Chemical Mass Shifts in Ion Trap Mass Spectrometry: Experiments

Anal. Chem. 1999, 71, 3405-3415

Chemical Mass Shifts in Ion Trap Mass Spectrometry: Experiments and Simulations J. Mitchell Wells, Wolfgang R. Plass,† Garth E. Patterson, Zheng Ouyang, Ethan R. Badman, and R. Graham Cooks*

Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-1393

Experimental data and simulations of trapped-ion motion are used to characterize the phenomenon of compounddependent mass shifts in a quadrupole ion trap mass spectrometer. The ratio of axial to radial dimensions of the ion trap and the nature and pressure of the bath gas are identified as experimental variables which influence the chemical mass shift. Systematic changes in chemical shifts occur with changes in the chemical structure of the ion, for example between members of a homologous series of alkylbenzene molecular ions. Simulations, performed using a new version of the program ITSIM, indicate that the mass shift is the result of two interacting factors: (i) delayed ion ejection from the trap during the mass analysis scan due to field imperfections associated with the end-cap electrode apertures and (ii) the compounddependent modification of this delay by collisions with the bath gas. Both elastic collisions and inelastic collisions, including those which lead to dissociation, appear to contribute to the shortening of the delay and hence to affect the magnitude of the chemical mass shifts. The quadrupole ion trap is a radio frequency device invented in 1953 by Paul.1 Since the introduction of the mass-selective instability scan by Stafford et al.,2 ion traps have become popular mass spectrometers, with some thousands currently in operation3 in a wide variety of applications ranging from biochemistry4-13 to † On leave from II Physikalisches Institut, Justus-Liebig Universita ¨t Giessen, 35392 Giessen, Germany. Work done in partial fulfillment of the requirements of the doctoral degree. (1) Paul, W.; Steinwedel, H. Z. Naturforsch 1953, 8a, 448. (2) Stafford, G. C.; Kelley, P. E.; Syka, J. E. P.; Reynolds, W. E.; Todd, J. F. J. Int. J. Mass Spectrom. Ion Processes 1984, 60, 85-98. (3) March, R. J. Mass Spectrom. 1997, 32, 263-276. (4) Cox, K. A.; Williams, J. D.; Cooks, R. G.; Kaiser, R. E. Biol. Mass Spectrom. 1992, 21, 226. (5) Kaiser, R. E.; Cooks, R. G.; Syka, J. E. P.; Stafford, G. C. Rapid Commun. Mass Spectrom. 1990, 4, 30. (6) Schwartz, J. C.; Bier, M. E. Rapid Commun. Mass Spectrom. 1993, 7, 27. (7) McLuckey, S. A.; Habibi-Goudarzi, S. J. Am. Soc. Mass Spectrom. 1994, 5, 740. (8) Qin, J.; Chait, B. T. Anal. Chem. 1996, 68, 2102-2107. (9) Qin, J.; Chait, B. T. Anal. Chem. 1996, 68, 2108-2112. (10) Steenvoorden, R. J. J. M.; Chait, B. T.; Qin, J. Anal. Chem. 1996, 68, 17841791. (11) Vachet, R. W.; Asam, M. R.; Glish, G. L. J. Am. Chem. Soc. 1996, 118, 6252-6256. (12) Rossi, D. T.; Hoffman, K. L.; Jankiczek-Dolphin, N.; Bockbrader, H.; Parker, T. D. Anal. Chem. 1997, 69, 4519-4523. (13) Ramsey, R. S.; McLuckey, S. A. J. Microcolumn Sep. 1997, 9, 523-528.

10.1021/ac9902289 CCC: $18.00 Published on Web 07/03/1999

© 1999 American Chemical Society

environmental and process monitoring,14-28 through fundamental studies of ion/molecule29 and ion/ion interactions.30-32 Numerous reviews describe the current status of the technique.3,33-37 State-of-the-art commercial instruments offer a mass/ charge range of up to 6000 Th (1 thomson ) 1 Da/charge38), mass measurement accuracy of 0.1 Th up to 2000 Th, and MSn capabilities. Even more remarkable performance data have been reported in experiments using specialized methods and/or (14) Hemberger, P. H.; Alarid, J. E.; Cameron, D.; Leibman, C. P.; Cannon, T. M.; Wolf, M. A.; Kaiser, R. E. Int. J. Mass Spectrom. Ion Processes 1991, 106, 299-313. (15) Wise, M. B.; Thompson, C. V.; Buchanan, M. V.; Merriweather, R.; Guerin, M. R. Spectroscopy 1993, 8, 14-22. (16) Cairns, T.; Chiu, K. S.; Navarro, D.; Siegmund, E. Rapid Commun. Mass Spectrom. 1993, 7, 971. (17) Lin, H. Y.; Voyksner, R. D. Anal. Chem. 1993, 65, 451. (18) Lausevic, M.; Jiang, X.; Metcalfe, C. D.; March, R. E. Rapid Commun. Mass Spectrom. 1995, 9, 927-936. (19) Hart, K. J.; Dindal, A. B.; Smith, R. R. Rapid Commun. Mass Spectrom. 1996, 10, 352-360. (20) Kok, G. L.; Cisper, M. E.; Hemberger, P. H. J. Am. Soc. Mass Spectrom. 1996, 7, 1172-1176. (21) Kotiaho, T. J. Mass Spectrom. 1996, 31, 1. (22) Gordon, S. M.; Callahan, P. J.; Kenny, D. V.; Pleil, J. D. Rapid Commun. Mass Spectrom. 1996, 10, 1038-1046. (23) Barshick, S.-A.; Mohill, M. L.; Britt, P. F.; Smith, D. H.; Barshick, C. M. Rapid Commun. Mass Spectrom. 1996, 10, 341-346. (24) Barshick, S.-A.; Worthy, S. M.; Griest, W. H. Rapid Commun. Mass Spectrom. 1996, 10, 263-268. (25) Dearth, M. A.; Asano, K. G.; Hart, K. J.; Buchanan, M. V.; Goeringer, D. E.; McLuckey, S. A. Anal. Chem. 1997, 69, 5121-5129. (26) Tiller, P. R.; El Fallah, Z.; Wilson, V.; Huysman, J.; Patel, D. Rapid Commun. Mass Spectrom. 1997, 11, 1570. (27) Johnson, R. C.; Srinivasan, N.; Cooks, R. G.; Schell, D. Rapid Commun. Mass Spectrom. 1997, 11, 363. (28) Wise, M. B.; Thompson, C. V.; Merriweather, R.; Guerin, M. R. Field Anal. Chem. Technol. 1997, 1, 251-276. (29) Vedel, F.; Vedel, M.; Brodbelt, J. S. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 1, p 343. (30) Stephenson, J. L.; Van Berkel, G. J.; McLuckey, S. A. J. Am. Soc. Mass Spectrom. 1997, 8, 637. (31) Stephenson, J. L.; McLuckey, S. A. J. Am. Chem. Soc. 1996, 118, 7390. (32) McLuckey, S. A.; Goeringer, D. E. J. Mass Spectrom. 1997, 32, 461. (33) Cooks, R. G.; Glish, G. L.; McLuckey, S. A.; Kaiser, R. E. Chem. Eng. News 1991, 69 (March 25), 26. (34) Cooks, R. G.; Chen, G.; Weil, C. In Mass Spectrometry in Biomolecular Sciences; Sindona, G., Caprioli, R. M., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1996. (35) Bier, M. E.; Schwartz, J. C. In Electrospray Ionization Mass Spectrometry; Cole, R. B., Ed.; John Wiley and Sons: New York, 1997; pp 235-289. (36) March, R. E.; Todd, J. F. J. In Modern Mass Spectrometry; Cairns, T., Ed.; CRC Press: Boca Raton, FL, 1995. (37) Jonscher, K. R.; Yates, J. R. Anal. Biochem. 1997, 244, 1-15. (38) Cooks, R. G.; Rockwood, A. L. Rapid Commun. Mass Spectrom. 1991, 5, 93.

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instrumentation. For example, ion traps have been used to trap and analyze singly charged ions of more than 70 000 Da,39 to provide mass resolution (but only in the full-width half-maximum definition) of up to 107,40 and to perform MSn experiments where n can be as large as 10 for demonstration purposes and is often 3 or 4.41,42 Ions generated by various ionization methods can be introduced from external sources,8,9,43,44 including electrospray ionization (ESI)45 and matrix-assisted laser desorption/ionization (MALDI).46 A method for reconstructing parent ion and neutral loss scans has been demonstrated.47,48 All these experiments show the ion trap to be potentially capable of extremely high performance. A key concern that underlies the present study is the mass/charge accuracy of ion traps, which at present is limited to 20-40 ppm.49,50 Early in the commercialization of the ion trap, Stafford and co-workers at Finnigan noticed that the mass/charge ratios of some ions, e.g. the radical cation of nitrobenzene, were incorrectly assigned. The error in mass/charge ratio was as much as 0.7 Th. This problem of mass shifts was solved by changing the geometry of the ion trap: specifically, this was achieved by altering the axial dimension (z0), viz. the closest distance between the end-cap electrodes and the center of the ion trap. This dimension was increased by 10.7% from the theoretically ideal value (for a trap of inscribed radius, r0, of 1.0 cm, the calculated z0 value is 0.707 cm and the stretched z0 value used in the Finnigan ITD, ITS40, Magnum, and ITMS instruments is 0.783 cm). Note that this change in the axial dimension was made without a corresponding change in the hyperbolic shape of the end-cap electrodes which would be necessary to maintain a purely quadrupole field at the new z0 value.51 The substantial higher order field contributions associated with stretching the trap were deliberately introduced to offset the field faults associated with the apertures in the endcap electrodes and electrode truncation. An instructive description of the field fault problem, as encountered in the commercialization (39) Kaiser, R. E.; Cooks, R. G.; Stafford, G. C.; Syka, J. E. P.; Hemberger, P. H. Int. J. Mass Spectrom. Ion Processes 1991, 106, 79-115. (40) Londry, F. A.; Wells, G. J.; March, R. E. Rapid Commun. Mass Spectrom. 1993, 7, 43. (41) Nourse, B. D.; Cox, K. A.; Morand, K. L.; Cooks, R. G. J. Am. Chem. Soc. 1992, 114, 2010. (42) Louris, J. N.; Brodbelt-Lustig, J. S.; Cooks, R. G.; Glish, G. L.; VanBerkel, G. J.; McLuckey, S. A. Int. J. Mass Spectrom. Ion Processes 1990, 96, 117. (43) Louris, J. N.; Amy, J. W.; Ridley, T. Y.; Cooks, R. G. Int. J. Mass Spectrom. Ion Processes 1989, 88, 97. (44) Doroshenko, V. M.; Cotter, R. J. J. Mass Spectrom. 1997, 32, 602-615. (45) McLuckey, S. A.; Van Berkel, G. J.; Glish, G. L.; Schwartz, J. C. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 2, p 89. (46) Brodbelt, J. S.; Vargas, R. R.; Yost, R. A. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 2, p 205. (47) Johnson, J. V.; Pedder, R. E.; Yost, R. A. Int. J. Mass Spectrom. Ion Processes 1991, 106, 197. (48) McClellan, J. E.; Quarmby, S. T.; Yost, R. A.; Borum, P. R. Proceedings of the 45th ASMS Conference on Mass Spectrometry and Allied Topics, Palm Springs, CA, 1997; p 575. (49) Cooks, R. G.; Cox, K. A.; Williams, J. D. In Methods in Protein Sequence Analysis; Imahori, K., Sakiyama, F., Eds.; Plenum Press: New York, 1994; p 135. (50) Wells, J. M.; Gill, L. A.; Ouyang, Z.; Patterson, G. E.; Plass, W.; Badman, E. R.; Amy, J. W.; Cooks, R. G.; Schwartz, J. C.; Stafford, G. C.; Senko, M. W. Proceedings of the 46th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, 1998; p 485. (51) Knight, R. D. Int. J. Mass Spectrom. Ion Phys. 1983, 51, 127.

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of ion trap mass spectrometers, has been provided by Syka.52 It should be noted that all commercially successful ion trap instruments to date have been modified to eliminate the chemical mass shift phenomenon. Wang and Franzen have made an extended study of the effect of trap geometry on trapping field imperfections,53 and they and others have shown that these effects lead to so-called “black holes” or “black canyons”, nonlinear resonance points in the ion trap stability space, which cause ion losses.54-57 Higher order fields have also been implicated in the degradation of resolution which occurs when scanning the ion trap in the reverse direction (from high mass to low mass) in a resonance ejection experiment.58 Despite the successful elimination of chemical mass shifts from commercial ion traps by changing z0, no systematic study of the effect of this variable on ion trap performance had been reported until the recent work of Gill et al.59 Their work described modest improvements in resolution and sensitivity, achieved by optimizing z0 to a value somewhat less than the commercial value of 0.783 cm, while maintaining mass accuracy. In a related study60 Gill et al. reported mass shifts for three compounds and showed that these shifts can be used to separate the signal of the shifting species from that of an isobaric or even isomeric nonshifting ion. Earlier, Syka reported shifts for some eight ions at four values of z052 while Traldi, Bortolini, and co-workers published a series of papers reporting mass shifts for a number of ions and sought to correlate them with the polarizability and dipole moments of the ions.61-63 The latter authors proposed that interactions of an induced dipole or the permanent dipole moment of the ion with the rf field could lead to power loss which would affect the rf voltage at which ions eject. However, Londry et al.64 showed that this effect is too small to lead to the observed shifts. In joint work between Los Alamos and this laboratory, we studied chemical shifts using a technique known as laser tomography.65 By rastering a laser beam, fired through apertures in the end-cap electrodes, across the plane of the ring electrode and monitoring the photodissociation products, it was possible to measure the radial size of the ion cloud. The radial distribution increased with the number of trapped ions, as expected due to mutual Coulombic (52) Syka, J. E. P. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 1, p 169. (53) Franzen, J.; Gabling, R.-H.; Schubert, M.; Wang, Y. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 1, pp 49-167. (54) Morand, K. L.; Lammert, S. A.; Cooks, R. G. Rapid Commun. Mass Spectrom. 1991, 5, 491. (55) Guidulgi, F.; Traldi, P. Rapid Commun. Mass Spectrom. 1991, 5, 343-348. (56) Eades, D. M.; Yost, R. A. Rapid Commun. Mass Spectrom. 1992, 6, 573578. (57) Alheit, R.; Kleineidam, S.; Vedel, F.; Vedel, M.; Werth, G. Int. J. Mass Spectrom. Ion Processes 1996, 154, 155-169. (58) Williams, J. D.; Cox, K. A.; Cooks, R. G.; McLuckey, S. A.; Hart, K. J.; Goeringer, D. E. Anal. Chem. 1994, 66, 725. (59) Gill, L. A.; Amy, J. W.; Vaughn, W. E.; Cooks, R. G. Int. J. Mass Spectrom. 1999, 188, 87-93. (60) Gill, L. A.; Wells, J. M.; Patterson, G. E.; Amy, J. W.; Cooks, R. G. Anal. Chem. 1998, 70, 4448-4452. (61) Bortolini, O.; Catinella, S.; Traldi, P. Org. Mass Spectrom. 1992, 27, 927. (62) Traldi, P.; Favretto, D.; Catinella, S.; Bortolini, O. Org. Mass Spectrom. 1993, 28, 745. (63) Bortolini, O.; Spalluto, G.; Traldi, P. Org. Mass Spectrom. 1994, 29, 269. (64) Londry, F. A.; Morrison, R. J. S.; R. E., M. Proceedings of the 45th ASMS Conference on Mass Spectrometry and Allied Topics, Atlanta, GA, 1995; p 1124. (65) Cleven, C. D.; Cooks, R. G.; Garrett, A. W.; Nogar, N. S.; Hemberger, P. H. J. Phys. Chem. 1996, 100, 40-46.

repulsion. More importantly, the rates of increase were different for compounds that experience large chemical shifts and those that do not. This was found to be the case both in ion traps with the calculated theoretical dimensions (r0 ) 1.0 cm, z0 ) 0.707 cm) and in those with the standard commercial dimensions (r0 ) 1.0 cm, z0 ) 0.783 cm). Chemical mass shifts were observed in the experiments in which the standard commercial electrode spacing was used, but with end caps that were modified from the commercial configuration by the inclusion of larger apertures machined into the end caps to allow for rastering of the probe laser. These shifts were attributed to the field faults produced by the larger end-cap apertures. To compensate for these additional field faults and so remove the chemical shift, the trap had to be stretched further, to a z0 value of 0.870 cm. Using this geometry, the chemical shifts measured for the molecular ions of nitrobenzene, n-butylbenzene, and acetophenone, and for the benzoyl and 3-methylbenzoyl cations, disappeared. In addition, the change in radial distribution with ion number was the same for all ions. It is clear from this and other work52 that further study of the effect of the axial dimension (z0) on chemical shifts is warranted. In this study, we use the apparatus described previously59 to investigate the effect of z0 on chemical shifts in a large set of ions and supplement these measurements with simulations of ion motion. A number of experimental factors have been identified that modify the rf voltage at which a particular ion is ejected during a mass-selective instability scan and hence affect the mass/charge ratio assigned to that ion. These were summarized recently,66 and they include the amplitude and frequency of the auxiliary ac potential used for axial modulation and resonance ejection,39 instabilities in the rf trapping voltage, the ion mass, the helium bath gas pressure, the number of ions, and the mass difference between the ions. The last two effects relate to the ionic environment in the ion trap cell and are generally referred to as space charge effects. It has been shown that as the number of ions in the trap is increased, ions are ejected later (at higher rf amplitudes) and hence are assigned to higher mass/charge ratios.67-69 Careful studies have shown that this phenomenon is stronger for lower mass ions when a large abundance of higher mass ions is present and becomes more pronounced as the difference in mass between the ions decreases.66 The latter phenomenon has been termed the local space charge effect. Note that space charge effects are also present in other types of mass spectrometers, in particular in FT-ICR instruments where an analogous but less pronounced degradation in performance occurs when large numbers of ions are present.70-76 (66) Cox, K. A.; Cleven, C. D.; Cooks, R. G. Int. J. Mass Spectrom. Ion Processes 1995, 144, 47-65. (67) Fischer, E. Z. Phys. 1959, 156, 1-26. (68) Fulford, J. E.; Hoa, D. N.; Hughes, R. J.; March, R. E.; Bonner, R. F.; Wong, G. J. J. Vac. Sci. Technol. 1980, 17, 829. (69) Guan, S.; Marshall, A. G. J. Am. Soc. Mass Spectrom. 1994, 5, 64. (70) Ledford, E. B.; Rempel, D. L.; Gross, M. L. Anal. Chem. 1984, 56, 2744. (71) Chen, S. P.; Comisarow, M. B. Rapid Commun. Mass Spectrom. 1992, 6, 1. (72) Uechi, G. T.; Dunbar, R. C. J. Am. Soc. Mass Spectrom. 1992, 3, 734. (73) Huang, J.; Tiedemann, P. W.; Land, D. P.; McIver, R. T.; Hemminger, J. C. Int. J. Mass Spectrom. Ion Processes 1994, 134, 11-21. (74) Peurrung, A. J.; Kouzes, R. T. Int. J. Mass Spectrom. Ion Processes 1995, 145, 139. (75) Easterling, M. L.; Mize, T. H.; Amster, I. J. Int. J. Mass Spectrom. Ion Processes 1997, 169, 387-400. (76) Easterling, M. L.; Mize, T. H.; Amster, I. J. Anal. Chem. 1999, 71, 624632.

The effects of ionic environment (space charge) and the other experimental variables listed above on peak position limit the mass measurement accuracy achievable with the quadrupole ion trap. These limitations have been addressed in a variety of ways, including peak-matching methods,77 extrapolation to zero ion abundance,66 and improvements in electronic control and stability, the results of which are mass accuracies of 20-40 ppm.50 The mass misassignments noticed by Syka and co-workers during the early development of the ion trap52 and those studied by Traldi et al.61-63 and Cleven et al.65 are clearly influenced by the experimental parameters listed above but cannot be fully explained by these experimental parameters alone. These mass misassignments seem to be related to the physicochemical properties of ions and have been variously (and confusingly) referred to as mass shift, compound-dependent mass shift, and chemical mass shift. We use the term chemical shift or chemical mass shift to denote mass misassignments which cannot be explained by space charge effects or by any of the more mundane experimental variables listed above.66 It should be noted that the work of Traldi et al.61-63 is differentiated from the work of Syka,52 Cleven et al.,65 and Gill et al.59,60 and the work reported here by their use of resonant ac axial modulation in combination with the mass-selective instability scan. The experimental work reported here is combined with simulations using the multiparticle ion trap simulation program ITSIM.78 The Windows version of the program79 allows a large number of ions, limited only by computer memory and speed, to be studied and provides realistic mass and kinetic energy data. The program is also capable of simulating the behavior of small numbers of ions in quasi-real time under a wide variety of operating conditions. The program was modified extensively for this work to allow a detailed study of the effects of changes in the geometry and other experimental variables on the ejection profile of a collection of ions of interest. In this paper, we report systematic studies of chemical mass shifts as a function of the axial dimension of the ion trap. In addition, we report observations on the effect of the buffer gas on chemical mass shifts. Similarities between the findings of experiment and simulation allow conclusions about the origin of chemical mass shifts. It is found that the apertures in the endcap electrodes lead to field faults which cause a significant delay in ion ejection during mass analysis. This delay can be shortened or fully removed by increasing the z0 dimension of the ion trap or by collisions with bath gas atoms. The probability of such collisions is a function of the nature of the ion; hence, there is a connection between the chemical mass shift and the nature of the ion. EXPERIMENTAL SECTION Experiments were performed using a prototype Finnigan ion trap mass spectrometer (ITMS), described previously.80 A custom(77) Williams, J. D.; Cooks, R. G. Rapid Commun. Mass Spectrom. 1992, 6, 524527. (78) Reiser, H.-P.; Julian, R. K.; Cooks, R. G. Int. J. Mass Spectrom. Ion Processes 1992, 121, 49. (79) Bui, H. A.; Cooks, R. G. J. Mass Spectrom. 1998, 33, 297-304. (80) Louris, J. N.; Cooks, R. G.; Syka, J. E. P.; Kelley, P. E.; Stafford, G. C.; Todd, J. F. J. Anal. Chem. 1987, 59, 1677-1685.

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designed mechanical system59 was used to change the z0 dimension of the trap under operating conditions during the course of a series of experiments. The end-cap electrodes were mounted on moving stages, and a tapered rod connected to a linear micrometer was used to vary the distance, 2z0, between the two electrodes. The linear micrometer has 2 in. (5 cm) of linear travel, delineated by 0.001 in. (2.54 × 10-3 cm) laser-etched travel graduations, and it allows incremental z0 adjustments as small as 0.003 ( 0.001 in. (0.0076 ( 0.0025 cm). Experiments were performed over a range of z0 dimensions corresponding to values ranging from -3.3% to +30.7% of the nominally ideal z0 value of 0.707 cm for a trap with radius r0 ) 1.0 cm. The rf amplitude scan function included periods of ionization, isolation, and cooling followed by a forward mass analysis ramp.2 The ions of interest were isolated at the apex of the stability diagram; then the dc was removed, and they were allowed to cool for 7 ms at an rf amplitude that corresponds to a low mass cutoff (LMCO) of 40 Th. All samples were ionized by internal electron ionization (EI), and the ions were detected using a conversion dynode/electron multiplier system operated at -5 and 2 kV, respectively. A digital oscilloscope (Model TDS 540, Tektronix Beaverton, OR) was used to acquire the signals produced by the preamplifier as a function of ion ejection time. Each spectrum represents the average of 100 individual scans. The point where the peak height was maximum was used as a measure of the ejection time for each ion of interest. Helium was used as the bath gas, and unless otherwise specified, uncorrected pressures measured using a Bayert-Alpert type ionization gauge are reported. The alkylbenzenes, substituted anilines, and other compounds used were commercial samples purchased from Aldrich (Milwaukee, WI). They were degassed with several freeze-pump-thaw sequences before introduction into the instrument. The organic vapors and helium were introduced into the vacuum chamber by separate Granville Phillips (Boulder, CO) variable-leak valves to uncorrected pressures of 6 × 10-7 and 1 × 10-4 Torr, respectively, except as noted. For the studies with mixed bath gases, after introduction of the analyte, krypton was added to the desired pressure, and then helium was added. Mass assignments were measured using the m/z 69, 100, and 131 fragment ions of perfluoro-n-tributylamine (PFTBA) as calibrant ions. To minimize space charge effects, the ionization time was adjusted so that the amplified peak area for each ion studied was maintained in the range 78-82 µV‚s, as measured using the digital oscilloscope. The ejection times of the calibrant ions were measured under the conditions described above. The m/z values and the ejection times of the calibrant ions were used to generate a mass/charge calibration line which was typically linear with a correlation coefficient (R2) of 0.999 98 or better. The ejection time of the sample ion was then used with the calibration data to calculate the measured m/z. Calibration was done for each measurement point within 10 min after sample measurement to minimize time-dependent instrumentation fluctuations. Replicate m/z measurements using a given set of conditions yielded a standard deviation of 0.05 Th. Note that, in the calibration and the chemical mass shift calculations, the exact, not nominal, masses of the ions of interest were used. Simulation Software. The multiparticle ion trap simulation program ITSIM78,79 was used to obtain qualitative and quantitative 3408 Analytical Chemistry, Vol. 71, No. 16, August 15, 1999

information about the effects of electrode geometry and other experimental variables on ion motion, including ejection time and hence chemical mass shift. Previous versions of ITSIM79 used a global multipole expansion to calculate the electric field in the ion trap. Advantages of this method are short computation time, the inherent smoothness of the solution, and high accuracy in cases where the expansion converges rapidly, especially in the central region of the ion trap. However, local field effects, for example those caused by the inclusion of end-cap holes, cannot be modeled accurately using this approach. When such effects are important, as in this study, it is more efficient to calculate the electric potential from the Laplace equation for a set of node points on a mesh which covers the trapping volume and then to obtain the electric field at arbitrary positions from the derivative of the interpolation polynomial (as illustrated elsewhere81,82). For an axially symmetrical field, the problem can be reduced to two dimensions. In the new version of ITSIM used here, the potential is calculated separately using the Poisson/Superfish software.82 The potential values corresponding to the nodes of a rectangular mesh are extracted from the solution file and saved in a potential array file, which can be read by ITSIM. Since potential values calculated by Poisson are less accurate in the vicinity of the symmetry axis, a fitting process is used to smooth the solution in that area. Before the start of a simulation, the components of the electric field vector are obtained from the potential on the node points using centered differencing. During the simulation, the electric field is determined at each time step for each ion position by bilinear interpolation from the electric field components on the adjacent node points. Further details on the implementation of the numerical potential methods in ITSIM will be given in a future publication.83 In the work presented here, the ion trap electrodes were modeled using a fixed ring electrode radius, r0 ) 1.0 cm, and different end-cap electrode spacings, z0. The electrodes were truncated at a distance R ) 2.5 cm from the ion trap center with boundary conditions set such that the equipotential lines in the truncation region were parallel to the electrode asymptotes. Both end caps had central holes with a diameter of 1.2 mm. Since the exit end cap used in all experiments reported here and in other recent publications from our laboratory59,60 had six additional holes with a diameter of 1.2 mm arranged on a circle around the axis of symmetry, the simulated exit end cap included an annulus with a thickness of 0.8 mm, which creates approximately the same electric fields as the actual end cap, while maintaining axial symmetry. A standard fourth-order Runge-Kutta method with a step size of 10 ns was used to integrate the equation of motion. A trapped ion can acquire a kinetic energy ranging from a few hundredths of an electronvolt to several hundred electronvolts. The probability of a collision between the ion and a buffer gas atom varies strongly with energy. In the low-energy limit, the collision cross section, σ, is given by Langevin theory84 as shown in eq 1, where e is the charge on the ion, 0 is the permittivity of (81) Humphries, S. Field Solutions on Computers; CRC Press: Boca Raton, FL, 1997. (82) Billen, J. H.; Young, L. M. Proceedings of the 1993 Particle Accelerator Conference; pp 790-792. (83) Plass, W. R.; Cooks, R. G. To be published. (84) Gioumousis, G.; Stevenson, D. P. J. Chem. Phys. 1958, 29, 294-299.

σ)

e 1 20 υ

xRµ

(1)

vacuum, R is the polarizability of the neutral bath gas, and v and µ are the relative velocity between ion and buffer gas atom and their reduced mass, respectively. In the high-energy limit, the collision cross section can be approximated by a velocityindependent hard-sphere cross section85 which depends on the geometry of the ion. The cross section used by ITSIM to calculate the collision probability can be chosen to be alternatively the Langevin or hard-sphere cross section, the maximum of both, or the sum. The last method was used for the simulations described here. At each time step of the simulation, a buffer gas atom is assigned a random velocity generated from a Maxwell-Boltzmann distribution. A random number from a uniform distribution is then compared to the collision probability to determine if a collision occurs. The change in the velocity of the ion upon collision is calculated by assuming an elastic collision and equally probable scattering angles in the center-of-mass frame. A more detailed description of the collision model will be part of a future publication on ITSIM.83 RESULTS AND DISCUSSION Experimental Factors That Affect Chemical Shift. The chemical mass shift is defined as the exact mass of the ion minus the measured mass as described in the Experimental Section (assuming unit charge in the mass/charge measurement). Hence, a positive chemical shift is a shift to lower apparent mass, a convention used in recent publications from our laboratory.59,60 Figure 1 illustrates the change in chemical mass shift as a function of z0 for the molecular ion of n-butylbenzene, chosen because this ion has been shown previously to experience a large chemical mass shift.64,65 Note again that, in this and all subsequent data figures, the instrument was calibrated for each data point with PFTBA using exactly the same experimental conditions as were used for the sample. This was done to eliminate the effects of ion number, buffer gas pressure, and rf voltage drift on mass assignment. The figure shows that, at the theoretical z0 value of 0.707 cm, n-butylbenzene displays a chemical mass shift of nearly 0.9 Th. The chemical mass shift decreases, in an approximately linear fashion, to zero as z0 is increased to a value of 0.78 cm. The removal of shift on stretching the ion trap was first observed by Syka and co-workers52 and examined in more detail in our preliminary experiments using the variable-z0 trap.59,60 The effect is due to the change in the higher order field content of the trapping field as the end caps are moved. Further consideration of the nature of the change in ion motion which produces the chemical mass shift is taken up below in the simulations section. The approximately linear decrease of the n-butylbenzene chemical mass shift differs somewhat from the behavior we reported previously for the molecular ions of nitrobenzene59 and nitrobenzene-d5,60 which both experience a slow decrease in chemical mass shift from z0 values of 0.707 to ca. 0.75 cm, followed by a more rapid decrease to zero from 0.75 to 0.78 cm. The significance of this different behavior is still under investigation; however, it (85) Julian, R. K.; Nappi, M.; Weil, C.; Cooks, R. G. J. Am. Soc. Mass Spectrom. 1995, 6, 57.

Figure 1. Chemical mass shift (actual mass/charge ratio minus experimental mass/charge ratio relative to fluorocarbon reference ions; see text) for the molecular ion of n-butylbenzene (m/z 134) recorded as a function of ion trap dimension z0 at a nominal helium bath gas pressure of 1 × 10-4 Torr. The straight line is a linear fit through all but the last three data points.

Figure 2. Chemical mass shift for n-butylbenzene recorded as a function of the nature and pressure of the bath gas at an ion trap z0 value of 0.737 cm. Note that the pressures on the abscissa were corrected using the standard ion gauge correction factors but that the ratios reported in the legend are nominal values (uncorrected pressures). The lines are drawn as guides in examining the data.

should be noted that in all cases the chemical mass shift decreased to zero at or before the commercial z0 value of 0.783 cm. Figure 2 shows the effect of the nature and pressure of the bath gas on the n-butylbenzene chemical mass shift at a fixed z0 value of 0.737 cm. Note that pressures shown on the abscissa of this figure are corrected using standard ion gauge correction factors for helium and krypton. The z0 value of 0.737 cm was chosen because the chemical mass shifts are still substantial while the peak intensity, which decreases as the shift increases, is still adequate. The most significant result shown in Figure 2 is that n-butylbenzene experiences no chemical mass shift in the absence of bath gas. Indeed, the shift remains indistinguishable from zero until a helium pressure of ca. 1.5 × 10-4 Torr is reached. Subsequently, the shift increases until reaching a plateau at 0.55 Th at a helium pressure of ca. 3.5 × 10-4 Torr. The increase in chemical mass shift with helium pressure has also been observed for ethylbenzene and nitrobenzene (data not shown). The effects of collisions on chemical shift were studied further by mixing krypton with the helium buffer gas. The results for krypton and helium with gauge pressure ratios of 0.25 and 1 are included in Figure 2. The presence of the larger krypton target causes the Analytical Chemistry, Vol. 71, No. 16, August 15, 1999

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Table 1. Chemical Shifts Relative to Fluorocarbon Reference Ions and Fragmentation Data ∑[F]/(total) species

Figure 3. Chemical mass shift for the m/z 134 isotope of xenon recorded as a function of (a) ion trap dimension z0 at a helium bath gas pressure of 1 × 10-4 Torr (uncorrected) and (b) corrected helium bath gas pressure at a z0 value of 0.707 cm. The lines are drawn as guides in examining the data.

onset of the chemical shift to occur at a lower bath gas pressure, consistent with the interpretation that collisions with bath gas are responsible for chemical mass shifts, a hypothesis that is developed more fully in the section below on simulations of ion motion. While all the organic ions studied here undergo positive chemical mass shifts (shifts to lower mass), some atomic ions shift to higher mass. Figure 3 shows data on the chemical shift vs z0 and helium pressure for the m/z 134 isotope of xenon. Note that the pressures reported in Figure 3b are corrected. The sign of the chemical mass shift is opposite but the effect of z0 and bath gas pressure is analogous to that found for ionized n-butylbenzene. The magnitude of the chemical shift is initially constant, or even increases as z0 is increased, and then it rapidly decreases to zero (the data in Figure 3 do show more experimental variability than was observed for n-butylbenzene). The chemical shift of the xenon ion is zero at zero pressure, and the magnitude increases with increasing helium pressure before reaching a plateau value. As shown in Figure 3, the onset of the shift occurs at a higher helium pressure than for n-butylbenzene. Data were also taken for Kr+• and I+ ions. A chemical shift of ca. -0.15 Th was observed at a z0 value of 0.707 cm and a helium pressure of 1 × 10-4 Torr for the I+ ion derived from methyl iodide. Krypton was found to display no measurable chemical shift, within error, under the same conditions. 3410 Analytical Chemistry, Vol. 71, No. 16, August 15, 1999

benzene toluene ethylbenzene n-propylbenzene n-butylbenzene n-amylbenzene n-hexylbenzene n-heptylbenzene n-octylbenzene styrene R-methylstyrene 1,2-dihydronaphthalene 1,2,3,4-tetrahydronaphthalene naphthalene aniline N-methylaniline 2-methylaniline 3-methylaniline N,N-dimethylaniline 2,6-dimethylaniline 3,5-dimethylaniline 2,4-dimethylaniline N-ethylaniline 4-ethylaniline 3-ethylaniline 2-ethylaniline N,N-diethylaniline 2,6-diethylaniline pyridine acetophenone benzonitrile nitrobenzene o-fluoronitrobenzene p-fluoronitrobenzene tetrahydrofuran dihydrobenzofuran hexachlorobutadiene (M+•) I+ (CH3I) Xe (m/z 134 isotope) Kr (m/z 84 isotope)

chem

shifta

(Th) EI datab MS/MSc

0.03 0.05 0.36 0.64 0.88 0.77 0.98 1.03 1.11 0.12 0.33 0.23 0.72 0.00 0.01 0.01 0.12 0.01 0.29 0.23 0.19 0.18 0.53 0.37 0.23 0.27 0.74 0.63 0.02 0.83 0.03 0.69 0.39 (0.737) 0.34 (0.737) 0.36 (0.714) 0.04 0.16 -0.15 -0.23 -0.08

0.55 0.76 0.87 0.90 0.93 0.91 0.92 0.95 0.93 0.69 0.76 0.73 0.89 0.46 0.55 0.76 0.78 0.70 0.81 0.72 0.76 0.75 0.83 0.88 0.79 0.87 0.88 0.90 0.60 0.90 0.49 0.89 0.80 0.80 0.89 0.73 0.89

0.12 0.47 0.48 0.57 0.60 0.58 0.51 0.50

0.32 0.29 0.24 0.30

0.58 0.41

0.13

a Data were taken at z ) 0.707 cm, unless noted, with a helium 0 bath gas pressure of 1 × 10-4 Torr (uncorrected). b EI fragmentation data were taken from the NIST Mass Spectral Database, version 4.0, 1992. c MS/MS data were taken on a TSQ 700 with a collision energy of 150 eV and a pressure of 2 × 10-3 Torr of helium in the second quadrupole.

Effects of Some Aspects of Chemical Structure on Chemical Mass Shifts. Previous reports from Traldi and Bortolini have speculated that the chemical mass shift might be related to dipole moment and/or polarizability.61,63,86,87 In an effort to learn something about the chemical factors that influence mass shifts, a series of compounds was tested to determine a response of chemical shift to simple structural changes in the ion. As shown in Table 1, ionized benzene, naphthalene, aniline, pyridine, and benzonitrile did not display chemical mass shifts within the error limits of this study. Nitrobenzene, however, displayed a substantial mass shift. A series of n-alkylbenzenes from toluene through n-octylbenzene was examined to extend the study of substituent effects more systematically. An approximately linear increase in chemical mass shift was seen as the length of the substituent increased up to n (86) Bortolini, O.; Olimpieri, L.; Traldi, P. Org. Mass Spectrom. 1994, 29, 1. (87) Bortolini, O.; Catinella, S.; Traldi, P. Org. Mass Spectrom. 1993, 28, 428.

Figure 4. Chemical mass shift for a series of alkyl-substituted benzenes recorded at a z0 value of 0.707 cm and a helium bath gas pressure of 1 × 10-4 Torr (uncorrected). The lines are drawn as guides in examining the data.

) 4 (Figure 4), and a more gradual and approximately linear increase occurred up to n ) 8. It is reasonable to assume, because these substituents are not rigid, that the longer chains can fold back, to internally solvate the charge site, altering both the collision cross section and polarizability. n-Amylbenzene is large enough to undergo internal solvation in this manner, possibly accounting for the change in the rate at which the shift increases. To further examine this specific point, 1,2,3,4-tetrahydronaphthalene was found to exhibit a chemical shift of 0.72 Th, similar to that for n-amylbenzene. The less saturated counterpart, 1,2dihydronaphthalene, was found to have a chemical shift of only 0.23 Th. No chemical shift for naphthalene was observed, within the error limits. Styrene was examined for comparison with n-ethylbenzene. It exhibited a smaller chemical shift (∼0.12 Th at a z0 of 0.707 and a He pressure of ∼1 × 10-4 Torr) than n-ethylbenzene (∼0.36 Th under the same conditions). A series of alkyl-substituted anilines was also examined. Following the trend exhibited in the alkylbenzenes, the chemical shift increased in absolute magnitude with the number of alkyl groups, e.g. from 0.01 Th for N-methylaniline to 0.53 Th for N-ethylaniline. Chemical shifts for ring-substituted anilines were also measured, and a compilation of all these results can be found in Table 1. N-Substituted anilines exhibited larger chemical shifts than did their ring-substituted isomers in cases where comparisons are possible. We recognize, of course, that many molecular ion properties change in the series of compounds examined. These include the physical size (cross section) of the ion, its polarizability, dipole moment, and other electrical properties, and its reactivity in terms of charge transfer and propensity for dissociation, and the number of degrees of freedom, among others. The clearest conclusion to come from the data of Table 1 is that the size of the ion appears to be a factor in determining the chemical mass shift. At this point, simulations of the phenomenon are reported, since they greatly assisted in clarifying the origins of the chemical mass shifts. Simulations of Ion Motion. Results of simulations of ion motion during ejection by an rf scan are shown in Figure 5 to qualitatively illustrate the effects of several experimental variables on ion behavior. The field was calculated for the electrode geometries described below using the numerical method detailed in the Experimental Section. Figure 5a shows the ejection profile

Figure 5. Simulations of ion motion (m/z 130) during an rf ramp at the standard rate of 5555Th/s: (a) ejection profile in an ideal trap (z0 ) 0.707) with no end-cap holes and with no collisions; (b) ejection profile in an ideal trap (z0 ) 0.707) with holes in both end caps (see Experimental Section) and with no collisions; (c) ejection profile in a commercial ion trap (z0 ) 0.783) with holes in both end caps and with no collisions; (d) ejection profile in an ideal trap (z0 ) 0.707) with holes and collisions with 1 mTorr of helium present in the trap.

in the axial (z) dimension in an ion trap of ideal geometry (r0 ) 1.0 cm, z0 ) 0.707 cm) but one in which there are no end-cap holes. The ion oscillation increases approximately exponentially as the ion reaches the stability boundary, as predicted by theory.88 The ion ejection profile in Figure 5b was obtained under conditions identical to those used in the simulation summarized in Figure 5a, except that the field was calculated for an ion trap with holes arranged as described in the Experimental Section. A significant delay (>250 µs) in ion ejection is evident in Figure 5b. The term “ejection delay” is used in the remainder of this paper to refer to this extended period between when the ions become unstable near the center of the trap and increase their oscillation amplitude and when they finally leave the electrode structure. We attribute the delay to the end-cap holes, which cause the field in the region near the end caps to increase less rapidly than would be the case for the ideal (without holes) geometry. The electric field in an ideal ion trap is purely quadrupolar; that is, the potential varies quadratically and the field varies linearly from the center of the device. Real ion traps deviate from these ideal conditions due to truncation of the electrodes to finite size, perforation of the electrodes to allow the entrance and egress of electrons and ions, and machining imperfections. The electric potential in the trap was calculated with the Poisson/Superfish program82 for the ideal electrode geometry (z0 ) 0.707) with a (88) Franzen, J. Int. J. Mass Spectrom. Ion Processes 1991, 106, 63.


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1.2 mm end-cap aperture. The equipotential lines obtained from this calculation in the vicinity of the end-cap electrode hole showed that significant penetration of the trapping field into this aperture occurs. This field penetration causes the ions to experience a weaker increase in field strength with position near the end cap than they do in the center of the trap, where the increase is linear. This weakened field leads to the observed ejection delay. As the rf amplitude is ramped during mass analysis, the ions become unstable when they reach qz ) 0.908,89 and their excursions therefore increase. Upon entering the less stongly increasing field region near the end-cap electrodes, the ions are stable due to the weakened field, and hence their oscillation amplitude decreases. The ion population then experiences the field with larger gradient near the center of the trap, becomes unstable, and increases its oscillation amplitude again. This series of events occurs repetitively and causes the delay in the ejection of the ion cloud, relative to the ideal case, evident in Figure 5b. Wang and Franzen have reported detailed simulation studies of the effects of the various higher order field components on ion motion53 when a global multipole expansion is used to represent the trapping field. They found, inter alia, that negative (according to Franzen’s convention53) higher order fields of even order (e.g., octapole fields) cause a delay in ion ejection which is similar to that described above. Figure 5c illustrates the ITSIM results for an ion trap with the standard commercial geometry (r0 ) 1.0 cm, z0 ) 0.78 cm) with all other variables identical to those in Figure 5b, including the presence of end-cap holes. The ejection delay has been removed upon increasing z0 to 0.78 cm; i.e., the ions rapidly increase their oscillation amplitude in an exponential fashion and eject from the trap within a few microseconds. Further calculations with the Poisson program and an in-house multipole expansion fitting program90 as well as reference to the literature53 show that increasing the z0 dimension of the trap introduces positive octapole and dodecapole components to the overall trapping field. These higher order components cause the field to increase more strongly as ions move from the center of the trap than would be the case for an ideal quadrupole ion trap, where the field increases linearly. This nonlinear increase in field strength compensates for the weakening effect caused by the end-cap apertures. Note that the overall change in field strength associated with the change in geometry from Figure 5a to Figure 5c was only approximately corrected by a change in rf voltage used to maintain the low mass cutoff at approximately 40 Th. This accounts for the small difference in ion ejection time between Figure 5c and Figure 5a; the important observation is that the ejection profiles are very similar to one another and very different from that shown in Figure 5b. Figure 5d illustrates the results of a simulation using conditions identical to those used for the data in Figure 5b, except that, in Figure 5d, the collision model was enabled to simulate ion/neutral collisions as described in the Experimental Section, assuming a collision cross section diameter of 8 Å. The simulation assumed helium bath gas at a pressure of 1 × 10-3 Torr. Comparison of Figure 5d to Figure 5b shows that although the ejection delay (89) March, R. E.; Hughes, R. J. Quadrupole Storage Mass Spectrometry; John Wiley and Sons: New York, 1989. (90) Badman, E. R.; Johnson, R. C.; Plass, W. R.; Cooks, R. G. Anal. Chem. 1998, 70, 4896-4901.


caused by the end-cap holes is still observable in Figure 5d, collisions have significantly reduced the delay relative to the nocollision case shown in Figure 5b. A dissociative collision (discussed in more detail below) would form product ions which which would lie far outside the stability region and hence would be immediately ejected. A scattering collision can cause the ion motion to change phase with respect to the rf trapping voltage. This phase change can cause ions to rapidly pick up energy from the field, increasing oscillation amplitude and leading to their ejection from the trap. A number of phase-changing collisions occur during the delay period, as evident in the significantly changed ion motion in Figure 5d relative to Figure 5b, but not every collision results in ion ejection. However, at the bath gas pressure used in this simulation, the collision frequency is sufficiently high that a collision which results in ejection does occur before the point of ejection shown in Figure 5b; therefore, the ejection delay is reduced relative to the no-collision case. The simulations indicate that the combination of the ejection delay and its modification by collisions with bath gas accounts for chemical mass shifts. It has been shown that the magnitude of the chemical mass shift depends on the size of the end-cap apertures,65 and the simulation results in Figure 5b show that the end-cap apertures lead to ejection delay. The experimental data of Figures 1 and 3a show that the chemical mass shift decreases to zero as z0 is increased, and the simulation results in Figure 5c show that the ejection delay is removed as z0 is increased. These facts clearly demonstrate the connection between chemical mass shift and the ejection delay; the removal of the ejection delay leads to the decrease of the chemical mass shift with z0 and its eventual leveling off at the z0 where the shift is completely removed. Also, Figures 2 and 3b show that the chemical mass shift depends on the pressure and nature of the bath gas, while Figure 5d shows that collisions with the bath gas modify the ejection delay. The cooling time before mass analysis was found to have no effect on chemical mass shift in the absence of helium over a range of cooling times from a few milliseconds to hundreds of milliseconds, where ions can be expected to be cooled by collisions with neutral background gas even without added helium (data not shown). This suggests that it is the presence of helium during mass analysis, not the increased collisional cooling caused by helium before mass analysis, that is the important factor in causing chemical shifts. These observations again suggest that collisions occurring during the delay are responsible for chemical shifts. When the ion trap z0 is increased so that the delay is removed (Figure 5c), all ions are rapidly ejected before collisions with bath gas can occur; thus no shift is measured. When the ion trap is set up so that the delay exists but there is no helium bath gas and hence very low collision probability during mass analysis (Figure 5b), all ions are subject to the same delay, and so again no chemical mass shift occurs. Only when the ions are subject to the ejection delay and the delay can be modified by collisions is a chemical mass shift observed. The chemical dependence of the mass shift observed here is due to differences in the probability of a delay-modifying collision between the analyte and the calibrants. This affects the ejection delay modification and hence the relative ejection time of the analyte and calibrant, and hence results in an apparent mass shift.

Table 2. Measured Ejection Times for the PFTBA Calibrant Ion m/z 131 and for the m/z 134 Isotope of Xenon as a Function of Bath Gas Pressure at z0 ) 0.737 cm ejection time (ms) helium pressure (uncorrected) (Torr) 0 5.00E-06 1.00E-05 5.00E-05 6.00E-05 7.50E-05 1.00E-04 2.00E-04

m/z 131, PFTBA

m/z 134, xenon

∆ ejection time (ms), xenon-PFTBA

15.792 15.790 15.791 15.778 15.777 15.751 15.746 15.711

16.299 16.302 16.301 16.294 16.297 16.297 16.290 16.249

0.507 0.512 0.510 0.516 0.520 0.546 0.544 0.538

Table 2 lists the absolute ejection times experimentally measured for the m/z 131 reference ion and the m/z 134 isotope of xenon as the bath gas pressure is increased at z0 ) 0.737 cm. These data show that xenon ejects earlier as the bath gas pressure increases but the m/z 131 reference ion shifts to an even earlier ejection time (i.e., the difference in ejection time increases); hence Xe+ has a relative mass shift to higher mass, as shown in Figure 3. Figure 6 shows the results of a simulation in which the apparent mass difference between an ion with m/z 130, collision cross section of 4 Å (the “analyte”), and one with m/z 130, collision cross section of 8 Å (the “calibrant”), is determined. Data are shown both as a function of z0 with a fixed helium pressure of 5 × 10-4 Torr and as a function of helium pressure at a fixed z0 value of 0.707 cm. Each simulation used 2000 ions and the scan rate was 5555 Th/second, starting at a low mass cutoff of 40 Th. At low z0, the smaller ion is shifted to higher mass relative to the larger ion, consistent with the experimental data for xenon shown in Figure 3. As in the experimental data, the chemical mass shift goes to zero as z0 is increased (Figure 6a). The atomic xenon ion is smaller than the fluorocarbon calibrant ions and so has a lower collision probability. This is a sufficient explanation of its longer ejection delay (Table 2). Note, however, that the reduced ejection delay which the reference ion, m/z 131, might experience due to fragmentation or inelastic collisions is an alternative explanation of the collision-mediated chemical mass shift data, although it does not account for the difference in shifts of the atomic ions, Xe+ and I+. The latter difference is the clearest evidence that elastic scattering contributes to chemical mass shifts. Further evidence for this is the fact that a number of molecular ions in Table 1 show no shift relative to the fluorocarbon reference ions; if fragmentation of the reference ions was a significant contributor to (absolute) mass shifts, then the effects of fragmentation on chemical shift would have to be the same for all of these molecular ions. The fact that the mass shift is produced by collisions is shown by the simulated data of Figure 6b, which shows zero shift at low pressure. The dependence of shift on bath gas pressure shown in Figure 6b is consistent with the experimental data shown in Figure 3b. The data in Figures 3 and 6 do not agree exactly, and there are a number of sources of error. Hard-sphere collision cross section data are not available for xenon or the fluorocarbon reference ions over the large energy range experienced in the

Figure 6. Simulation of the difference in measured m/z for an ion with a 4 Å and an 8 Å collision cross section as a function of (a) ion trap dimension z0 with collisions equivalent to a bath gas pressure of 5 × 10-4 Torr and (b) bath gas pressure at a z0 value of 0.707 cm. For each data point, a simulation of 2000 ions of m/z 130 and each diameter was conducted and the chemical mass shift was assigned as the difference between the simulated ejection times. Data were taken at the highest points of the peaks which resulted when ejection was simulated using an rf ramp of 5555 Th/s begun at a low mass cutoff of 40 Th.

ion trap, so the assumptions made in the simulation about relative size are only approximations. Possible inaccuracies in the collision model could lead to an equilibrium ion cloud size different from that which pertains in the actual experiment. This in turn could influence the length of the ejection delay and the measured ejection time, and hence the relative mass shift. In the ITMS, a conversion dynode held at -5 kV is located ∼2 cm from the exit end-cap electrode. The penetration of this high voltage into the end-cap holes could influence the trapping field and hence the chemical shift, a factor which is not considered in the simulation at this stage. Also, to calculate the field for the simulation, the electrodes were truncated farther from the center of the trap than the actual ITMS electrodes, which also influences the trapping field. Further sources of error, when elucidated, may help to refine our understanding of the chemical mass shift phenomenon. Fragmentation Efficiency. Despite the lack of exact agreement between the experiments and simulations, the arguments given above explain the negative chemical shift of xenon. Elastic collisions above, however, fail to adequately account for the large positive shift of the organic ions reported in Table 1 or for the magnitudes of the relative shifts. Consider, for example, the Analytical Chemistry, Vol. 71, No. 16, August 15, 1999

3413

chemical mass shifts of acetophenone and dihydrobenzofuran (DHBF), two structural isomers with the molecular formula C8H8O+•. The molecular ion of acetophenone experiences a chemical shift of 0.83 Th at z0 ) 0.707 cm, while the molecular ion of DHBF experiences little or no shift within the error limits of this study. We have shown previously60 that it is possible to resolve the signals due to these two isomeric molecular ions when both species are present in the trap because of the large chemical shift of acetophenone. Simulations of the type just described indicate that even a factor of 4 difference in the collision cross section of the analyte and calibrant ions leads to a relative shift of only ca. 0.25 Th at a z0 value of 0.707 cm. Even taking into account the deviations between the simulations and experiments discussed above, this result makes it difficult to imagine that the collision cross sections, which are dominated by the sizes of the ions, for these two structural isomers would differ enough to account for a relative shift of 0.8 Th. Despite the inadequacy of the size argument alone to account for the large positive chemical shift of organic ions, the fact that the effects of z0 and bath gas pressure correspond for xenon and the organic ions increases confidence in the proposed overall mechanism, viz. collisional modification of ejection delay. Having considered the effects of elastic scattering on the delay, this argument points to consideration of the effects of inelastic collisions, including those which lead to fragmentation of the ion. Fragmentation has been suggested previously as a possible cause of chemical shift.64,91,92 Simulations show that, during the ejection delay, the kinetic energy of the ions may reach 250 eV, which, for n-butylbenzene in a collision with helium, would yield a centerof-mass collision energy of up to ∼7 eV. This energy is sufficient to cause fragmentation even if only a single collision occurs, although impulsive collisions,93 if this is indeed the activation mechanism in this little-studied energy range, are likely to deposit insufficient energy in one collision. All fragment ions would be unstable and would be immediately ejected from the ion trap. Modification of the delay by dissociative collisions will depend on the energy transfer function as well as the collision cross section and the relative ease of fragmentation of the excited ion. Inelastic collisions which are not sufficiently endoergic to lead to dissociation are more likely than dissociative collisions and may change the ion motion sufficiently to cause instability. Clearly a complex set of interrelated factors are involved so that a simple relationship between molecular structure and chemical mass shift is not expected. A preliminary test of the proposal that fragmentation is the main factor which reduces the ejection delay and so causes chemical mass shifts was undertaken by simulation. A simple inelastic collision model which assumes that any collision during the mass analysis scan with a center-of-mass collision energy of 1 eV or higher could lead to fragmentation was developed to test this hypothesis. When the fragmentation probability for 1 eV and higher collisions was set to 30%, the simulation duplicated the (91) Vachet, R. W.; Hartman, J. A. R.; Callahan, J. H. J. Mass Spectrom. 1998, 33, 1209-1225. (92) A similar conclusion has been reached: McClellan, J. E.; Mulholland, J. J.; Murphy, J. P., III; Yost, R. A. Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics; Dallas, TX, 13-17 June 1999; Paper WOC 1015. (93) Uggerud, E.; Derrick, P. J. J. Phys. Chem. 1991, 95, 1430-1436.


behavior of the n-butylbenzene shift as a function of bath gas pressure, although the simulated shifts were approximately a factor of 2 smaller than the experimental values (data not shown). Further refinements of the simulation collision model are underway to more fully test this hypothesis, as the assumptions that 1 eV collision energy is sufficient for fragmentation and that 30% fragmentation efficiency would obtain are only initial approximations. Another test of the fragmentation hypothesis was performed by examining the ease of fragmentation of some of the ions included in Table 1. Column 3 shows the sum of the fragment ion intensities over the total ion intensity, compiled from 70 eV electron ionization (EI) spectra taken from the 1992 NIST Mass Spectral Database, version 4.0. While strict correlations between chemical mass shift and fragmentation probability are neither expected (vide supra) nor evident in Table 1, there is a general trend that species with a larger likelihood to fragment upon EI also experience a larger chemical mass shift. To test the hypothesis still further, tandem mass spectrometry experiments were performed using a triple quadrupole at high (150 eV) collision energy and under multiple-collision conditions. These conditions were chosen to more accurately duplicate the conditions experienced by the ion in the ion trap during the ejection delay. The results of these experiments are also tabulated in Table 1. Again, a strict correlation between chemical mass shift and ease of fragmentation is not evident in the MS/MS data, particularly for the four substituted anilines studied, but the general trend is toward a larger shift for more easily fragmenting species. It is clear that inelastic collisions must occur during the ejection delay and that they contribute to the chemical mass shift, but the relative contribution of inelastic and elastic collisions to chemical mass shift remains to be determined. CONCLUSIONS A large number of compounds have been examined, and many have been shown to experience a chemical shift when examined using the mass-selective instability scan in an ion trap with the theoretically ideal geometry. Insights into the cause of chemical mass shifts have been gained from experiments and simulation data. The chemical mass shift is removed on increasing z0, and this is attributed to compensation for the field faults originally introduced by the holes present in the end-cap electrodes. These higher order field components lead to a weakening of the field in the region near the electrodes, which causes a significant delay in ion ejection over the ideal field case. The collision-shortened ejection delay is proposed as the underlying cause of chemical mass shifts. Both elastic collisions and inelastic, dissociative collisions are shown to contribute to reducing the ejection delay. Chemical factors which cause variations in the number and nature of the collisions lead to different chemical mass shifts. While this presentation has concentrated on errors associated with the measurement of peak positions, it is important to realize that the underlying field fault and collision phenomena described here also affect peak widths and shapes and hence the resolution achievable using the ion trap mass spectrometer. We report elsewhere83 on simulations which deal with this issue. Future work will involve further testing of the proposed model through experiments and simulations, including improved models

for elastic and inelastic scattering. The effects of resonance ejection vs boundary ejection will be examined, as will the effect of scan direction in both the theoretical and commercial geometries. An explanation will be sought for the correlation65 of ion cloud radial dimension with chemical mass shift. The relationship between this work and more conventional ion mobility studies94 is recognized, and we will attempt to maximize the ejection delay to allow collisions more time to act to distinguish chemical species on the basis of their structure. This will facilitate attempts to develop the chemical mass shift as an additional analytical characteristic, e.g. of nitroaromatic compounds, where the chemical mass shift may yield additional selectivity for this class of

compounds and aid in their recognition in complex chemical mixtures.

(94) Clemmer, D. E.; Jarrold, M. F. J. Mass Spectrom. 1997, 32, 577-592.

AC9902289

ACKNOWLEDGMENT The authors acknowledge the financial support of the U.S. Department of Energy, Office of Basic Energy Sciences (Contract DE-FG02-94ER14470), and of the Finnigan Corp. through the Purdue University Industrial Associates Program. Jeff Denault’s help with the triple-quadrupole experiments and valuable discussions with Jon Amy, George Stafford, David Clemmer, and Jae Schwartz are appreciated. Received for review February 26, 1999. Accepted May 10, 1999.


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Chemical Mass Shifts in Ion Trap Mass Spectrometry: Experiments

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