Solvation Energy and Gas-Phase Stability Influences on Alkali Metal

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Anal. Chem. 1998, 70, 873-881

Solvation Energy and Gas-Phase Stability Influences on Alkali Metal Cluster Ion Formation in Electrospray Ionization Mass Spectrometry Guangdi Wang

Department of Chemistry, Xavier University of Louisiana, New Orleans, Louisiana 70125 Richard B. Cole*

Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148

The ability to observe abundant gas-phase metal cluster ions in electrospray ionization mass spectrometry (ESIMS) is highly dependent on experimental conditions. Alkali halides (MX) and other alkali metal salts were used to investigate the formation of cluster ions in ESI-MS. All compounds were found to give cluster ions of the form (Mn+1Xn)+ and (MnXn+1)-, with only two alkali salts yielding doubly charged cluster ions. In homologous alkali halide series, the relative abundances of cluster ions increased with increasing size of either the cation (positive ion mode) or the anion (negative ion mode). Calculations using an electrostatic model show that the gas-phase stability of cluster ions is greater for smaller cations or anions when a fixed counterion is employed. This stability calculation goes in a direction just opposite to the trend in cluster ion abundances observed in ESI-MS. Studies of equimolar mixtures consisting of two alkali halides reveal two distinct trends. When the equimolar mixture was composed of differing ions that participate in the droplet charge excess with the same counterion, the less solvated ions were found to form more abundant cluster ions. When the ions participating in the charge excess were fixed, the preferred counterion in observed clusters was the one that is more solvated in solution and forms more stable clusters in the gas phase. These observations can be rationalized by an extended form of the charged residue model where the weakly solvated ions that are part of the charge excess are preferentially enriched in offspring droplets during uneven fission. By contrast, transfer of a particular counterion located in the bulk of the droplets to the offspring droplets is not disfavored when this counterion is strongly solvated. The ESI process can be subdivided into three major events: the formation of small charged droplets, the evaporation and shrinking of the droplets accompanied by droplet fission, and the generation of gas-phase ions. The first two steps are better understood owing to direct experimental evidence.1-7 However, (1) Rayleigh, J. W. S. Philos. Mag. 1882, 14, 184. (2) Dole, M.; Mack, L. L.; Hines, R. L.; Mobley, R. C.; Ferguson, L. D.; Alice, M. B. J. Chem. Phys. 1968, 49, 2240-2249. S0003-2700(97)00919-0 CCC: $15.00 Published on Web 02/03/1998

© 1998 American Chemical Society

the picture becomes blurred as to the exact mechanism whereby gas-phase ions are formed from rapidly shrinking charged droplets, as these tiny droplets have thus far largely eluded chemical probes. It is well established1,5,6 that the evaporation of solvent from charged droplets leads to an increasing local electric field on the droplet as well as to an increasing nonvolatile solute concentration. In addition to the gas-phase ions observed in electrospray ionization (ESI) mass spectra, a solid aerosol carrying a certain amount of charge is formed from the droplet residue.3 The m/z values of these solid residues that are left behind are believed to be very high, with a broad distribution of values. Their presence has been related to the broad peaks observed in ion mobility studies of the electrospray process.2,3 Two proposed mechanisms provide qualitative accounts of the events occurring during the final stages of the electrospray ionization process: the ion evaporation model (IEM)3,8 and the charged residue model (CRM).2,8,9 The two mechanisms differ mainly in the depiction of the means in which gas-phase ions are generated from the charged droplets. The IEM contends that ions are formed by desorption into the gas phase when electric field conditions on the droplet are such as to favor relief of electrical stress by the departure of charged species rather than by droplet fission. Thus, ion desorption is considered to be a process occurring in conjunction with two other processes: droplet fission due to Rayleigh instability and formation of a solid residue as a result of solvent evaporation and depletion of excess charge. On the other hand, the CRM proposes that droplet fission continues until droplets containing single-solute species (or fewsolute species) are generated, which become gas-phase ions upon evaporation of the last solvent molecules. It seems inevitable that, at some point in the electrospray process, droplets containing several ion-paired solutes and one or more excess charges will exist. Kebarle and Tang showed qualitatively that, for an initial electrolyte concentration of 10-3 (3) Iribarne, J. V.; Thomson, B. A. J. Chem. Phys. 1976, 64, 2287-2294. (4) Yamashita, M.; Fenn, J. B. J. Phys. Chem. 1984, 88, 4451-4457 (5) Taflin, D. C.; Ward, T. L.; Davis, E. J. Langmuir 1989, 5, 376-384 (6) Gomez, A.; Tang, K. Phys. Fluids 1994, 6, 404-414. (7) Hager, D. B.; Dovichi, N. J.; Klassen, J.; Kebarle, P. Anal. Chem. 1994, 66, 3944-3949. (8) Fenn, J. B. J. Am. Soc. Mass Spectrom. 1993, 4, 524-535. (9) Kebarle, P.; Tang, L. Anal. Chem. 1993, 65, 972A-986A.

Analytical Chemistry, Vol. 70, No. 5, March 1, 1998 873

Table 1. Abundance of Cluster Ions of Alkali Halides in Positive Ion ESI-MS abundance (arbitrary units)a salt

M+

M2X+

M3X2+

M4X3+

M5X4+

M6X5+

M7X6+

M8X7+

NaCl KCl RbCl CsCl

4910 (100) 4040 (100) 4410 (100) 11780 (100)

314 (6.4) 372 (8.2) 379 (8.6) 1060 (9.0)

133 (2.7) 154 (3.4) 163 (3.7) 837 (7.1)

70 (1.4) 145 (3.2) 216 (4.9) 412 (3.5)

60 (1.2) 114 (2.5) 84 (1.9) 283 (2.4)

57 (1.3) 153 (1.3)

44 (1.0) 118 (1.0)

59 (0.5)

137 (2.3) 140 (3.5) 143 (3.0) 175 (3.8)

78 (1.3) 104 (2.6) 119 (2.5) 175 (3.8)

42 (0.7) 76 (1.9) 100 (2.1) 111 (2.4)

30 (0.5) 56 (1.4) 67 (1.4) 139 (3.0)

76 (1.9) 81 (1.7) 134 (2.9)

44 (1.1) 30 (0.6) 60 (1.4)

NaI KI RbI CsI a

5960 (100) 4000 (100) 4775 (100) 4630 (100)

280 (4.7) 460 (11.5) 425 (8.9) 421 (9.1)

Number in parentheses indicates abundance relative to the base peak M+ ) 100%.

M, a second-generation-offspring droplet (two successive uneven fission events) may contain about 3 excess charges and 10 ionpaired solute species.9 Further evaporation and droplet fission may result in some, but not necessarily all, droplets containing only one ion without any ion-paired solute molecules. At higher salt concentrations, one could expect offspring droplets to give rise to cluster ions consisting of the metal ions attached to one or more ion-paired species. The observation of cluster ions in ESI-MS has been reported previously.10-12 Meng and Fenn10 studied the factors that contribute to the degree of arginine cluster ion formation. Notably, in their study, doubly charged arginine cluster ions were observed. Anacleto et al.11 used several alkali metal salts as calibration compounds for pneumatically assisted ESI. Their results showed extensive cluster formation at elevated salt concentrations (0.1 M) in water-acetonitrile (50% v/v). On the other hand, early on it became clear that experimental conditions largely influence the ability to observe metal cluster ions in ESI-MS. For example, Kebarle and co-workers reported a complete absence of NaCl cluster ions from salt solutions run under their experimental conditions.9,13 Study of the formation of cluster ions generated by electrospray can shed light on the ESI mechanism. Factors that may influence the formation and abundances of cluster ions include solvent choice, electrospray instrumental conditions, salt concentration, solution pH, type of cations and anions constituting the salt, and gas-phase stability of the cluster ions. This paper investigates the effects of various parameters on the formation of cluster ions in ESI-MS for a variety of electrolytes. We begin by examining cluster ion formation for selected alkali halides. The relative stabilities of the smallest cluster ions, M2X+, will then be estimated using calculations based upon an electrostatic model. The effect of varying component cations and anions on cluster ion detection will also be investigated. Furthermore, the influence of electrolyte concentration on the abundances of the cluster ions will be examined. Finally, the implications of these results with regard to the electrospray ionization mechanism will be discussed. EXPERIMENTAL SECTION All electrospray ionization mass spectrometry experiments were performed on a Vestec-201 instrument (formerly of Houston, (10) Meng, C. K.; Fenn, J. B. Org. Mass Spectrom. 1991, 26, 542-549. (11) Anacleto, J. F.; Pleasance, S.; Boyd, R. K. Org. Mass Spectrom. 1992, 27, 660-666. (12) Wang, G.; Cole, R. B. Anal. Chem. 1994, 66, 3702-3708. (13) Ikonomou, M. G.; Blades, A. T.; Kebarle, P. Anal. Chem. 1991, 63, 19891998.

874 Analytical Chemistry, Vol. 70, No. 5, March 1, 1998

TX). Electrolyte solutions were prepared by dissolving the salts in either pure methanol or in 50:50 (v/v) water-methanol solvent, and the solutions were directly infused into the electrospray source by a Sage syringe pump (Orion Research, Boston, MA) at a flow rate of 1.6 µL/min. Except for minor adjustment of the electrospray voltage, and the needle-nozzle distance in order to obtain stable signals, each series of experiments was carried out under constant instrumental conditions. The temperature in the region of the electrospray needle was maintained at 56 ( 1 °C, while the source block temperature was held at 195 ( 1 °C. Electrostatic potentials were controlled in the range of 2.4-2.7 kV at the electrospray needle, 300 V at the “nozzle”, and between 16 and 25 V at the skimmer (minimal fragmentation conditions). All chemicals were purchased from Aldrich Chemical Co. (St. Louis, MO) and were used without further purification. HPLC-grade water and methanol were obtained from EM Science (Gibbstown, NJ). RESULTS AND DISCUSSION A total of 24 alkali salts were tested in ESI-MS with all compounds exhibiting various degrees of cluster ion formation. The cluster ions generally appeared in the form of Mn+1Xn+, where M+ represents an alkali metal cation, X- represents a halide anion, and n is the number of ion pairs constituting a particular cluster ion. Mass spectral data regarding cluster ions obtained from alkali salts in ESI-MS are given in Tables 1 and 2. A few general trends can be noted concerning the variety and abundances of observed positively charged cluster ions. First, for a fixed anion (e.g., Clor I-), the maximum observed cluster ion size, as well as the abundances (relative and absolute) of heavier clusters, progressively increases with increasing alkali cation size from Na+ to Cs+. This indicates that the formation of cluster ions is favored for larger alkali cations in a homologous series (constant halide counterion), other parameters being the same. Second, only singly charged cluster ions are observed for all alkali halides investigated under the employed conditions. Of all salts studied, only two salts gave rise to a series of doubly charged cluster ions, namely, CsClO4 and Cs2SO4 (Figure 1). Finally, the most abundant cluster ion for all alkali salts is consistently the smallest cluster ion, M2X+. The experimentally observed nonrandom cluster ion distributions arising from various alkali metal salts may provide important clues to elucidate the ESI mechanism that produced them. When comparing IEM and CRM, two pertinent aspects that differentiate the two models are as follows:

Table 2. List of Cluster Ions Observed in Positive Ion ESI-MS for Other Alkali Metal Compoundsa LiTFA NaTFA KTFA CsTFA NaBr NaOAc NaH2PO4 Na2C2O4 Na2SO4 Na2HPO4 CsBr CsOAc CsClO4b Cs2CO3 Cs2SO4b Cs2C2O4

Li+ (1), Li+ (2), Li+ (3), Li+ (4), Li+ (5), Li+ (6), Li+ (7), Li+ (8), Li+ (9) Na+ (1), Na+ (2), Na+ (3), Na+ (4), Na+ (5), Na+ (6), Na+ (7), Na+ (8), Na+ (9), Na+ (10), Na+ (11), Na+ (12), Na+ (13), Na+ (14) K+ (1), K+ (2), K+ (3), K+ (4), K+ (5), K+ (6), K+ (7), K+ (8), K+ (9), K+ (10) Cs+ (1), Cs+ (2), Cs+ (3), Cs+ (4), Cs+ (5), Cs+ (6), Cs+ (7) Na+ (1), Na+ (2), Na+ (3), Na+ (4), Na+ (5) Na+ (1), Na+ (2), Na+ (3), Na+ (4), Na+ (5), Na+ (6), Na+ (7) Na+ (1), Na+ (2), Na+ (3), Na+ (4), Na+ (5), Na+ (6), Na+ (7), Na+ (8) Na+ (1) Na+ (1), Na+ (2) Na+ (1), Na+ (NaH2PO4), Na+ (NaH2PO4)2, Na+ (NaH2PO4)3 Cs+ (1), Cs+ (2), Cs+ (3), Cs+ (4), Cs+ (5), Cs+ (6), Cs+ (7) Cs+ (1), Cs+ (2), Cs+ (3), Cs+ (4), Cs+ (5), Cs+ (6), Cs+ (7), Cs+ (8), Cs+ (9) Cs+ (1), Cs+ (2), Cs+ (3), Cs+ (4), Cs+ (5), Cs+ (6), Cs+ (7), Cs22+ (9), Cs22+ (11), Cs22+ (13), Cs22+ (15) Cs+ (1), Cs+ (2) Cs+ (1), Cs+ (2), Cs+ (3), Cs+ (4), Cs22+ (3), Cs22+ (5), Cs22+ (7), Cs22+ (9) Cs+ (1), Cs+ (2), Cs+ (3), Cs+ (4), Cs+ (5)

a Number in parentheses indicates number of ion-paired salt molecules attached to an alkali metal cation. b Alkali metal salts that yield doubly charged cluster ions in ESI-MS.

(1) In IEM, the relative solvation energy of a cluster ion is more critical to determining its relative abundance in the ESI mass spectrum because the solvation energy is directly proportional to the activation energy barrier that an ion must overcome to escape from the charged droplet. (2) In CRM, the relative gas-phase stability of a product cluster ion is more critical to determining its relative abundance because a negligible reverse activation barrier exists between the final “droplet” state and the gas-phase ion. Experimental results will be interpreted based on the above factors regarding CRM and IEM. Calculation of Gas-Phase Stability of the Cluster Ions. For the purpose of calculation, only the simplest cluster ion will be examined, namely, [M2X]+. Larger cluster ions of the form [Mn+1Xn]+ may be considered in the same manner in terms of their energies in the gas phase. However, it will be more difficult to determine the lowest energy structure of a larger cluster ion because of the numerous possible geometric arrangements. It is assumed that the three component ions in the cluster [M2X]+ will adopt a linear configuration (energetically most favorable) and the interionic distance, Rij, between the central anion and either cation is governed by the repulsive force due to overlapping outer electron shells of the two ions which is counteracted by the Coulombic attraction force between the positive and the negative ions.

The potential energy V(+) of a single cation is a result of its interaction with all other anions and cations present in the cluster:

V(+) ) (z+e2/4πo)

∑z /R i

+,i

(2)

i

where R+,i is the interionic distance between the positive ion and ion i present in the cluster. Likewise, the potential energy V(-) of an anion can be written as

V(-) ) (z-e2/4πo)

∑z /R i

-,i

(3)

i

where R-,i is the interionic distance between the negative ion and ion i present in the cluster. The potential energy V of a cationic cluster [M2X]+ is therefore

V ) 1/2(2V(+) + V(-)) ) (z+e2/4πo)(z-/R+,- + z+/R+,+) + 1

/2(z-e2/4πo)(z+/R-,+ + z+/R-,+) (4)

V ) e2/8πo(1/R+,+ - 4/R+,-)

(5)

where R+,+ is the interionic distance between the two positive ions. Because R+,+ ) 2R+,-

V ) -3e2/8πoR+,The potential energy of a pair of ions carrying opposite charges zie and zje separated by a distance Rij can be written as

Vij ) zizje2/4πoRij

(1)

where Vij is the mutual potential energy of two ions i and j, zi and zj are the number of elementary charges each ion carries, Rij is the interionic distance between the positive ion and the negative ion,14,15 and o is the vacuum permittivity.

(6)

The total internal energy of the cluster ion is the sum of the electrostatic energy and the contribution from the repulsive interactions that occur when the ions are pressed by the Coulombic force and their outer electrons start to overlap. This latter short-range repulsive term may be expressed as an exponential function of range R*, where R* is dependent on the compressibility (14) Pauling, L. The Nature of the Chemical Bond; Cornell University Press: New York, 1960; pp 505-562. (15) Atkins, P. W. Physical Chemistry, 2nd ed.; Freeman: San Francisco, 1982.

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875

a

b

Figure 1. Electrospray ionization mass spectra of (a) 10-3 M CsClO4 dissolved in methanol and (b) 10-3 M Cs2SO4 dissolved in methanol.

of the crystal. Thus, the total internal energy U of the cluster ion M2X+ can be written as

U ) -3e2/8πoR+,- + Ke(-R+,-/R*)

(7)

where K is a constant. The minimum value of this expression occurs when dU/dR+,-) 0, and this condition gives K as 2

/8πoR+,-2

(-R+,-/R*)

(8)

U ) -(3e2/8πoR+,-)[1 - (R*/R+,-)]

(9)

K ) 3e R*e Therefore

876

Analytical Chemistry, Vol. 70, No. 5, March 1, 1998

The molar internal energy of M2X+ is

Um ) 6.02 × 1023U

(10)

The interionic distances for alkali halide crystals of a rock salt structure are known (Table 3)14 and the observed distance between the cation and the anion in such crystals is taken as R+,in the above equations. For this calculation, R* is estimated based on the calculated lattice energy and the interionic distance for a given alkali halide.14,15,16 Equation 10 is then used to calculate

Table 3. Interionic Distances (Å) for Alkali Halogenide Crystals of Rock Salt Structure14

radius sum obs distance radius sum obs distance radius sum obs distance radius sum obs distance

FClBrI-

Li+

Na+

K+

Rb+

Cs+

1.96 2.01 2.41 2.57 2.55 2.75 2.76 3.02

2.31 2.31 2.76 2.81 2.90 2.98 3.11 3.23

2.69 2.67 3.14 3.14 3.28 3.29 3.49 3.53

2.84 2.82 3.29 3.29 3.43 3.43 3.64 3.66

3.05 3.01 3.50 3.47 3.64 3.62 3.85 3.83

Table 4. Calculated Molar Internal Energies of the Cluster Ions M2X+ (kJ/mol) X\M

Na+

K+

Rb+

Cs+

ClBrI-

-660 -629 -585

-602 -576 -542

-584 -560 -529

-565 -542 -516

the molar internal energy of the cluster ion M2X+; the results are shown in Table 4. The internal energies of the cluster ions shown in Table 4 are related to the enthalpy of the reaction 2M(g)+ + X(g)- f M2X(g)+ by H ) U + PV ) U + nRT. Thus, ∆H ) Um + ∆PV ) Um 2RT. Based upon these calculations, the molar internal energies of the cluster ions are seen to decrease with increasing radius of the cation or the anion. Thus, Na2Cl+ is more stable than Cs2Cl+ or Na2I+, and so on. However, the relative abundances of the cluster ions M2X+ in the ESI mass spectra of alkali halides showed trends in exactly the opposite direction (Table 1). Clearly, the relative stabilities of the cluster ions in the gas phase contribute very little to their relative abundances observed in ESI mass spectra. In other words, the stability difference of the products is likely overshadowed by other factors that more directly govern the route to gas-phase cluster ion formation. The above observations may be rationalized by either the charged residue model or the ion evaporation model. Due to solvent evaporation and droplet shrinkage, the nonvolatile solute (alkali salt) concentration may undergo a large increase in offspring droplets. It has been estimated that charged droplets prone to uneven fission give approximately 20 smaller droplets at the Rayleigh instability limit,17 and these offspring droplets may in turn produce third-generation droplets when the Rayleigh instability limit is again reached. An increase of nonvolatile solute concentration by a factor of 140 may be expected after three such uneven fission events,17 eventually leading to the formation of cluster ions. The least solvated ions, which constitute part of the charge excess on the droplet, are likely to be located nearest to the droplet surface. Uneven fission can allow for enhancement of the charge-to-mass ratio in offspring droplets if weakly solvated ions can be enriched in the offspring droplets via a “slip-over” effect9 whereby the least solvated species constituting the charge excess are preferentially driven into offspring droplets to relieve electrical stress. If such enrichment occurs, the ultimate charged (16) Handbook of Chemistry and Physics, 70th ed.; CRC Press: Boca Raton, FL, 1989. (17) Tang, L.; Kebarle, P. Anal. Chem. 1993, 65, 3654-3668.

residues will contain more abundant cluster ions of lower solvation energies than those of higher solvation energies as depicted in Table 1. On the other hand, varying yields of cluster ions observed in ESI-MS can also be rationalized by the ion evaporation model. At a sufficiently high initial concentration (e.g., g 10-3 M), the droplets undergoing ion evaporation may have highly augmented alkali salt concentrations due to solvent evaporation. Cluster ions start to form as the excess charges (alkali metal cations) on the droplets attach to ion pairs of electrolytes as the solvent is depleted. However, the degree of cluster formation (e.g., the maximum number of ion-paired salt molecules attached to a cation) and the charge associated with the cluster ions (e.g., singly charged or doubly charged) are dependent on the nature of the cations and anions. More importantly, according to IEM, the efficiency with which these clusters are converted into gas-phase ions is inversely correlated to the degree of solvation of the cluster ions. For alkali metal ions, the solvation energy (kJ/mol) in aqueous solution decreases in the following order, Li+ (519) > Na+ (406) > K+ (322) > Rb+ (293) > Cs+ (264)18 due to the increasing ionic radius. However, it should be borne in mind that, in IEM, it is solvated ions rather than naked ions that desorb into the gas phase. In fact, the radius of the hydrated alkali metal ion decreases in moving from Li+ to Cs+,18 which results in a considerable attenuation of the difference in the respective energy barriers for ion evaporation relative to the naked ions.3,17 In aqueous solution, the minimum free energies of transfer from gas phase to solution ( - ∆G°sol) for the hydrated alkali metal ions are as follows: -∆G°sol(Li+(H2O)m) (256 kJ/mol) > -∆G°sol(Na+(H2O)m) (236 kJ/mol) > -∆G°sol(K+(H2O)m) (233 kJ/mol) > ∆G°sol(Cs+(H2O)m) (226 kJ/mol), where m is the number of water molecules (between 5 and 7) that yields the lowest -∆G°sol for a given hydrated alkali metal ion.17 Evidently, even when hydrated, the solvation energy differences are still large enough to cause substantial increases in ESI-MS ion abundances in proceeding from Li+ to Cs+. Notably, Leize et al.19 reported an inverse relationship between alkali metal ion abundance in ESIMS and the solvation energy of the alkali metal ion. In the case of cluster ions, the solvation energy can be approximated to be proportional to the degree of solvation of the individual cations and anions constituting the cluster. As shown in Table 1, the relative abundances of larger cluster ions generally increase with increasing cationic radii from NaCl to CsCl and from NaI to CsI. The absolute abundances of cluster ions also increase from sodium salts to cesium salts, which occurs in parallel with the increasing absolute abundance of the respective naked cation. Here, if one compares the solvation energy of Na+ (406 kJ/mol) with that of Cs+ (264 kJ/mol) in aqueous solution,18 the higher degree of Na+ hydration is due to the higher electric field on the surface of Na+ (Esolv. ∝ ze/R2). Similarly, in the case of cluster ions, one can also apply electrostatic theory to estimate the solvation energy difference between Cs2Cl+ and Na2Cl+. Because Cl- is common for both cluster ions, the solvation energy difference between the two cluster ions must arise from the two pairs of cations present in Cs2Cl+ and Na2Cl+. Assuming that at (18) Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, 5th ed.; Wiley: New York, 1988; p 124. (19) Leize, E., Jaffrezic, A., Van Dorsselaer, A. J. Mass Spectrom. 1996, 31, 537544.

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Figure 2. Abundances of sodium cluster ions (Na2A+, where A represents an anion) from single-solute solutions containing only a sodium salt (empty bars) at a concentration of 10-3 M and from binary solutions containing an equimolar quantity (10-3 M) of sodium and cesium salts (hatched bars). This plot shows the effect of competing cations on the abundances of cluster ions in positive ion ESI-MS.

least half of the cationic surface in the cluster ion is effectively exposed to solvent molecules, the solvation energy difference between Cs2Cl+ and Na2Cl+ should be at least as large as the solvation energy difference between Cs+ and Na+ (i.e., 406 - 264 ) 142 kJ/mol). When considering the hydrated forms of clusters that are desorbed according to IEM, the difference in transfer free energies from gas phase to solution is surely attenuated relative to the naked ions. Yet, even small differences in the solvation energies can lead to substantial variations in ion evaporation rate constants,17 resulting in a lower abundance of Na2Cl+ as compared to Cs2Cl+. Furthermore, the difference between solvation energies of progressively larger clusters containing an increasing number of either Na+ or Cs+ (with fixed Cl- counterion) may be considered to incrementally widen. Indeed, in going from Na salts to Cs salts (Table 1), the differences in the relative abundances of successively larger cluster ions (Mn+1Xn+, n g 2) progressively increase. Effect of Varying the Ion Participating in Charge Excess, Constant Counterion Present. A series of experiments was designed to investigate competition between cations in the formation of cluster ions bearing a common anion. Equimolar mixtures containing two alkali metal salts (e.g., 10-3 M NaI and 10-3 M CsI in methanol) were subjected to ESI conditions. In the ESI mass spectra, it was observed that the Na+ peak and (Nan+1In)+ peaks were largely suppressed due to the presence of CsI, whereas the Cs+ peak and Cs cluster ions maintained almost the same abundances as compared to a solution that contained only 10-3 M CsI. As illustrated in Figure 2, the absolute abundance of Na2I+ from pure NaI solution is approximately 1 order of magnitude higher than that from the equimolar mixture solution containing NaI and CsI. Analogous results were obtained from three other binary solutions containing equimolar quantities of sodium and cesium salts: NaCl/CsCl, NaOAc/CsOAc, or NaTFA/CsTFA (Figure 2). In all cases, the abundances of sodium cluster ions from the equimolar mixture are reduced to 10-30% of those of pure sodium salt solutions. These results indicate that in the presence of a cation with a lower solvation energy (e.g., Cs+ and its cluster ions), the formation of cluster ions that are 878 Analytical Chemistry, Vol. 70, No. 5, March 1, 1998

Figure 3. Abundances of anions X- and MX2- from four separate equimolar mixtures consisting of two salt components obtained in negative ion ESI-MS.

more strongly solvated (e.g., Na+ and its cluster ions) is much less favored. The competition between anions in the formation of cluster ions containing a fixed cation was studied in negative ion ESIMS. Here, equimolar mixtures of two salts were also employed wherein the cation was the same and the anion was varied. These include separate two-component solutions consisting of 10-3 M NaCl/NaI, CsCl/CsI, NaOAc/NaTFA, or CsOAc/CsTFA. Results are shown in Figure 3, where the abundances of X- and MX2from the four solutions are plotted. It is evident from Figure 3 that the conversion of I- into the gas phase is more efficient than that of Cl-. Similarly, TFA- is transferred into the gas phase more readily than OAc-. More importantly, the absolute abundances of the associated cluster ions follow exactly the same pattern. Thus, NaI2- is 11 times more abundant than NaCl2-, CsI2- is 5 times more abundant than CsCl2-, and the abundances of NaTFA2- and CsTFA2- are 47 and 7 times higher than those of NaOAc2- and CsOAc2-, respectively. In comparing single-solute solutions to the binary mixtures, results strictly analogous to those given in Figure 2 were obtained for MX2- clusters. The above observations again point to the difference in solvation energies of the cluster ions as the underlying factor responsible for the variation in cluster ion abundances. The data also indicate that the gas-phase stabilities of the cluster ions are not important factors in determining relative cluster ion abundances because less stable alkali halide clusters consistently gave higher signals. The results can be explained by both IEM and CRM in qualitative terms. The solvation energy determines the activation energy barrier for cluster ion desorption when other parameters are held constant; therefore, the IEM predicts the weakly solvated cluster ions to evaporate more efficiently into the gas phase. On the other hand, cluster ions that are weakly solvated may be enriched in the offspring droplets during uneven fission; thus a modified CRM9 would also predict the same trend in which Cs2X+ and MI2- are formed more abundantly than Na2X+ and MCl2-, respectively. Effect of Varying the Counterion, Constant Ion Participating in Charge Excess Present. The next series of experiments examined the effect of eliminating the difference in solvation energies of the ions constituting the charge excess while varying the counterion. For positive ion ESI-MS experiments, four mixed solutions of either sodium or cesium salts were prepared that

a

b

Figure 4. (a) Positive ion ESI mass spectrum of equimolar CsCl/CsI (10-3 M) in methanol and (b) negative ion ESI mass spectrum of equimolar CsI/NaI (10-3 M) in methanol.

contained equimolar quantities of two different anions (i.e., Cland I-, or OAc- and TFA-). Another four equimolar mixtures of sodium and cesium salts were prepared for negative ion ESI-MS experiments, each containing a common anion and two different cations. The results are summarized in Table 5. In the positive ion series, two equimolar mixtures (i.e., NaCl/ NaI or CsCl/CsI) were used, both employing a single cation, which eliminates any cation effects (discussed above). As a result, the difference in the abundances of the two M2X+ ions is now determined mainly by two factors: (1) differences in the solvation energies of the salts brought about by the presence of different

anions (X-) and (2) the gas-phase stabilities of the particular cluster ions present. For a solution containing equimolar amounts of CsCl and CsI, the abundance of Cs2Cl+ was approximately 1.8 times higher than that of Cs2I+ (Figure 4a). Similarly, in the negative ion series where the anion was held constant (either Clor I-), differences in the cluster ion abundances cannot be attributed to anion effects. In this series, the cluster ions containing the sodium ion were more abundant than the cluster ions containing the cesium ion. For example, for a solution 10-3 M in both NaI and CsI, the abundance of NaI2- is about 7 times higher than that of CsI2- (Figure 4b). Analytical Chemistry, Vol. 70, No. 5, March 1, 1998

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Table 5. Results Summary for Equimolar Mixtures Containing Two Different Counterions equimolar mixture

relative ∆Gqion evap (extrapolated from solvation data)

calcd gas-phase stability ranking 10-3

ESI-MS relative abundance

NaCl + NaI CsCl + CsI

Positive Ion Mode (Each Salt M) Na2Cl+ > Na2I+ Na2Cl+ > Na2I+ Cs2Cl+ > Cs2I+ Cs2Cl+ > Cs2I+

Na2Cl+ (100) > Na2I+ (31) Cs2Cl+ (100) > Cs2I+ (55)

NaCl + CsCl NaI + CsI

Negative Ion Mode (Each Salt 10-3 M) NaCl2- > CsCl2NaCl2- > CsCl2NaI2- > CsI2NaI2- > CsI2-

NaCl2- (100) > CsCl2- (47) NaI2- (100) > CsI2- (14)

To explain the above results, we first examine the relative activation energy barriers and the relative gas-phase stabilities of the two-component mixtures (Table 5). In IEM, the activation energy barrier corresponds to the solvation energy that must be overcome for an ion to escape from the charged droplet. According to the principles of electrostatic theory, solvation is more extensive in the case of smaller cluster ions. Thus, the activation energy barriers for the ion evaporation of clusters bearing a constant counterion can be ranked in the following order: ∆Gq Mn+1Cln+ > ∆Gq Mn+1In+ and ∆Gq NanXn+1- > ∆Gq CsnXn+1-. This ranking holds true for ion evaporation of either solvated ions or naked ions, although a high degree of solvation will attenuate the difference. Notably, cluster ions predicted to have higher activation energy barriers are found to be more abundant in ESI mass spectra relative to those with lower predicted activation energy barriers. This contradiction speaks against formation of these cluster ions according to the ion evaporation model. Unlike the results obtained for ions participating in the charge excess, the trend in relative ESI-MS abundances with varying counterions goes in the same direction as the relative gas-phase stabilities of the cluster ions. This result can be rationalized by the charged residue model as follows. For the above equimolar mixtures, the ion participating in the droplet charge excess is common for each component of the binary mixture. Therefore no discrimination can exist in terms of which ion participating in the excess charge is preferentially enriched in offspring droplets during uneven fission events. Moreover, the two different counterions (Cl-, I-) present in equimolar quantities in the bulk of the droplet may have approximately equal opportunities to be carried over to the offspring droplets. If so, the ultimate charged residues should contain about the same number of the two different counterions. Because there is no appreciable reverse activation barrier between the final “droplet” state and the gasphase ion in CRM, the relative abundances of cluster ions containing each counterion observed in ESI mass spectra will be highly influenced by the relative gas-phase stabilities of the cluster ions. Effect of Concentration on the Abundances of Cluster Ions. Generally the abundances of cluster ions are expected to increase with increasing concentrations in initial solutions. On the other hand, the magnitude of the concentration effect on the signal may vary with different compounds. The effect of varying the alkali metal salt concentration on the abundances of cluster ions arising from a homologous series of alkali trifluoroacetates is shown in Figure 5. Three series of solutions containing increasing amounts of NaTFA, K-TFA, or CsTFA are used for comparison. The overall abundances of cluster ions (represented by the sum of all cluster ion abundances) are shown to increase 880 Analytical Chemistry, Vol. 70, No. 5, March 1, 1998

Figure 5. Semilogarithmic plot of the sum of cluster ions arising from three alkali trifluoroacetate salt solutions versus concentration.

when concentrations are raised from 1 × 10-4 to 1 × 10-2 M in four increments. The increase is most dramatic (steepest slope) for CsTFA, less so for K-TFA, and least for NaTFA. Moreover, at the lowest concentration of 10-4 M, only the CsTFA solution yields detectable cluster ions, which means that the minimum concentration required for the observation of cluster ions is compound dependent. In this case, cations (and cluster ions, given the same anion) having lower solvation energies tend to yield cluster ions at lower concentrations. This observation is consistent with the results discussed in the previous section where less solvated cluster ions were shown to exhibit higher abundances in ESI mass spectra. CONCLUSION Alkali halides and other selected alkali metal salts were found to yield cluster ions in electrospray ionization mass spectrometry when the initial salt concentrations were above approximately 10-3 M. The relative abundances, and the number of different cluster ions, however, depend on several factors that are intimately related to the ESI process. The abundances of cluster ions for homologous alkali halide series were found to increase with increasing size of either the cation in positive ion mode, or the anion in negative ion mode. In rationalizing these observations, gas-phase stability factors may be considered to be insignificant as calculations of the relative stabilities of cluster ions in the gas phase lie in opposition to this trend. However, when the ions participating in the charge excess are fixed, the preferred counterion in such a cluster is the one that forms the cluster ion with the highest gas-phase stability. The ensemble of results may be explained by an extended charged residue model wherein weakly solvated

ions participating in the charge excess are enriched in offspring droplets during the process of “uneven fission”. Thus, with a common counterion, a weakly solvated ion constituting the charge excess can end up in higher concentration in the offspring droplets, hence in higher abundances in the gas phase relative to a strongly solvated ion of the same charge (the gas-phase stability difference of the respective cluster ions is overshadowed). The charged residue model may also be applied to rationalize results obtained when the ion participating in the charge excess was fixed and the counterion was varied. Here, the relative abundances of competing cluster ions were observed to adhere to the relative order of gas-phase stability dictated by the particular counterion present. In this case, the weakly solvated counterion is not preferentially enriched in offspring droplets; hence cluster ion

stability in the gas phase likely plays a more critical role in determining the relative abundances of cluster ions observed in ESI mass spectra. The arguments that lead to the deduction that M2X+ and MX2- are most likely formed according to an extended CRM will only be fortified when larger cluster ions are considered. However, we have no comparable compelling arguments to establish that ion evaporation is not responsible for the desorption of monatomic alkali metal cations or halide anions.

Received for review August 20, 1997. Accepted December 17, 1997. AC970919+

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