The molecular properties of a neutral molecule are important in proton transfer reaction mass spectrometry (PTR-MS) because they affect the probability of the molecule undergoing proton transfer. Gas-phase molecular properties, such as proton affinity (PA) and ionization energy (IE) of the neutral analyte molecule are of utmost importance in the selection of appropriate reactant gas (ions) to be utilized in chemical ionization mass spectrometry (CI-MS). The PA of a molecule is a measure of its acidity and is one of the most important molecular properties that affect proton transfer. The PA of a molecule is the energy required to abstract a proton from the molecule in the gas phase. If the PA of a molecule is greater than the PA of the reagent ion (usually H₃O⁺, then the molecule will undergo proton transfer. The PA of a neutral molecule determines whether a reaction proceeds by proton transfer, typically with H₃O⁺ or NH₄⁺, fragmentation or adduct formation, as occurs in CI-MS. The H₃O⁺ ion is key to proton transfer reactions in the PTR-MS because of its high abundance in combination with the low PA. An effective exothermic proton transfer occurs in such analyte molecules that possess higher PA than H₂O i.e. 696.64 kj/mol. If a reactant gas with lower PA than H₂O is selected, the proton transfer is followed by fragmentation, whose extent depends on the size of the PA difference between an analyte and the H₂O molecule. On the other hand, reactant gases with very high PA than H₂O often lead to adduct formation. Moreover, NH₄⁺$-CI-MS ionization is useful for effective proton transfer reactions wherein the PA of a molecule is higher than H₂O, typically by 96.2 kj/mol. Apart from the standard reagent ions such as H₃O⁺ and NH₄⁺, water cluster ions (H₃O⁺(H₂O)$_{rm n}$) are also exploited as a protonating agent in ligand-switching reactions with unsaturated and saturated aldehydes.

Similarly, IE plays a crucial role in the selection of appropriate reagent ions to be used in the electron transfer reactions or adduct formation from NO⁺ and O₂⁺ reagent ions to the analyte molecule. The IE of a molecule is the energy required to remove an electron from the molecule in the gas phase. It is a measure of the electronegativity of the molecule. In electron transfer reaction mass spectrometry, an electron is transferred from a donor molecule (usually a radical anion) to an acceptor molecule. The reaction is exothermic (releases heat) and is only possible if the IE of the acceptor molecule is less than the IE of NO (9.2 eV) and O₂ (12.2 eV) molecules, respectively, then electron transfer is favored in CI-MS from their respective ions. Similarly, if the IE of the analyte is comparable to NO, then adduct ions are formed.. Therefore, electron transfer from NO⁺ and O₂⁺ ions can be used to selectively detect molecules with a low IE. The higher the ionization energy of a molecule, the less likely it is to be ionized by electron transfer. The ionization energy of a molecule can be affected by its structure, its polarity, and its substituents. This molecular data can be obtained for many important VOCs using the ab-initio and DFT methods with a reasonably good accuracy and with less computational power.

Choice of suitable reagent ions

NO⁺ and O₂⁺ ions are both commonly used in mass spectrometry as reagent ions. NO⁺ is a relatively soft ion, meaning that it does not fragment the molecules it ionizes as easily as other reagent ions, such as H3O+. This makes NO⁺ a good choice for analyzing molecules that are sensitive to fragmentation. O₂⁺ is a more harsh ion, and it is often used to fragment molecules for structural analysis. NO⁺ and O₂⁺ ions can be formed in a variety of ways in mass spectrometry. One common method is to use a corona discharge to generate a stream of electrons. These electrons can then react with NO or O2 molecules in the gas phase to form NO⁺ and O₂⁺ ions. Another method is to use a heated filament to generate a stream of ions. These ions can then react with NO or O2 molecules in the gas phase to form NO⁺ and O2+ ions.NO⁺ and O₂⁺ ions can be used to analyze a wide variety of molecules in mass spectrometry. Some of the most common applications include:

1. Analysis of volatile organic compounds (VOCs)
2. Analysis of explosives
3. Analysis of drugs
4. Analysis of food and beverage products
5. Analysis of environmental samples

NO⁺ and O₂⁺ ions are powerful tools for mass spectrometry, and they are used in a variety of applications. Other than H3O+, O₂⁺, NO⁺, NH₄⁺ ions verious other ions, such as Kr⁺, Xe⁺, and anions are also used for ionization.

Other molecular properties that can affect proton transfer include the dipole moment of the molecule, the polarizability of the molecule, and the structure of the molecule. The dipole moment of a molecule is a measure of the polarity of the molecule. The polarizability of a molecule is a measure of how easily the molecule can be distorted by an electric field. The structure of a molecule can affect the probability of proton transfer by affecting the accessibility of the molecule’s proton donor or acceptor sites.

By understanding the molecular properties of a molecule, it is possible to predict the probability of the molecule undergoing proton transfer. This information can be used to optimize the conditions for PTR-MS experiments and to improve the selectivity and sensitivity of the technique.

PTR-MS is a versatile technique that can be used to detect a wide variety of molecules, including volatile organic compounds (VOCs), alcohols, aldehydes, ketones, esters, acids, and amines. It is a particularly useful tool for environmental monitoring, as it can be used to detect trace levels of pollutants in the air. PTR-MS is also used in food science, medicine, and biology.

Here are some of the advantages of using PTR-MS:

1. It is a sensitive technique that can detect trace levels of molecules.
2. It is a selective technique that can be used to target specific molecules.
3. It is a versatile technique that can be used to detect a wide variety of molecules.
4. It is a fast technique that can provide real-time measurements.
5. It is a non-destructive technique that does not damage the molecules being analyzed.