Editing Chemical ionization

{{Short description|Technique in mass spectroscopy}}
{{Use American English|date = February 2019}}
[[File:Chemical Ionization.png|thumb|A schematic diagram of chemical ionization source]]
'''Chemical ionization''' ('''CI''') is a [[ionization|soft ionization]] technique used in [[mass spectrometry]].<ref name="pmid4569234">{{cite journal |vauthors=Fales HM, Milne GW, Pisano JJ, Brewer HB, Blum MS, MacConnell JG, Brand J, Law N |title=Biological applications of electron ionization and chemical ionization mass spectrometry |journal=Recent Prog. Horm. Res. |volume=28 |pages=591–626 |year=1972 |pmid=4569234 }}</ref><ref name=":5">{{Cite journal|last=Field|first=Frank H.|title=Chemical ionization mass spectrometry|journal=Accounts of Chemical Research|language=en|volume=1|issue=2|pages=42–49|doi=10.1021/ar50002a002|year=2002}}</ref> This was first introduced by Burnaby Munson and [[Frank H. Field]] in 1966.<ref name=":2">{{cite book|author=Alex. G. Harrison|title=Chemical Ionization Mass Spectrometry, Second Edition|url=https://books.google.com/books?id=HJ-j71b7yfIC&pg=PA1|date=15 June 1992|publisher=CRC Press|isbn=978-0-8493-4254-7|pages=1–}}</ref> This technique is a branch of gaseous ion-molecule chemistry.<ref name=":5" /> Reagent gas molecules (often methane or ammonia)<ref>{{Cite web |title=Mass Spectrometry Facility {{!}} CI |url=http://www.chm.bris.ac.uk/ms/ci-ionisation.xhtml |access-date=2022-04-30 |website=www.chm.bris.ac.uk |language=en}}</ref> are ionized by [[electron ionization]] to form reagent ions, which subsequently react with analyte molecules in the gas phase to create analyte ions for analysis by mass spectrometry. Negative chemical ionization (NCI), charge-exchange chemical ionization, [[atmospheric-pressure chemical ionization]] (APCI) and [[atmospheric pressure photoionization]] (APPI) are some of the common variants of the technique. CI mass spectrometry finds general application in the identification, [[structure elucidation]] and [[quantitation]] of organic compounds<ref name=":0">{{cite journal|last1=Hunt|first1=Donald F.|last2=McEwen|first2=Charles N.|last3=Harvey|first3=T. Michael.|title=Positive and negative chemical ionization mass spectrometry using a Townsend discharge ion source|journal=Analytical Chemistry|volume=47|issue=11|pages=1730–1734|doi=10.1021/ac60361a011|language=en|year=2002}}</ref> as well as some utility in biochemical analysis.<ref name=":0" /> Samples to be analyzed must be in vapour form, or else (in the case of liquids or solids), must be vapourized before introduction into the source.

==Principles of operation==
The chemical ionization process generally imparts less energy to an analyte molecule than does [[Electron ionization|electron impact]] (EI) ionization, resulting in less fragmentation<ref name=":5" /> and usually a simpler [[spectrum]]. The amount of fragmentation, and therefore the amount of structural information produced by the process can be controlled to some degree by selection of the reagent ion.<ref name=":5" /> In addition to some characteristic fragment ion peaks, a CI spectrum usually has an identifiable protonated [[molecular ion]] peak [M+1]<sup>+</sup>, allowing determination of the [[molecular mass]].<ref name="MSPA">{{cite book|title=Mass Spectrometry: Principles and Applications|last=de Hoffmann|first=Edmond|author2=Vincent Stroobant|publisher=John Wiley & Sons, Ltd.|year=2003|isbn=978-0-471-48566-7|edition=Second|location=Toronto|page=14}}</ref> CI is thus useful as an alternative technique in cases where EI  produces excessive fragmentation of the analyte, causing the molecular-ion peak to be weak or completely absent.

== Instrumentation ==
The CI source design for a mass spectrometer is very similar to that of the EI source. To facilitate the reactions between the ions and molecules, the chamber is kept relatively gas tight at a pressure of about 1 torr.<ref name=":1">{{cite book|last1=Dass|first1=Chhabil|title=Fundamentals of contemporary mass spectrometry|date=2007|publisher=Wiley-Interscience|location=Hoboken, N.J.|isbn=9780470118498|edition=[Online-Ausg.].}}</ref> Electrons are produced externally to the source volume (at a lower pressure of 10<sup>−4</sup> torr<ref name=":1" /> or below) by heating a metal filament which is made of [[tungsten]], [[rhenium]], or [[iridium]].<ref name=":0" /> The electrons are introduced through a small aperture in the source wall at energies 200–1000 eV<ref name=":1" /><ref name=":6">{{Cite journal |last=Vestal |first=Marvin L. |date=2000 |title=Methods of Ion Generation |url=http://www.igg.cas.cn/jgsz/zcxt/sygcxt/ggsys/djsdlztzp/201010/P020140310408095177115.pdf |journal=Chemical Reviews |volume=101 |issue=2 |pages=361–375|doi=10.1021/cr990104w |pmid=11712251 }}</ref> so that they penetrate to at least the centre of the box.<ref name=":6" /> In contrast to EI, the magnet and the electron trap are not needed for CI, since the electrons do not travel to the end of the chamber. Many modern sources are dual or combination EI/CI sources and can be switched from EI mode to CI mode and back in seconds.<ref>{{Cite book |last=Gross |first=J. H. |title=Mass Spectrometry |publisher=Springer |year=2004 |isbn=978-3-642-07388-5 |location=Berlin, Heidelberg |pages=331–354}}</ref>

==Mechanism==
A CI experiment involves the use of gas phase acid-base reactions in the chamber. Some common reagent gases include: [[methane]], [[ammonia]], [[water]] and [[isobutane]]. Inside the ion source, the reagent gas is present in large excess compared to the analyte. Electrons entering the source will mainly ionize the reagent gas because it is in large excess compared to the analyte. The primary reagent ions then undergo secondary ion/molecule reactions (as below) to produce more stable reagent ions which ultimately collide and react with the lower concentration analyte molecules to form product ions. The collisions between reagent ions and analyte molecules occur at close to thermal energies, so that the energy available to fragment the analyte ions is limited to the exothermicity of the ion-molecule reaction. For a proton transfer reaction, this is just the difference in proton affinity between the neutral reagent molecule and the neutral analyte molecule.<ref name=":6" /> This results in significantly less fragmentation than does 70 eV electron ionization (EI).

The following reactions are possible with methane as the reagent gas.

=== Primary ion formation ===

:<chem>CH4{} + e^- -> CH4^{+\bullet}{} + 2e^-</chem>

=== Secondary reagent ions ===

:<chem>CH4{} + CH4^{+\bullet} -> CH5+{} + CH3^{\bullet}</chem>

:<chem>CH4 + CH3^+ -> C2H5+ + H2</chem>

=== Product ion formation ===

:<chem>M + CH5+ -> CH4 + [M + H]+</chem> &nbsp;&nbsp; (protonation)

:<chem>AH + CH3+ -> CH4 + A+</chem> &nbsp;&nbsp; (<chem>H^-</chem> abstraction)

:<chem>M + C2H5+ -> [M + C2H5]+</chem> &nbsp;&nbsp; (adduct formation)

:<chem>A + CH4+ -> CH4 + A+</chem> &nbsp;&nbsp; ([[Charge-exchange ionization|charge exchange]])

If ammonia is the reagent gas,

:<chem>NH3{} + e^- -> NH3^{+\bullet}{} + 2e^-</chem>

:<chem>NH3{} + NH3^{+\bullet} -> NH4+{} + NH2</chem>

:<chem>M + NH4^+ -> MH+ + NH3</chem>

For isobutane as the reagent gas,

:<math chem>\ce{C4H10{} + e^- -> C4H10^{+\bullet}{} + 2e^-} (\ce{ + C3H7+} \text{and other ions}) </math>

:<chem>C3H7^+{} + C4H10^{+\bullet} -> C4H9^+{} + C3H8 </chem>

:<chem>M + C4H9^+ -> MH^+ + C4H8 </chem>

Self chemical ionization is possible if the reagent ion is an ionized form of the analyte.<ref>{{Cite journal | doi = 10.1021/ac00226a011 | title = Chemical ionization in Fourier transform mass spectrometry | year = 1981 |author1=Sahba Ghaderi |author2=P. S. Kulkarni |author3=Edward B. Ledford |author4=Charles L. Wilkins |author5=Michael L. Gross | journal = Analytical Chemistry | volume = 53 | pages = 428–437 | issue = 3}}</ref>

==Advantages and limitations==
One of the main advantages of CI over EI is the reduced fragmentation as noted above, which for more fragile molecules, results in a peak in the mass spectrum indicative of the molecular weight of the analyte. This proves to be a particular advantage for biological applications where EI often does not yield useful molecular ions in the spectrum.<ref name=":6" /> The spectra given by CI are simpler than EI spectra and CI can be more sensitive<ref name=":0" /> than other ionization methods, at least in part to the reduced fragmentation which concentrates the ion signal in fewer and therefore more intense peaks. The extent of fragmentation can be somewhat controlled by proper selection of reagent gases.<ref name=":1" /><ref name=":6" /> Moreover, CI is often coupled to chromatographic separation techniques, thereby improving its usefulness in identification of compounds.<ref name=":3">{{Cite journal|last=Byrdwell|first=William Craig|date=2001-04-01|title=Atmospheric pressure chemical ionization mass spectrometry for analysis of lipids|journal=Lipids|language=en|volume=36|issue=4|pages=327–346|doi=10.1007/s11745-001-0725-5|issn=0024-4201|pmid=11383683|s2cid=4017177 }}</ref> As with EI, the method is limited to compounds that can be vapourized in the ion source. The lower degree of fragmentation can be a disadvantage in that less structural information is provided. Additionally, the degree of fragmentation and therefore the mass spectrum, can be sensitive to source conditions such as pressure, temperature, and the presence of impurities (such as water vapour) in the source. Because of this lack of reproducibility, libraries of CI spectra have not been generated for compound identification.<ref name=":6" />

== Applications ==
[[File:NOAA PAN CIMS.jpg|thumb|250px|Peroxynitrate chemical ionization mass spectrometer at the US [[National Oceanic and Atmospheric Administration]]]]
CI mass spectrometry is a useful tool in structure elucidation of organic compounds.<ref name=":2" /> This is possible with CI, because formation of [M+1]<sup>+</sup> eliminates a stable molecule, which can be used to guess the functional groups present.<ref name=":2" /> Besides that, CI facilitates the ability to detect the molecular ion peak, due to less extensive fragmentation.<ref name=":2" /> Chemical ionization can also be used to identify and quantify an analyte present in a sample, by coupling chromatographic separation techniques to CI<ref name=":2" /> such as [[Gas chromatography|gas chromatography (GC)]], [[High-performance liquid chromatography|high performance liquid chromatography (HPLC)]] and [[Capillary electrophoresis|capillary electrophoresis (CE)]]. This allows selective ionization of an analyte from a mixture of compounds, where accurate and precised results can be obtained.

==Variants==<!--NGI, ECNCI redirects here-->

===Negative chemical ionization===
Chemical ionization for gas phase analysis is either positive or negative.<ref name="pmid7025931">{{cite journal |author=Dougherty R.C. |title=Negative chemical ionization mass spectrometry: applications in environmental analytical chemistry |journal=Biomed. Mass Spectrom. |volume=8 |issue=7 |pages=283–292 |year=1981 |pmid=7025931 |doi=10.1002/bms.1200080702}}</ref> Almost all neutral analytes can form positive ions through the reactions described above.

In order to see a response by negative chemical ionization (NCI, also NICI), the analyte must be capable of producing a negative ion (stabilize a negative charge) for example by [[electron capture ionization]]. Because not all analytes can do this, using NCI provides a certain degree of selectivity that is not available with other, more universal ionization techniques (EI, PCI). NCI can be used for the analysis of compounds containing acidic groups or electronegative elements (especially halogens).<ref name="MSPA"/>{{rp|23}}Moreover, negative chemical ionization is more selective and demonstrates a higher sensitivity toward oxidizing agents and alkylating agents.<ref name=":4">{{cite journal|last1=Dougherty|first1=Ralph C.|title=Negative chemical ionization mass spectrometry|journal=Analytical Chemistry|volume=53|issue=4|pages=625–636|doi=10.1021/ac00227a003|language=en|year=2002}}</ref>

Because of the high electronegativity of [[halogen]] atoms, NCI is a common choice for their analysis.  This includes many groups of compounds, such as [[polychlorinated biphenyls|PCBs]],<ref name=":4" /> [[pesticides]], and [[fire retardant]]s.<ref name=":4" /> Most of these compounds are environmental contaminants, thus much of the NCI analysis that takes place is done under the auspices of environmental analysis. In cases where very low limits of detection are needed, environmental toxic substances such as halogenated species, oxidizing and alkylating agents<ref name="pmid7025931" /> are frequently analyzed using an [[electron capture detector]] coupled to a [[gas chromatograph]].

Negative ions are formed by resonance capture of a near-thermal energy electron, dissociative capture of a low energy electron and via ion-molecular interactions such as proton transfer, charge transfer and hydride transfer.<ref name="pmid7025931" /> Compared to the other methods involving negative ion techniques, NCI is quite advantageous, as the reactivity of anions can be monitored in the absence of a solvent. Electron affinities and energies of low-lying valencies can be determined by this technique as well.<ref name="pmid7025931" />

===Charge-exchange chemical ionization===
This is also similar to CI and the difference lies in the production of a radical cation with an odd number of electrons. The reagent gas molecules are bombarded with high energy electrons and the product reagent gas ions abstract electrons from the analyte to form radical cations. The common reagent gases used for this technique are toluene, benzene, NO, Xe, Ar and He.

Careful control over the selection of reagent gases and the consideration toward the difference between the resonance energy of the reagent gas radical cation and the ionization energy of the analyte can be used to control fragmentation.<ref name=":1" /> The reactions for charge-exchange chemical ionization are as follows.

:<chem> He{} + e^- -> He^{+\bullet}{} + 2e^- </chem>
:<chem> He^{+\bullet}{} + M -> M^{+\bullet} </chem>
[[File:Apci.png|thumb|Atmospheric pressure chemical ionization source]]

===Atmospheric-pressure chemical ionization===
Chemical ionization in an atmospheric pressure electric discharge is called [[atmospheric pressure chemical ionization]] (APCI), which usually uses water as the reagent gas. An APCI source is composed of a [[Liquid chromatography–mass spectrometry|liquid chromatography]] outlet, nebulizing the eluent, a heated vaporizer tube, a corona discharge needle and a pinhole entrance to 10<sup>−3</sup> torr vacuum.<ref name=":3" /> The analyte is a gas or liquid spray and ionization is accomplished using an atmospheric pressure corona discharge. This ionization method is often coupled with high performance liquid chromatography where the mobile phase containing eluting analyte sprayed with high flow rates of [[nitrogen]] or [[helium]] and the aerosol spray is subjected to a corona discharge to create ions. It is applicable to relatively less polar and thermally less stable compounds. The difference between APCI and CI is that APCI functions under atmospheric pressure, where the frequency of collisions is higher. This enables the improvement in sensitivity and ionization efficiency.<ref name=":1" />

== See also ==
* [[Electrospray ionization]]
* [[Proton-transfer-reaction mass spectrometry]]

== References ==
{{reflist}}

==Bibliography==
*{{cite book|last1=Harrison|first1=Alex. G.|title=Chemical ionization mass spectrometry|date=1992|publisher=CRC Press|location=Boca Raton, Fla. [u.a.]|isbn=9780849342547|edition=2.}}
*{{cite journal|last1=Hunt|first1=Donald F.|last2=McEwen|first2=Charles N.|last3=Harvey|first3=T. Michael.|title=Positive and negative chemical ionization mass spectrometry using a Townsend discharge ion source|journal=Analytical Chemistry|volume=47|issue=11|pages=1730–1734|doi=10.1021/ac60361a011|language=en|year=2002}}
*{{cite book|last1=Dass|first1=Chhabil|title=Fundamentals of contemporary mass spectrometry|date=2007|publisher=Wiley-Interscience|location=Hoboken, N.J.|isbn=9780470118498|edition=[Online-Ausg.].}}

== External links ==
*[http://littlemsandsailing.wordpress.com/2011/05/01/chemical-ionization-gas-selection-and-manifold-construction/ Using Amines as Chemical Ionization Reagents and Building Custom Manifold]

{{Mass spectrometry}}
{{States of matter}}

{{DEFAULTSORT:Chemical Ionization}}
[[Category:Ion source]]
[[Category:Mass spectrometry]]
[[Category:Scientific techniques]]