B American Society for Mass Spectrometry, 2017 J. Am. Soc. Mass Spectrom. (2017) DOI: 10.1007/s13361-017-1736-6 RESEARCH ARTICLE Intramolecular Halogen Atom Coordinated H Transfer via Ion-Neutral Complex in the Gas Phase Dissociation of Protonated Dichlorvos Derivatives Xiaoping Zhang, Shuai Cheng Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang, 330013, People’s Republic of China Abstract. Intramolecular halogen atom coordinated H transfer reaction in the gas phase dissociation of protonated dichlorvos derivatives has been explored by electrospray ionization tandem mass spectrometry. Upon collisional activation, pro- tonated dichlorvos underwent dissociation reaction via cleavage of the P–O bond to give reactive ion-neutral complex (INC) intermediate, [dimethoxylphosphinoylium + dichloroacetaldehyde]. Besides direct dissociation of the complex, intramolecular chlorine atom coordinated H transfer reaction within the complex takes place, leading to the formation of protonated dimethyl chlorophosphate. To investigate the fragmen- tation mechanism, deuterium-labeled experiments and several other halogen- substituted (Br and F) analogs of dichlorvos were prepared and evaluated, which display a similar intramolecular halogen transfer. Density functional theory (DFT)-based calculations were performed and the computational results also support the mechanism. Keywords: Intramolecular halogen coordinated H transfer, Dichlorvos, Ion-neutral complex, Electrospray ionization-mass spectrometry Received: 4 February 2017/Revised: 25 May 2017/Accepted: 8 June 2017 Introduction modeled theoretically [29–37]. In the solution phase, intermo- lecular halogen transfer reactions have been frequently found lectrospray ionization-mass spectrometry (ESI-MS) com- in organic synthesis where the halogen atom transfers in the Ebined with collision-induced dissociation (CID) has been form of a radical [32, 34, 37]. Several types of gas-phase F- proven to be invaluable for the investigation of gas-phase atom transfer reactions of fluorinated compounds have been reactions [1–5] and to understand the detailed mechanisms of investigated by electron ionization mass spectrometry (EI-MS), reactions in the condensed phase [6, 7]. Such fundamental which involves an F-atom Bring-walk^ migration mechanism n studies are also important to underpin MS -based structure [35, 36]. Liu et al. have reported the F-atom migration from elucidation, which is challenged by rearrangement reactions trifluoromethoxy group to indole or phenol ring in atmospheric [4, 8–28], such as proton transfer [20], electron transfer [28], pressure ionization mass spectrometry [31]. Dissociation of hydride transfer [22], benzyl cation transfer [17], electrophilic protonated halogen-substituted amines has been reported to aromatic substitution [23], and nucleophilic aromatic substitu- occur intramolecular halogen transfer reaction in ESI-MS, tion [4]. which is achieved via an [amine/halonium ion] intermediate Intermolecular and intramolecular halogen transfer is of generated by cleavage of C–N bond of the precursor ion [29]. particular interest in both solution chemistry and gas-phase Picazas-Márquez et al. reported the gas-phase iodine transfer chemistry, and thus has been investigated experimentally and reaction in fragmentation of mono- and bis- haloethylphosphonates by gas chromatography mass spec- trometry (GC-MS) [33]. Transfer of a chlorine atom has also Electronic supplementary material The online version of this article (doi:10. been mentioned in gas-phase ion–molecule reaction of 1007/s13361-017-1736-6) contains supplementary material, which is available di di to authorized users. 2,2- chlorovinyl methyl phosphate (dichlorvos) by ion trap mass spectrometry (IT-MS) [30], but no detailed mechanism Correspondence to: Xiaoping Zhang; e-mail: [email protected] has been documented to our knowledge. X. Zhang and S. Cheng: Intramolecular Halogen Atom Coordinated H Transfer Dichlorvos, a typical organophosphorus pesticide (OP), is performed by using an excitation AC voltage to the end caps of widely used for agricultural activities because of its high insec- the ion trap to include collisions of the isolated ions (isolation ticidal activity, low price, and relatively low environmental width at 1 Da) for a period of 30 ms and variable excitation persistence [38–44]. However, the widespread use of dichlor- amplitudes. The CID-MS spectra of the protonated molecules vos in farming leads to its residues on vegetable, fruit skins, and were obtained by activation of the precursor ions at the nor- even in groundwater, which cause great harm to human health malized collision energy of 20%. and the environment [38–44]. MS technique has been used for the identification and structural characterization of dichlorvos Theoretical Calculations [38, 40, 43]. Nevertheless, previous studies mainly focused on the determination and quantification of dichlorvos by liquid Theoretical calculations were performed using the Gaussian 09 chromatography in conjunction with mass spectrometry (LC- program [47]. The geometries of the target species were opti- MS) [43] and EI-MS [30, 45]. In this study, we present results mized using the density functional theory (DFT) method at the from a detailed investigation on gas-phase fragmentation reac- B3LYP/6-311+G(2d,p) level. The optimized structures were tions of dichlorvos derivatives (Scheme 1), in which an intrigu- identified as a true minimum in energy by the absence of ing rearrangement phenomenon involving halogen atom trans- imaginary frequencies. Vibrational frequencies of all the key fer was observed. Isotopic labeling experiments in conjunction species were calculated at the same level of theory. The Carte- with auxiliary theoretical calculations are carried out to support sian coordinates of all structures involved are available as the proposed fragmentation mechanisms. supplementary data. The energies discussed here are the sum of electronic and thermal free energy. Experimental Result and Discussion Material and Methods The gas-phase halogen atom transfer reaction was explored by Methanol HPLC grade and methanol-d4 were purchased from investigating the MS fragmentation behavior of dichlorvos Sigma-Aldrich (St. Louis, MO, USA) and Cambridge Isotope derivatives. Dichlorvos (compound 1) was selected as a model Laboratories, Inc. (Andover, MA, USA), respectively. Dichlor- to perform a detailed investigation. The CID mass spectrum of vos (compound 1) and its derivatives (compounds 2 and 3) protonated dichlorvos [1 +H]+ at m/z 221 is depicted in were synthesized following reported procedures by reaction of Figure 1a, in which three predominant peaks at m/z 109, m/z trimethyl phosphite with the corresponding tri-halogenated 127, and m/z 145 are observed. Formation of these ions has (chloro-, bromo-, fluoro-) acetaldehydes, using the classic method (Scheme 1)[46]. The crude samples were analyzed directly by mass spectrometry after synthesis. Mass Spectrometry The samples were analyzed on an LTQ-XL advantage IT-MS equipped with an ESI interface in the positive ion mode (ThermoFisher, San Jose, CA, USA). Every diluted solution (1 μgmL–1 in methanol) was infused into the source chamber at a flow rate of 3 μLmin–1. The optimized ESI source conditions were as follows: ion-spray voltage, 3 kV; nebulizing gas (N2), 25 arbitrary units (a.u.); capillary temperature, 150 °C, capillary voltage in 80 V; tube lens in 100 V. Other LTQ- XL parameters were automatically optimized by the system. The ion trap pressure of approximately 1 × 10–5 Torr was maintained with a Turbo pump, and pure helium (99.99%) was used as the collision gas. The CID-MS experiments were 1O RFormulaMe1 3 2 7 R O P O 1 Cl C4H7Cl2O4P220 45 6O 2 Br C4H7Br2O4P308 R 3 FC4H7F2O4P188 Figure 1. Collision-induced dissociation mass spectra of the [M + H]+ ions of (a) 2,2-di35chlorovinyl dimethyl phosphate (m/z 1 Me : exactmassofmolecule 221), (b) 2-35chloro-2-37chlorovinyl dimethyl phosphate (m/z Scheme 1. Structures of dichlorvos derivatives 223), and (c) 2,2-di37chlorovinyl dimethyl phosphate (m/z 225) X. Zhang and S. Cheng: Intramolecular Halogen Atom Coordinated H Transfer been further consolidated by investigating the energy-resolved favored site of protonation for this compound is on the oxygen plots (see Supplementary Figure S1). The product ion at m/z atom with high proton affinity [30] (will be discussed later). In 109 (P1, 39.8%) is ascribed to dimethoxylphosphinoylium, route 1, the activated proton in MH1 is transferred from the O1 originating from the loss of C2H2Cl2O from the precursor ion to the C5 atom leading to an intermediate MH2, which triggers (m/z 221). The ion at m/z 127 (P2, 98.1%) was assigned as the the subsequent dissociation to form an ion-neutral complex hydrated product of P1, which can be attributed to an ion– INC-1 (dichloroacetaldehyde + dimethoxylphosphinoylium). molecule reaction between the dimethoxylphosphinoylium at AdirectseparationofINC-1 results in the formation of P1 at m/z 109 and residual water present in the vacuum system of ion m/z 109, wereas an INC-mediated chloride and hydrogen trap [48]. Mass selection of the ion at m/z 109 directly results in transfer in INC-1 lead to generation of INC-2 (dimethyl the abundant ion at m/z 127 in the MS3 experiment (see chlorophosphate + chloro-ethenone), which undergoes the sub- Supplementary Figure S2). sequent dissociation to afford P3 at m/z 145 and P4 at m/z 77. Here