Gas-phase acidities of diols

The gas-phase acidities of several α, ω-alkanediols were measured with the equilibrium method in an ion cyclotron resonance spectrometer. The values obtained imply cyclization of the structures via an intramolecular hydrogen bond. The results are in quantitative disagreement with those obtained by the method of dissociation of the excited dimer species; care must be used in applying that method to ensure that all of the criteria for relating kinetics to equilibria are met.     

Gas-phase basicities of polyamines

The gas-phase basicities of a group of multidentate polyamines have been determined by the bracketing method and range from 966 to 1021 kJ/mol. The compounds studied vary in the number and kind of basic sites, the number and orientation of carbon atoms, and the degree of flexibility. These important structural features were analyzed to understand the observed trends in basicity and semiempirical calculations were undertaken that support the experimental trends. The polyamines may find use as reference compounds for future gas-phase basicity measurements of larger, biologically active molecules such as peptides and proteins.     

Gas-phase hydrogen/deuterium exchange and conformations of deprotonated flavonoids and gas-phase acidities of flavonoids

Gas-phase hydrogen/deuterium (H/D) exchange was used to probe the conformations, gas-phase acidities, and sites of deprotonation of isomeric flavonoid aglycons and glycosides. The flavonoids in each isomer series were differentiated on the basis of their relative rate constants and total numbers of exchanges. For example, flavonoids that possess neohesperidose-type disaccharides may undergo faster and far more extensive exchange than isomeric rutinoside flavonoids. The structural factors that promote or prevent H/D exchange were identified and correlated with collisionally activated dissociation (CAD) patterns and/or molecular modeling data (both high-level ab initio acidity calculations and conformational analysis with molecular dynamics (MD) simulations), thus providing a framework for the use of H/D exchange reactions in the structural elucidation of new flavonoids.     

Gas-phase basicities of histidine and lysine and their selected di- and tripeptides

The gas-phase basicities (GB) of histidine, lysine, and di- and triglycyl peptides containing either one histidine or one lysine residue have been determined. In all, 12 compounds were examined in a Fourier transform ion cyclotron resonance mass spectrometer. The GBs of the biomolecules were evaluated by proton transfer reactions employing a range of reference compounds with varying gas-phase basicities. In addition, the GBs were determined by using the kinetic method of collision-induced dissociation on a proton-bound dimer containing the peptide and a reference compound. The GBs of histidine and lysine were both found to be 220.8 kcal/mol via proton transfer reactions. The kinetic method experiments, including dissociation of a proton-bound dimer containing both histidine and lysine, also suggest equivalent GBs for these amino acids. However, the small peptides containing lysine are generally more basic than the corresponding histidine-containing peptides. For the peptides, the data suggest that the protonation site is on the basic side chain functional group of the histidine or lysine residues. The GBs of the di- and tripeptides are dependent upon the location of the basic residue. For example, the GBs of the tripeptides glycylglycyl-l-lysine (GlyGlyLys) and l-lysylglycylglycine (LysGlyGly) were both determined to be 230.7 kcal/mol while a GB of kcal/mol was obtained for glycyl-l-lysylglycine (GlyLysGly). A similar GB trend is seen with the histidine-containing tripeptides. Generally, the GBs obtained by using the kinetic method are slightly higher than those obtained by deprotonation reactions; however, the trends in relative GB values are essentially the same with the two techniques.     

Metal-mediated formation of gas-phase amino acid radical cations

The results from an investigation of the collision-induced dissociation (CID) of the ternary complexes [Cu(II)(terpy)(AA)](2+) are presented (terpy = 2,2':6',2' '-terpyridine; AA = one of the twenty common amino acids). These complexes show a rich gas-phase chemistry, which depends on the identity of the amino acid. For the histidine-, lysine- and tryptophan-containing complexes, oxidative dissociation of the amino acid is observed, yielding the amino acid radical cation. The results of further mass selection and CID of these amino acid radical cations are presented. The CID of the series [Fe(III)(salen)(AA)](+) (where salen = N,N'-ethylenebis(salicylideneaminato)) is also examined. These complexes undergo loss of the neutral amino acid in all cases, although the radical cation of arginine is also produced and its subsequent fragmentation examined. B3-LYP/6-31G(d) computations were carried out to test aspects of the proposed fragmentation mechanism of the histidine and arginine radical cations.     

Gas-phase oxidation of isomeric butenes and small alkanes by vanadium-oxide and -hydroxide cluster cations

Bare vanadium-oxide and -hydroxide cluster cations (V(m)O(n)H(o)+, m = 2-4, n = 1-10, o = 0, 1) were generated by electrospray ionization in order to examine their intrinsic reactivity toward isomeric butenes and small alkanes using mass spectrometric techniques. Two of the major reactions described here concern the activation of C-H bonds of the alkene/alkane substrates resulting in the transfer of two hydrogen atoms and/or attachment of the dehydrogenated hydrocarbon to the cluster cations; these processes are classified as oxidative dehydrogenation (ODH) and dehydrogenation, respectively. For the dehydrogenation of butene, it evolved as a general trend that high-valent clusters prefer ODH resulting in the addition of two hydrogen atoms to the cluster concomitant with elimination of neutral butadiene, whereas low-valent clusters tend to add the diene with parallel loss of molecular hydrogen. Deuterium labeling experiments suggest the operation of a different reaction mechanism for V2O2(+) and V4O10(+) compared to the other cluster cations investigated, and these two cluster cations also are the only ones of the vanadium-oxide ions examined here that are able to dehydrogenate small alkanes. The kinetic isotope effects observed experimentally imply an electron transfer mechanism for the ion-molecule reactions of the alkanes with V4O10(+).     

Stable gas-phase radical cations of dimeric tryptophan and tyrosine derivatives

Stable radical cations of dimeric amino acid derivatives of tryptophan and tyrosine were generated by collision-induced dissociation of [Cu(II)(diethylenetriamine)(amino acid derivative)2]*2+. The yields of the dimer radical cations were dependent on both the auxiliary ligand and the tryptophan or tyrosine derivatives used. Amino acid derivatives with an unmodified carboxylic acid group did not generate dimer radical cations. For the amino acid derivatives Ac-Trp-OMe and Ac-Trp-NH2 (Ac is N-acetyl; OMe and NH2 are the methyl ester and amide modifications of the C-terminal carboxylic group), no auxiliary ligand was required for generating the dimer radical cations. Collision-induced dissociation of the [Cu(II)(amino acid derivative)4]*2+ precursor generated the dimer radical cation [(amino acid derivative)2]*+. Stabilizing interactions, most likely involving hydrogen bonding, between the two amino acid derivatives are proposed to account for observation of the dimer radical cations. Dissociation of these ions yields protonated or radical cationic amino acid derivatives; these observations are consistent with the expectation of proton competition between monomeric units, whose proton affinities were calculated using density functional theory.     

Substituent effects on the acidity of weak acids. 2. Calculated gas-phase acidities of substituted benzoic acids

To investigate the origin of substituent effects on the acidity of benzoic acids, the structures of a series of substituted benzoic acids and benzoates have been calculated at the B3LYP/6-311+G* and MP2/6-311+G* theoretical levels. The vibrational frequencies were calculated using B3LYP/6-311+G* and allowed corrections for the change in zero-point energies on ionization, and the change in energy on going from 0 K (corresponding to the calculations) to 298 K. A more satisfactory agreement with the experimental values was obtained by energy calculations at the MP2/ 6-311++G* level using the above structures. The resulting Delta H(acid) values agree very well with the experimental gas-phase acidities. The energies of compounds with pi-electron-accepting or -releasing substituents, rotated to give the transition state geometries, provided rotational barriers that could be compared with those found for the corresponding substituted benzenes. Isodesmic reactions allowed the separate examination of the substituent effects on the energies of the acids and on the anions. Electron-withdrawing groups stabilize the benzoate anions more than they destabilize the benzoic acids. Electron-donating groups stabilize the acids and destabilize the anions by approximately equal amounts. The gas-phase acidities of meta- and para-substituted benzoic acids are linearly related. This is also found for the acidities of substituted phenylacetic acids and benzoic acids. Since direct pi-electron interactions are not possible with the phenylacetic acids, this indicates that the acidities are mainly controlled by a field effect interaction between the charge distribution in the substituted benzene ring and the negative charge of the carboxylate group. The Hammett sigma(M) and sigma(P) values are also linearly related for many small substituents from NO(2) through the halogens and to OH and NH(2). Most of the other substituents fall on a line with a different slope     

Theoretical calculations of glycine and alanine gas-phase acidities

The gas-phase acidities of glycine and alanine were determined by using a variety of high level theoretical methods to establish which of these would give the best results with accessible computational efforts. MP2, MP4, QCISD, G2 ab initio procedures, hybrid Becke3-LYP (B3LYP) and gradient corrected Becke-Perdew (BP) and Perdew-Wang and Perdew (PWP) nonlocal density functionals were used for the calculations. A maximum deviation of approximately 13 and 18 kJ/mol from experimental data was observed for the computed delta Hacid and delta Gacid values, respectively. The best result was obtained at G2 level, but comparable reliability was reached when the considerably less time consuming B3LYP, BP, and PWP density functional approaches were employed.     

Gas-phase basicities of serine and dipeptides of serine and glycine

The gas-phase basicities of serine and dipeptides containing amino acid residues of serine and glycine were determined by proton transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer. The gas-phase basicity (GB) of L-serine was found to be 205.9 kcal/mol, with addition of a hydroxymethyl group (?CH₂OH) increasing the basicity by 4.5 kcal/mol relative to the simplest amino acid glycine (GB = 201.4 kcal/mol). This is attributed to a combination of intramolecular hydrogen bonding, induction, and symmetry effects. For the dipeptides, addition of a hydroxymethyl group does not result in a large increase in basicity relative to the basicity of glycylglycine (GB = 208.0 kcal/mol). The gas-phase basicities determined for glycyl-l-serine, l-serylglycine, and l-sery-l-serine are 209.3,210.6, and 210.9 kcal/mol, respectively. In comparison to glycylglycine, addition of the hydroxymethyl group at the N terminus has a greater impact on basicity than its placement at the C terminus. These data suggest that the protonation site for these dipeptides is the N-terminal amino nitrogen.     

Gas-phase basicities for ions from bradykinin and its des-arginine analogues

Apparent gas-phase basicities (GB(app)s) for [M + H]+ of bradykinin, des-Arg1-bradykinin and des-Arg9-bradykinin have been assigned by deprotonation reactions of [M + 2H]2+ in a Fourier transform ion cyclotron resonance mass spectrometer. With a GB(app) of 225.8 +/- 4.2 kcal x mol(-1), bradykinin [M + H]+ is the most basic of the ions studied. Ions from des-Arg1-bradykinin and des-Arg9-bradykinin have GB(app) values of 222.8 +/- 4.3 kcal x mol(-1) and 214.9 +/- 2.3 kcal x mol(-1), respectively. One purpose of this work was to determine a suitable reaction efficiency 'break point' for assigning GB(app) values to peptide ions using the bracketing method. An efficiency value of 0.1 (i.e. approximately 10% of all collisions resulting in a deprotonation reaction) was used to assign GB(app)s. Support for this criterion is provided by the fact that our GB(app) values for des-Arg1-bradykinin and des-Arg9-bradykinin are identical, within experimental error, to literature values obtained using a modified kinetic method. However, the GB(app)s for bradykinin ions from the two studies differ by 10.3 kcal x mol(-1). The reason for this is not clear, but may involve conformation differences produced by experimental conditions. The results may be influenced by salt-bridge conformers and/or by conformational changes caused by the use of a proton-bound heterodimer in the kinetic method. Factors affecting the basicities of these peptide ions are also discussed, and molecular modeling is used to provide information on protonation sites and conformations. The presence of two highly basic arginine residues on bradykinin results in its high GB(app), while the basicity of des-Arg1-bradykinin ions is increased by the presence of two proline residues at the N-terminus. The proline residue in the second position folds the peptide chain in a manner that increases intramolecular hydrogen bonding to the protonated N-terminal amino group of the proline at the first position.     

Ion/molecule reactions of isomeric bromobutene radical cations with ammonia

The ion/molecule reaction of the radical cations of three isomeric bromobutenes (2-bromobut-2-ene 1, 1-bromobut-2-ene 2, 4-bromobut-1-ene 3) with ammonia were studied by Fourier transform ion cyclotron resonance spectrometry to reveal the effect of a different position of the bromo substituent relative to the C-C double bond. Further, the reaction pathways of the ion/molecule reactions were analyzed by theoretical calculations at the level B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d). All three bromobutene radical cations 1(.+) to 3(.+) react efficiently with NH(3). The reactions of 1(.+) carrying the halogen substituent at the double bond follow the pattern observed earlier for other ionized vinylic halogenoalkenes. The major reaction corresponds to proton transfer to NH(3) as to be expected from the high acidity of but-2-ene radical cations exposing six acidic H atoms at allylic positions. The other, still important, reaction of 1(.+) is substitution of the Br substituent by NH(3). Although the radical cations 2(.+) and 3(.+) are expected to be as acidic as 1(.+), proton transfer is the minor reaction pathway of these radical cations. Instead, 2(.+) displays bomo substitution as the major reaction. It is suggested that the mechanism of this reaction is analogous to S(N)2' of nucleophilic allylic substitution. Substitution of Br is not efficient for the reactions of 3(.+)-the two major reactions correspond to C-C bond cleavage of the two possible beta-distonic ammonium ions which are generated by the addition of NH(3) to the ionized double bond of 3. This observation, as well as the results obtained for 1(.+) and 2(.+), emphasize the role of the fast and very exothermic addition of a nucleophile to the ionized double bond for the ion/molecule reactions of alkene radical cations. Clearly the energetically-excited distonic ion arising from the addition fragments unimolecularly by energetically accessible pathways. In the case of a halogene subsituent (except F) at the vinylic or allylic position, this is loss of thesubsituent. In the case of remote halogeno substituents, this is C-C bond cleavage adjacent to the radical site of the distonic ion.     

Polar group enhanced gas-phase acidities of carboxylic acids: an investigation of intramolecular electrostatic interaction

We studied the effects of polar groups on the gas-phase acidities of carboxylic acids experimentally and computationally. In this connection, the gas-phase acidities (DeltaH(acid), the enthalpy of deprotonation, and DeltaG(acid), the deprotonation free energy) of borane-complexed methylaminoacetic acid ((CH(3))2N(BH(3))CH(2)CO(2)H) and methylthioacetic acid (CH(3)S(BH(3))CH(2)CO(2)H) were measured using the kinetic method in a flowing afterglow-triple quadrupole mass spectrometer. The values of DeltaH(acid) and DeltaG(acid) of (CH(3))2N(BH(3))CH(2)CO(2)H were determined to be 328.8 +/- 1.9 and 322.1 +/- 1.9 kcal/mol, and those of CH(3)S(BH(3))CH(2)CO(2)H were determined to be 325.8 +/- 1.9 and 319.2 +/- 1.9 kcal/mol, respectively. The theoretical enthalpies of deprotonation of (CH(3))2N(BH(3))CH(2)CO(2)H (329.2 kcal/mol) and CH(3)S(BH(3))CH(2)CO(2)H (325.5 kcal/mol) were calculated at the B3LYP/6-31+G(d) level of theory. The calculated enthalpies of deprotonation of N-oxide-acetic acid (CH(3)NOCH(2)CO(2)H, 329.4 kcal/mol) and S-oxide-acetic acid (CH(3)SOCH(2)CO(2)H, 328.6 kcal/mol) are comparable to the experimental results for borane-complexed methylamino- and methylthioacetic acids. The enthalpy of deprotonation of sulfone-acetic acid (CH(3)SO2CH(2)CO(2)H, 326.1 kcal/mol) is about 2 kcal/mol lower than the S-oxide-acetic acid. The calculated enthalpy of deprotonation of sulfoniumacetic acid, (CH(3))2S+CH(2)CO(2)H, is 243.0 kcal/mol. Compared to the corresponding reference molecules, CH(3)NHCH(2)CO(2)H and CH(3)SCH(2)CO(2)H, the dipolar group and the monopolar group substituted carboxylic acids are stronger acids by 11-14 and 97 kcal/mol, respectively. We correlated the changes of the acidity upon a polar group substitution to the electrostatic free energy within the carboxylate anion. The acidity enhancements in polar group substituted carboxylic acids are the results of the favorable electrostatic interactions between the polar group and the developing charge at the carboxyl group.     

Side-chain radical losses from radical cations allows distinction of leucine and isoleucine residues in the isomeric peptides Gly-XXX-Arg

Sequencing of peptides via low-energy collision-induced dissociation of protonated peptides typically yields b(n) and y(n) sequence ions. The isomeric residues leucine and isoleucine rarely can be distinguished in these experiments since they give b(n) and y(n) sequence ions of the same m/z. Siu's pioneering work on electrospray ionization of copper complexes of peptides (Chu IK, Rodriquez CF, Lau TC, Hopkinson AC, Siu KWM. J. Phys. Chem. B 2000; 104: 3393) provides a way of forming radical cations of peptides in the gas phase. This method was used to generate M(+ small middle dot) ions of the two isomeric peptides Gly-Leu-Arg and Gly-Ile-Arg in order to compare their fragmentation reactions. Both radical cations fragment to give even electron y(2) and y(1) sequence ions as well as side-chain radical losses of CH(3) and CH(3)CH(2) for isoleucine and (CH(3))(2)CH for leucine. In contrast the [M + H](+) and [M + 2H](2+) ions do not allow distinction between the isomeric leucine and isoleucine peptides.     

Intramolecular hydrogen bonding and hydrogen atom abstraction in gas-phase aliphatic amine radical cations

The intramolecular hydrogen atom abstraction by the nitrogen atom in isolated aliphatic amine radical cations is examined experimentally and with composite high-level ab initio methods of the G3 family. The magnitude of the enthalpy barriers toward H-atom transfer varies with the shape and size of the cyclic transition state and with the degree of substitution at the nitrogen and carbon atoms involved. The lower barriers are found for 1,5- and 1,6-abstraction, for chairlike transition states, for abstraction reactions in ionized primary amines, and for abstraction of H from tertiary carbon atoms. In most cases, the internal energy required for 1,4-, 1,5-, and 1,6-hydrogen atom abstraction to occur is less than that required for gas-phase fragmentation by simple cleavage of C-C bonds, which explains why H-atom transfer can be reversible and result in extensive H/D exchange prior to the fragmentation of many low-energy deuterium labeled ionized amines. The H-atom transfer to nitrogen is exothermic for primary amine radical cations and endothermic for tertiary amines. It gives rise to a variety of distonic radical cations, and these may undergo further isomerization. The heat of formation of the gauche conformers of the gamma-, delta-, and epsilon-distonic isomers is up to 25 kJ mol(-1) lower than that of the corresponding trans forms, which is taken to reflect C-H-N hydrogen bonding between the protonated amino group and the alkyl radical site.