Anal. Chem. 1980,
1636
ACKNOWLEDGMENT
52, 1636-1641 (11) McCormack, A. J.; Tung, S.S.S.;Cooke, W. D. Anal. Chem. 1965, 37, 1470. (12) Bache, C. A.; Lisk, D. J. Anal. Chem. 1967, 39, 786. (13) McLean, W. R . ; Stanton, D. L.; Penketh. G. E. Analyst(London) 1973, 98, 432. Quimby, B. D.; Uden, P. C.; Barnes, R. M. Anal. Chem. 1978, 50,2112. Braun, W.; Peterson, N. C.; Bass, A. M.; Kurylo, M. J. J . Chromatog. 1971, 55, 237. Attar, A.; Forgey, R.: Horn, J.; Corcoran, W. H. J . Chromatogr. Sci. 1977, 15,222. Gebhart, J. E.; Frank, C. W. 29th Annual Pittsburg Conference on Analytical Chemistry and Applied Spectroscopy, . . . . Cleveland, Ohio, 1978; Paper number 356: Ellebracht, S. R.; Fairless, C. M.; Manahan, S. E. Anal. Chem. 1978, 50. 1649. Swaim, P. D.; Ellebracht, S. R . Anal. Chem. 1979, 5 1 , 1605. Skoaerboe. R. K.: Urasa. I. T.: Coleman. G. N. ADD/. Soectrosc. 1976.
The authors thank M. Landry for his work on the dc Plasma source.
LITERATURE CITED Mizany, A. I. J . Chromatogr. Sci. 1970, 8, 151. Stevens, R. K.; Mulik, J. E.; O'Keefe, A. E.; Krost, K. S. Anal. Chem. 1971, 43, 827. Sugiyama, T.; Suzuki, Y.; Takeuchi, T. J . Chromatogr. Sci. 1973, 1 1 , 639. Burnet, C. H.; Adams, D. F.; Farweli, S.0. J . Chromatogr. Sci. 1977, 15, 230. Brody. S. S.;Chaney, J. E. J . Gas Chromatogr. 1966, 4 ,42. Burgett. C. A.; Green, L. E. J . Chromatogr. Sci. 1974, 12, 356. Pearson, C. D.; Hines, W. J. Anal. Chem. 1977, 49, 123. Clay, D. A.; Rodgers, C. H.; Jungers, R. H. Anal. Chem. 1977, 49,126. Patterson, P. L.; Howe, R. L.; Abu-Shumays. A. Anal. Chem. 1978. 50. 339. Patterson, P. L. Anal. Chem. 1978, 5 0 , 345.
.
30,-500.
I
.
Matz. G. J. Am. Lab. 1973, 5(3), 7 5 .
RECEIVED for review January 25,1980. Accepted May 27,1980.
Liquid Chromatograph-Mass Spectrometer for Analysis of Nonvolat iIe SampIes C. R. Blakley, J. J. Carmody, and M. L. Vestal" Department of Chemistry, University of Houston, Houston, Texas 77004
A liquid chromatograph-mass spectrometer system has been developed for application to analyses of molecules of extremely low volatility. This LC-MS system uses oxy-hydrogen flames to rapidly vaporize the total LC effluent and molecular and particle beam techniques to efficiently transfer the sample to the ionization source of the mass spectrometer. The instrument is comparable in cost, complexity, and performance to a combined gas chromatograph-mass spectrometer (GC-MS) but extends the capabilities of combined chromatograph-mass spectrometry to a broad range of compounds not previously accessible.
The combination of high pressure liquid chromatography with mass spectrometry has been recognized for some time as possessing enormous potential for analyses of polar, nonvolatile, or thermally unstable compounds not amenable to GC/MS. It is equally well-known that the problems which must be solved to achieve a practical LC-MS combination are much more difficult than those encountered in the development of GC-MS. The approaches to LC-MS interfacing which have been developed were reviewed recently by Arpino and Guiochon (1). In our original approach to the problem of LC-MS coupling, we employed laser heating to rapidly vaporize both the solvent and the sample and molecular beam techniques to transport and ionize the sample with minimal contact with solid surfaces (2). The rationale for our approach is based in part on the work of Friedman and co-workers (3) in which it was shown that quite nonvolatile samples can be vaporized intact by employing rapid heating and by vaporizing the sample from weakly interacting surfaces such as Teflon. In our initial work, we found that we were unable to achieve stable vaporization of a liquid jet with the laser beam intersecting the liquid jet in free space; however, if the laser beam were shifted so that the liquid jet nozzle was heated by the laser beam, stable vaporization could be achieved. Further0003-2700/80/0352-1636$01 OO/O
more, even though the tip of the nozzle was often operated a t red heat, there was little indication that pyrolysis of the sample was occurring during the vaporization process. We also found in this earlier work that the pumping system in our original system was overdesigned. In particular, the large diffusion pump (4200 L/s) used to evacuate the chamber between the nozzle and skimmer was unnecessary and could be replaced by its mechanical backing pump (17 L/s). Using the results of our earlier studies, we have developed the completely redesigned system described in the present paper. This new instrument uses oxy-hydrogen flames to rapidly vaporize the total LC effluent. The pumping system has been drastically simplified so that the overall cost and complexity of the new instrument is comparable to that of a combined GC-MS. This new system has been applied to a variety of relatively nonvolatile biological molecules, and it appears to provide a useful and practical LC-MS system with a wide range of potential applications.
DESCRIPTION OF THE INSTRUMENT A schematic diagram of the apparatus is shown in Figure 1. The effluent from the LC enters the vaporizer through a stainless steel capillary tube (typically 0.015-cm i.d.) which is threaded about 0.3 cm into the end of a copper cylinder 0.8 cm 0.d. X 1 cm long. The copper cylinder is heated to bright red heat (ca. 1000 "C) by four small oxy-hydrogen flames positioned as indicated in Figure 1. As the LC effluent approaches the end of the stainless capillary, i t is very rapidly heated and partially vaporized producing a jet of vapor and aerosol. This jet is further heated as it passes through a 0.075-cm diameter stainless steel lined channel through the copper; it then undergoes an adiabatic expansion, and a portion passes through the skimmer to the ion source where the beam impinges on a nickel plated copper probe which is electrically heated to ca. 250 "C. All of the work described in the present paper employed an ion source configured for chemical ionization work; however, electron impact ionization can be employed with the same basic instrument with decreased skimmer aperture and C 1980 American Chemical Society
ANALYTICAL CHEMISTRY, VOL. 52. NO. 11, SEPTEMBER 1980
IY
J
- + 1 -
-
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Figure 1. Schematic diagram of t h e apparatus: (1) capillary tube carrying liquid effluent from LC; (2) oxy-hydrogen torch; (3) skimmer, (4) ion source; (5)heated probe; (6) electrostatic deflector; (7) quadrupole mass filter; (8) electron multiplier; (9) copper cylinder. The electron beam enters the ion source perpendicular to the plane of the
figure at the point (e) “open” ion source. For the present work, the skimmer aperture was 0.075 cm and it was located about 0.4 cm downstream from the vaporizer. The apertures in the ion source for electron beam entrance and ion exit were each 0.05 cm in diameter. The source is equipped with a differentially pumped electron gun of a simple design described previously ( 4 ) . This allows the rhenium filament to be removed from the hostile environment adjacent to the ion source and has increased filament life drastically. Ions produced by the source are accelerated to 1C-20 eV and deflected into the quadrupole mass analyzer by a 2.5-cm radius, 90’ cylindrical condensor. This condensor acts as a low resolution energy analyzer but its main function is to prevent high energy neutrals or photons produced in the ion source from being transmitted to the vicinity of the electron multiplier and producing ionization of the residual gas. This measure has proven effective in removing almost all of the “mass independent” background observed in our earlier work with the more conventional axial source and quadrupole alignment. The electron multiplier is mounted off-axis with deflectors for directing the ion beam t o t h e first dynode of the multiplier. The final deflector is attached to a guard ring which is part of the structure of this particular electron multiplier. For the detection of positive ions, this final deflector and guard ring are connected to first dynode potential of ca. -3 kV; for the detection of negative ions, the deflector and guard ring are biased a t ca. + 2 kV to serve as a conversion dynode in the manner developed by Stafford (5) and described by Hunt and Crow (6). Several stages of differential pumping are required to maintain sufficiently low pressure in the mass spectrometer and ion optics while injecting and vaporizing liquid flows up to 1mL/min. In this instrument, the outside of the vaporizer in the vicinity of the torches is open to the atmosphere. The region between the vaporizer and the skimmer is maintained at about 1 Torr by a 17 L/s mechanical pump. The ion source housing and ion optics are maintained at about 1 X Torr by a 1200 L / s diffusion pump. T h e quadrupole is pumped t o ca. 1 X Torr by a 285 L / s diffusion pump, and the electron gun housing is maintained below Torr by a 150 L / s diffusion pump. In operation, the ion source pressure is typically in the 1-to 2-Torr range. The ion source is connected by 1-cm i.d. tubing to a small mechanical pump; flow through this line can be regulated, if required, by a throttling valve. Usually, the best sensitivity has been found with this valve fully open. Under this condition 50-7070 of the total flow of vapor into the ion source exits through this auxiliary pump and the remainder through the electron entrance and ion exit apertures to the 1200 L / s pump. The detailed configuration of the apparatus described above has been developed through a fairly extensive series of experiments aimed at maximizing the sensitivity of the technique while minimizing pyrolysis of nonvolatile, thermally labile
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samples separated by reversed phase LC using water/ methanol as the mobile phase at flow rates between 0.2 and 1.0 mL/min. At first glance, it may be somewhat surprising that this can be accomplished by passing the sample through copper heated nearly to its melting point! The reasons that vaporization without pyrolysis can be accomplished in this manner appear to be that the sample spends a very short time in this high temperature region and that during this time it is protected from overheating by the solvent. T h e liquid entering the hot region is heated from ambient to the vaporization point in a few milliseconds and the vapor is expelled from the hot region in a millisecond or less after it is formed. In our studies we have found conditions under which nearly complete vaporization of liquid inputs up to at least 2 mL/min can be accomplished on this time scale; however, these conditions do not appear to correspond to optimum performance of the instrument. Under the operating conditions described above, it appears that about 95% of the liquid input is vaporized and the remainder is in the form of a highly collimated particle or aerosol beam which is accelerated to approximately sonic velocity by the rapid expansion of the vapor in the vaporizer. We estimate that these particles may typically have a mass of g and a velocity of ca. lo5 cm/s. Nonvolatile samples appear to be carried preferentially by the particles rather than the vapor. Since the particles have a very large axial momentum compared to the momentum of individual vapor molecules, they are transmitted with high probability through the skimmer to the ion source. As a result, high transmission efficiencies can be achieved for nonvolatile samples with removal of a significant fraction of the solvent. When the particle strikes the heated probe, it is wholly or partially vaporized and chemical ionization of the sample is produced in more or less the conventional manner, with ions produced from the solvent serving as the reagent ions.
EXPERIMENTAL All of the results presented in this paper were obtained using the mass spectrometer system described above coupled to a Perkin-Elmer Model 601 Liquid Chromatograph and a Finnigan-Incos Model 2300 data system. Samples were injected into the liquid effluent stream from the liquid chromatograph using a Rheodyne Model 7120 injection valve with a 20-fiL sample loop. Liquid phases used were dilute aqueous formic acid (0.01 to 0.2 M) or ammonium formate buffer (0.2 M, pH 5) at flow rates in the range from 0.3 to 1.0 mL/min. The total LC effluent was vaporized continuously in the mass spectrometer interface and the resulting vapor served as the reagent gas for the chemical ionization source. RESULTS AND DISCUSSION During the course of the development of the LC-MS system, spectra have been obtained on several hundred biologically important molecules; however, particular attention has been given to amino acids, peptides, nucleosides, and nucleotides. A few examples of recent results are presented in Figures 2 through 6, where both positive and negative CI mass spectra are presented for a few representative examples. These spectra were obtained under typical LC operating conditions but without a column installed. Results on two amino acids are presented in Figures 2 and 3. The relatively volatile amino acid, phenylalanine, presents no particular difficulty for conventional mass spectrometry, and spectra similar to those shown in Figure 2 may be obtained by conventional CI techniques. Arginine, on the other hand, is considered a difficult compound for conventional E1 or CI mass spectrometry and ions characteristic of the intact molecule are often not observed. In the present work the spectrum of arginine is qualitatively similar to that obtained for phenylalanine in that intense ions indicative of the molecular weight (M + H+ or M - H-) are observed along with a few structurally significant fragments. These results are typical of the 20
1638
ANALYTICAL CHEMISTRY, VOL. 52, NO. 11, SEPTEMBER 1980 PHENYLALANINE-POS IONS 100,
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amino acids which have been investigated. Several dipeptides have been studied; examples of the results are shown in Figure 4. The dipeptides appear similar to the amino acids in that they also generally yield intense ions characteristic of the molecular weight; however, the fragmentation patterns are considerably more complex. Insufficient data are presently available to determine the utility of the spectra for determination of the structure of the dipeptides. In most of our eariler work we used the elements of nucleic acids-bases, nucleosides, and nucleotides-as test compounds which provided a convenient series of biologically important molecules of increasing difficulty. The purine and pyrimidine bases present no particular problem; we have generally obtained spectra in which the protonated molecular ion is the base peak in the positive ion CI spectrum. The nucleosides are substantially more difficult. While the intensities of the fragment ions are relatively stable and easily reproduced, the intensity of the MH+ ion in positive CI is very sensitive to the operating conditions. A spectrum corresponding to perhaps the "best" positive CI result on adenosine is given in Figure 5a, and a fairly typical negative ion CI result is shown in Figure 5b. The positive CI result is in good agreement with the conventional CI results of Wilson and McCloskey (7). For all of the nucleosides studied the (b + 2H)' and b- ions are always observed as very intense fragments in the positive and negative ion CI, respectively, and are usually the base peaks in the spectra. In positive ion CI the MH+ ion is nearly always observed, but its relative intensity varies from being the base peak as shown in Figure 5a down to a few percent of the base peak depending on the nucleoside, the size of the sample, and details of the operating conditions which are not yet fully understood. Using formic acid or formate buffers, the formate adduct ion (mass 312 in Figure 5b) is usually observed as the highest mass ion identifiable in the spectrum. With pure water
ANALYTICAL CHEMISTRY, VOL. 52, NO. 11, SEPTEMBER 1980 AMP-POS
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the (M - 1)-ion is observed instead. The nucleotides represent the most difficult molecules which we have studied. Positive and negative CI spectra for the 5'-AMP are shown in Figure 6. T o the best of our knowledge, protonated molecular ions have not been observed in positive ion CI spectra of the nucleotides by conventional techniques; however, protonated AMP has been observed using a moving belt LC-MS interface (8). In our work, the intensities of the ions characteristic of molecular weight are very sensitive to the operating conditions. Spectra showing pseudo-molecular ion intensities comparable to or greater than those shown in Figure 6 have been obtained frequently for several nucleotides; on the other hand, under superficially similar operating conditions, the pseudo-molecular ions are sometimes not observed. Some further improvements in our techniques for operating the instrument and particularly in controlling and monitoring the vaporizer will probably be required before application of the combined LC-MS to molecules as nonvolatile and thermally labile as the nucleotides can be considered routine. Nevertheless, the present results do show that vaporization and ionization of intact nucleotide molecules are feasible.
EFFICIENCY AND SENSITIVITY An important consideration in combined chromatography-mass spectrometry is the efficiency with which sample eluting from the chromatograph is transferred to the ion source of the mass spectrometer. At the same time, it is usually necessary to allow only a small fraction of the solvent or carrier to be transferred. In our present apparatus about 3-570 of the solvent vapor is transferred to the ion source when the liquid flow is 0.5 mL/min of aqueous medium. The transfer efficiency for nonvolatile solutes is much higher. The results of a direct measurement of transfer efficiency are shown in Figure 7. In this experiment, the normal solvent vaporization
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Figure 6. Chemical ionization mass spectra of the nucleotide 5'adenosine monophosphate above 100 amu obtained using the new LC-MS system under the same conditions given in Figure 5
in 10
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Flgure 7. Mass chromatogram for the MH',
mass 132, from three 900-ng samples of norleucine. The peak on the left corresponds to placing the sample directly into the ion source using the direct insertion probe and the two later peaks correspond to duplicate injections using the LC interface conditions were employed with 0.2 M ammonium formate buffer (pH 5) a t a flow rate of 0.5 mL/min. A sample of norleucine was placed on the direct insertion probe and the mass spectrum was scanned repetitively from 70 to 300 amu as the probe was heated a t a rate of 50 'C/min to 250 OC. Immediately following this experiment, an identical sample of norleucine was injected using the LC injection valve. This was followed by a second injection of the same sample of norleucine. The mass chromatogram for the MH' ion, mass 132, for these three samples of norleucine is shown in Figure 7. The areas of the peaks corresponding to the injected samples are 49 and 5270,respectively, of the peak area for the probe sample. In all cases, the MH+ ion was the base peak in the spectrum above mass 70, and it represented more than 50% of the increase in the total ion current due to the sample.
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ANALYTICAL CHEMISTRY, VOL. 52, NO. 11, SEPTEMBER 1980
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SAMPLE (ng) Flgure 8. Log-log plot of the integral of the MH' intensity, mass 132, as a function of nanograms of norleucine injected (a). The points corresponding to the MH' intensity at larger sample sizes ( 0 )and to the total ion current (0)were obtained with the multiplier gain reduced by a factor of 64. The raw data for the larger samples were multiplied by this gain factor in preparing the plot T h e experimental parameters were constant for these experiments but, in the first case, the sample was inserted directly into the chemical ionization source and, in the others, the sample entered via the LC effluent and the vaporizer. Thus, we conclude that approximately 50% of the norleucine sample was transferred to the ion source of the mass spectrometer by the LC-MS interface. Similar experiments have been performed a number of times using several relatively nonvolatile amino acids and nucleosides with rather similar results. The less volatile samples, for example, adenosine, tend to give rather higher measured transfer efficiencies, but this may be because they do not vaporize cleanly from the direct insertion probe. An example of the response of the mass spectrometer as a function of sample size is shown in Figure 8, where the integral of the MH' intensity and the integral of the increase in total ion intensity are plotted as functions of nanograms of norleucine injected. The dashed lines on this log-log plot are drawn with unit slope corresponding to the relation expected if the response is directly proportional to sample size. As can be seen from Figure 8, the total ion current response is proportional to sample size a t the high end but the MH' response increases faster than linearly with sample size above ca. 500 ng. For an injection of 3.4 kg, the MH' intensity is nearly 90% of the total ionization attributable to the sample, while below 340 ng, MH' is about 20% of total ionization. For an injection of ca. 1kg, we estimate that the maximum sample concentration in the ion source (expressed as mole fraction) is about 5 X At this concentration, collisions between sample ions and sample molecules occur frequently. If the fragment ions react with the parent molecules to produce protonated parent ions, the apparent degree of fragmentation would decrease with increasing sample size in the manner shown in Figure 8. Similar effects have been observed for a number of the molecules studied. The smallest amount of sample detectable in this experiment was 1.4 ng which gave a response about twice the blank response. This result corresponds to a minimum detectable input rate of about 60 pg/s. The sensitivity a t mass 132 is limited by the presence of a background peak which is at least 100 times the minimum detectable ion signal. At higher masses where the background ionization is substantially lower, somewhat lower detection limits may be attained. The present system is applicable to a variety of LC separations including those requiring aqueous buffers and gradient elution. Our best results have been obtained with ammonium formate buffers, but alkali salts may also be used. Phosphate buffers are troublesome in that they cause buildup of phos-
6
uv
I
0
20
minutes
40
Figure 9. LC-MS analysis of a mixture of nucleosides and bases using gradient elution from ammonium formate buffer (0.2 M, pH 5)to methanol on 25 cm X 4.6 mm Partisil 10-ODS12 column at flow rate of 0.5 mL/min. Linear gradient started 12 min after injection, completed to pure methanol at 32 min. The lower trace is from UV detector (254 nm, 0.2 AUFS): the second trace from the bottom is the reconstructed liquid chromatogram (RLC) obtained by summing all ions above 100 amu. Individual mass chromatograms correspond to m l e 112, (b i2H)' cytidine: 126, MH' methylcytosine; 136, (b + 2H)' adenosine: 150 and 151, (b + 2H)' methyladenosine and methylinosine, respectivel 166, (b + 2H)' methylguanosine; 268, MH' adenosine; and 282, MH 1;methyladenosine. Components in the mixture were (1) 5methylcytosine, (2) cytidine, (3)7-methylinosine,(4) 1-methyladenosine, (5)7-methylguanosine, (6) adenosine
phate deposit in the interface and may eventually lead to plugging of the inlet capillary. An example of a reversed phase separation of bases and nucleosides using gradient elution from ammonium formate buffer to methanol is shown in Figure 9. In this particular example, the ( b + 2H)' ions for all of the nucleosides are prominent in the mass chromatograms, but MH' ions were detected only for adenosine and l-methyladenosine. A substantial amount of work remains to establish the full utility of the new LC-MS system. A feature of the present system which may prove somewhat troublesome in practice is that the LC solvent vapor also serves as the CI reagent gas. This dual role of the same substance may cause difficulty in the simultaneous optimization of both the LC separation and the mass spectrometric detection. Otherwise, the present system appears generally applicable to a wide range of LC separation techniques presently employed. For very large molecules which are nonvolatile or thermally labile, some pyrolysis will undoubtedly occur during vaporization; however, the mass spectrometer may still prove to be a useful detector even in these cases. These problems will be addressed in the evaluation and applications phase of this work which is now under way. CONCLUSION While we are just beginning to apply the new LC-MS system to real analyses, it appears that we have met all of the design goals which we set for ourselves a t the beginning of this development effort (2). In particular, u p to 1 mL/min of aqueous LC effluent can be vaporized without degrading the LC performance and a t least 50% of the sample present can be transferred to the ion source of the mass spectrometer along with, a t most, 5% of the solvent vapor. In its present configuration, the instrument can normally be operated for periods of at least several weeks without shutdown for cleaning or replacement of components. The sample transfer efficiencies and detection limits appear to be comparable to those
Anal. Chem. 1980, 52, 1641-1650
currently obtained in GC-MS, but the LC-MS system substantially expands the range of samples for which combined chromatography-mass spectrometry is applicable.
ACKNOWLEDGMENT T h e authors thank L. M. Marks for preparing the figures for publication, and are particularly grateful to J. A. McCloskey for providing samples of nucleosides and nucleotides. LITERATURE CITED (1) P . J. Arpino and G. Guiochon, Anal. Chem., 51, 683A (1979). (2) C. R. Blakley, M. J. McAdams, and M. L. Vestal, J . Chromatogr., 158, 261 (1978).
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(3) R. J. Buehler. E. Flanigan, L. J. Green, and L. Friedman, J . Am. Chem. Soc., 96, 3990 (1974). (4) M. L. Vestal, C. R. Blakley, P. W. Ryan, and J. H. Futrell, Rev. Sci. Instrum., 47, 15 (1976). (5) G .C. Stafford. Jr., patent pending. (6) D. F. Hunt and F. W. Crow, Anal. Chem., 5 0 , 1781 (1978). (7) M. S. Wilson and J. A. McCloskey, J . Am. Chem. Soc., 97, 3436 (1975). (8) W. H. McFadden, Finnigan Instruments, 845 W. Maude Ave., Sunnyvale, Calif., private communication.
RECEIVED for review March 21, 1980. Accepted May 20, 1980. This work was by the Institute Of Medical Sciences (NIH) under Grant GM 24031.
Copper(1) Chemical Ionization-Mass Spectrometric Analysis of Esters and Ketones R. C. Burnier, G. D. Byrd, and B. S. Freiser" Department of Chemistry, Purdue University, West Lafayette, Indiana 47907
The present work lays the foundation for the understanding and evaluation of atomic metal ions as a new class of chemical ionization reagent ions. I n particular, a thorough study of the gas phase ion chemistry of Cu', generated by laser ionization from the pure metal, with a series of oxygenated compounds is reported. Definite patterns of reactivity for different classes of oxygenated compounds are observed which, together with an understandlng of the reactlon mechanisms, provide the basis for predicting the Cu+ chemical ionization mass spectra of new compounds with analogous functional groups. The chemistry of Cu' is found to be dramatically different from that of Ti+ and Li' reported earlier providing a significant indication of the flexibility and selectivity afforded by atomic metal reagent ions.
Chemical ionization (CI) is a technique in which the sample is ionized by a reagent ion in an ion-molecule reaction. In general CI has the advantage of being a "soft" ionization technique in that, as a rule, far less energy is transferred to the sample than by conventional 70-eV electron impact. The sample ion is, therefore, less likely to fragment and greater information about the intact sample molecule may be obtained. An added dimension of this technique is that, unlike electron impact, different reagent ions may be chosen to be as selective or "universal" as desired because the ionization process, as the name of the technique implies, is coupled to a chemical reaction. Because of these advantages, the popularity of CI for analytical applications is likely to continue its rapid increase. The choice of reagent ions has remained remarkably limited to date, however, and future developments in the area call for exploring the utility of a wider range of CI reagent ions. The reagent gas utilized has been mainly methane, and although an increasing amount of work is appearing in which the reagent gas is varied (ammonia, isobutane, and methanol are common), the majority of the reagent ions produced from these gases are protonating agents. Atomic metal ions hold promise as CI reagents by offering a significantly enlarged 0003-2700/80/0352-1641$01 .OO/O
flexibility of choice of Lewis acids and charge transfer agents. Ultimately, the application of metal ions as useful reagent ions will be determined only by studying the ion chemistry of various metal ions with various classes of molecules until patterns of reactivity can be identified useful in predicting the gas phase chemistry. Such work is under way in several laboratories. Ridge et al. (1-3) have been especially active in this area reporting the chemistry of Ni+, Co', Fe+, Cr', and Ti+ with a variety of compounds. Studies involving U+ ( 4 ) , Al+ (5,6),and alkali ions (7-9) have also been reported. Of these latter ions, the alkalis have received the most attention since they can be readily generated by thermionic emission. Generation of transition metal ions has been mainly by electron impact on volatile inorganics such as carbonyl compounds. Recently we reported the novel application of a pulsed laser source with an ion cyclotron resonance (ICR) spectrometer which demonstrated that virtually any atomic metal ion could be generated and its chemistry studied (10, 1 1 ) . The laser source lends itself particularly well to ICR spectrometry and offers the advantage that a far wider variety of simple atomic metal ions can be generated and their chemistry studied without interference of reaction products from other fragment ions or reactions with the parent neutral complexes such as occur in the electron impact studies. We reported a brief study on the reactions of Ag+ and Cu+ with isopropyl chloride (11) and a comparison of the coordination chemistry of Cu+ in the gas phase and in solution (10). In this paper, we report a study of the reactions of Cu+ with a series of esters and ketones in the gas phase. Particular emphasis is placed on determining the mechanisms of the reactions in order to permit the prediction and interpretation of Cu+ chemical ionization mass spectra from unknown samples having the same functional groups. Studies involving atomic metal ions are not only important for applications involving chemical ionization but also yield critical thermodynamic, kinetic, and mechanistic information about the intrinsic organometallic and coordination chemistry of metal ions in the absence of complicating solvent effects. In addition to elucidating the reactions to be expected of Cu+ with esters CE 1980 American Chemical Society
