Béla Paizs

Formation of b2+ ions from protonated peptides: an ab initio study

Systematic ab initio calculations were performed to reveal the mechanism of formation of stable b2+ ions formed during fragmentation of protonated peptides and proteins. Stable oxazolone-type cyclic b2+ ions are formed from parent ions containing the -C(O)-N-C-C(O)-unit in a two-step process. In the first step the C–N bond of an N-protonated peptide breaks and, simultaneously, ring closure takes place in the remainingxad-C(O)-N-C-C(O)- fragment leading to the formation of a charged oxazolone-type ring. This reaction takes place through an approximately 10u2005kcal mol−1 high barrier. The product of this step is a charge-transfer type ion-molecule complex which decomposes in the next step to form the b2+ ion by dropping the amine analogue (C-terminal amino acid or peptide fragment). The dissociation energy of the complex is larger than the height of the barrier through which it was formed so that when the complex decomposes there is not much excess energy to be released as kinetic energy. The alternative multistep mechanism, involving formation of an open-chain acylium ion in the first step and ring closure in the second, is energetically highly unfavorable. Copyright

Comparative study of BSSE correction methods at DFT and MP2 levels of theory

A comparative study of intermolecular potential energy curves is performed on the complexes H2O(SINGLE BOND)HF, H2O(SINGLE BOND)H2O, H2O(SINGLE BOND)H2S, and H2S(SINGLE BOND)H2S using nine different basis sets at the MP2 and DFT (BLYP and B3LYP) levels of theory. The basis set superposition error is corrected by means of the counterpoise scheme and based on the “chemical Hamiltonian approach.” The counterpoise and CHA‐corrected DFT curves are generally close to each other. Using small basis sets, the B3LYP functional cannot be favored against the BLYP one because the BLYP results sometimes get closer to the MP2 values than those of B3LYP. From the results—including the available literature data—we suggest that one has to use at least polarized‐valence triple‐zeta‐quality basis sets (TZV, 6‐311G) for the investigation of hydrogen‐bonded complexes. Special attention must be paid to the physical nature of the binding. If the dispersion forces become significant DFT methods are not able to describe the interaction. Proper correction for the basis set superposition error is found to be mandatory in all cases.u2003© 1998 John Wiley & Sons, Inc.u2003J Comput Chem 19: 575–584, 1998

Proton mobility in protonated peptides: a joint molecular orbital and RRKM study

The mobile proton model was critically evaluated by using purely theoretical models which include quantum mechanical calculations to determine stationary points on the potential energy surface (PES) of a model compound, and Rice-Ramsperger-Kassel-Marcus (RRKM) calculations to determine the rate constants of various processes (conformational changes, proton transfer reactions) which occur during mass analysis of protonated peptides. Extensive mapping of the PES of protonated N-formylglycinamide resulted in various minima which were stabilized by one or more of the following types of interaction: internal hydrogen bond, charge transfer interaction, charge delocalization, and ring formation. The relative energies of most of the investigated minima are less then 20 kcal mol(-1) compared with the most stable species. More importantly, the relative energies of the transition structures connecting these minima are fairly low, allowing facile transitions among the energetically low-lying species. It is demonstrated that a path can be found leading from the energetically most stable species, protonated on an amide oxygen, to the structure from which the energetically most favorable fragmentation occurs. It is also shown that the added proton can sample all protonation sites prior to fragmentation. The RRKM calculations applied the results of ab initio computations (structures, energetics, vibrational frequencies) to the reactions (internal rotations, proton transfers) occurring in protonated N-formylglycinamide, and clearly lend additional evidence to the mobile proton model. Based on the results of the PES search on protonated N-formylglycinamide, we also comment on the mechanism proposed by Arnot et al. (Arnot D, Kottmeier D, Yates N, Shabanowitz J, Hunt D F. 42(nd) ASMS Conference on Mass Spectrometry, 1994; 470) and Reid et al. (Reid G E, Simpson R J, OHair R A J. J. Am. Soc. Mass Spectrom. 1998; 9:945) for the formation of b(2)(+) ions. According to the high level ab initio results, the mechanism relying on amide oxygen protonated species seems to be less feasible than the one which involves N-protonated species.

Formation of a2+ ions of protonated peptides. An ab initio study

The mechanism of the formation of a2+ ions from b2+ ions occurring during fragmentation of protonated peptides is investigated using quantum chemical methods. The geometries of the stationary structures involved in two possible mechanisms, namely, a two-step mechanism via an open-chain acylium ion and a concerted pathway involving rupture of two covalent bonds of the cyclic isomer of the b2+ ion, as well as the energetics of the reactions, were calculated at the MP2 and B3LYP levels, both combined with the 6-31G(d,p) as well as the 6-31++G(d,p) basis sets for the simplest analog of the b2+ ion. The energetically favored path is the direct expulsion of the CO molecule from the cyclic b2+ ion. The ZPE-corrected barrier height for this reaction is 26.2 kcal mol(-1) at the MP2/6-31G(d,p) level, while the highest barrier along the two step path is 31.4 kcal mol(-1). The barrier height for the reverse reaction is 3.8 kcal mol(-1), significantly smaller than the average kinetic energy release (KER) measured for larger b2+ ions. The barrier height for the reverse reactions of the MeCO-NH-CHMeCO+, NH2-iBuCH-CO-NH-CH2CO+, and NH2-CH2-CO-NH-CH(i-Bu)CO+ b2+ ions was found to be 11.3, 9.6, and 18.4 kcal mol(-1), in reasonable agreement with the measured KER for these reactions, indicating that the simplest model compound has unique properties in this respect. Based on comparisons with G2-MP2 calculations, comments are made on the applicability of various levels of theory for the description of the reaction.

RING INVERSION BARRIER OF DIAZEPAM AND DERIVATIVES : AN AB INITIO STUDY

Systematic ab initio calculations were performed to investigate the ring inversion process of various 1,4-diazepines including diazepam, N(1)-desmethyldiazepam, and 3-methyl-N(1)-desmethyldiazepam. The diazepine ring adopts a shape of a boat; owing to asymmetric substitution two such boats are possible in mirror image relation to each other. In the present study both structural and solvent effects were investigated on the energetics of ring inversion of nine diazepine derivatives. The calculated ring inversion barriers for diazepam (17.6 kcal/mol) and N(1)-desmethyldiazepam (10.9 kcal/mol) are in good agreement with the corresponding experimental data. In the cases of diazepam and N(1)-desmethyldiazepam, the calculated minimum energy path of the ring inversion is asymmetric contrary to the fact that the terminals (M and P conformers) are equienergetic.

Coupled perturbed Hartree—Fock equations. An alternative derivation and generalization to non-orthogonal orbitals

Abstract An alternative derivation of the coupled perturbed Hartree—Fock equations is given including the most general case of non-orthogonal molecular orbitals and non-Hermitian Fockians.

An exploratory study of 1,2-cis- and 1,2-trans-thiocarbamates of glucofuranosyl- and glucopyranosylamine

Abstract Total energies of various conformations of 2,3-thiocarbonyl-2-amino-3-hydroxy-tetrahydrofuran ( 7 ) and 2,3-thiocarbonyl-2-amino-3-hydroxy-tetrahydropyran ( 8 ) were computed at HF/6–31G* and B3LYP/6–31G* levels of theory for modelling the energy differences between 1,2-cyclic thiocarbamates of glucofuranosylamine ( 5a ) and its pyranosylamine analogues ( 5b and 6 ). Conformational parameters and stabilization energies were calculated for all the model structures of 7 and 8 , as well as for the transition from tetrahydrofuran ( 1 ) to tetrahydropyran ( 2 ). Using the appropriate isodesmic reaction equation, 2 was found to be more stable than 1 , in accordance with the stability difference between five- and six-membered cycloalkanes. In the case of 2,3-cyclic thiocarbamates of 1 and 2 ( 7 and 8 , respectively), cis isomers were more stable than trans ones and cis-envelope conformers in geometry A were the global minima. The energy difference between these and the local minimum of the cis pyranoid structure, however, is a very small factor in determining the outcome of the formation of 1,2-cyclic thiocarbamates of monosaccharides.

An ab initio study on selected models of 1,2-cis-and 1,2-trans-cyclic carbamates of glucopyranosyl amine

Abstract Total energies of various conformations of trans- and cis-isomers of 2-amino-cyclohexanol (5) and those of 2-amino-3-hydroxy-tetrahydropyrane (6) as well as those of 2,3-cyclic carbamates of 2-amino-3-hydroxy-tetrahydropyrane (7) were computed at HF/6-31G and HF/6-31G∗∗ level of theory for modelling the energy differences between trans- and cis-1,2-cyclic carbamates of gluco- and xylopyranosyl amine (1,2 and 3,4, respectively). In the case of the chair forms of both 5 and 6, the trans isomers were found to be more stable than the cis ones. The stability of the different structures was also governed by the internal hydrogen bonds involving NH2 and OH groups, as well as the ring oxygen atom. In the case of 7, the formation of the oxazolinone ring results in decreasing the total energy of the cis isomer with respect to the trans compound. Using appropriate isodesmic reaction equations, stabilization energies were calculated for all of the model structures of 5–7, as well as for the transition from cyclohexane to tetrahydropyrane. The energy values indicated that the introduction of the ring oxygen causes stabilization in all cases.

The quality of ab initio quantum mechanical prediction of vibrational transition dipole directions and infrared intensities

Abstract This is a preliminary report of our research aimed at the joint use of up-to-date experimental (polarized infrared spectra of oriented samples) and theoretical (ab initio quantum chemical) methods of determining the vibrational electric transition moment directions to help in the assignment of infrared absorption spectra of polyatomic molecules. The systems studied include ethylene, p -nitrobromobenzene, thiosemicarbazide and N , N -dimethyl- S -methylmonothiobarbamate. Our results show that this bilateral approach works well for molecules with orthogonal ( C 2 ν or higher) symmetry. Special emphasis was given to testing the capabilities of the method for systems with lower symmetry ( C 2h , C s , etc.) where it proved to be no more successful than the prediction of infrared intensities: agreement between the calculated and measured band polarization values within tight limits is quite rare, while completely wrong results have also been obtained, especially in the presence of unaccounted hydrogen bonding.