Experimental and theoretical studies of sodium cation complexes of the deamidation and dehydration products of asparagine, glutamine, aspartic acid, and glutamic acid

The deamidation and dehydration products of Na+(L), where L = asparagine (Asn), glutamine (Gln), aspartic acid (Asp), and glutamic acid (Glu), are examined in detail utilizing collision-induced dissociation (CID) with Xe in a guided ion beam tandem mass spectrometer (GIBMS). Results establish that the Na+(L) complexes decompose upon formation in our dc discharge/flow tube ion source to form a bis-ligand complex, Na+(L-HX)(HX), composed of a sodium cation, the (L-HX) decomposition product, and HX, where HX = NH3 for the amides and H2O for the acids. Analysis of the energy-dependent CID cross sections for the Na+(L-HX)(HX) complexes provides unambiguous identification of the (L-HX) fragmentation products as 3-amino succinic anhydride (a-SA) for Asx and oxo-proline (O-Pro) for Glx. Furthermore, these experiments establish the 0 K sodium cation affinities for these five-membered ring decomposition products and the H2O and NH3 binding affinities of the Na+(a-SA) and Na+(O-Pro) complexes after accounting for unimolecular decay rates, the internal energy of reactant ions, and multiple ion-molecule collisions. Quantum chemical calculations are determined for a number of geometric conformations of all reaction species as well as a number of candidate species for (L-HX) at the B3LYP/6-311+G(d,p) level with single-point energies calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. This coordinated examination of both the experimental work and quantum chemical calculations allows for a complete characterization of the products of deamidation and dehydration of Asx and Glx, as well as the details of Na+, H2O, and NH3 binding to the decomposition species.     

Theoretical study on the insertion reactions of the germylenoid H2GeClMgCl with RH (R = F, OH, NH2)

The insertion reactions of the germylenoid H₂GeClMgCl with RH (R = F, OH, NH₂) have been studied by using the DFT B3LYP and QCISD methods. The geometries of the stationary points on the potential energy surfaces of the reactions were optimized at the B3LYP/6-311+G(d, p) level of theory. The calculated results indicate that all the mechanisms of the three insertion reactions are identical to each other. The QCISD/6-311++G(d, p)//B3LYP/6-311+G(d, p) calculated potential energy barriers for the three insertion reactions of R = F, OH, and NH₂ are 164.62, 193.30, and 200.73 kJ mol^?1, and the reaction energies for the three reactions are ?57.46, ?35.65, and ?22.22 kJ mol^?1, respectively. Under the same situation, the insertion reactions should occur easily in the following order H-F > H-OH > H-NH₂. In THF solvent the insertion reactions get more difficult than in gas phase.     

Ligand‐Exchange Processes on Solvated Beryllium Cations. Part III

On the basis of DFT calculations (B3LYP/6‐311+G**), the possibility to include solvent effects is considered in the investigation of the H₂O‐exchange mechanism on [Be(H₂O)₄]²⁺ within the widely used cluster approach. The smallest system in the gas phase, [Be(H₂O)₄(H₂O)]²⁺, shows the highest activation barrier of +15.6 kcal/mol, whereas the explicit addition of five H‐bonded H₂O molecules in [{Be(H₂O)₄(H₂O)}(H₂O)₅]²⁺ reduces the barrier to +13.5 kcal/mol. Single‐point calculations applying CPCM (B3LYP(CPCM:H₂O)/6‐311+G**//B3LYP/6‐311+G**) on [Be(H₂O)₄(H₂O)]²⁺ lower the barrier to +9.6 kcal/mol. Optimization of the precursor and transition state of [Be(H₂O)₄(H₂O)]²⁺ within an implicit model (B3LYP(CPCM:H₂O)/6‐311+G** or B3LYP(PCM:H₂O)/6‐311+G**) reduces the activation energy further to +8.3 kcal/mol but does not lead to any local minimum for the precursor and is, therefore, unfavorable.     

A study of methanetetraol dehydration to carbonic acid

Two alternative dehydration reactions C(OH)₄ → (HO)₂CO + H₂O and C(OH)₄ + H₂O → (HO)₂CO + 2H₂O are studied by ab initio Becke3LYP/6–311 + G^** and MP2/6–31G^** methods. Calculated energy and geometry characteristics of intermediates and transition states predict a catalytic effect of one water molecule and the exothermism of the transformations. Relevant HF/6–311 + G^**, HF/6–31G^**, HF/6–31G, and HF/3–21G calculations were performed for comparison. © 1997 John Wiley & Sons, Inc.     

DFT investigation of the mechanism of CH2CO + O(3P) reaction

A detailed theoretical survey of the potential energy surface (PES) for the CH₂CO + O(³P) reaction is carried out at the QCISD(T)/6‐311+G(3df,2p)//B3LYP/6‐311+G(d,p) level. The geometries, vibrational frequencies, and energies of all stationary points involved in the reaction are calculated at the B3LYP/6‐311+G(d,p) level. More accurate energy information is provided by single‐point calculations at the QCISD(T)/6‐311+G(3df,2p) level. Relationships of the reactants, transition states, intermediates, and products are confirmed by the intrinsic reaction coordinate (IRC) calculations. The results suggest that P1(CH₂+CO₂) is the most important product. This study presents highlights of the mechanism of the title reaction. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

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.     

The DFT study on mechanisms for NCO with C2H5 reaction

A detailed investigation has been performed at the QCISD(T)/6‐311++G(d,p)//B3LYP/6‐311+G(d,p) level for the reaction of NCO with C₂H₅ by constructing singlet and triplet potential energy surfaces (PES). The results show that the title reaction is more favorable on the singlet PES than on the triplet PES. On the singlet PES, the initial addition processes are barrierless and release lots of energy. The dominant channel occurs via the fragmentations of the initial adduct C₂H₅NCO and C₂H₅OCN to form C₂H₄ + HNCO and HOCN, respectively. With higher barrier heights, other products such as CH₄ + HNC + CO, CH₃CHNH + CO, CH₃CH + HNCO, and CH₃CN + H₂ + CO are less competitive. On the triplet PES, the entrance reactions surpass significant barriers; therefore, it could be negligible at the normal atmospheric condition. However, the most feasible channel on the triplet PES is the direct hydrogen abstraction channel to form CH₂CH₂ + HNCO. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Theoretical predictions of the structure, gas-phase acidity and aromaticity of 1,2-diseleno-3,4-dithiosquaric acid

Results of ab initio self-consistent-field (SCF) and density functional theory (DFT) calculations of the gas-phase structure, acidity (free energy of deprotonation, ΔG^o), and aromaticity of 1,2-diseleno-3,4-dithiosquaric acid (3,4-dithiohydroxy-3-cyclobutene-1,2-diselenone, H₂C₄Se₂S₂) are reported. The global minimum found on the potential energy surface of 1,2-diseleno-3,4-dithiosquaric acid presents a planar conformation. The ZZ isomer was found to have the lowest energy among the three planar conformers and the ZZ and ZE isomers are very close in energy. The optimized geometric parameters exhibit a bond length equalization relative to reference compounds, cyclobutanediselenone, and cyclobutenedithiol. The computed aromatic stabilization energy (ASE) by homodesmotic reaction (Eq 1) is −20.1 kcal/mol (MP2(fu)/6-311+G** //RHF/6-311+G**) and −14.9 kcal/mol (B3LYP//6-311+G**//B3LYP/6-311+G**). The aromaticity of 1,2-diseleno-3,4-dithiosquaric acid is indicated by the calculated diamagnetic susceptibility exaltation (Λ) −17.91 (CSGT(IGAIM)-RHF/6-311+G**//RHF/6-311+G**) and −31.01 (CSGT(IGAIM)-B3LYP/6-311+G**//B3LYP/6-311+G**). Thus, 1,2-diseleno-3,4-dithiosquaric acid fulfils the geometric, energetic and magnetic criteria of aromaticity. The calculated theoretical gas-phase acidity is ΔG^o _1(298K)=302.7 kcal/mol and ΔG^o _2(298K)=388.4 kcal/mol. Hence, 1,2-diseleno-3,4-dithiosquaric acid is a stronger acid than squaric acid(3,4-dihydroxy-3-cyclobutene-1,2-dione, H₂C₄O₄). Received: 11 April 2000 / Accepted: 7 July 2000 / Published online: 27 September 2000     

Transition structures and reaction barriers in the styrene–acrylonitrile copolymerization system according to quantum mechanical calculations

The geometries and electronic properties of substrates, transition structures (TS), and product radicals in modeled elementary propagation reactions were studied for the styrene–acrylonitrile monomer system by use of quantum‐mechanical calculations: (DFT/B3‐LYP/6–31G(d), ROMP2/6–311+G(3df,2p)//DFT/B3‐LYP/6–31G(d), and DFT/B3‐LYP/6–311+G(3df,2p)//DFT/B3‐LYP/6–31G(d)) and for some parameters, the high‐level composite method G3 (Gaussian‐3, G3/MP2). Activation enthalpies (ΔH^act) and reaction enthalpies (ΔH_r) for modeled propagation reactions at 298.15 K were evaluated. The enthalpy of activation energy (ΔH^act, kJ/mol) for the investigated elementary reactions rises for the B3‐LYP calculation in the following order: (CH₃A?+S) < (CH₃A?+A) < (CH₃S?+A) < (CH₃S?+S). For three propagation reactions, (CH₃A?+A), (CH₃A?+S), and (CH₃S?+A), correlation between reaction enthalpy and enthalpy of activation suggests weak or negligible polar effects reflecting the Evans–Polanyi relation. However, from the electron affinities and ionization energies values data, it is not excluded that at least for [CH₃A?+S[b]] and [CH₃S?+A[b]] reactions, nucleophilic and electrophilic polar effects, respectively, can also be expected. The dependencies between TS geometries, electronic parameters, and enthalpic effects suggest the presence of a steric factor in all TS, including its exceptionally high contribution to the activation enthalpy for the CH₃S?+S addition. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1827–1844, 2005     

Reaction of CH3CHO with Y+: A density functional theoretical study

The reaction mechanism of the Y⁺ cation with CH₃CHO has been investigated with a DFT approach. All the stationary points are determined at the UB3LYP/ECP/6-311++G** level of the theory. Both ground and excited state potential energy surfaces are investigated in detail. The present results show that the title reaction start with the formation of a CH₃CHO-metal complex followed by C-C, aldehyde C-H, methyl C-H and C-O activation. These reactions can lead to four different products (Y⁺CH₄ + CO, Y⁺CO + CH₄, Y⁺COCH₂ + H₂ and Y⁺O + C₂H₄). The minimum energy reaction path is found to involve the spin inversion in the different reaction steps, this potential energy curve-crossing dramatically affects reaction exothermic. The present results may be helpful in understanding the mechanism of the title reaction and further experimental investigation of the reaction.     

Experimental and theoretical studies of sodium cation interactions with the acidic amino acids and their amide derivatives

The binding of Na+ to aspartic acid (Asp), glutamic acid (Glu), asparagine (Asn), and glutamine (Gln) is examined in detail by studying the collision-induced dissociation (CID) of the four sodiated amino acid complexes with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Analysis of the energy-dependent CID cross sections provides 0 K sodium cation affinities for the complexes after accounting for unimolecular decay rates, internal energy of the reactant ions, and multiple ion-molecule collisions. Quantum chemical calculations for a number of geometric conformations of each Na+(L) complex are determined at the B3LYP/6-311+G(d,p) level with single-point energies calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. This coordinated examination of both experimental work and quantum chemical calculations allows the energetic contributions of individual functionalities as well as steric influences of relative chain lengths to be thoroughly explored. Na+ binding affinities for the amide complexes are systematically stronger than those for the acid complexes by 14 +/- 1 kJ/mol, which is attributed to an inductive effect of the OH group in the carboxylic acid side chain. Additionally, the Na+ binding affinity for the longer-chain amino acids (Glx) is enhanced by 4 +/- 1 kJ/mol compared to the shorter-chain Asx because steric effects are reduced.     

Computational study on nonenzymatic peptide bond cleavage at asparagine and aspartic acid

Nonenzymatic peptide bond cleavage at asparagine (Asn) and glutamine (Gln) residues has been observed during peptide deamidation experiments; cleavage has also been reported at aspartic acid (Asp) and glutamic acid (Glu) residues. Although peptide backbone cleavage at Asn is known to be slower than deamidation, fragmentation products are often observed during peptide deamidation experiments. In this study, mechanisms leading to the cleavage of the carboxyl-side peptide bond of Asn and Asp residues were investigated using computational methods (B3LYP/6-31+G**). Single-point solvent calculations at the B3LYP/6-31++G** level were carried out in water, utilizing the integral equation formalism-polarizable continuum (IEF-PCM) model. Mechanism and energetics of peptide fragmentation at Asn were comparatively analyzed with previous calculations on deamidation of Asn. When deamidation proceeds through direct hydrolysis of the Asn side chain or through cyclic imide formationvia a tautomerization routeit exhibits lower activation barriers than peptide bond cleavage at Asn. The fundamental distinction between the mechanisms leading to deamidationvia a succinimideand backbone cleavage was found to be the difference in nucleophilic entities involved in the cyclization process (backbone versus side-chain amide nitrogen). If deamidation is prevented by protein three-dimensional structure, cleavage may become a competing pathway. Fragmentation of the peptide backbone at Asp was also computationally studied to understand the likelihood of Asn deamidation preceding backbone cleavage. The activation barrier for backbone cleavage at Asp residues is much lower (approximately 10 kcal/mol) than that at Asn. This suggests that peptide bond cleavage at Asn residues is more likely to take place after it has deamidated into Asp.     

Theoretical investigation on the reaction of N2O and CO catalyzed by Fe(C6H6)

The reaction of N₂O with CO, catalyzed by Fe⁺(C₆H₆) and producing N₂ and CO₂, has been investigated at the UB3LYP/6-311+G(d) level. The computation results revealed that the reaction of Fe⁺(C₆H₆), N₂O and CO, is an O-atom abstraction mechanism. For the reaction channels, the geometries and the vibrational frequencies of all species have been calculated and the frequency modes analysis also have been given to elucidate the reaction mechanism. On the basis for geometry optimizations, the thermodynamic data of these reactions channels have been calculated using the statistical theory at 295.15 K and pressure of 0.35 Torr. Using Eyring transition state theory with Wigner correction, the activation thermodynamic data, rate constant and frequency factors for the these reaction channels also have been given. The results showed that CO and N₂O do not react without catalyst and Fe⁺(C₆H₆) can excellently mediate the reaction of N₂O and CO.     

A density functional investigation of the reaction mechanism of H2O + HCNO

A theoretical investigation of the H₂O + HCNO reaction, which is carried out by means of CCSD(T)/6‐311G(d,p)//B3LYP/6‐311G(d,p)+ZPVE computational method to determine a set of reasonable pathways, there are seven product pathways, P _i with i = 1 , 2 , …, 7 are involved. It is shown that P ₁ (H₂O + NCOH), P ₂ (CO + NH₂ + OH), P ₄ (HCN + HO₂ + H), and P ₆ (CO + NH₂OH) are the major product channels; and P ₇ (HOC + H₂ + NO) is the minor product channels, whereas the other channels for P ₃ (HNO + HCOH) and P ₅ (HNO + H₂CO) are very minor, the minor product channels. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Evidence for Interchange Ligand‐Exchange Processes on Solvated Beryllium Cations

The ligand‐exchange mechanism of solvated Be²⁺ cations has been studied by means of DFT calculations (RB3LYP/6‐311+G**). Ligand exchange around [BeL₄]²⁺, where L=H₂O, NH₃, CO₂, formaldehyde (H₂CO), HCN, N₂, and CO, was found to follow an associative interchange (I_a) process in all cases. The size of the activation barrier is almost independent of the type of donor atom, and depends mainly on the hybridization undergone by the donor atom. This, in turn, suggests that steric effects play a major role in solvent‐ and ligand‐exchange reactions in Be²⁺ systems.     

Theoretical and kinetic study of the H + C2H5CN reaction

The reaction of H radical with C₂H₅CN has been studied using various quantum chemistry methods. The geometries were optimized at the B3LYP/6‐311+G(d,p) and B3LYP/6‐311++G(2d,2p) levels. The single‐point energies were calculated using G3 and BMC‐CCSD methods based on B3LYP/6‐311++G(2d,2p) geometries. Four mechanisms were investigated, namely, hydrogen abstraction, C‐addition/elimination, N‐addition/elimination and substitution. The kinetics of this reaction were studied using the transition state theory and multichannel Rice‐Ramsperger‐Kassel‐Marcus methodologies over a wide temperature range of 200–3000 K. The calculated results indicate that C‐addition/elimination channel is the most feasible over the whole temperature range. The deactivation of initial adduct C₂H₅CHN is dominant at lower temperature with bath gas H₂ of 760 Torr; whereas C₂H₅+HCN is the dominant product at higher temperature. Our calculated rate constants are in good agreement with the available experimental data. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010