Investigation of substituted-benzene dopants for charge exchange ionization of nonpolar compounds by atmospheric pressure photoionization

Abstract

Atmospheric pressure photoionization (APPI) using a dopant enables both polar and nonpolar compounds to be analyzed by LC/MS. To date, the charge exchange ionization pathway utilized for nonpolar compounds has only been efficient under restrictive conditions, mainly because the usual charge exchange reagent ions-the dopant photoions themselves-tend to be consumed in proton transfer reactions with solvent and/ or dopant neutrals. This research aims to elucidate the factors affecting the reactivities of substituted-benzene dopant ions; another, overriding, objective is to discover new dopants for better implementing charge exchange ionization in reversed-phase LC/MS applications. The desirable properties for a charge exchange dopant include low reactivity of its photoions with solvent and dopant neutrals and high ionization energy (IE). Reactivity tests were performed for diverse substituted-benzene compounds, with substituents ranging from strongly electron withdrawing (EW) to strongly electron donating (ED). The results indicate that both the tendency of a dopant's photoions to be lost through proton transfer reactions and its IE depend on the electron donating/withdrawing properties of its substituent(s): ED groups decrease reactivity and IE, while EW groups increase reactivity and IE. Exceptions to the reactivity trend for dopants with ED groups occur when the substituent is itself acidic. All told, the desirable properties for a charge exchange dopant tend towards mutual exclusivity. Of the singlysubstituted benzenes tested, chloro-and bromobenzene provide the best compromise between low reactivity and high IE. Several fluoroanisoles, with counteracting EW and ED groups, may also provide improved performance relative to the established dopants. . Despite its name, analyte ionization in APPI is mostly due to ion-molecule reactions, following the photoionization of a primary reagent. The primary reagent is usually added purposefully, and is then termed a dopant, though this may not be required if a bulk component of the sample stream itself is photoionizable. Once the primary reagent ions are generated, the ensuing ion-molecule reactions may lead to analyte ionization through either proton transfer or charge exchange (electron transfer), depending upon the properties of the analyte and the chemical environment of the source. In general, polar compounds may be readily Address reprint requests to Michael W. Blades, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B.C., Canada, V6T 1Zl, Canada. E-mail: blades@chem.ubc.ca ionizable via either ionization pathway, whereas nonpolar compounds are less amenable to proton transfer and may require charge exchange. To date, the charge exchange ionization pathway has only been efficient under restrictive conditions, mainly because of the tendency of the usual dopant ions to react by proton transfer with reversed-phase solvents and/or dopant neutrals. No study of the factors affecting the reactivity of dopant ions with solvent or dopant neu...

Charge Exchange Reaction in Dopant-Assisted Atmospheric Pressure Chemical Ionization and Atmospheric Pressure Photoionization

“…In DA-APPI, the chlorobenzene radical cation appeared as the most abundant solvent ion at 0.05 and 0.1 mL/ min flow rate, but an ion at m/z 108 was the most prominent at higher flow rates. Robb et al have also reported the m/z 108 reagent ion for chlorobenzene in DA-APPI-MS under slightly different experimental conditions [12]. Here, in DA-APPI, the MS/MS measurement showed that the fragmentation of the m/z 108 ion is identical to that of M +.…”

“…Robb et al [12] previously suggested that in DA-APPI the m/z 108 ion (anisole) is formed in a substitution reaction between neutral methanol and chlorobenzene radical cation following a general reaction scheme for several halobenzenes:…”

“…In APPI, a lot of effort has been invested into tailoring the gas-phase chemistry to favor charge exchange reaction (Scheme 2, Reaction 6) in reversed-phase liquid chromatography (RPLC) conditions [11,12] because this reaction route makes possible the ionization of nonpolar compounds that are difficult to ionize by proton transfer reactions. One of the most successful charge exchange dopants has been chlorobenzene [12,13], which has IE of 9.1 eV [14].…”

“…One of the most successful charge exchange dopants has been chlorobenzene [12,13], which has IE of 9.1 eV [14]. The chlorobenzene radical cation does not go through proton transfer reaction with solvent clusters (Scheme 2, Reaction 3) in RPLC-APPI-MS conditions [12], and is therefore not depleted in the ion source in the presence of LC solvents but is, instead, available for charge exchange with the analytes.…”

“…One of the most successful charge exchange dopants has been chlorobenzene [12,13], which has IE of 9.1 eV [14]. The chlorobenzene radical cation does not go through proton transfer reaction with solvent clusters (Scheme 2, Reaction 3) in RPLC-APPI-MS conditions [12], and is therefore not depleted in the ion source in the presence of LC solvents but is, instead, available for charge exchange with the analytes. In the case of APCI, only a few literature reports have shown that dopants (i.e., benzene and chlorobenzene) can also be used in APCI to enhance the ionization of analytes through charge exchange [15,16].…”