Structural basis for reductive radical formation and electron recycling in (R)-2-hydroxyisocaproyl-CoA dehydratase

The radical enzyme (R)-2-hydroxyisocaproyl-CoA dehydratase catalyzes the dehydration of (R)-2-hydroxyisocaproyl-CoA in the fermentation of l-leucine by the human pathogenic bacterium Clostridium difficile. In contrast to other radical enzymes, such as bacterial class II ribonucleotide reductase or biotin synthase, the Fe/S cluster containing (R)-2-hydroxyisocaproyl-CoA dehydratase requires no special cofactors such as coenzyme B(12) or S-adenosylmethionine for radical generation. Instead it uses a single high-energy electron that is recycled after each turnover. The catalyzed reaction, an atypical α/β-dehydration, depends on the reductive formation of ketyl radicals on the substrate generated by injection of a single electron from the ATP-dependent activator protein. So far, it is unknown how the active electron is recycled and how unwanted side reactions are prevented, allowing for up to 10,000 turnovers. The crystal structure reveals that the heterodimeric protein contains two [4Fe-4S] clusters at a distance of 12 ?, each coordinated by three cysteines and one terminal ligand. The cluster in the α-subunit is part of the active site. In the absence of substrate, a water/hydroxide ion acts as the fourth ligand. The substrate replaces this ligand and coordinates the cluster via the carbonyl-oxygen of the thioester group. The cluster in the β-subunit has a terminal sulfhydryl/sulfido ligand and can act as a reservoir to protect the electron from unwanted side reactions via a recycling mechanism. The crystal structure of (R)-2-hydroxyisocaproyl-CoA dehydratase serves as a model for the reductively radical-generating metalloenzymes of the (R)-2-hydroxyacyl-CoA dehydratase and benzoyl-CoA reductase families.     

Organometallic dithiolene complexes of the group 8-10 metals: reactivities, structures and electrochemical behavior

Research progress in the organometallic dithiolene complexes such as [Cp(or Cp*)M(dithiolene)] (M = Co, Rh, Ir, Ni), [(C(6)R(6))Ru(dithiolene)] and [(C(4)R(4))Pt(dithiolene)] complexes during the past decade is described and the reactivities, structures and electrochemical behavior are summarized in this paper. The five-membered metalladithiolene ring (MS(2)C(2)) undergoes addition reactions to the M[double bond, length as m-dash]S bond to form 18-electron adducts by an imido, alkylidene, alkene or norbornene group and also undergoes dimerizations on the basis of the unsaturation in the ring. The aromaticity of the ring causes substitution reactions on the dithiolene carbon by a C-centered radical, S-centered radical or succinimide group when the ring has a C-H bond. Furthermore a dithiolene-dithiolene homo-coupling reaction by an acid or dithiolene-aryl cross-coupling occurs based on the aromaticity in the ring. Dissociations of the 18-electron adducts are observed by those thermolyses, photolyses, electrochemical redox reactions and other chemical reactions with tertiary phosphorus compounds. One representative example of them is the imido adduct dissociation with PR(3) under heating toward the intramolecular imido migration to a Cp ligand. Since all products are rearomatized by those adduct dissociations, it is concluded that the 'coexistence of aromaticity and unsaturation' in the metallacycle mediates the diverse chemical reactions.     

PhSeSiR(3)-Catalyzed Group Transfer Radical Reactions

A novel design for initiating radical-based chemistry in a catalytic fashion is described. The design of the concept is based on the phenylselenyl group transfer reaction from alkyl phenyl selenides by utilizing PhSeSiR(3) (1) as a catalytic reagent. The reaction is initiated by the homolytic cleavage of -C-Se- bond of an alkyl phenyl selenide by the in situ generated alkylsilyl radical (R(3)Si(*)), obtained by the mesolysis of PhSeSiR(3)](*)(-)( )()(1(*)(-)). The oxidative dimerization of counteranion PhSe(-) to PhSeSePh functions as radical terminator. The generation of 1(*)(-) is achieved by the photoinduced electron transfer (PET) promoted reductive activation of 1 through a photosystem comprising of a visible-light (410 nm)-absorbing electron rich DMA as an electron donor and ascorbic acid as a co-oxidant (Figure 1). The optimum mole ratio between the catalyst 1 and alkyl phenyl selenides for successful reaction is established to be 1:10. The generality of the concept is demonstrated by carrying out variety of radical reactions such as cyclization (10, 15-18), intermolecular addition (25), and tandem annulations (32).     

The formation of Grignard compounds—II

Detailed investigations of CIDNP phenomena during Grignard formation reactions are reported. CIDNP was found in the main product RMgX, as well as in the byproducts R(H) and R(-H) and in one case in the starting halide, i-C₃H₇I. The radical pair$\text{R R}$is shown to be involved in the formation of the polarized products. Furthermore it is proposed that the first step in the reaction sequence is a one electron transfer from magnesium to the organic halide to form the radical anion R-X

which dissociates rapidly to furnish radical R.     

Beta-elimination in the reactions of .CR1R2CR3R4X radicals with metal powders immersed in aqueous solutions

The reactions of several radicals of the type .CR1R2CR3R4X (where X = OH or NH3+) with metal powders that have been immersed in aqueous solutions were studied. The radicals were formed by radiation chemical techniques. One of the products in all these reactions is the corresponding alkene, R1R2C=CR3R4. The results are in accord with a mechanism in which the radicals react with the metals that are forming transients with metal-carbon sigma bonds. The latter transients decompose via two competing reactions: (a) heterolysis of the metal-carbon sigma bond and (b) beta-elimination of X-. Moreover, the dehalogenation of BrCH2CH2NH3+ and ClCH2(CH3)2COH by metal powders was studied. Also in these reactions, the corresponding alkene is one of the products. This result is consistent with the suggestion that, in the dehalogenation reaction, an alkyl radical is formed in the first step. This radical then reacts with the metal. Alternatively, the transients with metal-carbon sigma bonds in the dehalogenation processes might be formed via a concerted mechanism.     

Theoretical studies on the mode of inhibition of ribonucleotide reductase by 2'-substituted substrate analogues

Several 2'-substituted-2'-deoxyribonucleotides are potent time-dependent inactivators of the enzyme ribonucleotide reductase (RNR), which function by destructing its essential tyrosil radical and/or by performing covalent addition to the enzyme. The former leads to inhibition of the R2 dimer of RNR and the latter to inhibition of the R1 dimer. Efforts to elucidate the mechanism of inhibition have been undertaken in the last decades, and a general mechanistic scheme has emerged. Accordingly, two alternative pathways lead either to the inhibition of R1 or R2, for which the 2'-chloro-2'-deoxynucleotides serve as the model for the inhibition of R1 and the 2'-azido-2'-deoxynucleotides the model for the inhibition of R2. However, the underlying reason for the different behavior of the inhibitors has remained unknown until now. Moreover, a fundamental mechanistic alternative has been proposed, based on results from biomimetic reactions, in which the 2'-substituents would be eliminated as radicals, and not as anions, as previously assumed. This would lead to further reactions not predicted by the existing mechanistic scheme. To gain a better understanding we have performed high-level theoretical calculations on the active site of RNR. Results from this work support the general Stubbe's paradigm, although some changes to that mechanism are necessary. In addition, a rational explanation of the factors that determine which of the dimers (R1 or R2) will be inactivated is provided for the first time. It has been demonstrated also that the 2'-substituents are indeed eliminated as anions, and not as radicals. Biomimetic experiments have led to different results because they lack a basic group capable of deprotonating the 3'-HO group of the substrate. It has been found here that the chemical character of the leaving group (radical or anionic) can be manipulated by controlling the protonation state of the 3'-HO group.     

Uncovering the fundamental chemistry of alkyl + O2 reactions via measurements of product formation

The reactions of alkyl radicals (R) with molecular oxygen (O(2)) are critical components in chemical models of tropospheric chemistry, hydrocarbon flames, and autoignition phenomena. The fundamental kinetics of the R + O(2) reactions is governed by a rich interplay of elementary physical chemistry processes. At low temperatures and moderate pressures, the reactions form stabilized alkylperoxy radicals (RO(2)), which are key chain carriers in the atmospheric oxidation of hydrocarbons. At higher temperatures, thermal dissociation of the alkylperoxy radicals becomes more rapid and the formation of hydroperoxyl radicals (HO(2)) and the conjugate alkenes begins to dominate the reaction. Internal isomerization of the RO(2) radicals to produce hydroperoxyalkyl radicals, often denoted by QOOH, leads to the production of OH and cyclic ether products. More crucially for combustion chemistry, reactions of the ephemeral QOOH species are also thought to be the key to chain branching in autoignition chemistry. Over the past decade, the understanding of these important reactions has changed greatly. A recognition, arising from classical kinetics experiments but firmly established by recent high-level theoretical studies, that HO(2) elimination occurs directly from an alkylperoxy radical without intervening isomerization has helped resolve tenacious controversies regarding HO(2) formation in these reactions. Second, the importance of including formally direct chemical activation pathways, especially for the formation of products but also for the formation of the QOOH species, in kinetic modeling of R + O(2) chemistry has been demonstrated. In addition, it appears that the crucial rate coefficient for the isomerization of RO(2) radicals to QOOH may be significantly larger than previously thought. These reinterpretations of this class of reactions have been supported by comparison of detailed theoretical calculations to new experimental results that monitor the formation of products of hydrocarbon radical oxidation following a pulsed-photolytic initiation. In this article, these recent experiments are discussed and their contributions to improving general models of alkyl + O(2) reactions are highlighted. Finally, several prospects are discussed for extending the experimental investigations to the pivotal questions of QOOH radical chemistry.     

A theoretical approach to dehydrodimerization reactions

In this work, the sequence of two elementary processes called dehydrodimerization, namely (i) RH+M^.→R^.+HM and (ii) 2R^.→RR are considered. These reactions are particularly helpful for cleaning a medium from free radicals (radioprotection of the medium). In the first step the trapping of radical M^. generates a hydrogenated product MH and another radical R^. which disappears in the second step. Both abstraction and recombination reactions obey an Evans—Polanyi type of relation: the activation energies linearly depend on the dissociation energies of the bond (s) involved in the corresponding process. In this paper, a theoretical approach to the classification of RH compounds according to their capability to behave as good radical scavengers is proposed. It is shown that good candidates should have a small BDE (RH) and correspond to RR dimers having either very small or rather large BDE(RR).     

Analyses of in-cage singlet radical-pair motions from irradiations of 1-naphthyl (R)-1-phenylethyl ether and 1-naphthyl -2-phenylpropanoate in n-alkanes

[reaction: see text] The regio- and stereochemistries of photo-Claisen reactions of 1-naphthyl (R)-1-phenylethyl ether ((R)-2), in combination with photo-Fries and photo-Claisen-type reactions of 1-naphthyl (R)-2-phenylpropanoate ((R)-1), have been investigated in n-alkanes of different viscosities and at several temperatures. Analyses of the results provide detailed information about the in-cage motions of the singlet prochiral 1-naphthoxy/1-phenylethyl radical pairs (radical-pair B) that are formed directly from (R)-2 and indirectly from (R)-1 via decarbonylation of singlet chiral 1-naphthoxy/2-phenylpropanoyl radical pairs (radical-pair A). In hexane at 23 degrees C, the photo-Claisen products from irradiations of (R)-2 retain up to 31% enantiomeric excess (ee), but the ees of the same photoproducts from (R)-1 are near 0%. This disparity is attributed to differences between the initial orientations of the constituent radicals of radical-pair B at the moment of their "birth". The regio- and stereoselectivities reach plateau values as the solvent viscosity increases, indicating that the relationships between the rates of radical-radical bond formation and either translational or tumbling motions within a solvent cage reach an asymptotic limit. Detailed analyses are presented of the various motions that are in competition within a solvent cage during the very short lifetimes of the radical pairs. The data, in toto, present interesting insights into how radical pairs move during short periods and over short distances when their solvent cages have walls of varying flexibility.     

Pb deposition on I-coated Au(111). UHV-EC and EC-STM studies

This article concerns the growth of an atomic layer of Pb on the Au(111)( radical3 x radical3)R30 degrees -I structure. The importance of this study lies in the use of Pb underpotential deposition (UPD) as a sacrificial layer in surface-limited redox replacement (SLRR). SLRR reactions are being applied in the formation of metal nanofilms via electrochemical atomic layer deposition (ALD). Pb UPD is a surface-limited reaction, and if it is placed in a solution of ions of a more noble metal, redox replacement can occur, but limited by the amount of Pb present. Pb UPD is a candidate for use as a sacrificial layer for replacement by any more noble element. It has been used by this group for both Cu and Pt nanofilm formation using electrochemical ALD. The I atom layer was intended to facilitate electrochemical annealing during nanofilm growth. Two distinctly different Pb atomic layer structures are reported, studied using in situ scanning tunneling microscopy (STM) with an electrochemical flow cell and ultrahigh vacuum surface analysis combined directly with electrochemical reactions (UHV-EC). Starting with the initial Au(111)( radical3 x radical3)R30 degrees -I, 1/3 monolayer of I on the Au(111) surface, Pb deposition began at approximately 0.1 V. The first Pb UPD structure was observed just below -0.2 V and displayed a (2 x radical3)-rect unit cell, for a structure composed of 1/4 monolayer each of Pb and I. The I atoms fit in Pb 4-fold sites, on the Au(111) surface. The structure was present in domains rotated by 120 degrees. Deposition to -0.4 V resulted in complete loss of the I atoms and formation of a Pb monolayer on the Au(111), which produced a Moiré pattern, due to the Pb and Au lattice mismatch. These structures represent two well-defined starting points for the growth of nanofilms of other more noble elements. It is apparent from these studies that the adsorption of I- on Pb is weak, and it will rinse away. If Pb is used as a sacrificial metal in an electrochemical ALD cycle and adsorbed I atoms are employed for electrochemical annealing, I atoms will need to be applied each cycle.     

Electron-transfer fluorescence quenching of aromatic hydrocarbons by europium and ytterbium ions in acetonitrile

To make the effects of molecular size on photoinduced electron-transfer (ET) reactions clear, the ET fluorescence quenching of aromatic hydrocarbons by trivalent lanthanide ions M3+ (europium ion Eu3+ and ytterbium ion Yb3+) and the following ET reactions such as the geminate and free radical recombination were studied in acetonitrile. The rate constant k(q) of fluorescence quenching, the yields of free radical (phi(R)) and fluorescer triplet (phi(T)) in fluorescence quenching, and the rate constant k(rec) of free radical recombination were measured. Upon analysis of the free energy dependence of k(q), phi(R), phi(T), and k(rec), it was found that the switchover of the fluorescence quenching mechanism occurs at deltaG(fet) = -1.4 to -1.6 eV: When deltaG(fet) < -1.6 eV, the fluorescence quenching by M3+ is induced by a long-distance ET yielding the geminate radical ion pairs. When deltaG(fet) > -1.4 eV, it is induced by an exciplex formation. The exciplex dissociates rapidly to yield either the fluorescer triplet or the geminate radical ion pairs. The large shift of switchover deltaG(fet) from -0.5 eV for aromatic quenchers to -1.4 to -1.6 eV for lanthanide ions is almost attributed to the difference in the molecular size of the quenchers. Furthermore, it was substantiated that the free energy dependence of ET rates for the geminate and free radical recombination is satisfactorily interpreted within the limits of the Marcus theory.     

Compatible injection and detection systems for studying the kinetics of excess electron transfer

[reaction: see text] A design for fast kinetic studies of electron transfer in radical anions is reported. alpha-Hydroxy radicals formed by 355 nm laser flash photolysis of alpha-phenacyl alcohols are deprotonated under basic conditions to give ketyl radical anions that serve as electron injectors in inter- and intramolecular electron-transfer reactions. The 2,2-diphenylcyclopropyl group serves as a reporter. When an electron is injected and transferred such that spin character is adjacent to the reporter, cyclopropyl ring opening gives a readily detected diphenylalkyl radical.     

Carbon-carbon bond formation by radical addition-fragmentation reactions of O-alkylated enols

Alpha-tert-butoxystyrene [H2C=C(OBut)Ph] reacts with alpha-bromocarbonyl or alpha-bromosulfonyl compounds [R1R2C(Br)EWG; EWG =-C(O)X or -S(O2)X] to bring about replacement of the bromine atom by the phenacyl group and give R1R2C(EWG)CH2C(O)Ph. These reactions take place in refluxing benzene or cyclohexane with dilauroyl peroxide or azobis(isobutyronitrile) as initiator and proceed by a radical-chain mechanism that involves addition of the relatively electrophilic radical R1R2(EWG)C* to the styrene. This is followed by beta-scission of the derived alpha-tert-butoxybenzylic adduct radical to give But*, which then abstracts bromine from the organic halide to complete the chain. Alpha-1-adamantoxystyrene reacts similarly with R1R2C(Br)EWG, at higher temperature in refluxing octane using di-tert-amyl peroxide as initiator, and gives phenacylation products in generally higher yields than are obtained using alpha-tert-butoxystyrene. Simple iodoalkanes, which afford relatively nucleophilic alkyl radicals, can also be successfully phenacylated using alpha-1-adamantoxystyrene. O-Alkyl O-(tert-butyldimethylsilyl) ketene acetals H2C=C(OR)OTBS, in which R is a secondary or tertiary alkyl group, react in an analogous fashion with organic halides of the type R1R2C(Br)EWG to give the carboxymethylation products R1R2C(EWG)CH2CO2Me, after conversion of the first-formed silyl ester to the corresponding methyl ester. The silyl ketene acetals also undergo radical-chain reactions with electron-poor alkenes to bring about alkylation-carboxymethylation of the latter. For example, phenyl vinyl sulfone reacts with H2C=C(OBut)OTBS to afford ButCH2CH(SO2Ph)CH2CO2Me via an initial silyl ester. In a more complex chain reaction, involving rapid ring opening of the cyclopropyldimethylcarbinyl radical, the ketene acetal H2C=C(OCMe2C3H5-cyclo)OTBS reacts with two molecules of N-methyl- or N-phenyl-maleimide to bring about [3 + 2] annulation of one molecule of the maleimide, and then to link the bicyclic moiety thus formed to the second molecule of the maleimide via an alkylation-carboxymethylation reaction.     

The reversible addition‐fragmentation chain transfer process and the strength and limitations of modeling: Comment on “the magnitude of the fragmentation rate coefficient”

There is appreciable uncertainty concerning the magnitude of the fragmentation rate coefficient of the intermediate radical in reversible addition‐fragmentation chain transfer (RAFT) polymerizations. A large proportion of the experimental and theoretical evidence suggests that it is a stable species with a lifetime longer than 0.0001 s. This is particularly the case when the intermediate macro‐RAFT radical is stabilized by a phenyl group attached to the radical center or has a poor leaving group. Although the occurrence to some extent of irreversible termination reactions cannot be excluded, we argue that such reactions are more likely to be a result of slow fragmentation of the intermediate macro‐RAFT radical. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2828–2832, 2003     

Photodecomposition of organic peroxides containing coumarin chromophore: spectroscopic studies

The photodecomposition of coumarin-3-t-Bu peroxyester (1) and coumarin-3-carbonyl-m-chlorobenzoylperoxide (2) has been studied using nanosecond and femtosecond spectroscopy to elucidate the nature of transient species involved. Excitation of the coumarin chromophore leads to its singlet excited-state decaying with the rate 9 x 10(9) s(-1) that results from a composite of emission, intersystem crossing, thermal relaxation, and -O-O- bond homolysis. Dissociation of the weak oxygen-oxygen bond proceeds from both triplet and singlet excited states. The nature of this combination of states is predissociative rather than dissociative as demonstrated by the relatively slow rates of oxygen-oxygen bond rupture. The decomposition of 1 and 2 leads to the formation of coumarin-3-carbonyloxyl radical (R1). The later was observed spectroscopically on the nanosecond time scale using both time-resolved FTIR and UV-vis transient techniques. R1 is consumed in two competitive processes: unimolecular decarboxylation and bi-molecular hydrogen atom transfer. The rates of these reactions are 4.3 x 10(5) s(-1) and 1 x 10(6) M(-1) s(-1) respectively. The transition state geometries and energies of decarboxylation of R1 have been determined using DFT calculations and are compared with values for the benzoyloxyl radical. The decarboxylation of R1 proceeds via a transition state in which the carboxyl group is almost perpendicular (dihedral angle 114 degrees) to the plane of the coumarin chromophore. The transition state of the benzoyloxyl radical, in contrast, is flat (0 degrees). The varied transition state energies of the radicals (13.6 kcal/mol for coumarin carboxyl radical vs 8 kcal/mol for benzoyloxyl radical) correlate with different decarboxylation rates of these two species.     

Persilylated phosphoranyl radicals: the first persistent noncyclic phosphoranyl radicals

Persistent noncyclic phosphoranyl radicals have been prepared and observed by electron paramagnetic resonance (EPR) for the first time. They were obtained by UV-photolysis of a solution containing a bis(trialkylsilyl) peroxide (R = Me, Et) and a tris(trialkylsilyl) phosphite (R = Me, Et, iPr). EPR parameters (a(P) approximately 100 mT) are typical of phosphoranyl radicals exhibiting a trigonal-bipyramidal structure, with the odd electron in an equatorial site. Analysis of the pseudo-first-order decay shows that these phosphoranyl radicals decay by S(H)2 homolytic substitution on the bis(trialkylsilyl) peroxide and by loss of a trialkylsilyloxyl radical (alpha-scission reaction). Both the S(H)2 and alpha-scission reactions depend on the steric bulk of the alkyl groups, that is, the bulkier the alkyl group, the slower the S(H)2 and alpha-scission reactions.     

Vicinal alkylation-carboxymethylation of electron-poor alkenes by radical-chain reactions with O-alkyl O-silyl ketene acetals and their [3+2] annulation by reaction with O-cyclopropylcarbinyl O-silyl ketene acetals

O-Silyl ketene acetals of the type H₂CC(OR)OSiMe₂Bu^t, in which R is a tertiary or secondary alkyl group, react with electron-poor alkenes to bring about vicinal alkylation-carboxymethylation of the latter. When R is a cyclopropyldimethylcarbinyl group such reactions take a more complex course involving ring opening of the cyclopropylcarbinyl radical and lead ultimately to [3+2] annulation of the alkene.     

Formation of β-distonic oxonium ions: Study of ROCH2CH2OR′ radical cations

Radical cations derived from the ethers ROCH₂CH₂OR′ (R, R′ = H, CH₃, C₂₅) were studied, since β-distonic oxonium ions are often prepared from ionized ethers of glycol. The first step in the fragmentation is a 1,5-transfer of an α-hydrogen to oxygen of a terminal alkoxy group leading to a δ-distonic oxonium ion. This step is thermo-neutral and reversible in the ROCH₂CH₂OH radical cations and exothermic and irreversible in the dialkyl ether radical cations. Depending on R and R,′ these δ-distonic oxonium ions fragment by three reactions: the loss of an alcohol or a water molecule, the formation of a β-distonic oxonium ion ˙CH₂CH₂O(H)⁺R and a 1,4-H migration between carbon atoms. Competition between these processes is discussed.     

Oxidation of tertiary benzamides by 5,10,15,20-tetraphenylporphyrinatoironIII chloride-tert-butylhydroperoxide

Tertiary benzamides are oxidized by the 5,10,15,20-tetraphenylporphyrinatoiron(III) chloride-Bu'(t)OOH system at the alpha-position of the N-alkyl groups. The major products are N-acylamides, although small amounts of secondary amides, the products of dealkylation, are also formed. Plots of initial rate versus initial substrate concentration for these reactions are curved, suggesting formation of an oxidant-substrate complex. The reaction rates are almost insensitive to the substituent in the benzamide moiety, but there is a kinetic deuterium isotope effect of 5.6 for the reaction of the N,N-(CH(3))(2) and N,N-(CD(3))(2) compounds. Comparison of the reaction products from N-alkyl-N-methylbenzamides reveals that, for all compounds studied except N-cyclopropyl-N-methylbenzamide, oxidation of the alkyl group is preferred, strongly so (by a factor of ca. 8) for N-allyl-N-methylbenzamide. In contrast to microsomal oxidation, there is no steric hindrance to oxidation of an isopropyl group. Thus, we propose that these reactions proceed via hydrogen atom abstraction to form an alpha-carbon-centred radical and we attribute the observed diminished reactivity of the N-cyclopropyl group to its known reluctance to form a cyclopropyl radical. Oxidation of N-methyl-N-(2,2,3,3-tetramethylcyclopropyl)methylbenzamide provides preliminary evidence for rearrangement of an intermediate radical. While it remains unclear how these reactions proceed directly to the N-acyl products, we have established that N-hydroxymethyl, N-alkoxymethyl and N-alkylperoxymethyl intermediates are not involved.     

Fragmentation reactions of alkylphenylammonium ions

The fragmentation reactions of a variety of alkylphenylammonium ions, C(6)H(5)NH(3 -n)R(n)(+) (n >/= 1, R = CH(3), C(2)H(5), i-C(3)H(7), n-C(4)H(9)) were studied by energy-resolved mass spectrometry. Ionization was by fast atom bombardment (FAB) or electrospray ionization. Energy-resolved fragmentation data were obtained by low-energy collision-induced dissociation (CID) in the quadrupole cell of a hybrid sector/quadrupole instrument following FAB ionization and by cone-voltage CID in the interface region of the electrospray/quadrupole instrument. A comparison of the two methods of obtaining energy-resolved data showed that very similar results are obtained by the two methods. The fragmentation reactions of the alkylphenylammonium ions are rationalized in terms of competitive formation of an [R(+)-NC(6)H(5)H(3-n)R(n-1)] complex or a [C(6)H(5)H(3-n)R(n-1)N(+.)-(.)R] complex. The former complex fragments by internal proton transfer to yield C(6)H(5)H(3 -n)R(n -1)NH(+) and [R -H] whereas the latter complex fragments to form C(6)H(5)H(3 -n)R(n -1)N(+) and an alkyl radical. Alkane elimination, which is very prominent for tetraalkylammonium ions, most likely involves sequential elimination of an alkyl radical and either an H atom or an alkyl radical for the phenyl-substituted ammonium ions. Copyright 1999 John Wiley & Sons, Ltd.