Anal. Chem. 1988, 60, 1300-1307
1300
Factors Determining Relative Sensitivity of Analytes in Positive Mode Atmospheric Pressure Ionization Mass Spectrometry Jan Sunner,l Gordon Nicol, and Paul Kebarle*
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2N2
The sensitivity of atmospheric pressure ionization mass spectrometry to a range of analytes was studled with a SCIEX TAGA 6000E mass spectrometer. The reagent gas was air containing 5 Torr water. Analytes with gasphase baslcitles (OB) greater than ca. 200 kcaVmd have untfonnly very high and nearly equal sensltlvlties determined by fast kinetics for proton transfer from the reagent H,O+( H20),, (kinetic control). Most analytes (B) with OB less than ca. 200 kcaVmd have sene#hrl#ea that are daefmined by the thennal equliibrium dlstrlbutions of BH+(H,O), and H,O+( H20),, (thermodynamic conkd). For these mostly oxygen bases, the senstMy increases wlth the gasphase baddty of B. Several analytes, notably sutfur and carbon bases, have much lower sensitivities than expected from their OB’S. The hydrates BH+(H20), of this group are dlstingulshed by very low staMmy. The elucldatlon of the above factors leads to measures by which the response for the lowest sensttlvlty compounds can be increased by many orders of magnitude.
Atmospheric pressure ionization mass spectrometry
(API-MS)was introduced as an analytical technique by Carroll et al. (I). Based upon the high sensitivity for trace compounds in air, API has since developed into a mass spectrometric technique in its own right ( 2 4 ) . In addition to the monitoring of trace organic compounds in ambient air, a major analytical application of API is as an interface for liquid chromatography/mass spectrometry (LC/MS) (5). Ionization of moist air initiates a sequence of ion/molecule reactions (6) that results, within microseconds, in the formation of hydronium ion-water clusters, H30+(H20)h. A simplified reaction scheme is given by eq 1-5.
02+, On++ H20
-
O2+(HZ0)
+ HzO e 02+(H20)2 * H,O+(OH) + 0 2 H30+(OH) + H20 =+ H30+(H20) + OH
02’(H20)
(3) (4)
(5)
The hydronium ion-water clusters undergo successive clustering H30+(H20)+ HzO = H30+(H20)2
(6)
+ HzO = H@+(H2O)h+l
(7)
H@+(HzO)h
In this way, an equilibrium cluster distribution is attained. A t 25 OC and with 5 Torr partial water pressure (relative humidity (RH) = 21%))the majority of the clusters contain Present address: Department of Chemistry, Montana State
University, Bozeman, M T 59717.
0003-2700/88/0360-1300$01.50/0
from ca. five to ca. eight water molecules at thermal equilibrium (7). These hydronium ion-water cluster ions are the main reagent ions in positive ion API,and they can protonate molecules with gas-phase basicities (GB) higher than that of water according to the general reaction H30+(HzO)h
+ B = BH’(Hz0)b + (h + 1 - b)H2O
(8)
The main characteristic of API derives from the fact that the ions in reaction 8 are solvated by several water molecules. In the absence of solvation, proton transfer is known to proceed at nearly every ion/molecule collision, i.e. k8(h = 0, b = 0) = lz, = 2 X 10+ cm3~molecule-1~s-1 for most compounds B with GB higher than that of water (8). Proton transfer at every collision will of course lead to the highest analyte detection sensitivity. The kinetics of proton-transfer reactions involving large clusters, i.e. h = 5 to 8, have not been studied; however, work with smaller h and a few analytes, B, has been reported (9, 10). One would think that after several years of use of API ion sources, the factors influencing analyte sensitivities would be well understood. However, this is not the case. As an example, a compound like acetonitrile has a high sensitivity allowing for sub-part-per-billion detection in ambient air whereas another compound like thiophene with a similar GB has virtually no sensitivity at all in the API source. The available experimental data for the kinetics of proton transfer from hydronium ion-hydrate clusters to bases B indicate only a moderate decrease in the rate constants for increasing gas-phase hydration (IO). This fails to explain the extremely low sensitivity for thiophene or, to give another example, why the sensitivity for ethanol is several hundred times lower than the sensitivity for pyridine. Many of the compounds with very low sensitivities in the API source, like sulfur compounds and chlorinated hydrocarbons, are environmentally important. This unfortunate coincidence is one of the main reasons why many users of API have switched to low-pressure chemical ionization (CI) sources. It has been stated that API mass spectra reflect “... conditions of chemical and thermal equilibration” rather than “... relative rates of ionization reactions” (2). However, to our knowledge this point has never been experimentally verified. Also, it is not clear what “chemical and thermal equilibrium” implies in terms of ion intensities in the API source. This paper presents measurements of sensitivities in API for a number of compounds with a range of gas-phase basicities. The results obtained are explained in terms of the kinetics and thermodynamics of reaction 8. The results and conclusions in this paper are restricted to API conditions where the hydronium ion-hydrate clusters are the dominating ions in the mass spectra. Thus, the concentrations of compounds with high GB’s was always below ca. 0.1 ppm. If for example ammonia is present, as is the case in LC/MS applications, the hydronium ion-hydrate clusters are replaced by ammonium-hydrate clusters (NH4+(H20),) as the main reagent ions. The insights provided by the present work lead also to general criteria for relative analyte sensi0 1988 American Chemical Society
ANALYTICAL CHEMISTRY, VOL. 60, NO. 13, JULY 1, 1988
I
- 1 atm
(Me),";
1301
I
PyrH'
Air sampling
Corona
0 001
discharge needle -re 1. TAGA 6000 atmospheric pressure ion source (API): (a) inlet tube: (b) ionizing needle; (c) inner ion source cavity filled with flowing interface gas, ultrahigh-purity nitrogen: (d) sampling orifice, diameter 100 pm.
tivities in such LC/MS applications.
EXPERIMENTAL SECTION A Sciex TAGA 6OOOE triple quadrupole MS/MS equipped with an API source (4) was used for the experiments. The source region of this instrument is shown in Figure 1. Air at atmospheric pressure enters the ion source through the 18 mm i.d. glass tube (a). The air flow rate was 1.0 L/s at 700 Torr (ambient pressure at 600 m over sea level). Ionization in the source is accomplished by means of a needle corona discharge (b) running at a constant discharge current of 2.0 PA. The needle was at a potential of ca. 5 kV above ground. The ions drift toward the interface plate (c) which is at 650 V. A fraction of the ions drifta through the orifice in the interface plate into the inner cavity (d) which is filled with interface (curtain) gas. This gas was nitrogen, Linde minimum purity 99.9995%, maximum moisture 2 ppm. The ions are sampled by a 100-pm orifice into the vacuum and mass analyzed by the triple quadrupole. The potential of the orifice was 50 V, except for a few compounds for which 65 V was used. The ion source was at room temperature, 25 "C. The interface gas fulfills several functions. First, it keeps the vacuum chamber and the quadrupoles clean as only nitrogen gas and ions enter through the sampling orifice into the mass analyzer region. Second, cluster ions that drift through the dry interface gas undergo extensive thermal declustering (4). Thus, H30+(H20)h clusters with h = 4 to 8 decluster to smaller clusters with h = 1 to 3. Analyte BH+(H20)bclusters often decluster all the way to the bare protonated analyte (BH'). Thus, with the TAGA essentially no information is obtained on the detailed cluster distribution prevailing in the ion source. What can be measured is the sum of all the clusters of a given core ion. The extent of the declustering in the interface gas can be quite successfully modeled by using thermodynamic data for the clusters; see Appendix I. The formation of a gas jet at the orifice corresponds to a conversion of thermal energy into energy of motion. This leads to a very significant drop of temperature in the jet. The ion/ molecule clustering promoted by the low temperature (11) can be very severe if water is present. Thus, with no interface gas flow, very large hydrate clusters were observed in the TAGA. However, with a dry interface gas like N2,which has a very low tendency to cluster, only weakly bonded ion (N2)nclusters are formed which are easily collisionally declustered in the jet as the ions are accelerated by suitable electric fields. The analytes were added to the air in known concentrations between ca. 1ppb and 100 ppm. This was done by preparing an analyte/air mixture in a heated Pyrex bulb. Liquid analytes were injected with a syringe through a septum into the bulb. The partial pressure of the analytes in the bulb was in the 0.5-100 Torr range. Air was added to a total pressure of ca. 1200 Torr. All air mixtures were prepared with pyridine also present as a standard. The gas mixture from the Pyrex bulb was added to the inlet air stream through a 0.009 in. i.d. stainless capillary. The pressure drop over the capillary (1-250 Torr) was measured with a Validyne capacitance manometer. The flow through the capillary was calibrated by following the pressure drop in the Pyrex bulb as a function of time. The rapid gas flow through the inlet tube
L 50
io0
150 m /e
200
L 250
300
Flgure 2. Mass dependent transmission (T,) of the ion sampling
including the triple quadrupole, see text. Transmission curves are shown for two different values of the orifice voltage (OR); Pr, Bu, Pe, and He refer to n-propyl, n-butyl, n-pentyl, and n-heptyi, respectively. Observe that the mass discrimination is unusually large in the present experiments. ensures efficient turbulent mixing in the tube. This was experimentally verified by displacing the inlet tube sideways: see Figure 1.
The triple spectrometer was run with both quadrupoles in resolving mode and with higher than unity resolution. This was necessary in order to reduce the sensitivity enough to ensure that the counting circuit for the secondary electron multiplier did not saturate. For the purpose of the present paper it was necessary to obtain quantitative measurements of relative ion concentrations in the ion source. Therefore, discrimination effects in the sampling process had to be corrected for. Discrimination probably occurs at several stages in the ion sampling process. Ions are lost in the curtain gas and in the gas jet. Most importantly, the quadrupoles discriminate heavily against high mass ions. The mass-dependent discrimination was measured in the following way. A high-GB compound, B, was added to the air stream into the ion source. At high concentrations of B, the spectrum is totally dominated by B-derived ions. For some B compounds like trialkylamines, both the BH+(H20)band the B2H+(H20)b cluster ions are weak so that the spectrum is dominated by a single ion, BH+. The intensities of such single peaks for a series of compounds B, relative to that of pyridine, are plotted in Figure 2, as a function of the mass of BH+. (For some compounds in the lower mass range, corrections were made for the presence of minor BH+-hydrates.) If it is assumed that the total number of ions in the ion source is the same irrespective of what analyte is added, the graph in Figure 2 will also give the massdependent transmission efficiency (T,) of the sampling process. All measured ion intensities of ions M+ with mass m were corrected according to ZJM+) = Z(M+)/T,
(9)
where ZQ is the transmission corrected intensity and Z is the measured intensity (current). T,,, is the transmission efficiency for mass rn read off from Figure 2. It is further assumed that the transmission-corrected intensity is propcrtional to the concentration of the corresponding ions in the ion source. For the water clustered ions, this proportionality holds only for the sums of concentrations and intensities of the given core ions since declustering changes the number of water molecules prior to detection. This proportionality condition is expressed in b
b
CZ&&O+(HzO)/J = C C[H~O+(HZO)~I (lob) h
where the sums are taken over all hydrates. In most cases the analyte cluster distribution was dominated by the bare BH+ ion so that CItABH+(H&)& 0 Ztr(BH+)
(11)
In the sensitivity measurements, the analyte ions were monitored together with protonated pyridine (PyH') in a selected ion
1302
ANALYTICAL CHEMISTRY, VOL. 60, NO. 13, JULY 1, 1988
I
/ /
10
t-BuOH
NH3)
1I
t
'
1"'
1
'
1
,
1"'
I
I
10 CONCENTRATION
, , #
100
/
,
I , , , , , ,
1000
3-CI-Pyr
MFA
.. . ..-.
]Me%!~~[/r
pip
*I. 1I
*L,
T
t
1
l0,oOO A
PPI
-
*t
lndol
W
Figure 3. Intensities of BH+ peaks as a function of concentration of B, where B is pyridine (V)and acetone (0).The figure illustrates the linear response in the signal at low concentrations of B. Sensitivities
are artificially depressed; see text. monitoring mode, while changing the analyte concentration in the ion source. For high-sensitivity compounds the measurements were typically made at ca. 2.5, 5, 10, 25, 50, and 130 ppb. Oxygenated compounds with lower sensitivity usually required concentrations 10 times as high. Compounds with very low sensitivity were also studied at much higher concentrations, up to 100 ppm. The transmission-corrected sensitivity for a compound B (when BH+ is the only detected analyte ion) is given by eq 12a and the sensitivity relative to pyridine is given by eq 12b. The detection
S(B) = IJBH+I / P
I
S,,(B) = S(B)/S(PY)
10-5
c' +--Ferrocene
I
Thiophene
Furan
(Me12S
(Ea) (193)
circuit in the TAGA 6000 is based on ion counting. Sensitivities were therefore evaluated in (counts/s)/pptr (counts per second per parts per trillion).
RESULTS AND DISCUSSION Sensitivities for Analytes B in API at 25 O C and 5 Torr Water Pressure. Here, we describe the results of the study of the sensitivities for analytes B in the atmospheric pressure ionization source. The sensitivities refer to 25 "C and to a partial water pressure of 5 Torr. The details of the experiment are discussed in the Experimental Section. The sensitivities for the compounds studied were found to be constant over a wide range of concentrations, i.e. the BH+ intensity increased proportionally to the concentration of B in the ion source. This is illustrated for pyridine and acetone in Figure 3. As the reagent ions become depleted, the BH+ intensity begins to saturate; i.e. the sensitivity decreases. This occurs under the present experimental conditions above ca. 0.1 ppm for compounds with high sensitivities like pyridine (Figure 3). For compounds with low sensitivities, saturation occurs at higher concentrations; see result for acetone in Figure 3. The experimentally determined sensitivities relative to pyridine for analytes B (S,,,(B)), see Experimental Section, eq 12b, are plotted in Figure 4 vs the gas-phase basicity of B (GB(B)) (12). It is seen in the figure that the relative sensitivities of the analytes vary from ca. 1 down to very low values. The data points in Figure 4 can broadly be divided into three groups. (a) Analytes with GB > ca. 200 kcal/mol are seen to have high and relatively uniform sensitivities, i.e. S,,(B) = 1. This behavior is illustrated in the figure with the line marked "K". The compounds in this group are mostly nitrogen bases. (b) Most analytes with GB < ca. 200 kcal/mol have lower sensitivities which show a rough correlation with GB, i.e. the sensitiSity increases with increasing GB; see line "T" in the Figure 4. Most of these compounds are oxygen
bases. (c) A number of analytes with GB < 200 kcal/mol have much lower sensitivities than expected solely from their GB's. These low-sensitivity compounds, called group "L", include pyrrole and furan, as well as the sulfur bases dimethyl sulfide and thiophene and the organometallic ferrocene. The interpretation of the results in Figure 4 will be given later in this section. Since the gas-phase solvation by water molecules of the protonated molecules is quite extensive a t the high water concentrations in the API source, it seems reasonable to expect that the aqueous basicities of the analytes should show some correlation with the sensitivities. For this reason, the sensitivity values in Figure 4 were plotted also vs the aqueous basicities (pKBH+) in Figure 5. Inspection of the figure shows that for the compounds studied and for the present experimental conditions, one can make the following simple generalization: Analytes with aqueous basicities higher than that of water have high sensitivities in the API source, whereas analytes with aqueous basicities lower than that of water have lower sensitivities with no apparent correlation between aqueous basicity and sensitivity. It should be observed, however, that there are considerable uncertainties in the aqueous pKBH+values in the literature for compounds whose aqueous basicities are considerably lower than that of water (13). Variation of Ion Intensities with Ion Drift Time. The ionization region of the corona discharge is near the tip of the needle where the voltage drop is largest (14). The positive ions that exit from the ionization region drift to the interface electrode (c); see Figure 1. Essentially no ion destruction occurs in this drift region, which is the effective ion/molecule reaction chamber. The ion drift time determines the average residence time, i.e. reaction time (tres)for the ions. Due to the high water pressure, the hydronium ion-hydrate equilibrium distribution establishes at the very start of the ion
ANALYTICAL CHEMISTRY, VOL. 60, NO. 13, JULY 1, 1988
1303
THE "CLIFF"
2
PKH30
- - + -.1
0
lo
7
*I
io?
10-1
10-2
,03 W
cn
4w
25
?
'r
I I
*
0
17
'2
1
I
I I I 27
20 15 10 Needle -orifice distancelrnrn
Flgure 6. Change in intensity of observed reagent H,0+(H20) ions and of protonated pyridine (PyH') and protonated acetone as the tip of ionizlng needle is moved along the central axis of the ion source. The ion residence time increases from right to left.
10'4
IT
io 10-6
l O - 1 10-71 I I -10
I I I
31 1
1
I
1
I
.11,,,, 1 1 1 1 , , ( -5
0
5
,
I
,
,
1 , 10
P~BH'
Flgure 5. Relative sensitivity for the compounds In the API source as a function of the aqueous basicity (pKW+). The numbers identify the compounds: 1, tripentylamlne; 2, tripropylamine;3, triethylamine; 4, piperidine; 5, pyridine; 6, propylamine; 7, dimethylacetamide; 8, 3chloropyridlne; 9, methylamine; 10, dimethyl sulfoxide; 11, aniline; 13, ammonia; 14, acetophenone; 15, diethyl ether; 16, benzaldehyde; 17, ethyl methyl ketone; 19, acetone; 20, benzonitrile; 25, acetonltrile; 26, ethanol; 27, methanol; 28, indole: 29, pyrrole; 30, ferrocene; 31, dimethyl sulfide; 32, anisole.
drift. The proton transfer reaction eq 8 to the analyte, which is at very low concentrations, occurs over the total length of the drift region. As the needle is moved further away from the interface plate, the residence time in the ion source increases. This expectation is supported by the results given below. Thus, needle to interface plate distance is an important experimental variable. Figure 6 shows the behavior of the intensities of three different ions as the needle is moved. The residence time increases from right to left. The reagent H30+(H20)hions are seen to decrease with increasing t,,,. This decrease is a consequence of the decreasing fraction of total ions entering the interface region as the needle distance is increased. The protodated pyridine ion which belongs to the group K, see Figure 4,shows an increase in intensity with increase oft,,,. Protonated acetone which belongs to the group T shows a quite different behavior. On the logarithmic scale in Figure 6, the vertical difference between reagent H30+(H20)hions and product acetone ions (BH+) is constant. This means that the ratio between these ions stays constant with increasing hew
The behavior shown for pyridine ions in Figure 6 above was found to be characteristic for all of the high GB compounds, group K, in Figure 4. Likewise the behavior of the acetone ion was found to be characteristic of most of the oxygen bases, group T in Figure 4. A few of the oxygen bases with the highest sensitivities showed an intermediate behavior in that
with the needle tip close to the interface plate, the i m s behaved more like the K group of ions. Most of the compounds with low intensities (group L in Figure 4) showed a behavior similar to that of group T as the needle was moved. Pyrrole wm an exception in that it behaved more like group K. Kinetic Control of Ion Intensities i n API. The results for the high-GB analytes (group K in Figure 4)are consistent with the interpretation that the intensities of these BH+ ions are determined by the rate of proton transfer from the reagent hydronium ion-hydrate ions to the analytes. This type of behavior will be termed "kinetic control". For example, as the residence time for the ions in the API source is increased by retracting the ionizing needle, it was seen above (Figure 6) that the intensities of the analyte ions increased relative to the reagent ions. This is the expected behavior for a kinetically controlled product ion as shown by eq 13 which is deduced in Appendix 11. k , is the collision rate constant for
CItr(BH+(HzO)J= [BIt,e,k,CI,r(H30'(H20),) b
h
(3)
proton transfer to the analyte and the summation is over the intensities of the hydrates. The equation predicts an increase of BH+ with increased residence time. Also predicted by eq 13 is the linear dependence of the analyte signal on the concentration of B. This is valid for analyte concentration in the parts-per-trillion range where there is essentially no depletion of the reagent hydronium ions. This region corresponds to the linear region for pyridine shown in Figure 3. One can use eq 13 for the evaluation of t,,, from the experimentally determined I,,(BH+) and the corresponding hydronium hydrate intensities observed for a given needle cm3-moleposition. Using the rate constant k , = 1.7 X cu1e-l.s-l for B = pyridine (15),one obtains t,,, = 0.3 X s for a typical needle to interface orifice distance of 15 mm. This residence time should be considered only as a typical value. The residence time depends also on the discharge current and voltage. Increases of the voltage lead to increase of current and a decrease of residence time as evaluated via eq 13. Presumably, this is largely due to the higher drift velocities of the ions due to the higher drift field. In order to achieve a better understanding of the ion chemistry involved in the API source, parallel experiments were performed with one of our pulsed electron high-pressure mass spectrometers (PHPMS) (26,17).The detailed results of these experiments are presented elsewhere (15). However,
ANALYTICAL CHEMISTRY, VOL. 60, NO. 13, JULY 1, 1988
1304 a
100
j PhCOCH3
2
L’
Tirnehsec
0 PHPMS X API l
,
I
,
I
/
I
,
180
160
I
200
GB/ kcal mol-’
Flgure 8. Comparison between Re, for selected compounds determined with A P I (X) and with PHPMS (0).
c
c 50
- , 0
05
10
15
20
Timelmsec Flgure 7. Time dependence of cluster ion concentrations observed in PHPMS (Nicol 88): (a) B = pyridine, kinetic control; (b) B = thiophene, the approach to the equilibrium ratio is s e e n to be very fast, thermodynamic control. some of the key findings will be used here. In the PHPMS, the electron beam is pulsed and the concentration changes of the ions as a function of ion source residence time after the very short pulse can be observed. The results in Figure 7a illustrate the time dependence for a system under kinetic control. The partial pressure of B = pyridine used was 1.1 X Torr. This is about 100 times higher than the partial pressure of B at ca. 1ppb and 700 Torr air in the API source. Since the product [B]t determines the extent of proton transfer, see eq 13, the API system with ita t , = 300 ps would correspond in extent of proton transfer to that observed in , in the earliest and linear region Figure 7a after ca. 3 ~ s i.e. of the plot. Thermodynamic Control of Analyte Ion Intensities in API. It was seen in Figure 4 that most oxygen bases (group T compounds) have lower sensitivities in API than the group K analytes. A lower proton transfer rate constant (k8)would be the first explanation that comes to mind for these compounds. However, the variable residence time API results in Figure 6 demonstrated that these compounds maintain a ( H ~ as o ) ht )is constant ~ ~ ( B H + ( H z o ) b ) / ~ h ~ ( H 3 0 +ratio changed in the 0.1-0.4-ms range. Such a constant ratio would be expected if the proton transfer reactions (eq 8) had reached equilibrium at times shorter than 0.1 ms. A confirmation that equilibrium is indeed attained was obtained from experiments with the pulsed electron instrument (PHPMS). When compounds of the group T and L were used, a very rapid establishment of the proton transfer equilibria (eq 8) was observed. An example of the ion-time profiles observed with the PHPMS is shown in Figure 7b,
which gives results for the analyte B = thiophene. A visual comparison of parts a and b of Figure 7 gives a striking demonstration of the different conditions under kinetic and thermodynamic control. Even though the analyte concentration is very much the same in both experiments, the I(BH+) to hydronium ion intensity ratio in Figure 7b becomes constant; i.e. equilibrium is achieved at the shortest time accessible to observation. Parenthetically, one observes also a gradual decrease of I(BH+) and of &I(H30+(HzO),) at constant ratio. This decrease is due to proton transfer to a kinetically controlled minute trace analyte B = NH, (actually a chance impurity in the system). A thermodynamic treatment given in Appendix I1 provides
where Re, is a constant at a given temperature and ion source water concentration, [H20]. Re, can be evaluated from thermodynamic data on the BH+(H20),and the H30+(HzO)h cluster stabilities together with the gas-phase basicities of B and HzO (15). A linear response to [B], i.e. a constant sensitivity, is predicted by eq 14 for conditions where the reagent ion depletion is small. The linear response region predicted by eq 14 should correspond to the linear region observed for the thermodynamically controlled acetone in Figure 3. The PHPMS apparatus has been used very successfully for many ion-cluster equilibria measurements (16). It is therefore of interest to compare the equilibria results from the TAGA and the PHPMS for the thermodynamically controlled analytes. According to eq 14, when the same water pressure is used in both instruments, the equilibrium ratio R, shown in eq 14 measured with the two instruments should be the same. A plot a Re, for different thermodynamically controlled analytes measured with the TAGA and the PHPMS at the same water pressure vs gas-phase basicity for several thermodynamically controlled analytes B is shown in Figure 8. It can be seen that the agreement for the two instruments is quite close. It is interesting to note that Re, corresponds to the sensitivity ratio for B and H 2 0 as shown in eq 15. This
S(B) Re, = -S(H20)
cI(BH+(Hzo)b)/ [Bl b
CI(H,O+(H,O),) h
/ [H,O]
(15)
ANALYTICAL CHEMISTRY, VOL. 60, NO. 13, JULY 1, 1988
means that the relative TAGA sensitivities for thermodynamically controlled analytes can be predicted from thermodynamic data, i.e. Re, measured in instruments like the PHPMS. Kinetic and Thermodynamic Control and Its Relationship to the Stability of the Hydrates BH+(H20)bIn this section we address the questions: (a) what properties of the analyte lead to kinetic or thermodynamic control; (b) what distinguishes the thermodynamically controlled analytes with very low sensitivities (group L) from group T; (c) how can proton transfer equilibrium be established so fast for thermodynamically controlled analytes. In the more detailed PHPMS study (15) it was established that the forward direction of the proton transfer reactions H,O+(H,O),
+ B = BH+(H20), + H 2 0
(16)
is fast when the reaction is exoergic, i.e. AGOl6 < 0. The free energy change depends on the difference of the gas-phase basicities and the relative hydration free energies of H30+and BH+ as shown in eq 17. The hydration clustering free enAGO16 = GB(H20) - GB(B) AGoo,,(BH+)- AGoo,n(H30+)(17)
+
BH+
1305
Scheme I
situation becomes directly evident on examination of Figure 7b. It should be noted that the protonated oxygen bases, BH+, that form the group T, Figure 4,in general hydrate well. On the other hand, the bases of the unusually low sensitivity group, L, like furan and thiophene, hydrate very poorly. This is due to the fact that these bases protonate on the carbon; i.e. they are carbon bases (18). The protonation can occur either on the a or /3 carbon and according to ref 18 a protonation is more favorable. In either carbon-protonated structure little positive charge is concentrated in any one of the hydrogens and this leads to poor bonding of the ion to water. The resonance structures of the a protonated furan are shown in Scheme I. Structure I illustrates the strong R
I -O-H**.O
/H 'H
+ n ( H 2 0 ) = BH+(H20),
AGoo,,(BH+)
(18)
ergies, AGO,,,, are defined in eq 18. It should be noted that AGO,, are available for B = H 2 0 and most other analytes B from previous (16) and new PHPMS measurements (15). Thus, the energetics of the proton transfer reaction 16 are quite well defined for many analytes. The reader interested in the detailed data is referred to ref 15. Here, we will consider only general trends. An important general finding is that H30+ forms the most stable hydrates of the whole group of compounds. Thus, in general, the hydration energy difference, AGo,,(BH+) - AGoo,,(H30+),see eq 17, is always positive, i.e. endothermic and unfavorable. This endothermicity must be compensated for by the gas-phase basicity difference. For the high GB analytes, group K, which are kinetically controlled, AGO16 < 0 for all n of the abundant hydrates. This comes about because the gas phase basicity difference is so large that it always compensates for the hydration energy endothermicity. For the group T, oxygen bases, which have sensitivity decreasing with GB(B), the gas phase basicity difference is not quite sufficient to compensate for the hydration endoergicity. As a consequence, some or most of the abundant hydronium hydrates do not engage in proton transfer. Only the lowest water content H30+(H20),species can engage in exoergic proton transfer. The effective rate of forward proton transfer thus decreases. For lower GB analytes the exoergicity in the forward direction even a t low n approaches zero while simultaneously the reverse proton transfer reaction (eq 16) speeds up. Note that the reactions (eq 16) are bimolecular in the forward and reverse directions and therefore are expected to be involved in the kinetic maintenance of the proton transfer equilibria. When AGOl6 = 0 both kf and k , become of similar magnitude and smaller than the collision limit k , (15). Due to the very much higher concentration of HzO relative to B, the reverse rate is then very much faster. Since the relaxation time for the equilibrium, eq 16, depends on the sum of the pseudo-first-order rate constants kf[B] and kr[HzO], as shown in eq 19, equilibrium is i
reached very rapidly since k,[HzO] is very large. Expressing this somewhat differently, one can say that equilibrium is reached rapidly because the equilibrium is displaced so far to the left that it takes only a relatively very small extent of analyte protonation in order to get to equilibrium. This
I
hydrogen bond expected for an oxygen protonated alcohol due
to the large positive charge on the hydroxylic hydrogens. The very weak bonding of water to charge delocalized protonated carbon bases has been discussed previously in ref 19. The free energies for the hydration of the protonated pyrrole, furan, and thiophene were determined with PHPMS (15)and were found to be, as expected, very small relative to those for the oxygen bases. The hydration of protonated dimethyl sulfide and other protonated sulfur bases is also very much weaker than that of protonated oxygen bases of similar gas phase basicities (20). This effect can be attributed also to the relatively much lower partial positive charge on the protic H atom expected for the protonated sulfur bases. The very low sensitivity for the group L compounds is due to protonation equilibria, eq 16, which are shifted almost completely to the left due to the very unfavorable hydration energetics of BH+. In LCMS applications frequently the reagent ions are not H30+(H20),clusters. Instead other clusters like NH,+(H20),, due to the presence of ammonium buffer, may be dominant. Again, gas phase basicity differences and hydration energy differences will be involved as factors determining the protonation efficiency and thus the sensitivity of the analytes. Analyte sensitivities would be predictable on basis of a treatment analogous to that given above for H30+(HzO), reagent ions. Achieving High Sensitivities for All Analytes B. In the preceding sections, the reasons for the very different sensitivities of analytes B of groups K, T, and L were established. Once the factors involved are understood, one can make a rational search for a remedy. Obviously, to achieve nearly uniform and high sensitivity, i.e. shift all B into group K, one must reduce the hydration of the reagent H30+(HzO)h ions. Water removal from air, prior to admission into the A P I source, does not appear a viable alternative since the removal of water may also lead to removal of the parts-per-billion level analytes. However, the H30+(HzO)hcan be dehydrated also by the use of higher temperature. Results to be described in the following article of this iasue (21)shows that this approach is successful and leads to sensitivity increases of group L by many orders of magnitude. Validity of Results for Conventional API Apparatus. The design of the TAGA 6000 differs from other conventional
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ANALYTICAL CHEMISTRY, VOL. 60, NO. 13, JULY 1, 1988
API apparatus (I,2) particularly by the provision of the dry N2 interface gas region prior to the expansion into the vacuum of the mass analyzer. Most of the present findings regarding the sensitivities of analytes, i.e. Figure 4, and the interpretation in terms of kinetics and thermodynamics of reaction 8 are valid also for the processes occurring in the ion source of the conventional apparatus. I t is more difficult to predict what the effect will be of cooling due to the adiabatic expansion of the ion source gas mixture that occurs in the conventional apparatus. For kinetically controlled analytes, the sensitivity should be little affected if one uses the sum of the hydrates, C,J(BH+(HzO)b); see eq 13. However, the cooling will lead to an increase of b and to a broader hydrate distribution which in practice means a lower ability to detect the analyte. A similar situation may be expected for the thermodynamically controlled analytes, groups T and L. In this case an unfavorable shift of equilibria 8 toward H30+(HZO)h,due to the lower temperature in the expanding gas may occur also. For temperature effects, see ref 21.
APPENDIX I As the large thermalized cluster ions, H30+(HzO)hand ; BH+(H20)b,pass through the dry interface gas, they undergo thermal consecutive declustering reactions
H30+(H~o)hk~~1H30+(HzO)h-l + H@
(20)
BH+(HzO), = BH+(HZO)b-l+ HzO
(21)
The rates of reactions 20 and 21 can be roughly estimated in the following way, which here is exemplified for the hydronium ion-water clusters. It is assumed that the reverse clustering reaction H30+(HzO)h-1 + H@kzhH30+(H20)h
(22)
is in the high-pressure regime; i.e. reaction 22 is second order and the rate is assumed to be collision limited, kz2 = 2 X lo-' ~m~-molecule-~-s-~. The ratio between the rates for the forward, eq 22, and the reverse, eq 20, reactions should equal the equilibrium constant
Thus IZh-l,h IZh,h-l
=Kh-l,h
Kh-l,h is obtained from thermodynamic data for consecutive clustering reactions (7). The drift time for the ions in the interface gas can be estimated from the depth of the gas barrier (ca. 5 mm) and the electric field strength (ca. 1400 V/cm). Under these conditions the drift time should be of the order of 0.1 ms (22). I t is found from eq 24 that on this time scale all dissociation reactions down to the formation of H30+(Hz0)3are very fast. The rate constant for the dissociation of H30+(HzO)3to give H3O+(HZO),is calculated to be 5900 s-l. Thus, in 0.1 ms, 44% of the n = 3 clusters would dissociate. The two remaining dissociation reactions to give H30+(HzO)and H30+are both found to be slow. The equilibrium hydronium ion-water cluster distribution as obtained with PHPMS (7) a t p(HzO) = 5 Torr and 25 "C is shown in Figure 9a. Part b of the same figure shows the cluster distribution that results from the thermal distribution passing through the interface gas according to the calculations above. The observed cluster distribution is shown in part c of Figure 9. I t can be seen that the thermal declustering in
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150
50
100
150
EXD
E
a o
0
50
100
150
Timehsec Figure 9, Hydronium ion-hydrate cluster distributlons in API: (a) calculated equilibrium distribution at 25 'C and 5 Torr partial water pressure; (b) calculated cluster distribution after the ions have spent 0.1 ms in the interface gas; (c) observed cluster distribution.
the interface gas is modeled quite well by the simple calculations described here. In addition to the thermal declustering, some clustering may also occur since the interface gas still contains up to 2 ppm of water. Declustering occurs not only in the interface gas but also in the gas jet on the vacuum side of sampling orifice. This is due to collisional excitation of the ions as they drift in the electrical field through the neutral gas jet. The extent of declustering can be varied by changing the electrical potentials on the electrodes in the jet region and both H30+(HzO)and H30+can become dominating peaks. The cluster spectrum in Figure 9, part c, was obtained by using electrode potentials which minimize the declustering in the jet. Since the hydrate binding energies in BH+(H20), are generally considerably lower than those for H30+(HzO)h,essentially complete thermal declustering is expected for most analytes. The extent of dehydration increases for the protonated bases in the following order: oxygen < nitrogen
