Organic Mass Spectrometry


Mailing Address:

Dr J.K. Terlouw

Director, Regional Facility

For Mass Spectrometry
Department of Chemistry
McMaster University
Hamilton, ON L8S 4M1


Office: ABB-455
Laboratory: ABB-473, 474


Voice (905) 525-9140, ext. 27111
FAX   (905) 522-2509





The research of my group lies in the development of strategies and methods to study the chemistry of solitary ions and neutrals generated in the diluted gas phase within the mass spectrometer. Intermolecular interactions are absent under these conditions and this affords unique circumstances for experimental and theoretical studies of the chemistry of both ions and neutrals. Such research also provides a better rationale for the interpretation of mass spectra of unknown compounds than the empirical procedures on which it is still largely based.


Current research in ion chemistry focuses on ions with intriguing properties: ylide and distonic ions and in particular the more recently discovered class of hydrogen-bridged radical cations (HBRC’s) which appear to play a role in so-called proton transport catalysis reactions. Of related interest are ion-dipole complexes and destabilized carbenium ions.


The second line of the research deals with the use and development of Neutralization-Reionization Mass Spectrometry (NRMS). This technique allows the synthesis in tailored experiments of a variety of counterparts. Thus, neutral species which because of intermolecular processes cannot be prepared in solution or even in a matrix [1] can be studied. Much of our recent work in this field focuses on the hydrogen shift isomers of simple N-heterocycles [217, 206, 192, 190, 183] and other small reactive intermediates of general interest [213, 211, 205].


Integration of experimental results from various (tandem) mass spectrometry based techniques on labelled precursor molecules with the results of ab initio MO calculations characterizes this research on reaction mechanisms and ion or neutral structures. From a methodological point of view, major developments are the use of multiple collision experiments – where possible in conjunction with “survivor” collision induced dissociation (CID) spectra to probe the isometric purity of the ions – and the growth of computational chemistry into a mature key-player in mechanistic and energetic studies [214].


The instrumentation available involves a state-of-the-art custom-built Micromass (VG Analytical) ZAB-R instrument [5]. The ZAB-R is a three sector BEE type magnetic deflection instrument equipped with a specially designed second field free region which accommodates collision chambers for neutralization experiments with a wide range of target vapours and a quadrupole mass analyser perpendicular to one of the neutralization cells. A collision gas chamber in front of the second electric sector permits the CID mass spectral analysis of NR “survivor” ions and other multiple collision experiments [217].


Proton transport catalysis in ionized molecules and ion-molecule complexes


The interaction between an ion and neutral molecule in the gas phase yields an encounter complex in which reactions can take place. An interesting case occurs when the neutral promotes the tautomerization of the ionic component of the complex, a process termed proton-transport catalysis in a review article by Böhme [2]. Such a proton transport reaction has been demonstrated in several small systems, e.g. the carbon monoxide assisted isomerization of ionized H-CºN into its more stable H-NºC tautomer.


More recently, elegant experimental and theoretical studies [3] have reported mechanisms by which a gaseous conventional radical cation [H-X-Y]·+ isomerizes into its more stable distonic isomer [X-Y-H]·+ via interaction with a single solvent molecule B. One prominent example concerns X = CH2 and Y = OH, that is the a-distonic [CH2OH2]·+ ion, the methylene oxonium ion. This ion is c. 7 kcal/mol more stable than its isomer of the conventional structure, [CH3OH]·+, but the two isomers do not interconvert because the 1,2-H shift involved imposes a barrier of 26 kcal/mol. However, a molecule of water (B) catalyses this shift and promotes a smooth transformation of [CH3OH]·+ into [CH2OH2]·+. From detailed ab initio calculations it follows that O·H·O and C·H·O hydrogen-bridged radical cations play a prominent role in this transformation. In more general terms the “catalysis” has been proposed to take place when the proton affinity (PA) of the base B, lies between the PA of [X-Y] at X and Y, according to :


[H-X-Y]·+ + B ® [B···H+··· (X-Y)·] ® [B···H+··· (Y-X) ·] ® B + [X-Y-H]·+


As we have shown in a recent study [210] even the vary large 1,2-H shift barrier of the pyridine radical cation can be lowered by proton-transport catalysis yielding the a-ylide isomer (the Hammick intermediate [183]) as the more stable isomer. An even more challenging case involves the tautomerization of dimethyl phosphonate ions [214].


The solvent molecule assisted enolization of acetone and acetamide ions


Enolization of the acetone radical cation into its more stable enol isomer does not occur unassisted because the associated 1,3-H shift imposes a high energy barrier. However, benzonitrile (BN) has a PA which is close to that for protonation at O in the CH2=C(O·)CH3 radical and, as we have shown recently [215, 197], it successfully catalyzes the enolization. Under conditions of chemical ionization, a mixture of BN and acetone yields a fair quantity of [C6H5CºN···”acetone”]·+ dimer radical cations. It is the CID mass spectrum of the m/z 58 ions produced from this complex that reveals enolization has taken effect. Moreover, the m/z 58 ions sampled from the source also display CID mass spectra characteristic of the enol structure. These experiments clearly show that the initially formed adduct ion converts into a [BN/enol of acetone]·+ complex, likely the HBRC [C6H5CºN···H-O-C(CH3)=CH2]·+, thereby lowering the barrier to isomerization below the dissociation threshold and successfully catalyzing the isomerization. Confirmatory evidence for the presence of the above HBRC comes from the NR spectrum: as expected, a survivor signal is clearly absent and instead the spectrum displays narrow peaks at m/z 58 and m/z 103, indicative of the collisional ionization of the neutral components of the complex. A CID experiment on the m/z 58 ions leaves no doubt that they have the enol structure. Neutralization of the complex therefore yields the neutral enol and not the more stable keto form, thereby attesting that we are indeed dealing with the above HBRC. Experiments with acetone-D6 further showed that the isomerization does not involve a quid pro quo interaction with a hydrogen from the base. For the H2O assisted isomerization of [CH3OH]·+ such an interaction was calculated to lead to a (marginally) more favourable pathway for the isomerization. In contrast, enolization of the acetamide radical cation occurs by an entirely different mechanism, see reference 215.


Hydrogen-bridged radical cations (HBRC’s) and their role in the dissociation of molecular ions: intramolecular proton-transport catalysis


Such a catalysis not only occurs under certain conditions in bimolecular reactions, but, as has become clear from our work on the dissociative rearrangement of oxygen-containing radical cations via double H transfer, it also is a key step in dissociative ionization reactions.


Radical cations obtained by electron impact ionization of organic molecules are renowned for their propensity to rearrange prior to dissociation. This is especially true for the so-called metastable ions. In the context of such ionic rearrangements, O·H·O bonded HBRC’s [224, 207, 194, 184] have become key intermediates to rationalize the seemingly unintelligible dissociation behaviour of oxygen containing radical cations. These proposals were inspired by the growing realization, both from experiment and theory, that such ions can be thermodynamically as stable as the unrearranged reactant ion making them energetically attractive intermediates. The first indications that HBRC’s might well be very stable species were presented by us some fifteen years ago for the [CH2=CHOH/OH2] ·+ system. Other HBRC’s have been generated as stable species, including [O=C=O···H-O-H] ·+, which could be differentiated from its covalently bonded isomer carbonic acid by its different CID and NR spectra.


Ab initio calculations invariably show that such O·H·O bridged radical cations can best be described as H-bridged ion-dipole complexes of the type [M-H+···R·] or [M···HR·+] (M = molecule, R = radical) where most of the stabilization energy is provided by ion-dipole attractions. The hydrogen bridge does furnish additional stabilization (~5 kcal/mol) but its main function as a reactive intermediate is that it directs the course of isomerization by allowing a relatively facile proton transfer.


A first indication that Böhme’s concept of “proton-transfer catalysis” is ion-molecule encounter complexes [2] may also play a role in the dissociation chemistry of an ionized molecule that has rearranged to a HBRC, comes from Ruttink’s computational study in 1989 on ionized glyoxal [4]. Since then, considerable progress has been made, not least because of the impressive advances in computational chemistry, to establish the role of this concept in the dissociation chemistry of oxygen containing molecules that lose a radical via a so-called double hydrogen transfer [207].


A case in point is the dissociation of ionized 1,2-ethanediol to [CH3OH2]+ + [H-C=O] ·, for which over the past decade no less than four mechanisms have been proposed. Our present proposal, discussed in detail in ref. 195, satisfies all of the experimental observations and features intramolecular proton-transport catalysis in combination with an electron transfer taking place in intermediate ion-dipole complexes.


The graduate students working in the group are also exposed to various aspects of (bio)analytical mass spectrometry [218, 204, 203, 193]. Apart from the ZAB-R research instrument, the laboratory houses several modern analytical mass spectrometers, including a LC ESI MS/MS type instrument, a MALDI-TOF instrument and a GC-(oa)TOF instrument equipped with EI, CI and FI options. These instruments are used for internal and external service, including (collaborative) project research by manager Dr M. Kirk Green and the technicians in the context of the work of the Regional Facility for Mass Spectrometry.


References (references in the text in bold apply to the list of publications on this site)


1.            For a selected review see : N. Goldberg and H. Schwarz, Acc. Chem. Res., 27 (1994) 34.

2.            D.K. Böhme, Int. J. Mass Spectrom. Ion Processes, 115 (1992) 95.

3.            For leading references see : (a) H.-E. Audier, D. Leblanc, P. Mourgues, T.B. McMahon and S. Hammerum, J. Chem. Soc. Chem. Commun. (1994) 2329 ; (b) J.W. Gauld, H.-E. Audier, J. Fossey and L. Radom, J. Am. Chem. Soc., 118 (1996) 6299 ; (c) J.W. Gauld and L. Radom, J. Am. Chem. Soc., 119 (1997) 9831 ; (d) A.J. Chalk and L. Radom, J. Am. Chem. Soc., 119 (1997) 7573 ; (e) A.J. Chalk and L. Radom, J. Am. Chem. Soc., 121 (1999) 1574 ; (f) A. Cunje, C.F. Rodriguez, S. Petrie, D.K. Böhme and A.C.J. Hopkinson, J. Phys. Chem. A, 102 (1998) 478.

4.            P.J.A. Ruttink, in R. Naaman and Z. Vager (Ed.) The Structure of Small Radicals and Ions, Plenum Press New York, 1989, p.243.

5.            H.F. van Garderen, P.J.A. Ruttink, P.C. Burgers, G.A. McGibbon and J.K. Terlouw. Int. J. Mass Spectrom. Ion Proc. 121 (1992) 159.