An Investigation of Protonation Sites and Conformations of Protonated Amino Acids by IRMPD Spectroscopy

The protonation sites and structures of a series of protonated amino acids (Gly, Ala, Pro, Phe, Lys and Ser) are investigated by means of infrared multiple‐photon dissociation (IRMPD) spectroscopy and electronic‐structure calculations. The IRMPD spectra of the protonated species are recorded using the combination of a free‐electron laser (FEL) and an electrospray‐ion‐trap mass spectrometer. The structures of different possible isomers of these protonated species are optimized at the B3LYP/6‐311+G(d, p) level of theory and the IR spectra calculated using the same computational method. For every amino acid studied herein, the current results indicate that a proton is bound to the α‐amino nitrogen, except for lysine, in which the protonation site is the amino nitrogen in the side chain. According to the calculated and experimental IRMPD results, the structures of the protonated amino acids may be assigned unambiguously. For Gly, Ala, and Pro, in each of the most stable isomers the protonated amino group forms an intramolecular hydrogen bond with the adjacent carbonyl oxygen. In the case of Gly, the isomer containing a proton bound to the carbonyl oxygen is theoretically possible. However, it does not exist under the experimental conditions because it has a significantly higher energy (i.e. 26.6 kcal mol^?1) relative to the most stable isomer. For Ser and Phe, the protonated amino group forms two intramolecular hydrogen bonds with both the adjacent carbonyl oxygen and the side‐chain group in each of the most stable isomers. In protonated lysine, the protonated amino group in the side chain forms two hydrogen bonds with the α‐amino nitrogen and the carbonyl oxygen, which is a cyclic structure. Interestingly, for protonated lysine the zwitterionic structure is a local minimum energy isomer, but the experimental spectrum indicates that it does not exist under the experimental conditions. This is consistent with the fact that the zwitterionic isomer is 9.2 kcal mol^?1 higher in free energy at 298 K than the most stable isomer. The carbonyl stretching vibration in the range of 1760–1800 cm^?1 is especially sensitive to the structural change. In addition, IRMPD mechanisms for the protonated amino acids are also investigated.     

Potential energy surface of thionylimide

The potential energy surface (PES) of thionylimide has been searched using ab initio MO and density functional calculations. The electronic structures of the isomers of HNSO have been studied using the HF/6‐31+G*, MP2(full)/6‐31+G*, and B3LYP/6‐31+G* levels. Final energies of these molecules have been calculated at the high‐accuracy G2 and CBS‐Q levels. The probable pathways of isomerization of thionylimide to its isomers (e.g., thiocyanic acid, HONS, nitrosothiols) have been explored by studying the three‐ or four‐membered transition states. This study identified total eight possible isomers ( 1–8 ) of HNSO, of which four ( 1–4 ) have already been realized experimentally. Of the remaining four ( 5–8 ), at least two ( 5, 7 ) can be generated experimentally. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

A quantum mechanical approach to the kinetics of the hydrogen abstraction reaction H2O2 + •OH → HO2 + H2O

The kinetics of the hydrogen abstraction from H₂O₂ by ^?OH has been modeled with MP2/6‐31G*//MP2/6‐31G*, MP2‐SAC//MP2/6‐31G*, MP2/6‐31+G**//MP2/6‐31+G**, MP2‐SAC// MP2/6‐31+G**, MP4(SDTQ)/6‐311G**//MP2/6‐31G*, CCSD(T)/6‐31G*//CCSD(T)/6‐31G*, CCSD(T)/6‐31G**//CCSD(T)/6‐31G**, CCSD(T)/6‐311++G**//MP2/6‐31G* in the gas phase. MD simulations have been used to generate initial geometries for the stationary points along the potential energy surface for hydrogen abstraction from H₂O₂. The effective fragment potential (EFP) has been used to optimize the relevant structures in solution. Furthermore, the IEFPCM model has been used for the supermolecules generated via MD calculations. IEFPCM/MP2/6‐31G* and IEFPCM/CCSD(T)/6‐31G* calculations have also been performed for structures without explicit water molecules. Experimentally, the rate constant for hydrogen abstraction by ^?OH drops from 1.75 × 10^?12 cm³ molecule^?1 s^?1 in the gas phase to 4.48 × 10^?14 cm³ molecule^?1 s^?1 in solution. The same trend has been reproduced best with MP4 (SDTQ)/6‐311G**//MP2/6‐31G* in the gas phase (0.415 × 10^?12 cm³ molecule^?1 s^?1) and with EFP (UHF/6‐31G*) in solution (3.23 × 10^?14 cm³ molecule^?1 s^?1). © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 502–514, 2005     

An Ab Initio Molecular Orbital Study of Valence Bond Isomers of Silabenzene and Phosphabenzene

Ab initio molecular orbital calculation at HF/6-31G*, HF/6-31G**, HF/6-311G**, HF/6-311++G**, RMP2-FC/6-31G*, and B3LYP/6-31G* levels of theory for geometry optimization and MP4(SDQ)/6-31G* for a single point total energy calculation are reported for silabenzene ( 7 ), phosphabenzene ( 8 ) and 16 valence bond isomers of silabenzene and phosphabenzene ( 9-24 ). The calculated energy difference (19.78 kcal mol m 1 ) between silabenzene and the most stable valence bond isomer of silabenzene (1-silabenzvalene, 9 ) is much smaller than the difference (73.60 kcal mol m 1 ) between benzene and benzvalene ( 2 ). The energy difference between phosphabenzene and the most stable valence bond isomer of phosphabenzene (1-phosphabenzvalene, 17 ) is calculated to be 43.29 kcal mol m 1 .     

Quantum chemistry study of H+(H2O)8: a global search for its isomers by the scaled hypersphere search method, and its thermal behavior

The structures of the protonated water cluster H+(H2O)8 have been globally explored by the scaled hypersphere search method. On the Hartree-Fock potential energy surface 174 isomers were found, among which 168 were computed to be minima at the B3LYP/6-31+G** level, and their energies were further refined at the level of MP2/6-311++G(3df,2p). The global minimum on the potential energy surface computed at the B3LYP/6-31+G** level shows a cagelike structure with the "Eigen" motif, while the lowest-free-energy isomer has a five-membered-ring structure at 170 K and a chain form at 273 K. The present results are well in line with previous experimental findings. In addition, the ADMP (atom-centered density matrix propagation) simulation indicates that the extra proton in the lowest-free-energy isomer (170 K), which has a five-membered ring and the "Zundel" feature, is often in an asymmetrical hydrogen bond.     

A computational study of intramolecular proton transfer in gaseous protonated glycine

The minimum energy paths for intramolecular proton transfer between the amino nitrogen and carbonyl oxygen atoms in gaseous protonated glycine were estimated at the Hartree-Fock (HF) and second-order M?ller-Plesset Perturbation (MP2) levels of theory. Potential energy profiles and their associated reactant, transition state, and product species calculated at the MP2/6-31G* level were shown to differ significantly from those obtained at the HF/6-31G* level. Effects of electron correlation and basis functions on the calculated geometries and energies of relevant species were examined at the HF, MP2, MP4, CCSD, and B3LYP levels using the 6-31G*, 6-31G**, 6-31+G**, 6-311+G**, 6-31+G(2d,2p), 6-311+G(3df,2p), cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ basis sets. The HF and MP2 optimized levels with the 6-31G*, 6-31G**, 6-31+G**, and 6-311+G** bases were used to calculate the thermodynamic and kinetic properties of the proton transfer reaction at 298.15 K and 1 atm, which include enthalpy, entropy, Gibbs free energy, equilibrium constant, potential energy barriers, tunneling transmission coefficients, and rate constants. Results indicate that the proton in a carbonyl O-protonated glycine undergoes a rapid migration to the amino nitrogen atom, while the reverse process is extremely unfavorable. The objective of this work is to develop practical theoretical procedures for studying proton transfer reactions in amino acids and peptides and to assemble physical data from these model calculations for future references.     

Theoretical Studies on Electronic Structures and NMR Spectra of Oligo(4‐vinylpyridine)

Poly(4‐vinylpyridine) was determined to possess conductivity in the experiment. In order to understand properties of the polymer, a series of 4‐vinylpyridine oligomers were designed. The structures of these oligomers were optimized using density function theory (DFT) at B3LYP/6‐31G(d) level. The energy gaps and thermal stabilities of the oligomers were decreased when the chain lengths were increased. These properties were also decreased owing to the protonation of the pyridine ring. The holes were easily injected into the oligomers in the presence of hydrochloride. The electrons were conducted in the side chain composed of the pyridine rings rather than the main chain owing to the saturation of the main chain. The ¹³C nuclear magnetic resonance (NMR) spectra and nucleus independent chemical shifts (NICS) of these compounds were calculated at B3LYP/6‐31G(d) level. The chemical shifts of the carbon atoms connected with the nitrogen atoms in the protonated pyridines were moved upfield in comparison with those of the pyridines. The addition of hydrochloride on the pyridine ring in the oligomers led to the increase of the aromaticities, namely the aromaticities of the oligomers were obviously improved when the pyridine rings were protonated.     

Ab initio study of reactions of 1‐halogen‐3‐methoxy‐1‐propynes with Grignard reagent

The structures of coordination complexes of methylmagnesium chloride with 1‐halogen‐3‐methoxy‐1‐propynes have been studied by means of ab initio methods (RHF/3‐21G*, RHF/6‐31G* and RHF/6‐31G**), taking into account the electron correlation by Møller‐Plesset perturbation theory (MP2). Two pathways of the nucleophilic halogen substitution reaction between the reagents have been considered. The calculations predict the addition–elimination mechanism as advantageous for the reaction. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

A Quantum Chemical Study of N14 Cluster

Ab initio molecular orbital theory and density functional theory have been employed to study N₁₄ cluster with low spin at the HF/6-31G*, B3LYP/6-31G*, B3PW91/6-31G*, BP86/6-31G*, and BHLYP/6-31G* levels of theory. Twelve isomers were studied, including one previously investigated cage molecule. The most stable isomer of N₁₄ is a C _2h -symmetric molecule that contains two separated five-membered nitrogen rings connected by a —N=N—N=N— bridge. The second, third, and fifth most stable isomers each have one five-membered nitrogen ring. The theoretical results suggest that the five-membered nitrogen ring gives rise to a particularly stable structural unit, and the more side chains that the five-membered nitrogen ring links with, the less stable the structure will become.     

Quantum chemical investigation of the structures of ionic liquids based on 1-ethyl-3-methylimidazolium halides: IR spectra and hydrogen bonds

Hydrogen bonds, structures, and vibrational spectra of 1-ethyl-3-methylimidazolium halides ([emim][Hal]) were analyzed in the framework of the Hartree—Fock method (HF/6-31G*, 6-31+G*) and the density functional theory (B3LYP/6-31G*, 6-31+G*, 6-31G**, 6-31+G**). It is shown that the use of the approximation of an isolated ion pair cation—anion is incorrect for the ionic liquids studied. It is more reasonable to consider “clusters” including at least two-three cations and being more appropriate models for the study of hydrogen bonds and vibrational spectra of ionic liquids of this type.     

Proton affinities of molecules containing nitrogen and oxygen: comparing ab initio and semiempirical results to experiments

We report a comparison of theoretical and experimental proton affinities at nitrogen and oxygen sites within a series of small molecules. The calculated proton affinities are determined using the semiempirical methods AM 1, MNDO , and PM 3; the ab initio Hartree–Fock method at the following basis levels: 3-21G //3-21G , 3-21+G //3-21G , 6-31G *//6-31G *, and 6-31+G (d, p)//6-31G *; and Møller–Plesset perturbation calculations: MP 2/6-31G *//6-31G *, MP 3/6-31G *//6-31G *, MP 2/6-31G +(d, p)//6-31G *, MP 3/6-31G +(d, p)//6-31G *, and MP 4(SDTQ )/6-31G +G (d, p)//6-31G *. The semiempirical methods have more nonsystematic scatter from the experimental values, compared to even the minimal 3-21G level ab initio calculations. The thermodynamically corrected 6-31G *//6-31G * proton affinities provide acceptable results compared to experiment, and we see no significant improvement over 6-31G *//6-31G * in the proton affinities with any of the higher-level calculations. © 1992 John Wiley & Sons, Inc.     

Conformational study of the structure of 12-crown-4-alkali metal cation complexes

A conformational search was performed for the 12-crown-4 (12c4)-alkali metal cation complexes using two different methods, one of them is the CONFLEX method, whereby eight conformations were predicted. Computations were performed for the eight predicted conformations at the HF/6-31+G*, MP2/6-31+G*//HF/6-31+G*, B3LYP/6-31+G*, MP2/6-31+G*//B3LYP/6-31+G*, and MP2/6-31+G* levels. The calculated energies predict a C4 conformation for the 12c4-Na+, -K+, -Rb+, and -Cs+ complexes and a C(s) conformation for the 12c4-Li+ complex to be the lowest energy conformations. For most of the conformations considered, the relative energies, with respect to the C4 conformation, at the MP2/6-31+G*//B3LYP/6-31+G* are overestimated, compared to those at the MP2/6-31+G* level, the highest level of theory considerd in this report, by 0.2 kcal/mol. Larger relative energy differences are attributed to larger differences between the B3LYP and MP2 optimized geomtries. Binding enthalpies (BEs) were calculated at the above-mentioned levels for the eight conformations. The agreement between the calculated and experimental BEs is discussed.     

Role of the sulfhydryl group on the gas phase fragmentation reactions of protonated cysteine and cysteine containing peptides

The gas phase fragmentation reactions of protonated cysteine and cysteine-containing peptides have been studied using a combination of collisional activation in a tandem mass spectrometer and ab initio calculations [at the MP2(FC)/6-31G*//HF/6-31G* level of theory]. There are two major competing dissociation pathways for protonated cysteine involving: (i) loss of ammonia, and (ii) loss of the elements of [CH₂O₂]. MS/MS, MS/MS of selected ions formed by collisional activation in the electrospray ionization source as well as ab initio calculations have been carried out to determine the mechanisms of these reactions. The ab initio results reveal that the most stable [M + H − NH₃]⁺ isomer is an episulfonium ion (A), whereas the most stable [M + H − CH₂O₂]⁺ isomer is an immonium ion (B). The effect of the position of the cysteine residue on the fragmentation reactions of the [M + H]⁺ ions of all the possible simple dipeptide and tripeptide methyl esters containing one cysteine (where all other residues are glycine) has also been investigated. When cysteine is at the N-terminal position, NH₃ loss is observed, although the relative abundance of the resultant [M + H − NH₃]⁺ ion decreases with increasing peptide size. In contrast, when cysteine is at any other position, water loss is observed. The proposed mechanism for loss of H₂O is in competition with those channels leading to the formation of structurally relevant sequence ions.     

Tautomerism and the maximum hardness principle

Through the application of the atom–bond electronegativity equalization method (ABEEM) to the calculation of the hardnesses of more than 300 tautomers, it can be seen that the maximum hardness principle is nearly useless to account for their relative stabilities. Moreover, by calculating the energies of these tautomers with the HF, B3LYP, B3PW91, and MP2 methods at the 6‐31G, 6‐31G*, 6‐31G**, 6‐31+G**, 6‐311G**, or 6‐311++G** level, it is found that all these methods may not be always reliable in predicting their relative stabilities. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Investigation on Structure and Bonding of As_4S_4 Isomers

Mineral medicine, especially those containing heavy metals, is one of the characteristics of traditional Chinese medicine. A famous mineral medicine, realgar, containing heavy metal arsenic with a chemical formula of As_4S_4, has the function of detoxification, killing bacteria and viruses, and eliminating dampness and phlegm. Different As_4S_4 isomers are likely to have different drug effects and pharmacological actions. Therefore, it is of great scientific significance to find more stable As_4S_4 isomers. In view of this, ab initio molecular orbital theory and density functional theory(DFT) have been used to study ten isomers of As_4S_4 at the B3LYP/6-31 G*, B3LYP/6-311+G*, B3LYP/6-311+G(3 df, 2 p) and MP2/(6-311+G*, LanL2 MB) levels of theory. In addition to the two isomers having been studied previously, eight new isomers were investigated in the present paper. All the ten As_4S_4 isomers were proved to be true local minima on their potential energy surfaces. The calculated NICS values and molecular orbital analyses showed that, the D_(2d) symmetric As_4S_4, isomer 1, may be s-aromatic. The study proves that ten As_4S_4 isomers are stable thermodynamically, and are highly desirable for the future theoretical study of realgar.     

Structural and Energetic Effects in the Molecular Recognition of Acetylated Amino Acids by 18-Crown-6

Absolute 18-crown-6 (18C6) binding affinities of four protonated acetylated amino acids (AcAAs) are determined using guided ion beam tandem mass spectrometry techniques. The AcAAs examined in this work include: N-terminal acetylated lysine (N_???CAcLys), histidine (N_???CAcHis), and arginine (N_???CAcArg) as well as side chain acetylated lysine (N_???CAcLys). The kinetic-energy-dependent cross sections for collision-induced dissociation (CID) of the (AcAA)H⁺(18C6) complexes are analyzed using an empirical threshold law to extract absolute 0 and 298?K (AcAA)H⁺?18C6 bond dissociation energies (BDEs) after accounting for the effects of multiple collisions, kinetic and internal energy distributions of the reactants, and unimolecular dissociation lifetimes. Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the AcAAs as well as the proton bound complexes of these species, (AcAA)H⁺(18C6), at the B3LYP/6-311+G(2d,2p)//B3LYP/6-31?G* and M06/6-311+G(2d,2p)//B3LYP/6-31G* levels of theory. For all four (AcAA)H⁺(18C6) complexes, loss of neutral 18C6 corresponds to the most favorable dissociation pathway. At elevated energies, products arising from sequential dissociation of the primary CID product, H⁺(AcAA), are also observed. Protonated N_???CAcLys exhibits a greater 18C6 binding affinity than other protonated N_???CAcAAs, suggesting that the side chains of Lys residues are the preferred binding sites for 18C6 complexation to peptides and proteins. N_???CAcLys exhibits a greater 18C6 binding affinity than N_???CAcLys, suggesting that binding of 18C6 to the side chain of Lys residues is more favorable than to the N-terminal amino group of Lys.     

Proton affinity of uracil. A computational study of protonation sites

Relative stabilities of uracil tautomers and cations formed by gas-phase protonation were studied computationally with the B3LYP, MP2, QCISD, and QCISD(T) methods and with basis sets expanding from 6-31G(d,p) to 6-311+G(3df,2p). In accordance with a previous density functional theory study, the dioxo tautomer 1a was the most stable uracil isomer in the gas phase. Gibbs free energy calculations using effective QCISD(T)/6-311+G(3df,2p) energies suggested >99.9% of 1a at equilibrium at 523 K. The most stable ion isomer corresponded to N-1 protonated 2,4-dihydroxypyrimidine, which however is not formed by direct protonation of 1a. The topical proton affinities in 1a followed the order O-8 > O-7 > C-5 > N-3 > N-1. The thermodynamic proton affinity of 1a was calculated as 858 kJ mol⁻¹ at 298 K. A revision is suggested for the current estimate included in the ion thermochemistry database.     

Struktur und Eigenschaften des Hydridomethyltetrafluorphosphatanions, [CH3PF4H]—

Structure and Properties of the Hydridomethyltetrafluorophosphate Anion, [CH₃PF₄H]^— Methyltrifluorphosphorane reacts with strong fluoride donors like CsF, (CH₃)₄NF and (CH₃)₄PF with formation of the corresponding hydridomethyltetrafluorophosphates. The salts are characterized by NMR, IR and Raman spectroscopy. The experimental results show that only the trans isomer is formed. For both isomers theoretical calculations (B3LYP/6‐31+G* and RHF/6‐31+G*) were carried out. The difference for the Gibbs free energy between the isomers was calculated to be 35.4 kJ/mol (B3LYP/6‐31+G*). The RHF/6‐31+G* calculation yields, for the almost octahedral trans isomer, bond distances of r(PF) = 167 pm, r(PC) = 184.5 pm and r(PH) = 138.1 pm.     

Proton affinity of β-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.