, for the Quattro LC instrument.

The distributions of cluster ions obtained from RbCland CsCl are similar to each other in that singly charged

cluster ions, either positively charged or negatively charged,are formed throughout the limited range of n D 1� 13.In addition, cluster ions with n D 16, 17, 22 and 23were observed in the higher mass/charge ratio region. Themass spectra for positively charged clusters of RbCl andCsCl are shown in Figs 9(c) and (d), respectively. Doublycharged cluster ions were observed only for n ½ 26. Froma comparison of Fig. 2(b) with Figs 9(c) and (d) and notingthat the major portion of each of Figs 9(c) and (d) has beenamplified by a factor of 15, it can be seen that the numberof salt molecules in the RbCl and CsCl cluster ions observedis markedly fewer than in the NaCl and KCl cluster ions.In addition, minor series of cluster ions that contained othercations (such as NaC and KC) were observed; such clusterions have been labelled in Figs 9(c) and (d) and are presumedto have arisen from impurities in the salts.

A second series of salts was examined wherein the cationwas held constant, by the use of sodium throughout, and theanion was varied. In this manner, it was possible to examinethe effect of anion radius on the distribution of cluster ionsgenerated by ESI. Positive-ion mass spectra of cluster ionsformed from sodium salts NaB (where B D I�, HCOO�,CH3COO�, NO2

� and NO3�) and observed with a cone

voltage of 75 V are shown in Fig. 10(a)–(e), respectively.Above the mass spectrum in Fig. 10(a) is shown the massspectrum in the high mass/charge ratio range obtained bythe Q-TOF-2 instrument. It should be noted that NaI solutionproduced cluster ions up to m/z 6000 that may be used forhigh mass range calibration.

The mass spectra of cluster ions of HCOONa andCH3COONa, shown in Figs 10(b) and (c), respectively, areremarkably similar to each other. The largest cluster ionobserved for HCOONa corresponds to n D 31 while thatfor CH3COONa corresponds to n D 32. Despite the fact thatthese mass spectra were obtained under NCV conditions,cluster ions having the normal magic numbers of moleculesdo not dominate the mass spectrum. A few doubly chargedcluster ions were observed with n in the region of 25 andone has been identified in each of Figs 10(b) and (c). Afurther point of similarity is that the triply charged clusterion (NaB)61Na3

3C was detected in each system. It wouldappear that this cluster ion may be of enhanced stabilityand it is of interest to consider the structure assumed bythe 125 constituent ions. The simplest structure that comesto mind is a 5ð 5ð 5 cube composed of 62 molecules anda sodium ion where an additional sodium ion has beensubstituted for a chloride ion.

The mass spectra of cluster ions of NaNO2 and NaNO3,shown in Fig. 10(d) and (e), respectively, are also remarkablysimilar to each other and to those of HCOONa andCH3COONa with respect to each of the points of similaritydiscussed immediately above. The triply charged clusterion (NaB)61Na3

3C is identified in Fig. 10(e) and cluster ion(NaB)67Na3

3C in Fig. 10(d).Negative-ion mass spectra of cluster ions formed from

the same sodium salts NaB and observed under the sameconditions are shown in Fig. 11(a)–(e), respectively. For eachsalt, the mass spectra of positively charged [Fig. 10(a)–(e)]and negatively charged [Fig. 11(a)–(e)] cluster ions are



Figure 9. Full-scan ESI mass spectra of a 0.05 M solution (50% waterC 50% methanol) of alkali metal chlorides obtained at a conevoltage of 75 V. (a) Positive-ion mass spectrum of LiCl; (b) negative-ion mass spectrum of LiCl; (c) positive-ion spectrum of RbCl;and (d) positive-ion spectrum of CsCl.

similar. It should be pointed out that Fig. 11(c) shows aseries of cluster ions containing one HCOONa molecule. Theformation of such mixed cluster ions appears to be at theexpense of doubly charged ions.

Let us now compare the mass spectral results for saltswith a common anion, that is, the alkali metal chlorides andthe salts with a common cation, that is, NaCl, NaI, HCOONa,CH3COONa, NaNO2 and NaNO3. All of the cluster ionsobserved are shown in Table 9. The distributions of clusterions obtained from HCOONa, CH3COONa, NaNO2 andNaNO3 are generally similar to each other. A type of clusterion that is unique to CH3COONa is the cluster of theform (CH3COONa)n(HCOONa)CH3COO� where n D 8–14.Among all of the observations presented, those for LiCl andNaI stand out from the others. LiCl is an exceptional saltwith respect to cluster ion formation in that it produces nofewer than 246 different cluster ions in all; 167 are positivelycharged and 79 are negatively charged. Furthermore, LiCl

produced the cluster ion having the greatest number ofmolecules, that is, n D 152. NaI is also exceptional becauseit alone forms a series of 40 quadruply charged clusters(n D 65–104, x D 4), but only in the positive ion mode witheach cluster containing four sodium ions.

Let us consider a possible structure for (NaI)65Na44C.

Sixty-five NaI molecules could form a wafer of 2ð 5ð 13atoms where, necessarily, the four sodium ions must belocated near the iodide ions situated in the corners of oneof the two 5ð 13 faces. This arrangement is the simplest forachieving maximum separation between the four sodiumions. Similarly, the structure for (NaI)104Na4

4C could be awafer of 2ð 8ð 13 atoms where the four sodium ions arelocated near the iodide ions situated in the corners anddiametrically opposed on each of the two 2ð 8 faces. Itshould be noted that the structures of this series of quadruplycharged ions cannot necessarily be regular and compact aswas the proposed structure for (NaCl)47Na4

4C discussed


94 C. Hao et al.

Figure 10. Positive-ion ESI mass spectra of 0.05 M solutions of sodium salts NaB, where B D (a) I�, (b) NO2�, (c) NO3

�, (d) HCOO�,and (e) CH3COO�. Mass spectra were obtained at a cone voltage of 75 V. The upper mass spectrum in (a) shows NaI cluster ions inthe high (3000–6000 Th) mass/charge ratio range detected by the Q-TOF-2.

above. The four sodium ions in (NaCl)47Na44C form part of

the regular rectangular structure rather than being attachedto the corners of the wafer-like crystal. The stability of aregular rectangular wafer-like structure in which all of theconstituent ions are located is expected to be of greaterstability than that of a wafer with ions attached to it andprotruding from it. The greater stability of (NaCl)47Na4

4C

is not unexpected because (NaCl)47Na44C is observed as

a product of CID of its precursor ion, (NaCl)53Na66C, as

shown in Fig. 6(e). Multiply charged ions having proposedregular rectangular structures to which excess charges areattached are observed only as primary ions formed in theESI process. A general observation is that negative clusterions of charge >2 are relatively rare. Curiously, althougha quadruply charged cluster ion of NaI, (NaI)65Na4

4C, wasobserved as shown in Fig. 10(a), no triply charged clusterions were observed with NaI.

Positively and negatively charged cluster ions formedfrom 10 salts were examined in this study. Because six ofthe 10 salts used were sodium salts, a considerable amount

of data has been obtained that illustrates the propensityof sodium salts to form positively and negatively chargedcluster ions. Three principal observations are made on thisbody of data. First, 10 of the 12 types of cluster ions formedfrom sodium salts consist of singly charged ions having up toa maximum of 25–37 molecules. Second, nine of the 12 typesof cluster ions consist of doubly charged cluster ions havinga minimum of 21–27 molecules. Third, five of the 12 types ofcluster ions exhibit triply charged ions where the minimumnumber of molecules in a triply charged ions ranges from61 to 67 molecules. Taken together, these three observationsmay indicate that, in the ESI process, the last sodium ion toleave a cluster is forced to do so, owing to cluster instability,only where the number of molecules remaining falls belowa critical value. Let us consider a cluster of 70 moleculesand three ions. If this cluster loses some molecules, an ionwill be ejected along with one or more molecules once thethreshold of 61–67 molecules is approached, according to thespecific salt; dications will be observed at this point. If thiscluster continues to lose some molecules, a second ion will be



Figure 11. Negative-ion ESI mass spectra of 0.05 M solutions of sodium salts NaB, where B D (a) I�, (b) NO2�, (c) NO3

�,(d) HCOO� and (e) CH3COO�. Mass spectra were obtained at a cone voltage of 75 V.

Table 9. A tabulation of the positively and negatively charged ion clusters observed in the mass range m/z 20–4000 fromsolutions of each of 10 saltsa

Salt formula x D 1 x D 2 x D 3 x D 4

nP nN nP nN nP nN nP nN

LiCl 1–51 1–36 31–101 29–71 109–152 — — —NaCl 1–67 1–55 26–128 25–104 — 79–102 — —KCl 1–53 1–53 26–106 26–106 — — — —RbCl 1–13, 16, 17, 22, 23 1–13, 16, 17, 22, 23 26, 44 26, 44 — — — —CsCl 1–13 1–13 26 26 — — — —NaI 1–26 1–25 25–53 25–48 — — 65–104 —NaNO2 1–35 1–28 23–68 25–50 61–93 37–69 — —NaNO3 1–37 1–40 21–64 25–80 61–96 67–99 — —HCOONa 1–31 1–31 25–58 27–58 61–84 — — —CH3COONa 1–32 1–34 27–58 — — — — —

a Each cluster ion is identified according to the number, x, of charges borne and the number, n, of constituent salt molecules. Thecluster ions were observed under NCV conditions. nP and nN refer to n in positive- and negative-ion modes, respectively.

ejected along with one or more molecules once the thresholdof 21–27 molecules is approached, according to the specificsalt; monocations will be observed beyond this point.

A further interesting feature arises from the clusterdistributions observed with LiCl, NaCl and KCl. With thesesalts, and let us discuss LiCl to illustrate the case, the

maximum value of n for a singly charged cluster ion, that isnmax for x D 1, is half that of the nmax for x D 2 and a thirdof that of the nmax for x D 3, such that each has the samemass/charge ratio. This feature may be due to the propertyof cluster ions or may simply be due to the mass transmissionfunction of the spectrometer.


96 C. Hao et al.

CONCLUSION

The influences on the total positive ion and negative ioncurrents of variation of solvent, solution concentration, pH,desolvation temperature, solution flow rate, capillary voltageand cone voltage were investigated for 10 salts. Of thesevariables, cone voltage was found to affect dramaticallythe distribution of salt cluster ions. Cluster ions containinga magic number of molecules are not in great evidencewhen the ions are detected under LCV conditions. Withan LCV (¾10 V), the distribution of cluster ions detected ischaracterized by a relatively low average mass/charge ratioowing to the presence of multiply charged cluster ions withup to six charges. This distribution is thought to reflect theinitial distribution of nascent gaseous ion clusters. With anNCV (¾70 V), ions are accelerated, collide energetically withgas molecules and undergo collisional dissociation leadingto the observation of cluster ions having magic numbers ofmolecules with high relative signal intensity.

MS/MS of cluster ions revealed several characteristicdissociative processes. Singly charged salt clusters gener-ated singly charged clusters of lower mass/charge ratio byloss of neutral salt molecules. Doubly charged clusters eitherlost one to several salt molecules to form doubly chargedfragment ions of lower mass/charge ratio or lost chargedentities to form singly charged fragment ions of both lowerand higher mass/charge ratio depending on the cluster mass.Multiply charged clusters bearing three, four or six chargesundergo predominantly charge separation at relatively lowcentre-of-mass collision energies. Product ion mass spectraare characterized by a base peak having a magic numberof molecules that is less than and closest to the number ofmolecules in the precursor ion. When n < 21–27 (dependingon the salt), no doubly charged ions are detected. Structureshave been proposed for doubly charged ions with n D 28and quadruply charged ions with n D 47, 65 and 104.

Observations of positive and negative ions of NaClclusters at pH 3 and 11 showed the presence of mixedclusters of NaCl with HCl and NaOH, respectively. The finestructure of the effect of cation to anion radius ratio foreach salt on the 20 distributions of cluster ions observed isnot readily discerned. For relatively high radius ratios, e.g.RbCl (0.81) and CsCl (0.92), the range of cluster ions is smallwhereas for a low ratio, LiCl (0.38), the range is large withrespect to both number and charge.

AcknowledgementsFinancial support from each of the Natural Sciences andEngineering Research Council of Canada, the CanadaFoundation for Innovation and the Ontario Research andDevelopment Challenge Fund is gratefully acknowledgedby the authors.

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electrospray ionization tandem mass spectrometric study of salt

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