Ab Initio MO Theory Research Articles

FTIR ATR spectral and theoretical based vibrational studies of uracil in dimethylsulfoxide or diethylsulfoxide solutions

In this work the solutions of uracil in pure dimethylsulfoxide (DMSO) and diethylsulfoxide (DESO) have been studied by both FTIR ATR spectroscopy and quantum-chemical calculations. The remarkable changes were observed in the C=O, N—H (1745—1630 cm–1) and in S=O stretching region (1100—970 cm–1). The changes of the aforementioned frequencies are explained by the destruction of self-associates of sulfoxides in the presence of uracil and formation of uracil/DMSO (DESO) complexes via hydrogen-bond of the uracil N—H group with the S=O group of sulfoxides. Structural, energetic and vibrational characteristics for the hydrogen-bonded molecular complex of uracil/DMSO (DESO) in the gas phase and in solution have been studied by DFT and ab initio MO theory. It revealed, that the uracil/DMSO complex is more compact compared with uracil/DESO complex due to additional hydrogen bonds via C=O group of uracil and —CH group of DMSO. The observed wavenumbers are in good agreement with calculated wavenumbers.

A computational study of gas-phase acidity and basicity of azulene-based uracil analogue

In this paper, we suggest a computational scheme for the theoretical estimation of gas-phase acidity and basicity of azulene-based uracil analogue. The proton affinities (PAs) of the two oxygen and of the two nitrogen atoms and the deprotonation energies (DPEs) of the two NH and of the two OH bonds of azulene-based uracil analogue isomers are calculated by density functional theory (DFT) using the 6-31+G(d,p) basis set and by high ab initio MO theory (CBS-QB3) method. The PAs of the oxygen and nitrogen atoms of 13 tautomers range from 197.9 to 230.4 kcal/mol and the DPEs of the OH and NH groups from 300 to 342.3 kcal/mol. The proton affinities of di-keto form AZU1 followed the order O9 (N1 site), O9 (N3 site), O11 (N3 site), and O11 (H13 site).

Ab Initio Chemical Kinetics for H + NCN: Prediction of NCN Heat of Formation and Reaction Product Branching via Doublet and Quartet Surfaces

The reaction of NCN with H atoms has been investigated by ab initio MO and RRKM theory calculations. The mechanisms for formation of major products on the doublet and quartet potential energy surfaces have been predicted at the CCSD(T) level of theory with the complete basis set limit. In addition, the heat of formation for NCN predicted at this rigorous level and those from five isogyric reactions are in close agreement with the best value based on the isodesmic process, (3)CCO + N2 = (3)NCN + CO, 109.4 kcal/mol, which lies within the two existing experimental values. The rate constants for the three possible reaction channels, H + NCN → CH + N2 (k(P1)), HCN + (4)N (k(QP1)), and HNC + (4)N (k(QP2)), have been calculated in the temperature range 298-3000 K. The results show that k(P1) is significantly higher than k(QP1) and k(QP2) and that the total rate constant agrees well with available experimental values in the whole temperature range studied. The kinetics of the reverse CH + N2 reaction has also been revisited at the CCSD(T)/CBS level; the predicted total rate constants at 760 Torr Ar pressure can be represented by kr = 4.01 × 10(-15) T(0.90) exp(-17.42 kcal mol(-1)/RT) cm(3) molecule(-1) s(-1) at T = 800-4000 K. The result agrees closely with the most recent experimental data and the best theoretical result of Harding et al. (J. Phys. Chem. A 2008, 112, 522) as well as that of Moskaleva and Lin (Proc. Combust. Inst. 2000, 28, 2393) evaluated with a steady-state approximation after a coding error correction made in this study.

Ab initio MO Theory – An Important Tool in Foldamer Research: Prediction of Helices in Oligomers of ω‐Amino Acids

AbstractThe enormous developments of computer technologies allow the broad employment of ab initio MO theory in foldamer research. In this review, we demonstrate the efficiency and reliability of ab initio MO methods for the description of the helix formation in oligomers of ω‐amino acids on the basis of representative examples. Thus, ab initio MO theory successfully accompanies foldamer research by confirmation and interpretation of experimental results and stimulation of future experiments. The high predictive power of the methods opens the way to novel structure classes with special properties. Nowadays, ab initio MO theory has become an inherent part in the arsenal of methods applied in foldamer research.

Synthesis of C-linked carbo-β2-amino acids and β2-peptides: design of new motifs for left-handed 12/10- and 10/12-mixed helices

C-linked carbo-β(2)-amino acids (β(2)-Caa), a new class of β-amino acid with a carbohydrate side chain having d-xylo configuration, were prepared from d-glucose. The main idea behind the design of the new β-amino acids was to move the steric strain of the bulky carbohydrate side chain from the Cβ- to the Cα-carbon atom and to explore its influence on the folding propensities in peptides with alternating (R)- and (S)-β(2)-Caas. The tetra- and hexapeptides derived were studied employing NMR (in CDCl(3)), CD, and molecular dynamics simulations. The β(2)-peptides of the present study form left-handed 12/10- and 10/12-mixed helices independent of the order of the alternating chiral amino acids in the sequence and result in a new motif. These results differ from earlier findings on β(3)-peptides of the same design, containing a carbohydrate side chain with d-xylo configuration, which form exclusively right-handed 12/10-mixed helices. Quantum chemical calculations employing ab initio MO theory suggest the side chain chirality as an important factor for the observed definite left- or right-handedness of the helices in the β(2)- and β(3)-peptides.

How many hydrogen-bonded α-turns are possible?

The formation of α-turns is a possibility to reverse the direction of peptide sequences via five amino acids. In this paper, a systematic conformational analysis was performed to find the possible isolated α-turns with a hydrogen bond between the first and fifth amino acid employing the methods of ab initio MO theory in vacuum (HF/6-31G*, B3LYP/6-311 + G*) and in solution (CPCM/HF/6-31G*). Only few α-turn structures with glycine and alanine backbones fulfill the geometry criteria for the i←(i + 4) hydrogen bond satisfactorily. The most stable representatives agree with structures found in the Protein Data Bank. There is a general tendency to form additional hydrogen bonds for smaller pseudocycles corresponding to β- and γ-turns with better hydrogen bond geometries. Sometimes, this competition weakens or even destroys the i←(i + 4) hydrogen bond leading to very stable double β-turn structures. This is also the reason why an "ideal" α-turn with three central amino acids having the perfect backbone angle values of an α-helix could not be localized. There are numerous hints for stable α-turns with a distance between the C(α)-atoms of the first and fifth amino acid smaller than 6-7 Å, but without an i←(i + 4) hydrogen bond.

A Network of Small Molecules Connected by Cross-Linked NH Bonds

The synthesis of the small pseudopeptide Boc-l-Phe-d-Imz-OBn (Imz = imidazolidin-2-one-4-carboxylate) is reported. Crystallization of this peptide from methanol, ethanol, and isopropanol leads to isostructural solvates when the solvent is methanol or ethanol with a peptide/solvent ratio of 2:1 and to an unsolvated polymorph in the case of isopropanol. The solvate peptide crystallizes forming infinite chains with the monomers in parallel orientation connected by a single hydrogen bond. The chains are arranged in antiparallel direction and cross-linked through the NH group of the imidazolidin heterocycle with formation of a stable two-dimensional (2D) network. Crystals from isopropanol form a different 2D network. The degree of order in the crystal assembly decreases from methanol and ethanol solvates to the unsolvated pseudopeptide grown from isopropanol. Quantum chemical calculations at the HF/6-31G* level of ab initio MO theory, carried out on the two different packings, show a slight preference for the ...

Theoretical and Experimental Studies on α/ε-Hybrid Peptides: Design of a 14/12-Helix from Peptides with Alternating (S)-C-Linked Carbo-ε-amino Acid [(S)-ε-Caa(x)] and l-Ala

An (S)-C-linked carbo-epsilon-amino acid [(S)-epsilon-Caa((x))] was prepared from the known (S)-delta-Caa. This monomer was utilized together with l-Ala to give novel alpha/epsilon-hybrid peptides in 1:1 alternation. Conformational analysis on penta- and hexapeptides by NMR (in CDCl(3)), CD, and MD studies led to the identification of robust 14/12-mixed helices. This is in agreement with the data from a theoretical conformational analysis on the basis of ab initio MO theory providing a complete overview on all formally possible hydrogen-bonded helix patterns of alpha/epsilon-hybrid peptides with 1:1 backbone alternation. The "new motif" of a mixed 14/12-helix was predicted as most stable in vacuum. Obviously, the formation of ordered secondary structures is also possible in peptide foldamers with amino acid constituents of considerable backbone lengths. Thus, alpha/epsilon-hybrid peptides expand the domain of foldamers and allow the introduction of desired functionalities via the alpha-amino acid constituents.

Helix formation in ε-amino acid oligomers

A complete overview on all possible helix types with unidirectional hydrogen bonds in oligomers of ε-amino acids is given on the basis of a systematical conformational analysis employing ab initio MO theory (HF/6-31G ∗, B3LYP/6-31G ∗, PCM//HF/6-31G ∗). The conformational search provides a wide variety of folding patterns which makes the class of ε-peptides interesting for a rational peptide design by selection of suited backbone substituent patterns. The relationships between the predicted secondary structures for the ε-peptides and other peptide foldamer classes, as for instance α/β-hybrid peptides, are demonstrated.

Sequence-Specific Unusual (1→2)-Type Helical Turns in α/β-Hybrid Peptides

This article describes novel conformationally ordered alpha/beta-hybrid peptides consisting of repeating l-proline-anthranilic acid building blocks. These oligomers adopt a compact, right-handed helical architecture determined by the intrinsic conformational preferences of the individual amino acid residues. The striking feature of these oligomers is their ability to display an unusual periodic pseudo beta-turn network of nine-membered hydrogen-bonded rings formed in the forward direction of the sequence by 1-->2 amino acid interactions both in solid-state and in solution. Conformational investigations of several of these oligomers by single-crystal X-ray diffraction, solution-state NMR, and ab initio MO theory suggest that the characteristic steric and dihedral angle restraints exerted by proline are essential for stabilizing the unusual pseudo beta-turn network found in these oligomers. Replacing proline by the conformationally flexible analogue alanine (Ala) or by the conformationally more constrained alpha-amino isobutyric acid (Aib) had an adverse effect on the stabilization of this structural architecture. These findings increase the potential to design novel secondary structure elements profiting from the steric and dihedral angle constraints of the amino acid constituents and help to augment the conformational space available for synthetic oligomer design with diverse backbone structures.

BINOL-Based FoldamersAccess to Oligomers with Diverse Structural Architectures

In this article, we report on the synthesis and conformation of a new family of aromatic oligoamide foldamers based on binaphthol (BINOL) monomers. A series of oligomers with differing chirality of the individual BINOL building blocks and mixed sequences of alternate BINOL and pyridyl building blocks has been synthesized and structurally characterized. NMR and quantum chemical calculations on the basis of ab initio MO theory were performed to obtain insight into the conformational features of these oligomers. It is shown that the combination of these inherently chiral aromatic building blocks provides a novel access to a wide variety of conformationally ordered synthetic oligomers with diverse and dazzling structural architectures distinct from those classically observed.

Synthesis and Secondary Structure of Alternate α,β‐Hybrid Peptides Containing Oxazolidin‐2‐one Moieties

AbstractThe synthesis and conformational analysis of a novel class of foldamers containing (S)‐β3‐homophenylglycine [(S)‐β3‐hPhg] and D‐4‐carboxy‐oxazolidin‐2‐one (D‐Oxd) residues in alternate order is reported. The experimental conformational analysis performed in solution by IR, 1H NMR, and CD spectroscopy unambiguously proved that these oligomers fold into ordered structures with increasing sequence length. Theoretical calculations employing ab initio MO theory suggest a helix with 11‐membered hydrogen‐bonded rings as the preferred secondary structure type. The few formal helix alternatives can be excluded in particular by steric effects of the oxazolidin‐2‐one rings. The novel structures enrich the field of peptidic foldamers and might be useful in the mimicry of native peptides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Enforcing Periodic Secondary Structures in Hybrid Peptides: A Novel Hybrid Foldamer Containing Periodic γ-Turn Motifs

This note describes the design, synthesis, and conformational studies of a novel hybrid foldamer that adopts a definite compact, three-dimensional structure determined by a combined effect of the special conformational properties of the foldamer constituents. The striking feature of this de novo designed foldamer is its ability to display periodic gamma-turn conformations stabilized by intramolecular hydrogen bonds. Conformational investigations by single-crystal X-ray studies, solution-state NMR, and ab initio MO theory at the HF/6-31G* level strongly support the prevalence of gamma-turn motifs in both the di- and tetrapeptide foldamers, which are presumably stabilized by bifurcated hydrogen bonds in the solid and solution states. The strategy disclosed herein for the construction of hybrid foldamers with periodic gamma-turn motifs has the potential to significantly augment the conformational space available for foldamer design with diverse backbone structures and conformations.

Molecular Structures of arachno-Decaborane Derivatives 6,9-X2B8H10 (X = CH2, NH, Se) Including a Gas-Phase Electron-Diffraction Study of 6,9-C2B8H14

The molecular structures of the three heterodecaboranes arachno-6,9-C2B8H14, arachno-6,9-N2B8H12, and arachno-6,9-Se2B8H10 have been determined by ab initio MO theory. In addition, the structure of arachno-6,9-C2B8H14 was experimentally determined using gas-phase electron diffraction (GED). The accuracy of all four of these structures has been confirmed by the good agreement of the (11)B chemical shifts calculated at the GIAO-MP2 level with the experimental values. A comparison of the GIAO-HF and GIAO-MP2 methods shows that for these heteroborane clusters, electron correlation effects on the computed delta((11)B) values are quite substantial and that it is necessary to go beyond the HF level in the NMR computation.

Helix Formation in α,γ- and β,γ-Hybrid Peptides: Theoretical Insights into Mimicry of α- and β-Peptides

Alpha,gamma- and beta,gamma-hybrid peptides, which are composed of two different homologous amino acid constituents in alternate order, are suggested as novel classes of peptide foldamers. On the basis of a systematic conformational search employing the methods of ab initio MO theory, the possibilities for the formation of periodic secondary structures in these systems are described. The conformational analysis provides a great number of helix conformers widely differing in energy, which can be arranged into three groups: (i) helices with all hydrogen bonds formed in forward direction along the sequence, (ii) helices with all hydrogen bonds in backward direction, and (iii) helices with alternate hydrogen-bond directions (mixed or beta-helices). Most stable are representatives of beta-helices, but their stability decreases considerably in more polar environments in comparison to helix conformers from the other two classes. There is a great similarity between the overall topology of the most stable hybrid peptide helices and typical helices of peptides which are exclusively composed of a single type of homologous amino acids. Thus, the helices of the beta,gamma-hybrid peptides mimic perfectly those of the native alpha-peptides as, for instance, the well-known alpha-helix, whereas the most stable helix conformers of alpha,gamma-hybrid peptides correspond well to the overall structure of beta-peptide helices. The two suggested novel hybrid peptide classes expand considerably the pool of peptide foldamers and may be promising tools in peptide design and in material sciences.

Ab initio Computational Modeling of Glyphosate Analogs: Conformational Perspective

A historical perspective on the application of conformational analysis to structure-based ligand design approach is presented. The application of isodensity molecular electrostatic potential surfaces with the conformational energy surfaces (CES) have allowed us to reach pertinent conclusions for aiding synthetic and biochemical studies. Here we illustrate such an application on the modeling of the potent analogs of an important, environmentally stringent herbicidal compound glyphosate by constructing conformational energy surfaces. The systems were modeled by substituting F, Cl, and NH— OH moiety to the position of pharmacophoric nitrogen center in glyphosate structure. All the calculations were thoroughly performed with ab initio MO theory at Hartree–Fock method using 3-21G(d) basis functions. On the basis of the results, we identified the bioactive conformations for N-fluoro-glyphosate, N-chloro-glyphosate, and N-hydroxyamino-glyphosate as (−38∘, 77∘), (−61∘, 111∘), and (−167∘, −169∘), respectively. Geometry optimization of certain selected conformations of these compounds using hybrid DFT method with 6–31+G(d) basis functions provides nearly equal values of φ and ψ. Moreover, the results indicate that the global minimum structures of N-fluoro and N-chloro analogs of glyphosate show cyclic conformation whereas the N-hydroxyamino-glyphosate global minimum structure shows spyrocyclic and zig-zag conformation. Also, the predicted bioactive conformation of N-hydroxyamino analog optimally overlaps with glyphosate backbone in EPSPS complex with 0.1 A RMSD value. However, the other two compounds slightly deviate from the backbone of glyphosate with RMSD of 0.92 A for N-fluoro-glyphosate and 0.83 A for N-chloro-glyphosate. The linear N-hydroxyamino-glyphosate exhibits relatively more number of intermolecular hydrogen bond interactions as compared to the other two analogs. Further, comparison of CES of previously studied glyphosate analogs such as N-hydroxy-glyphosate (2.2 μM) and N-amino-glyphosate (0.61 μM) with the present systems reveals the order of activity as: N-hydroxyamino-glyphosate > N-fluoro-glyphosate > N-chloro-glyphosate based on CES flexibility. Also, the calculated heats of formation of N-fluoro-glyphosate, N-chloro-glyphosate, and N-hydroxyamino-glyphosate are −288, −209, and −288 kcal/mol, respectively, which clearly indicate that the N-hydroxyamino and N-fluoro analogs of glyphosate are thermodynamically more stable than N-amino-glyphosate (−278 kcal/mol).

Control of Helix Formation in Vinylogous γ-Peptides by (E)- and (Z)-Double Bonds: A Way to Ion Channels and Monomolecular Nanotubes

[structure: see text] A complete overview on the alternative and competitive helices in vinylogous gamma-peptides is given, which was obtained on the basis of a systematic conformational analysis at various levels of ab initio MO theory (HF/6-31G*, DFT/B3LYP/6-31G*, PCM/HF/6-31G*). Contrary to the parent gamma-peptides, there is a strict control of helix formation by the configuration of the double bond between the C(alpha) and C(beta) atoms of the monomer constituents. (E)-Double bonds favor helices with larger pseudocycles beginning with 14- up to 27-membered hydrogen-bonded rings, whereas the (Z)-configuration of the double bonds supports a distinct preference of helices with smaller seven- and nine-membered pseudocycles showing interactions between nearest-neighbor peptide bonds. The rather stable helices of the (E)-vinylogous peptides with 22-, 24-, and 27-membered hydrogen-bonded pseudocycles have inner diameters large enough to let molecules or ions pass. Thus, they could be interesting model compounds for the design of membrane channels and monomolecular nanotubes. Since (E)- and (Z)-vinylogous gamma-amino acids and their oligomers are synthetically accessible, our study may stimulate structure research in this novel field of foldamers.

Two-photon vibronic spectroscopy of allene at 7.0–10.5 eV: experiment and theory

2 + 1 resonance-enhanced multiphoton ionization (REMPI) spectra of allene at 7.0–10.5 eV have been observed. The excited vibronic symmetry has been determined from polarization-ratio measurements. Based on the vibronic energies and peak intensities calculated using ab initio MO and time-dependent density functional theory, the very congested REMPI spectra have been assigned as due to π* ← π, 3p ← π, 4s ← π, 4p ← π, and 4d ← π transitions. Vibrational progressions related to the CH2 twisting (ν4 ∼770 cm−1) have been observed for several excited electronic states. Calculated Franck–Condon factors also confirm that CH2 twisting is the most active mode in the vibronic spectra of allene. In this study, theoretical calculations of two-photon intensities and polarization ratios have been made through the ab initio computed one-photon transition dipole moments to various electronic states as intermediates. As a starting point to interpret the complicated vibronic spectrum of allene, the theoretical approach, without vibronic couplings, has been applied to predict the peak positions, spectral intensities, and polarization ratios of Rydberg states, and qualitatively shows a considerable agreement with experimental observations.

Conformation and function of N-hydroxy-glyphosate and N-amino-glyphosate: a comparative study using ab initio MO theory

Extensive ab initio Molecular Orbital calculations were carried out at HF/3-21G(d) level to study the conformational energy surfaces of N-hydroxy-glyphosate and N-amino-glyphosate. Efforts were made to analyze the trends in observed energy difference between low-energy conformer and bioactive conformer using Density Functional Theory at B3LYP/6-31+G(d) level. The conformational energies were computed as a function of Φ and Ψ. The results indicate that the most stable conformation is found to be at (144°, −80°) for N-hydroxy-glyphosate and (−49°, 87°) for N-amino-glyphosate with relative energies of −4.82 and −1.47 kcal/mol, respectively. The predicted biologically active conformation for these two compounds prefers (t,t) arrangement with a relative energy of −0.74 kcal/mol for N-hydroxy-glyphosate and 0.48 kcal/mol for N-amino-glyphosate. Also, the bioactive conformers are found to superimpose optimally with glyphosate found in EPSPS complex with a RMSD of 0.09 Å for N-hydroxy-glyphosate and 0.1 Å for N-amino-glyphosate. Moreover, the predicted biologically active conformation of N-hydroxy-glyphosate shows higher stability due to strong intramolecular hydrogen bonds as compared to N-amino-glyphosate. Several other conformers of N-hydroxy-glyphosate are also stabilized by relatively more stronger hydrogen bonds than that of N-amino-glyphosate. Further, the calculated heat of formation using AM1 hamiltonian reveals that the N-hydroxy-glyphosate is more negative (−313 kcal/mol) than that of N-amino-glyphosate (−278 kcal/mol) indicating higher stability of the first compound. Thus, the results of the present study, reveal that due to higher stability of bioactive conformer and favourable interactions of phosphonate and carboxyl group with surrounding amino acid residues, the N-hydroxy-glyphosate acts as a better herbicide though its inhibitory constant is higher ( k i=2.2 μM) than that for N-amino-glyphosate ( k i=0.61 μM).

The hydrogen bonding and tautomerism of pyrimidine containing macrocycles. IR, UV and quantum chemical studies

A new type of macrocycle containing 2-thio-4-aminopyrimidine and 6-methyluracil moieties has been studied by IR and UV spectroscopy. The vibrational spectra, conformations and amine–imine tautomerism of the aminopyrimidine fragments have been analysed within the framework of ab initio MO theory (HF/6-31G**, MP2/6-31G**) and density functional theory (B3LYP/6-31G**). According to experimental and theoretical results, the amino form is preferred in these compounds. Both intra- and intermolecular hydrogen bonds of the type NH⋯N are present in crystals, whereas in solutions, conformational equilibria with free NH groups are also obtained.