CHEMICAL IONIZATION M A S S SPECTROMETRY BURNABY M U N S O N Department of Chemistry University of Delaware Newark, Del. 19711
C h e m i c a l ionization ( C I ) mass spectrometry is a relatively new technique for the production of mass spectra of compounds in which the ions from the molecules of interest are formed by ion-molecule reactions. The method of ion production is different from that used in electron ionization (EI), field ionization (FI), or photoionization (PI) mass spectrometry, and the decomposing species and consequent C I mass spectra are very different from the spectra produced by the other techniques. The technique is the outgrowth of mass spectrometric studies of ion-molecule reactions. Since the introduction of the technique in 1966 i l ) ,about 35 papers have been published in this area. At present, there are about 10 laboratories studying C I mass spectrometry. (The use of this technique is covered by US.Patent 3,555,272 by F. H. Field and hf. S.B. Munson, assigned to Esso Research and Engineering Co., with exclusive manufacturing rights to Scientific Research Instruments Corp., Baltimore, Md.) Principles of Operation
The technique itself is a relatively simple one, but modifications are necessary on conventional mass spectrometers to allow the C I technique to be used. The majority of the instruments presently being used have been built or modified by the researchers (1-4), but modifica28A
tions are now commercially available for the major instruments ( 5 ) . Since C I mass spectrometers must operate a t source (or ionization) chamber pressures of the order of 1 torr torr (much higher than the maximum of conventional mass spectrometers), the major modifications are the addition of diffusion pump capacity and the reduction in size of the electron entrance and ion exit slit& t o the source chamber. With these modifications, it is possible to maintain the pressures in the flight tube or analyzer section of the mass spectrometer a t less than torr. N o modifications of the mass separation, mass measurement, recording, or data-handling equipment associated with conventional instruments are necessary. The basic technique requires a large amount of a reactant gas and a small amount of the sample to be analyzed. The ratio of reactant gas t o sample should be of the order of lo3, although this ratio is not a critical parameter. Ions are produced in the mixture of these two gases which react with the neutral molecules to form a distribution of ions which is characteristic of both sample and reactant gases. The ions are generally formed initially with high-energy electrons (50-500 eT7). Because of the very large excess of the reactant gas, ions from the reactant gas are essentially the only ones produced by electron ionization, and it is the subsequent reactions of these ions that are impor-
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
tant and produce the C I spectra of the samples. Systematic studies have been inade of several classes of compounds: alkanes ( 6 ) ,cycloalkanes (71, alkylbenzenes (8), alkenes and alkynes (Q),alkanols (10)) esters of monocarboxylic acids (11), esters of di- and tricarboxylic acids ( 1 2 ) , alkaloids ( 1 3 ) , amino acids ( l 4 ) ,barbiturates ( 1 5 ) , substituted benzophenones ( Z ) , aryl ketones (16)) steroids ( I s ) ,and dimeric cyclic ketones ( 1 7 ) . Somewhat less extensive studies have been made on several other systems : amines (1), CrHR isomers (18),R X and RCOR’ ( X = C1, Br, I ; R = CnHzn+ 1) (191, RCOOCHZOCHS (20), RCOOCHaSCH? (21) , borazine ( 2 2 ) , pristane ( E ? ) , and botryodiplodin ( 2 4 ) . Preliminary results have been given of the sequencing of peptides as simple peptides (25, 26) and as the phenylthiohydantoin derivatives formed by the Edman degradation ($71 , Nucleosides also appear to be susceptible to analysis by chemical ionization (28). The basic principles of C I mass spectrometry have been reviewed previously elsewhere (4, 19, 2 9 ) . The most common reactant gas for C I studies has been methane, because it was the first reactant gas tried and because it generally gives information about molecular weight and molecular structure from (M I ) + and fragment ions ( 1 , 6-9, 11, 15-15, 17, 25-26). Isobutane,
+
REPORT FOR ANALYTICAL CHEMISTS
Chemical ionization mass spectra of compounds are produced by ions formed by ion-molecule reactions. In the basic technique, a small amount of sample is used with a large amount of reactant gas. Conventional mass spectrometers can be modified to use this relatively new technique and the spectra produced are very different from the spectra in other types of mass spectrometry
as a reactant gas, produces less fragmentation of the sample than methane and has been used for several studies (10, 12, 20, 21, 2 7 ) . Propane is intermediate between methane and isobutane in the abundance of fragment ions produced from the samples (2). Preliminary results have been reported for basic cornpounds with N H Band with C D 4 as the reactant gases (28). Combinations of gas chromatography and chemical ionization mass spectrometry have been made in which the carrier gas for the chromatograph has been used as the reactant gas for the C I technique (30, 3 1 ) . Such a combination is now commercially available ( 5 ) . High-resolution C I mass spectrometry and precise mass measurements for the determination of elemental compositions have been reported. D a t a have been obtained in high-pressure operation ( C I ) a t resolutions of 10,000-50,000 (2, 3, 13a, 24, 32, 3 3 ) . Degradation of resolution from t h a t obtained in low-pressure operation occurs only with inadequate pumping a t high pressures when the pressure in the analyzer section becomes sufficiently high to cause collisional broadening of the peaks ( 2 ) . Mixtures of perfluorinated or perdeuterated hydrocarbons have been found successful as reference materials for precise mass measurement ( 3 3 ) . As long as the ions of the reactant gases are unaffected by instrumental changes. the C I mass spectra
should be independent of these changes. Recently, i t has been shown t h a t the C I mass spectra are independent of electron energy, electron current, and accelerating voltage (16). If the pumping is adequate such t h a t the pressure in the region outside the source is sufficiently low, then the spectra are independent of the pressure of reactant gas within the source chamber (2, 1 6 ) . As the size of the sample increases, the concentration of sample xithin the source chamber increases and collisions of sample ions with sample molecules occur frequently to form ( 2 Jf 1 ) + ions from reactions of the ( M 1 ) + ions with polar samples (16, 34). However, the spectra are independent of sample size for small samples when the (2 Jf 1) + ions are less than a few percent of the sample ionization (16). Temperature and repeller voltage within the source have noticeable effects on the C I spectra. An increase in fragmentation is noted with an increase in temperature (6, 11, 20, 21, 34, 3 5 ) . The temperature effects are more pronounced with isobutane than with methane (34, 3 5 ) . Although the C I spectra are substantially independent of repeller for low voltages (0-10 v) ( 1 6 ) , appreciable changes are produced in C I spectra a t high-repeller voltages (>30 V) , particularly with isobutane ( 2 ) . The high-repeller field probably gives the sample ions
+
+
+
sufficient translational energy t h a t some decompose on collisions within the source. T h e analytical possibilities of this technique have been mentioned ( 2 ) . There are not yet enough data available for the same compounds on different instruments to make valid comparisons of spectra obtained with different instruments. S o r is there yet agreement on a standard set of conditions for comparison of spectra among different workers. The few data available suggest reasonably good agreement (f?, 16) ; however, all instrumental parameters have not yet been thoroughly investigated. A rigorous comparison of the sensitivities of C I and E1 mass spectrometry cannot be made a t present. The sensitivities appear roughly comparable, however, and useful C I spectra have been obtained on a fern tenths to a few micrograms of sample (16. 25,26,28). Since the number of ion-molecule collisions increases rapidly with increasing pressure, the fraction of sample ionization can be expected to increase with increasing pressure. However, because of ion scattering and other loss phenomena, the absolute ion current per unit of sample can be expected t o maximize on any instrument in C I operation as the pressure is increased. Very little work has been reported on quantitative analyses of mixtures. There should not be major difficulties in the development of
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
29A
Report for Analytical Chemists
quantitative analyses, however. I n the first report of this technique, an analysis was made of simple mixtures of n-alkanes using a known mixture to obtain the relative sensitivities of the compounds under the experimental conditions ( 1 ) . Quantitative analyses have been reported on samples of phenylthiohydantoin derivatives of amino acids from proteins; in these experiments, an internal standard was necessary since the materials were introduced into the source chamber with a directinsertion probe (27). Since the most common reactant gas for chemical ionization studies has been methane, a description of this system will be used to illustrate the CI technique.
40
30 c 0 *
. N_ C 9 20 4-
m
: 2 10
0 10
20
30
50
40 ~
Figure 1.
60
~~
~
Typical high-pressure mass spectrum of methane
Reactant Gas, Methane
The direct ionization of methane with high-energy electrons ( E > 50 eV) gives several ions:
+ c-
CH,
+
C€L+,CHz+, C H P , .
.
(1)
However, C H 4 + and C H 3 + are by far the most abundant of these ions, being formed in approximately equal amounts and comprising about 90% of the total ionization. Since the sample/methane ratio is of the order of lo+, only a very small fraction of the ions are produced by direct ionization of the sample. CH4+ and C H , < + the , major ions produced by direct ionization of the reactant gas, will collide with the methane molecules, which are by far the most abundant species in the mixture, to produce other ions by well-established, very rapid reactions (36): CHI' CHj+
+ CH,+ + CH,
+ CH, + Hz
CH,+ + C2Hj+
(2) (3)
Some collisions occur between CH4+ or CH,+ and the sample molecules. These reactive collisions will produce ions dependent upon the sample. The rate constants for reactions of CH4+ or CH3+ with methane and the rate constants for reactions of CH4- or CH3+ with the sample are of the same order of magnitude. Consequently, because of the factor of lo3 between the concentrations of CH, and sample, the major reactions of CH4+ and CH3+ are those indicated with methane, Reactions 2 and 3. A small fraction 30A
of ions from the sample may be a t tributed to reactions of CH4+ and CH,5 7 ) . Prelimins-rry results have been given on chemical ionization reactions Tvith negative ions that suggest useful applications (58). =Ilt.hough chemical ionization iiiass spectrometry is associated with the transfer o i rriasaive particles! the s:me iiiitrum~~iitation caii be u>ed to >tuciy charge exchange or electron tranpfer reactions a t high pre>sures. The majority of charge exchange reaction? vhich have been > t 11 d i e d un 1: i 1 r ec en t 1y have been .>tudied a t ,elatively low pressures i n tandem instruments ( 5 9 ) or rvith t h e Cermak: .>ource 160). Experiniciits h a w heen performed in a high-pressure source with several gases no nh y clr o gen - c o n t :i in i n g Tvliich produce rhargci exchange Jcctra. The rare gases) Y2, 02, 0;CO,, S O , CF,. ank. CC1, have lieen tried (61 1 . CO allpears to be a particularly ii-eful gas, giving cpcctra w1iic.h coiitain both -\I+ and >tructurally wefill fragment ions. T lie 11 i gh - pi'ez ;u re c 11 a r ge ex c 11an ge spectra of a few pecticides have been ohtained and compared x i t h thcir E1 anti C I q m t r a ( 4 1) . The charge exchange spectra are niore nearly like convcintional E1 spectra than CI spectra and perhaps may he easier for inass spectronietriets to interpret. The exist,in g cor re 1a t i o i i s het we (3 t i structure anti E1 spectrn may be useful in the interpretation of charge exchange spectra. T h e interpretation of c 11enii c a 1 ion i z a t i o n SI,e ct ra wi 11 be helped by .? knorledgti of acidic solutions, hut more atructure-spectra correlatison. are needed. Acknowledgment
The author is grateful to S o e l Eiiiolf and John 1Iiclinowicz for their help in preparing this report. References
B.31111i.wiianti I:. H.Field. J .
' / ~ c T ?.SO?.. L, 88, 1621 (1966) icl~iio\r.ir~z :uicl B. SIiinson, Org .urns S / , ' e c t i ~ f , n l. 4, 451 (1970).
( 3 ) J . H . Futrrll nnd L.H. K o j c i k . R e i , . sei. I / f , > t r t / v 42, , , 214 (19711'
R. Wallcr. Ed..
.
'w T o r k . Y.I-., 1971 (in press), CIRCLE 109 ON READER SERVICE CARD
40A
A N A L Y T I C A L CHEMISTRY, VOL. 43, NO. 1 3 , NOVEMBER 1971
Dual Channel Probe-Magnet Air Gap 3.2 cm
For the kind of pulse required in tomorrow's NMR research, we have the perfect heart today. It's our PFT-100 Fourier Transform system. A system desi ned with incredible power, unusual versatility. ?he PFT-100 is capable of a 15 F e c . pulse sufficient to produce a 90" 13C magnetization vector tipping. Complete controls permit fine adjustments to regulate Pulse Width, Interval and Repetition. The system design allows you to select sin le or multiple Dulse Droarams such as FT, DEFT, S FT and more.
F
P k - 1 0 0 Pulse Programmer
It has a hetero-nucleus Ex-
ternal lock, as well. You choose a fixed or replaceable insert probe which permits 5, 8 and lOmm/OD variable temperature sample tubes. There's more. Push button controls and the solid state desim of the PS-1OOCW/NMR. There is also complete compatibility with most existing FT data reduction systems. They combine to make it a total research NMR system. Our literature and demonstrations make it more appealing and are yours for the asking. From the newest laboratory in the country devoted to NMR research -JEOL, 235 Birchwood Avenue, Cranford, New Jersey 07016.
Give your pulse a heart.
NMR SpectrometersiMass SpectrmetersiESR Spectrmetersilaser Raman SpectrophotometersiLabratory CmputersiScanning Electron Microscopes Electron MicroscopesiX-ray Diffractmeters/Amino Acid Analyzers
CIRCLE 90 ON READER SERVICE CARD
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
41 A
11
The moment of truth!
If you had to determine the sulfur content of steel 450 times a shift, could your lab do it?
‘
Only if you had a
n@aD 60-second s u ur dete rmi nato r If
i
You may never be faced with such a herculean task, but if you were you could depend on our new IR-32 Sulfur Determinator to do the job accurately and with reproducible results. Its infrared detection system cuts to 60 seconds or less the time required for automatic sulfur determination in iron, steel or other materials. Results are displayed as percent of sulfur on a direct digital readout, with the range for a %-gram sample .0002% to 2%. Simple to operate, the new LECO 60-second Sulfur Determinator has a built-in digital weight compensator which permits easy adjustment for sample weight variations, to eliminate time-consuming manual calculations. There is no titrating, no solution to prepare or handle. And LECO solid state design increases calibration stability and simplifies service. LAB0 RAT0RY EQUIPMENT CORPORATION 3000 Lakeview Avenue, St. Joseph, Michigan 49085
I
CIRCLE 99
42A
ON READER SERVICE CARD
(5) Scientific Research Instruments Corp.. 6707 Whitestone Rd., Baltimore, Md. 21207. (6) F. H. Field, M . S. B. Munson, and D. A. Becker, Advan. Chem. Ser., No. 58, 167 (1966). (7) F. H. Field and M. S. B. Munson, J . Amer. Chem. SOC.,89,4272 (1967). (8) M. S. B. Munson and F. H. Field, zbid.. D 1047. (9) F.’H.Field, ibid., 90,5649 (1968). (10) F. H. Field, ibid., 92, 2672 (1970). ( l l ) , M . S. B. Munson and F. H. Field, zbzd., 88,4337 (1966). (12) H. M. Fales, G. W. A . Milne, and R . S. Sicholson, ibid., to be published. (13a) H. M. Falep, G. W. A. Milne, and M. L. Vestal, zbzd., 91, 3682 (1969). (13b) H. M. Fales, H. A. Lloyd, and G. W.A . Milne, zbzd., 92, l5W (1970). (14) G. W.A , , Milne, T. Axenrod, and H. M. Fales, zbzd., p 5170. (15) H. M. Fales, G. W. A . Milne, and T. Axenrod, ANAL. CHEM., 42, 1432 (1970). (16) John Michnowicz, PhD thesis, University of Delaware, 1971. (17) H. Ziffer, H. M. Fales, G. W. A. Milne, and F. H. Field, J . Amer. Chem. Soc., 92,3682 (1969). (18) F. H. Field, ibid., 89, 5328 (1967). (19) F. H. Field, Advan. Mass Spectrom., Vol. 4, E. Kendrick, Ed., Institute of Petroleum, 1968, p 645. (20) D. P. Weeks and F. H. Field, J . Amer. Chem. Soc., 92, 1600 (1970). (21) F. H. Field and D. P. Weeks, ibid., p 6521. (22) R. F. Porter and J. J. Solomon, ibid., 93, 56 (1971). (23) E. Gelpi and J. Oro, ANAL.CHEM., 39, 388 (1967). (24) G. P. Arsenault, J. R. Althaus, and P. V. Divekar, Chem. Commun., 1414 (1969). ( 2 5 ) W. R. Gray, L. H. Wojcik, and J. H. Futrell, Biochem. Biophys. Res. Commun., 41, 1111 (1970). (26) 8.A. Kiryushkin, H. M. Fales, T. Axenrod, E. J. Gilbert, and G. W. A. Milne, Org. Mass Spectrom., 5 , 19 (1971). (27) H. M . Fales, Y. Nagai, G. W. A. Milne. H. B. Brewer, Jr., T. J. Bronaert, and J. J. Pisano, Anal. Biochem., to be published, 1971. (28) M. S. Wilson, I. Dzidic, and J. A. McCloskey, Biochim. Biophys. Acta, 240,623 (1971). (29) F. H. Field. Accounts Chem. Res., 1, 42 (1968). (30) G. P. Arsenault and J. J. Dolhun, Chem. Commun., 1542 (1970). (31) D . M. Schoengold and B. Munson, ASAL. CHEM.,42, 1811 (1970). (32) J. H. Futrell, Tech. Rep. AFMLTR-70-65, 1970. (33) I. Dzidic, D. M : Desiderio, M . S. Wilson, P. F. Crain, and J. A. McCloskey, submitted for Dublieation. (34)-F. H. Field, J.-Amer. Chem. Soc.. 91, 2827 (1969). (35) F. H. Field, ibid., p 6334. (36) F. H. Field and M . S. B. Munson, ibid., 87, 3289 (1965). (37) J. Long and B. Munson, J . Chem. Phys., 53, 1356 (1970). (38a) L. Wolniewicz, ibid., 43, 1087 (1965).
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
Report for Analvtlcal Chemists
(38b) W. A. Chupka and M. E . Russell, ibid.,49,5426 (1968). (39) Estimate by author. (40) H. D. Beckey, J. Amer. Chem. Soe., 88, 5333 (1966). (41) N. Einolf, J. Michnowicz, and B. Munson, paper presented a t 19th Annual Conference on Mass Spectrometry Atlanta. Gn., May 1971. (42) H. M. Rosenstoek and M. Krauss, in Mass Spectrometry of Organic Ions,” F. W. McLaffcrty, Ed., AcadPmic Press, New York, N.Y., 1963, p 2. (43) F. H . Field and D . P. Beggs, J . Amer. Chem. Sac., 93, 1585 (1971). (44) M. A. Haney and J. L. Franklin, J . Phys. Chem., 73,4328 (1969). (45) G. A. Olah, J. Amer. Chem. Soe., 81, 1103 (1965). (46a) R . T. Morrison and R . N. Boyd, “Organic Chemistry,” Allyn and Bacon, Boston, Mass., 1959. (46b) G. A. Olah, J. Sommer, and E. Namanuorth, J. Amer. Chem. Sac., 89, 3576 (1967). ( 4 7 ) John Michnowicz, unpublished data, these laboratories. (48) G. A. Olah, M. Cali”, and D. H. O’Brien, J. Amer. Chem. Soe., 89, 3586 (1967). (49) C. Fenselau, J. Duncan, and H. M Fales, paper presented a t 19th Meeting on Mass Spectrometry, Atlanta, Ga., May, 1971. (50) F. H. Field and M. S. B. Munson, unpublished data, 1966.
J. H . Beynon, R. A. Saundem, and A. E . Williams, “The Mass Spectra of Organic Molecules,” Elsevier, New York, N.Y., 1968. (52) N. Einolf, J. Lehman, and J. Michnowies, unpublished data, these lahoratories. (53) R. C. Dougherty and J. Dalton, I per presented a t 18th Meeting on M, Spectrometry, San Francisco, Ca June, 1970. (54) For a brief review of I C R mass sp trometry, see J. M. S. Henis, AN CHEM.,41 (10),22A (1969). ( 5 5 ) M. M. Bumey, T. A. Elwood, M. Hoffman, T . A. Lehman, and J. Tesarek, ibid., 42, 1370 (1970). (56) Rodger Fultz, paper presented at 19th Mreting on Mass Spectrometry At,lmta, Ga., May 1971. (57) D. M . Schoengold, PhD Thesis, University of Delaware, 1971. (58) R. C. Dougherty, paper presented a t 19th Meeting on Mass Spectrometry, Atlanta, Ga., May 1971. (59%) E. Lindholm, in Advan. Chem. Set.. No. 58,l (1966). (59b) J. H. Putre11 and F. P. Abramson, ibid., p 107. (60~) Cermak and Z. Herman, Nueleonzes, 19, 106 (1961). (60b) R. H. Shapiro and J. Turk, paper presented a t Int. Coni. on Mass Spretrometry, Brussels, Belgium, Septemher 1970. (61) W. N. Einolf, PhD Thesis, Univer(51)
v.
slty,
aby Munson zs assomate projessor of chemistry at the University of Delaware. Dr. Munson earned his BA, MA, and PhD degrees from the University of Texas in 1954, 1956, and 1959, respectively. He was associated v i t h the Esso Research and Engineering Co. from 1959 until 1967 when he j o k e d the Faculty at the University of Delaware. Dr. Munson was co-inventor with Frank Field of the chemical ionization technique while at Esso. His current research interests are in electron and chemical ionization mass spectrometry, kinetics, and the thermochemistry of ion-molecule reactions.
The following spectrum is brought to you by the new EM-600, a medium resolution mass spectrometer system that costs a mere $6925: 1
I
..
I11
clQ-cH3 CI
I
I
.
Before leaving, we might mention that the 60”sector, magnetically scanned EM-600 is a complete, easy-to-use system which also features a heated inlet for volatile organic compounds up to mass 330 or higher and linear mass readout. For complete details or a demonstration, call (415) 326-4000 Ext. 2207. Or write Varian Anaspect, 611 Hansen Way, Palo Alto, California94303. *S6210 without rewrder
@varian anaspect
”See Anaspeci CIRCLE 191 ON READ
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
43 A
