P. Watts

Fragmentation and reactions of organophosphate ions produced by electrospray ionization

Abstract Electrospray ionization of some organophosphate esters has been studied in both an LCQ ™ ion trap mass spectrometer and a VG Quattro II ™ triple quadrupole mass spectrometer. The structures and fragmentations of the ions have been investigated by CID experiments with up to MS 4 being performed in the ion trap. There is a difference in the CID of the protonated methyl esters compared with that of the ethyl and isopropyl esters with the former eliminating methanol and the latter alkenes. Use of partially deuterated dimethyl methylphosphonate has allowed the observation of the migration of a methyl group from the phosphorus to the oxygen of a PO bond. A process which we describe as a ‘pseudometastable decay’ of an ion has also been observed.

In vitro studies on the reactivation by oximes of phosphylated acetylcholinesterase—I: On the reactions of P2S with various organophosphates and the properties of the resultant phosphylated oximes

The rates of formation and decomposition of a series of phosphylated oximes derived from P2S (2-hydroxy-iminomethyl-1-methylpyridinium methane-sulphonate) have been measured. The rates of inhibition of AChE by these phosphylated oximes and the parent (and related) organophosphates have also been measured. Possession of these rate data now permits a detailed analysis of the reactivation of phosphylated AChE by P2S to be made (see following paper).

Fragmentation and reactions of two isomeric O-alkyl S-(2-dialkylamino)ethyl methylphosphonothiolates studied by electrospray ionization/ion trap mass spectrometry

An initial investigation into the electrospray ionization ion trap mass spectrometry (ESI/ITMS) of simple organophosphorus compounds [1] demonstrated that detailed structural information could be obtained by sequential fragmentation of the ions using collision induced dissociation (CID). Several novel fragmentations/rearrangements were observed and it was apparent that the full potential of this approach could not be exploited until a more detailed understanding of the ion fragmentations was obtained. Such an understanding will only result from a detailed study of a wide range of compounds. The present paper describes the investigation of two isomeric organophosphates of particular relevance to chemical warfare convention (CWC) considerations.

Gas phase ionic reactions of freons and related compounds: reactions of some halogenated methanes with O− and O2−

Abstract Rate coefficients and branching ratios have been measured for the reactions of O − and O 2 − with CCl 4 , CCl 3 F, CCl 2 F 2 , CClF 3 , CF 4 , CHCl 3 , CH 2 Cl 2 , and CH 3 Cl using a selected ioin flow tube at 300 K and 0.6 Torr. Measured rate coefficients for all reactions (except for O − 2 /CClF 3 and O − 2 and O − /CF 4 which do not react) are at or close to the collisional rate. Where electron transfer is exoergic it is observed for the chlorofluoromethanes but not for the chloromethanes. It is suggested that nucleophilic attack of O − and O − 2 on both chlorine and carbon (in the case of the chlorofluoromethanes) and on chlorine, carbon and hydrogen (in the case of the chloromethanes) are required to produce the observed products. It is also suggested that, with the exception of methyl chloride, the halide ion, X − (X = Cl or F), is not formed directly, but by the decomposition of ClX − which is formed with excess vibrational energy. Following a discussion of the relevance of our results to the effects of oxygen doping upon the response of an electron capture detector (ECD) to halocarbon, it is concluded that the currently accepted mechanism to explain the observed increased sensitivity of the ECD is partially in error.

The interaction of carbamates with acetylcholinesterase

Abstract It has been shown that the kinetic schemes proposed by earlier workers to describe the reactions of carbamates with acetylcholinesterase are incomplete. A reaction scheme has been developed and tested by the use of methyl- and dimethyl-carbamoylcholines; it adequately explains the reactions observed in the carbamate-enzyme system, including the catalysis of decarbamoylation of carbamoylated acetylcholinesterase by excess carbamate. This study has been extended to include the reaction of acetylcholinesterase with more complex carbamates. pyridostigmine, physostigmine. mobam and decarbofuran.

The reactivation by oximes of phosphonylated acetylcholinesterase: The possible erroneous interpretation of reactivating potency

A comparative study of the reactivation by two oximes of acetylcholinesterase inhibited by several organophosphates has been made, with particular reference to the dependence of the degree of reactivation produced by an oxime (reactivating potency) upon the concentration of inhibited enzyme. In the case of one inhibitor it is demonstrated that the relative reactivating potency of the two oximes can be reversed by a change in experimental conditions. It is concluded that the measurement of the reactivation produced by two or more oximes, particularly when carried out under standardized conditions, is of little value in determining their relative reactivating potencies, and of negligible value in predicting their likely therapeutic effectiveness against organophosphate poisoning.

STUDIES ON GAS-PHASE POSITIVE ION-MOLECULE REACTIONS OF RELEVANCE TO ION MOBILITY SPECTROMETRY. THE REACTIONS OF 2-METHYL-2-PROPANOL (T-BUTYL ALCOHOL) WITH PROTONATED WATER CLUSTERS IN AN ION MOBILITY SYSTEM

Abstract An understanding of the chemistry of the ion—molecule reactions occurring in an ion mobility system (IMS) is a prerequisite to fully exploiting the potential of IMS for the detection and monitoring of pollutants. Whilst it is commonly thought that clustering around a proton is the dominant process occurring in the positive ion mode, previous studies have shown that much more complex processes can and do occur. In a previous paper we reported the reactions of 2-methyl-2-propanol (t-butyl alcohol) initiated by proton transfer from H3O+ in a Fourier transform mass spectrometer at low pressure. The present paper reports complementary studies in an IMS coupled to a mass spectrometer at pressures approaching atmospheric. B.V.

On the reactions of perfluoroisobutene with some anions in the gas phase: studies in an ion mobility spectrometer

Abstract An ion mobility spectrometer (IMS), operating in air in the negative ion mode, has been shown to have potential for detecting and monitoring perfluoroisobutene (PFIB), a toxic perfluorocarbon and potential industrial hazard. Complex spectra with a variety of product ions are observed. Most of these ions result from reactions of PFIB with the negative reactant ions although some important product ions (particularly at high PFIB concentrations) are attributed to reactions with reactive transient species (including electrons) in the ionization region of the IMS system. The ions have been identified using mass spectrometry and a wide variety of isotopic tracers. The results of our parallel studies using a selected ion flow tube have been included where appropriate.

In vitro studies on the reactivation by oximes of phosphylated acetylcholinesterase—II: On the formation of O, O-diethyl phosphorylated AChE and O-ethyl methylphosphonylated AChE and their reactivation by P2S

The in vitro reactivation profiles of O,O-diethyl phosphorylated AChE and O-ethyl methyl phosphonylated AChE by P2S (2-hydroxy iminomethyl-1-methyl-pyridinium methane sulphonate) have been determined. Whilst reinhibition of the reactivated AChE by phosphorylated oxime (POX) is not important in determining the reactivation profile of O,O-diethyl phosphorylated AChE, reinhibition of the reactivated AChE by phosphonylated oxime can, however, be important in determining the reactivation profile of O-ethyl methylphosphonylated AChE and the extent of this reinhibition is determined by the initial concentration of phosphonylated AChE. Kinetic analysis of the reactivation profiles demonstrated that the generally accepted scheme for this reactivation process is incorrect and that phosphylated AChE cannot be considered as a single species although an adequate description of the present data is afforded by a model using a 1:1 mixture of two species each with its own rate of reactivation. In the case of O,O-diethyl phosphorylated AChE the main kinetic difference between these two species is found not in the formation or stability of the phosphorylated AChE-P2S complex but in its subsequent reaction. From results with O-ethyl methylphosphonylated AChE prepared from two pairs of enantiomers as well as from the racemic fluoridate it was concluded that phosphonylation of AChE may not always occur via a mechanism involving inversion of configuration at phosphorus but can also occur with retention of configuration. Reactivation by P2S of O-ethyl methylphosphonylated AChE prepared from (S) organophosphates proceeds with inversion of configuration at phosphorus. Inversion also occurs in the reinhibition of AChE by the POX produced in the initial reactivation.

Fragmentations and reactions of three isotopically labelled dimethyl methylphosphonate ions produced by electrospray ionisation in an ion trap mass spectrometer

In an initial investigation into the electrospray ionisation ion trap mass spectrometry (ESI/ITMS) of simple organophosphate esters we reported that in one of the collision induced fragmentation steps of protonated dimethyl methylphosphonate (DMMP), formaldehyde was eliminated with a concomitant partial scrambling of the methyl group attached to the phosphorus and a methoxy group. The present paper describes a further investigation of this reaction. Three novel isotopomers of DMMP were used for this study and their synthesis and properties are reported. A mechanism for the formaldehyde elimination and scrambling of the methyl groups is proposed and supported by a kinetic analysis of a limiting case. During this study ‘black holes’ were found to occur in one of the ITMS instruments used and it is shown that these could lead to severe distortions in the amounts of product ions observed. A brief analysis of this observation is presented