Chemical ionization mass spectrometry

Chemical ionization mass spectrometry (CI-MS) is a technique used to analyze chemical compounds by ionizing them in the gas phase using chemical reactions rather than electron impact ionization, which is commonly used in electron ionization mass spectrometry (EI-MS). In CI-MS, the sample molecules are ionized by reacting them with reagent ions in the gas phase. This results in the formation of ions that can be analyzed using mass spectrometry.

Popular reagent ions and their reactions

Hydronium ion (H₃O⁺):
Using H₃O⁺ ions as the reagent ion in CI-MS is a common technique, especially in positive ion mode CI-MS. In this method, hydronium ions are introduced into the ionization chamber, where they react with the sample molecules to form protonated ions (MH⁺). This reaction typically occurs through a proton transfer process, where a proton from the hydronium ion is transferred to the sample molecule, resulting in the formation of a protonated analyte ion. The general reaction for proton transfer in CI-MS using hydronium ions can be represented as follows:
$$\rm H_{3}O^{+}+\rm M \longrightarrow \rm MH^{+}+\rm H_{2}O\,, \qquad \text{Proton transfer}$$ In this reaction, M represents the sample molecule being analyzed. The H₃O⁺ ion transfers a proton to the sample molecule, forming a protonated molecular ion (MH⁺), while a water molecule (H₂O) is generated as a byproduct. This method is particularly useful for analyzing compounds that readily accept a proton, such as organic molecules containing functional groups like alcohols, amines, and carbonyls. H₃O⁺ will transfer its proton to the analyte molecule if the molecule possess proton affinity greater than H₂O molecule (691 KJ/mol) which comprise a great fraction of VOCs. Hydronium ions are advantageous in CI-MS because they are easily generated and are highly reactive, facilitating efficient proton transfer reactions with the analyte molecules. An exothermic proton transfer occurs on every collision of the reactant molecule, M, as long as the exothermicity of the proton transfer reaction exceeds about 25 KJ/mol. However, fragmentations of nascent (MH⁺) can occur in some proton transfer reactions for example in aliphatic alcohols. Under varying energetic conditions within the PTR-MS drift tube, alternative reaction pathways may arise, including the reaction of water cluster ions, association reactions, and dissociative proton transfer. Nevertheless, the formation of cluster ions is typically minimized and circumvented in PTR-MS experiments through the application of an electric field. Overall, the use of hydronium ions in CI-MS enables the selective and sensitive detection of a wide range of analytes, making it a valuable tool in analytical chemistry for the identification and quantification of organic compounds.
Ammonium ion (NH₄⁺):
Ammonium ions are often used as reagent ions in CI-MS, particularly in positive ion mode, where they can react with analyte molecules to form protonated molecules through proton transfer reactions. Utilizing NH₄⁺ as a reagent ion in CI-MS presents several advantages, including streamlined mass spectra, reduced fragmentation, and enhanced selectivity. With the evolution of PTR-MS instrumentation, NH₄⁺ ions are generated from H₂O vapor, while N₂ gas mitigates the use of toxic and corrosive ammonia, which was prevalent in earlier instruments. Ionization via NH₄⁺ is more precise, targeting only volatile molecules with proton affinity values surpassing that of ammonia (NH₃ = 853.50 kJ/mol). Given the substantial proton affinity of ammonia, only molecules with higher proton affinities will register, while others remain undetected. The reaction predominantly proceeds as an exothermic reaction.
$$\rm NH_{4}^{+}+\rm M \longrightarrow \rm MH^{+}+\rm NH_{3}\,, \qquad \text{Proton transfer}$$ In addition to proton transfer reactions, cluster formation involving NH₄⁺.M is frequently observed, particularly with molecules possessing lower proton affinities than NH₃. Specifically, in cases where two molecules exhibit identical nominal masses with H₃O⁺, NH₄⁺ offers a method to differentiate between these compounds. NH₄⁺-CIMS is well-suited for the characterization and measurement of amines, nitrogen-containing compounds, and polycyclic aromatic hydrocarbons.
Nitrosonium ion (NO⁺):
NO⁺ is another frequently employed ion in CI-MS analysis, valued for its capacity to detect alkanes and organic nitrates. It plays a crucial role in discerning isobaric compounds, making it indispensable for identification purposes. When NO⁺ interacts with an analyte molecule, it typically generates only one or two product ions. This ion selectively transfers electrons to molecules with ionization energies lower than NO itself, which is 9.26 eV. Production of NO⁺ ions occurs by passing ambient air through a charcoal filter. In the course of reactions with analyte molecules, NO⁺ predominantly engages in three modes: charge transfer, addition or adduct formation, and hydride ion abstraction.
$$\rm NO^{+}+\rm M \longrightarrow \rm M^{+}+NO\,, \qquad \text{Charge transfer}$$ $$\rm NO^{+}+\rm M \longrightarrow \rm [M.NO]^{+}\,, \qquad \text{Association}$$ $$\rm NO^{+}+\rm M \longrightarrow \rm [M-H]^{+}+HNO\,, \qquad \text{Hydride abstraction}$$ When dealing with compounds possessing exceptionally high ionization energies, the formation of adduct ions predominates. Conversely, in compounds with lower ionization energies, favor tends towards charge exchange reactions. Association between the reactant ion and molecule occurs when both molecules involved in the reaction exhibit comparable ionization energies.
Dioxygenyl ion (O₂⁺):
The O₂⁺, a radical cation, boasting an ionization energy of 12.02 eV, stands out as the most energetically charged ion in CI-MS. Within the source region, O₂⁺⋅ ions originate from pure air. Their interactions with most VOCs typically involve charge exchange and dissociative reactions, yielding a substantial quantity of fragments. The rate of fragmentation in CI-MS is regulated by the applied field or, more precisely, the reduced electric field E/N value, which represents the ratio of the field strength E to the number density N. Charge transfer is thermodynamically preferred for molecules with ionization energies lower than that of O₂. The ionization of O₂⁺⋅ proves particularly advantageous in monitoring analytes unresponsive to NO⁺ and H₃O⁺ reagent ions, such as smaller hydrocarbons.
$$\rm O_{2}^{+}+\rm M \longrightarrow \rm M^{+}+O_{2}\,, \qquad \text{Charge transfer}$$ $$\rm O_{2}^{+}+\rm M \longrightarrow \rm [M-Fragments]^{+}\,, \qquad \text{fragmentation}$$ In molecules featuring small ionization energies, charge transfer predominantly results in one or two product ions. However, there exists a notable likelihood that an extensive surplus of energy will be imparted to the product ion, potentially triggering dissociative charge transfer and yielding multiple fragmented daughter ions. As a consequence, this process can generate intricate mass spectra. Real-time separation of isomeric compounds has become achievable by employing a diverse range of reagent ion configurations, encompassing not only H₃O⁺, NO⁺, O₂⁺, and NH₄⁺ but Kr⁺ and Xe⁺ as well. Additional cations and anions find utility in CI-MS tailored to specific applications. Reagent ions are generated through a microwave discharge in air. CI-MS instruments typically incorporate anions, including OH^–, O₂^–, NO₂^–, and NO₃^–.