Homo- and Heteronuclear Group 12 Metallothionein Type B Cluster Analogs: Synthesis, Structure, 1H NMR and ESI-MS.

Metallothioneins (MTs) are a ubiquitous class of small cysteine-rich metal-binding proteins involved in metal homeostasis and detoxification with highly versatile metal binding properties. Despite the long-standing association of MT with M3S3 and M4S5 metal clusters, synthetic complexes with these core architectures are exceptionally rare. Here, we demonstrate an approach to synthesizing and characterizing aggregates of group 12 metal ions with monocyclic M3S3 cores in acetonitrile solution without the protection of a protein. Multidentate monothiol ligand N,N-bis(2-pyridylmethyl)-2-aminoethanethiol (L1H) provided [Cd3(L1)3](ClO4)3 (1), the first structurally characterized nonproteinaceous aggregate with a metallothionein-like monocyclic Cd3S3 core. In addition, [Zn3(L1)3](ClO4)3·4CH3CN (2·4CH3CN) was characterized by X-ray crystallography. The complex cations of 1 and 2 had comparable structures despite being nonisomorphic. Variable temperature and concentration 1H NMR were used to investigate aggregation equilibria of 1, 2, and a precipitate with composition "Hg(L1)(ClO4)" (3). Cryogenic 1H NMR studies of 3 revealed a J(199Hg1H) coupling constant pattern consistent with an aggregate possessing a cyclic core. ESI-MS was used for gas-phase characterization of 1-3, as well as mixed-metal [M2M'(L1)3(ClO4)2]+ ions prepared in situ by pairwise acetonitrile solution combinations of the group 12 complexes of L1. Access to synthetic variants of metallothionein-like group 12 aggregates provides an additional approach to understanding their behavior.

Structures and Electron Affinities of Aluminum Hydride Clusters AlnH (n = 3-13).

Low-energy structures and electron affinities (EAs) for aluminum hydride clusters AlnH (n = 3-13) have been calculated using ab initio and density functional calculations. Geometries were optimized at the PBE0/def-2-TZVPP level of theory, which has been shown to match the currently accepted lowest-energy structures for the all-aluminum clusters Aln and their anions. Neutral hydride clusters with n = 4, 7, and 9-12 are predicted to adopt terminal structures with the hydrogen atom bound to only one aluminum atom and with only minor alterations of the aluminum atom arrangement from that of the all-aluminum cluster. Clusters with n = 3 and 13 are predicted to adopt "face-centered" geometries, and the n = 6 cluster is predicted to prefer an isomer with the hydrogen atom bridging two aluminum atoms, also with little or no distortion to the aluminum atom arrangement from the all-aluminum cluster. Addition of a hydrogen atom to clusters with n = 5 and 8 is predicted to distort the aluminum atom arrangement significantly from that of the corresponding all-aluminum cluster. In the anionic clusters, terminal clusters are preferred for all cluster sizes except for n = 6 that prefers a face-centered arrangement. Minor distortions in the aluminum scaffolding for Al11 and Al12 were found, while all other anionic clusters adopt structures with little or no deviation in the aluminum atom arrangement from the corresponding all-aluminum cluster. Raw adiabatic electron affinities were computed using CCSD(T)/aug-cc-pVTZ single-point energies for the anionic and neutral hydride clusters at their respective DFT geometries. Isodesmic electron affinities for the hydride clusters were computed relative to their all-aluminum counterparts and show an even-odd alternation with cluster size. Derived EAs alternate in magnitude between even- and odd-numbered clusters, with the even-numbered clusters having relatively larger EAs.

Toward a quantitative analysis of the temperature dependence of electron attachment to SF6.

New flowing afterglow/Langmuir probe investigations of electronic attachment to SF6 are described. Thermal attachment rate constants are found to increase from 1.5 × 10-7 cm3 s-1 at 200 K to 2.3 × 10-7 cm3 s-1 at 300 K. Attachment rate constants over the range of 200-700 K (from the present work and the literature), together with earlier measurements of attachment cross sections, are analyzed with respect to electronic and nuclear contributions. The latter suggest that only a small nuclear barrier (of the order of 20 meV) on the way from SF6 to SF6 - has to be overcome. The analysis shows that not only s-waves but also higher partial waves have to be taken into account. Likewise, finite-size effects of the neutral target contribute in a non-negligible manner.

Catalytic Oxidation of CO by N2O Enabled by Al2O2/3+: Temperature Dependent Kinetics and Statistical Modeling.

The reactions of Al2O2+ + N2O and Al2O3+ + CO, forming a catalytic cycle oxidizing CO by N2O, have been investigated from 300 to 600 K in a variable ion source, temperature adjustable, selected-ion flow tube (VISTA-SIFT). Reaction coordinates have been calculated using density functional theory and statistical modeling of those surfaces compared to experimental kinetics data for mechanistic insight. The reaction of Al2O2+ + N2O proceeds at the Su-Chesnavich collisional limit at all temperatures studied, yielding only Al2O3+, with the exception of a small (<5%) amount of association product, Al2O2(N2O)+ at 300 K. The reaction of Al2O3+ with CO produces Al2O2+ with a rate constant of 4.7 ± 1.2 × 10-10 cm3 s-1 at 300 K, decreasing with temperature as T-0.5±0.2. In addition, a significant amount of association product, Al2O3(CO)+, was observed with rate constants for formation ranging from 10-11 to 10-10 cm3 s-1 dependent upon He buffer gas concentration and temperature. Implications of these kinetic measurements with regard to the reactive surface are discussed.

Redefining the Mechanism of O2 Etching of Aln- Superatoms: An Early Barrier Controls Reactivity, Analogous to Surface Oxidation.

New insights into aluminum anion cluster reactivity with O2 were obtained through temperature-dependent kinetics measurements. Overall reactivity is controlled by a barrier at an avoided crossing where charge is transferred from the cluster to the O2, mechanistically similar to what occurs as O2 approaches a bulk Al surface. Contrary to prior interpretations, spin conservation does not inhibit the reaction of clusters with an odd number of Al atoms. In fact, the only spin constraint in these systems is on the reactivity of even clusters due to repulsive surfaces, not previously recognized. Although the superatom nature of Al13- is manifest in its high electron binding energy (EBE), the mechanism of its reactivity is not special; it reacts with O2 as if it were a small piece of bulk Al. These experiments highlight the sensitivity of Al cluster reactivity with O2 to temperature and EBE, uncovering routes to industrial scale use of aluminum superatom-based materials.

How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3.

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide-copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue.

Spectroscopic Evidence for Lactam Formation in Terminal Ornithine b2+ and b3+ Fragment Ions.

Infrared multiple photon dissociation action spectroscopy was performed on the AlaOrn b2+ and AlaAlaOrn b3+ fragment ions from ornithine-containing tetrapeptides. Infrared spectra were obtained in the fingerprint region (1000-2000 cm-1) using the infrared free electron lasers at the Centre Laser Infrarouge d'Orsay (CLIO) facility in Orsay, France, and the free electron lasers for infrared experiments (FELIX) facility in Nijmegen, the Netherlands. A novel terminal ornithine lactam AO+ b2+ structure was synthesized for experimental comparison and spectroscopy confirms that the b2+ fragment ion from AOAA forms a lactam structure. Comparison of experimental spectra with scaled harmonic frequencies at the B3LYP/6-31+G(d,p) level of theory shows that AO+ b2+ forms a terminal lactam protonated either on the lactam carbonyl oxygen or the N-terminal nitrogen atom. Several low-lying conformers of these isomers are likely populated following IRMPD dissociation. Similarly, a comparison of the experimental IRMPD spectrum with calculated spectra shows that AAO+ b3+-ions also adopt a lactam structure, again with multiple different protonation sites, during fragmentation. This study provides spectroscopic confirmation for the lactam cyclization proposed for the "ornithine effect" and represents an alternative bn+ structure to the oxazolone and diketopiperazine/macrocycle structures most often formed.

Infrared Multiple Photon Dissociation Spectroscopy of Cationized Canavanine: Side-Chain Substitution Influences Gas-Phase Zwitterion Formation†.

Infrared multiple photon dissociation spectroscopy was performed on protonated and cationized canavanine (Cav), a non-protein amino acid oxy-analog of arginine. Infrared spectra in the XH stretching region (3000 - 4000 cm-1) were obtained at the Centre Laser Infrarouge d'Orsay (CLIO) facility. Comparison of the experimental infrared spectra with scaled harmonic frequencies at the B3LYP/6-31+G(d,p) level of theory indicates that canavanine is in a canonical neutral form in CavH+, CavLi+, and CavNa+; therefore, these cations are charge-solvated structures. The infrared spectrum of CavK+ is consistent with a mixture of Cav in canonical and zwitterionic forms leading to both charge-solvated and salt-bridged cationic structures. The Cav moiety in CavCs+ is shown to be zwitterionic, forming a salt-bridged structure for the cation. Infrared spectra in the fingerprint region (1000 - 2000 cm-1) obtained at the FELIX Laboratory in Nijmegen, Netherlands support these assignments. These results show that that a single oxygen atom substitution in the side chain reduces the stability of the zwitterion compared to that of the protein amino acid arginine (Arg), which has been shown previously to adopt a zwitterionic structure in ArgNa+ and ArgK+. This difference can be explained in part due to the decreased basicity of Cav (PA = 1001 kJ/mol) as compared to arginine (PA = 1051 kJ/mol), but not entirely, as lysine, which has nearly the same proton affinity as Cav, (~993 kJ/mol) forms only canonical structures with Na+, K+, and Cs+. A major difference between the zwitterionic forms of ArgM+ and CavM+ is that the protonation site is on the side chain for Arg and on the N-terminus for Cav. This results in systematically weaker salt bridges in the Cav zwitterions. In addition, the presence of another hydrogen-bonding acceptor atom in the side chain contributes to the stability of the canonical structures for the smaller alkali cations.

Infrared Multiple-Photon Dissociation Action Spectroscopy of the b2+ Ion from PPG: Evidence of Third Residue Affecting b2+ Fragment Structure.

Infrared multiple-photon dissociation (IRMPD) action spectroscopy was performed on the b2+ fragment ion from the protonated PPG tripeptide. Comparison of the experimental infrared spectrum with computed spectra for both oxazolone and diketopiperazine structures indicates that the majority of the fragment ion population has an oxazolone structure with the remainder having a diketopiperazine structure. This result is in contrast with a recent study of the IRMPD action spectrum of the PP b2+ fragment ion from PPP, which was found to be nearly 100% diketopiperazine (Martens et al. Int. J. Mass Spectrom. 2015, 377, 179). The diketopiperazine b2+ ion is thermodynamically more stable than the oxazolone but normally requires a trans/cis peptide bond isomerization in the dissociating peptide. Martens et al. showed through IRMPD action spectroscopy that the PPP precursor ion was in a conformation in which the first peptide bond is already in the cis conformation and thus it was energetically favorable to form the thermodynamically-favored diketopiperazine b2+ ion. In the present case, solution-phase NMR spectroscopy and gas-phase IRMPD action spectroscopy show that the PPG precursor ion has its first amide bond in a trans configuration suggesting that the third residue is playing an important role in both the structure of the peptide and the associated ring-closure barriers for oxazolone and diketopiperazine formation. Graphical Abstract ᅟ.

Metal Substitution and Solvomorphism in Alkylthiolate-Bridged Zn3 and HgZn2 Metal Clusters.

The impact of substituting Hg(II) for Zn(II) in a thiolate-bridged trinuclear cluster with parallels to a metallothionein metal cluster was investigated. A new solvomorph of [Zn(ZnL)2](ClO4)2 (1) (L = N-(2-pyridylmethyl)-N-(2-(ethylthiolato)-amine) and five solvomorphs of a new compound [Hg(ZnL)2](ClO4)2 (2) were characterized by single-crystal X-ray crystallography. The interplay of hydrogen bonding and aromatic-packing interactions in producing lamellar, 2D lamellar, and columnar arrangements of complex cations in the crystalline state is discussed. Both variable temperature proton nuclear magnetic resonance and electrospray ion-mass spectrometry (ESI-MS) suggest that the complex ions of 1 and 2 are the predominant solution species at moderate concentrations. ESI-MS was also used to monitor differences in metal ion redistribution as 1 was titrated with Hg(ClO4)2 and [HgL(ClO4)]. These studies document the facile replacement of Zn(II) by Hg(II) with the preservation of the overall structure in thiolate-rich clusters.

Investigations of the mechanism of the "proline effect" in tandem mass spectrometry experiments: the "pipecolic acid effect".

The fragmentation behavior of a set of model peptides containing proline, its four-membered ring analog azetidine-2-carboxylic acid (Aze), its six-membered ring analog pipecolic acid (Pip), an acyclic secondary amine residue N-methyl-alanine (NMeA), and the D stereoisomers of Pro and Pip has been determined using collision-induced dissociation in ESI-tandem mass spectrometers. Experimental results for AAXAA, AVXLG, AAAXA, AGXGA, and AXPAA peptides are presented, where X represents Pro, Aze, Pip, or NMeA. Aze- and Pro-containing peptides fragment according to the well-established "proline effect" through selective cleavage of the amide bond N-terminal to the Aze/Pro residue to give yn (+) ions. In contrast, Pip- and NMA-fragment through a different mechanism, the "pipecolic acid effect," selectively at the amide bond C-terminal to the Pip/NMA residue to give bn (+) ions. Calculations of the relative basicities of various sites in model peptide molecules containing Aze, Pro, Pip, or NMeA indicate that whereas the "proline effect' can in part be rationalized by the increased basicity of the prolyl-amide site, the "pipecolic acid effect" cannot be justified through the basicity of the residue. Rather, the increased flexibility of the Pip and NMeA residues allow for conformations of the peptide for which transfer of the mobile proton to the amide site C-terminal to the Pip/NMeA becomes energetically favorable. This argument is supported by the differing results obtained for AAPAA versus AA(D-Pro)AA, a result that can best be explained by steric effects. Fragmentation of pentapeptides containing both Pro and Pip indicate that the "pipecolic acid effect" is stronger than the "proline effect."

Carbonate-templated self-assembly of an alkylthiolate-bridged cadmium macrocycle.

In the presence of Cd(ClO4)2 and a base, a new mixed N,S-donor alkylthiolate ligand supported both carbonate formation from atmospheric CO2 and the self-assembly of a novel bicapped puckered (CdS)6 molecular wheel. The remarkable stability of the complex was demonstrated by slow intermolecular ligand exchange on the (2)J(HH) and J((111/113)Cd(1)H) time scales at elevated temperature. Both CO2 and the base were required to convert amorphous "CdLClO4" precipitated in the absence of air to the carbonate complex. The complex shares structural features with the ζ-carbonic anhydrase class associating cadmium(II) with the biogeochemical cycling of carbon and is the first structurally characterized carbonate complex of any metal involving an alkylthiolate ligand.

The Curtin-Hammett principle in mass spectrometry.

The Curtin-Hammett principle (CHP) is an important concept in physical organic chemistry and is often utilized in the investigation of reaction mechanisms. Two reactants, A and B, in rapid equilibrium, react to form products P(A) and P(B) with rates k(A) and k(B), respectively. If the reaction is under kinetic control and the rate of equilibration between the two reactants is much faster than the reactions to form products, then the branching ratio of products P(A) and P(B) depends solely on the difference in barrier heights for the two product channels. The CHP is based on the fact that the ratio of products formed is not determined by the reactant population ratio. However, the CHP also applies to studies in other areas of chemistry, including mass spectrometry. This Account describes work from our groups in which the results must be interpreted in light of the CHP. These studies illustrate two important implications of the CHP. First, they demonstrate how product distributions cannot be used to assess reactant structure in mechanistic studies in Curtin-Hammett systems. A recent investigation of the structure of hydroxysiliconate anions demonstrated that it was not possible to distinguish between the possible reactant ion structures. A second important implication of the CHP is that the structure of the reactant does not affect the product branching ratio and therefore does not need to be a consideration if the CHP applies. We address this aspect of the discussion through kinetic method studies of the acidities of amino acids and proton affinities of bifunctional compounds. Recently reported mass spectrometric studies illustrate how the CHP puts limitations on what conclusions can be drawn from product distribution studies but also allows experimental methods, such as the kinetic method, to be carried out for complicated systems without having to know all the details of the reactant ion structures. These studies show that although the CHP is most commonly applied in mechanistic studies in physical organic chemistry, it also applies to other areas of chemistry, including mass spectrometry. Although the CHP in some cases limits the conclusions that can be drawn from an experimental study, its proper application can often be used to greatly simplify very complicated chemical systems. Therefore, it is important in mass spectrometry, and indeed, in all areas of chemistry, to recognize those systems in which the CHP should and should not apply.

IRMPD spectroscopy shows that AGG forms an oxazolone b2+ ion.

Infrared multiple photon dissociation (IRMPD) spectroscopy combined with theoretical vibrational spectra provides a powerful tool for probing structure. This technique has been used to probe the structure of protonated cyclic AG and the b(2)(+) ion from AGG. The experimental spectrum for protonated cyclo AG compares very well with the theoretical spectra for a diketopiperazine. The spectrum corresponds best to a combination of two structures protonation at the alanine and glycine amide oxygens. The experimental spectrum for the b(2)(+) ion from protonated AGG matches best to the theoretical spectrum for an oxazolone structure protonated on the ring nitrogen. In particular, the carbonyl stretching band at 1970 cm(-1) is blue-shifted by approximately 200 cm(-1) compared to the experimental spectrum for protonated cAG, indicating that these two structures are distinct. This is the first time that an IRPD spectrum of a b(2)(+) ion has been obtained and, for this ion, the oxazolone structure proposed based on prior calculations and experiments is confirmed by the spectroscopic method.

Are carboxyl groups the most acidic sites in amino acids? Gas-phase acidity, H/D exchange experiments, and computations on cysteine and its conjugate base.

Hydrogen-deuterium exchange experiments were carried out on the conjugate base of cysteine with four different deuterated alcohols. Three H/D exchanges are observed to take place in each case, and a relay mechanism which requires the SH and CO2H groups to have similar acidities and subsequently proceeds through a zwitterionic intermediate is proposed. Gas-phase acidity measurements also were carried out in a quadrupole ion trap using the extended kinetic method and in a Fourier transform mass spectrometer by an equilibrium determination. The results are in excellent accord with each other and high-level ab initio and density functional theory calculations and indicate that the side-chain thiol in cysteine is more acidic than the carboxyl group by 3.1 kcal mol-1. Deprotonated cysteine is thus predicted to be a thiolate ion. A zwitterionic species also was located on the potential energy surface, but it is energetically unfavorable (+10.1 kcal mol-1).

Proton affinity of canavanine and canaline, oxyanalogues of arginine and ornithine, from the extended kinetic method.

The absolute proton affinities of the nonprotein amino acids canavanine and canaline have been determined using the extended kinetic method in an electrospray ionization quadrupole ion trap instrument. Canavanine results from the substitution of an oxygen atom for the delta-CH2 group in the side chain of the protein amino acid arginine, whereas canaline results from a similar substitution at the delta-CH2 group in the side chain of ornithine. Absolute proton affinities of 1001+/-9 and 950+/-7 kJ/mol are obtained for canavanine and canaline, respectively. For canaline, this proton affinity is in excellent agreement with theoretical predictions obtained using the hybrid density functional theory method B3LYP/6-311++G**//B3LYP/6-31+G*. For canavanine, theory predicts a somewhat larger proton affinity of 1015 kJ/mol. Oxygen atom substitution in these nonprotein amino acids results in a decrease in their proton affinities of 40-50 kJ/mol compared to arginine and ornithine.

Absolute rate coefficients and branching percentages for the reactions of POxCly- + N (4S(3/2)) and POxCly- + O (3P) at 298 K in a selected-ion flow tube instrument.

The absolute rate coefficients and product ion branching percentages at 298 K for the reactions of several POxCly- species with atomic nitrogen (N (4S(3/2))) and atomic oxygen (O (3P)) have been determined in a selected-ion flow tube (SIFT) instrument. POxCly- ions are generated by electron impact on POCl3 in a high-pressure source. O atoms are generated by quantitative titration of N atoms with NO, where N atoms are produced by microwave discharge on N2. The experimental procedure allows for the determination of rate coefficients for the reaction of the reactant ion with N (4S(3/2)) and O (3P) as well as with N2 and NO. None of the ions react with N2 or NO, giving an upper limit to the rate coefficient of <5 x 10(-12) cm3 molecules(-1) s(-1). POCl3- and POCl2- do not react with N atoms, giving an upper limit to the rate coefficient of <1 x 10(-11) cm3 molecules(-1) s(-1). The major product ion for POCl3- and POCl2- reacting with O involves loss of Cl from the reactant ion, accounting for >85% of the products. PO2- is a minor product (

Theoretical and experimental investigation of the energetics of cis-trans proline isomerization in peptide models.

The energetics of cis-trans proline isomerization in small peptide models have been investigated using the hybrid density functional theory method B3LYP with a 6-31+G* basis set. The molecules studied are models for the phospho-Ser/Thr-Pro substrate for Pin-1, a peptidyl-prolyl isomerase (PPIase) involved in cell division. Pin-1 requires phosphorylation of a Ser or Thr residue adjacent to a Pro residue in the substrate and catalyzes cis-trans isomerization about the proline amide bond. The dihedral angle that would correspond to the reaction coordinate for isomerization of the omega peptide bond was investigated for several small models. Relaxed potential energy scans for this dihedral angle in N-methylacetamide, 1, N,N-dimethylacetamide, 2, acetylpyrrolidine, 3 and acetylproline, 4, were carried out in 20 degrees steps using the B3LYP/6-31+G* level of theory. In addition, similar scans were carried out for 1-4 protonated on the acetylamide carbonyl oxygen. Optimized structures for 1-4 protonated on the amide nitrogen were also obtained at B3LYP/6-31+G*. Relative proton affinities were determined for each site at various angles along the reaction coordinate for isomerization. The relative proton affinities were anchored to experimental gas phase proton affinities, which were taken from the literature for 1 and 2, or determined in an electrospray ionization-quadrupole ion trap instrument using the extended kinetic method for 3 and 4. Proton affinities of 925 +/- 10 and 911 +/- 12 kJ/mol were determined for 3 and 4, respectively. These studies suggest that the nitrogen atom in these amides becomes the most basic site in the molecule at a dihedral angle of ca. 130 degrees . In addition, the nitrogen atoms in 2-4 are predicted to attain basicities in the range 920-950 kJ/mol, making them basic enough to be the preferred site for hydrogen bonding in the Pin-1 active site, in support of the proposed mechanism for PPIases.

Absolute rate coefficients for the reactions of O2- + N(4S(3/2)) and O2- + O(3P) at 298 K in a selected-ion flow tube instrument.

The absolute rate coefficients at 298 K for the reactions of O(2) (-) + N((4)S(3/2)) and O(2) (-) + O((3)P) have been determined in a selected-ion flow tube instrument. O atoms are generated by the quantitative titration of N atoms with NO, where the N atoms are produced by microwave discharge on N(2). The experimental procedure allows for the determination of rate constants for the reaction of the reactant ion with N((4)S(3/2)) and O((3)P). The rate coefficient for O(2) (-) + N is found to be 2.3x10(-10)+/-40% cm(3) molecule(-1) s(-1), a factor of 2 slower than previously determined. In addition, it was found that the reaction proceeds by two different reaction channels to give (1) NO(2)+e(-) and (2) O(-)+NO. The second channel was not reported in the previous study and accounts for ca. 35% of the reaction. An overall rate coefficient of 3.9 x 10(-10) cm(3) molecule(-1) s(-1) was determined for O(2) (-) + O, which is slightly faster than previously reported. Branching ratios for this reaction were determined to be <55%O(3) + e(-) and >45%O(-) + O(2).

Proton affinity of beta-oxalylaminoalanine (BOAA): incorporation of direct entropy correction into the single-reference kinetic method.

A new version of the single-reference-extended kinetic method is presented in which direct entropy correction is incorporated. Results of calibration experiments with the monodentate base pyridine and the bidentate base ethylenediamine are presented for which the method provides proton affinities in excellent agreement with published values and reasonable predictions for the protonation entropies. The method is then used to determine the proton affinity and protonation entropy of the non-protein amino acid beta-oxalylaminoalanine (BOAA). The PA of BOAA is found to be 933.1 +/- 7.8 kJ/mol and a prediction for the protonation entropy of -39 J mol(-1) K(-1) is also obtained, indicating a significant degree of intramolecular hydrogen bonding in the protonated form. These results are supported by hybrid density functional theory calculations at the B3LYP/6-311++G**//B3LYP/6-31+G* level. They indicate that the preferred site of protonation is the alpha-nitrogen atom (PA = 935.0 kJ/mol) and that protonated BOAA has a strong hydrogen bond between the hydrogen on the alpha-amino group and one of the carbonyl oxygen atoms on the side chain.