Novel consecutive beta- and gamma-turn mimetics composed of alpha-aminooxy tripeptides

[structure: see text] To develop novel consecutive beta- and gamma-turn mimetics, we designed and characterized alpha-aminooxy tripeptides (trimers) consisting of oxanipecotic acid dimer and alpha-aminooxy acid. According to FT-IR and NMR data, as well as ab initio quantum calculations, the trimers adopted unusual folded structures with consecutive beta- and gamma-turnlike conformations.     

Computational study on the structural diversity of amyloid Beta Peptide (abeta(10-35)) oligomers

We studied the oligomerization of Alzheimer amyloid beta peptide (Abeta) using a replica exchange molecular dynamics (REMD) simulation. The simulation was performed with Abeta(10-35) dimers, trimers, and tetramers. Extensive REMD simulations illustrated several possible oligomer conformations. As the size of the oligomer increased from a dimer to a tetramer, the number of possible configurations was reduced. We identified all the possible conformations for each oligomer and characterized their temperature dependence. It was found that the detailed structures of the oligomers, which may act as folding intermediates, are highly sensitive to the parameters of the simulation environment such as temperature and concentration. Structural diversities of Abeta oligomers suggest multiple pathways of the aggregation process.     

Synthesis, crystal structure, and different local conformations of pyridine-imide oligomers

In this article, we report a new approach toward synthesis of pyridine-imide oligomers (PIOs). Using this approach, both dimer and trimer were one-pot synthesized from acylation of monomeric monoamide with monomeric dichloride. The yield of trimer was dependent on the alkoxyl terminals: it was 30% for methoyl group, whereas it was 95% for 3-chloro-1-propoxyl terminal. Acylation of dimeric monoamide with monomeric dichloride produced trimer, tetramer, and pentamer in a yield of 34%, 33%, and 28%, respectively. The synthesis was proposed to be mediated through an exchange between pyridine-2-carboxamide and pyridine-2-carbonyl chloride, both forming intramolecular or intermolecular hydrogen-bonds between pyridine-nitrogen and pyridine-2-amide hydrogen atoms. Crystal structure from three trimers with different terminal groups was reported. Analysis on the crystal structures revealed that these three trimers had different local conformations. The different local conformations were originated from the structural tunability of the imide unit in either the coplanarity or bond parameters.     

叠氮二氢硼多聚体结构和性质的理论研究(英文)

本文采用DFT-B3LYP方法,以不同基组对叠氮二氢硼多聚体(H2BN3)n (n=1-4)进行计算研究.二聚体(H2BN3)2(C2h对称性)中含B2N2平面四元环结构.船式(Cs对称性)和椅式(C3v对称性)三聚体(H2BN3)3的结合能相近(-122 和 -126 kJ·mol-1),其中均含B3N3六元环结构.拥有B4N4八元环结构的四个四聚体的结合能只有稍微差别.与单体相比,簇合物的结构参数变化较大.由ΔG0T可知,298.2 K下单体形成二聚体在热力学上是不利的,而形成三聚体和四聚体是有利的.     

Peptide pinwheels

Electrospraying a mixture of Ac-(GA)7K and Ac-A(GA)7K (Ac = acetyl, G = glycine, A = alanine, and K = lysine) peptides produces strong signals for unsolvated dimers and trimers. The conformations of these multimers have been examined with use of ion mobility measurements in conjunction with molecular dynamics simulations. The results suggest that the trimers adopt a pinwheel arrangement of helices with the C-termini tethered together by the protonated lysine side chain from one peptide interacting with the C-terminus of a neighboring helix. This arrangement leads to a cooperative electrostatic stabilization of all the helices through the interaction of the combined charge with the helix dipoles. The dimer adopts a related V-shaped arrangement of helices which is also cooperatively stabilized.     

Molecular origin of anticooperativity in hydrophobic association

The structuring of water molecules in the vicinity of nonpolar solutes is responsible for hydrophobic hydration and association thermodynamics in aqueous solutions. Here, we studied the potential of mean force (PMF) for the formation of a dimer and trimers of methane molecules in three specific configurations in explicit water to explain multibody effects in hydrophobic association on a molecular level. We analyzed the packing and orientation of water molecules in the vicinity of the solute to explain the effect of ordering of the water around nonpolar solutes on many-body interactions. Consistent with previous theoretical studies, we observed cooperativity, manifested as a reduction of the height of the desolvation barrier for the trimer in an isosceles triangle geometry, but for linear trimers, we observed only anticooperativity. A simple mechanistic picture of hydrophobic association is drawn. The free energy of hydrophobic association depends primarily on the difference in the number of water molecules in the first solvation shell of a cluster and that in the monomers of a cluster; this can be approximated by the molecular surface area. However, there are unfavorable electrostatic interactions between the water molecules from different parts of the solvation shell of a trimer because of their increased orientation induced by the nonpolar solute. These electrostatic interactions make an anticooperative contribution to the PMF, which is clearly manifested for the linear trimer where the multibody contribution due to changes in the molecular surface area is equal to zero. The information theory model of hydrophobic interactions of Hummer et al. also explains the anticooperativity of hydrophobic association of the linear trimers; however, it predicts anticooperativity with a qualitatively identical distance dependence for nonlinear trimers, which disagrees with the results of simulations.     

Aromatic-aromatic interactions in proteins: beyond the dimer

Aromatic residues are key widespread elements of protein structures and have been shown to be important for structure stability, folding, protein-protein recognition, and ligand binding. The interactions of pairs of aromatic residues (aromatic dimers) have been extensively studied in protein structures. Isolated aromatic molecules tend to form higher order clusters, like trimers, tetramers, and pentamers, that adopt particular well-defined structures. Taking this into account, we have surveyed protein structures deposited in the Protein Data Bank in order to find clusters of aromatic residues in proteins larger than dimers and characterized them. Our results show that larger clusters are found in one of every two unique proteins crystallized so far, that the clusters are built adopting the same trimer motifs found for benzene clusters in vacuum, and that they are clearly nonlocal brining primary structure distant sites together. We extensively analyze the trimers and tetramers conformations and found two main cluster types: a symmetric cluster and an extended ladder. Finally, using calmodulin as a test case, we show aromatic clsuters possible role in folding and protein-protein interactions. All together, our study highlights the relevance of aromatic clusters beyond the dimer in protein function, stability, and ligand recognition.     

Oligomeric liquid crystals: From monomers to trimers

A homologous series of linear liquid crystal trimers, the 4,4′-bis[ω-(4-methoxyazobenzene-4′-yloxy)alkoxy]azobenzenes, has been synthesized and characterized. The transitional properties of the trimers are compared with those of the corresponding series of dimers, the α,ω-bis(4-methoxyazobenzene-4′-oxy)alkanes, and monomers, the 4-methoxy-4′-alkoxyazobenzenes. Characteristically pronounced odd-even effects were seen for the transitional properties of both dimers and trimers on varying the spacer lengths. The clearing temperatures of the trimers were higher than those of the corresponding dimers, but as the length of the flexible spacers was increased this difference became rather small. The ratios of T _NI, and ΔS _NI/R for monomer:dimer and dimer:trimer are discussed. These are very similar to reported values for similar materials, suggesting that there may be a rather general relationship between the transitional properties of liquid crystal oligomers as the number of mesogenic units is increased.     

The IR spectrum of supercritical water: Combined molecular dynamics/quantum mechanics strategy and force field for cluster sampling

Supercritical water was analyzed recently as a gas of small clusters of waters linked to each other by intermolecular hydrogen‐bonds, but unexpected “linear” conformations of clusters are required to reproduce the infra‐red (IR) spectra of the supercritical state. Aiming at a better understanding of clusters in supercritical water, this work presents a strategy combining classical molecular dynamics to explore the potential energy landscape of water clusters with quantum mechanical calculation of their IR spectra. For this purpose, we have developed an accurate and flexible force field of water based on the TIP5P 5‐site model. Water dimers and trimers obtained with this improved force field compare well with the quantum mechanically optimized clusters. Exploration by simulated annealing of the potential energy surface of the classical force field reveals a new trimer conformation whose IR response determined from quantum calculations could play a role in the IR spectra of supercritical water. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Theoretical Study on Intermolecular Interactions and Thermodynamic Properties of Dimethylnitroamine Clusters

Ab initio SCF and Mφller-Plesset correlation correction methods in combination with counterpose procedure for BSSE correction have been applied to the theroetical studying of dimethylnitroamine and its dimers and trimers.Three optimized stable dimers and two trimers have been obtained.The corrected binding energies of the most stable dimer and trimer were predicted to be -24.68kJ/mol and -47.27kJ/mol,respectively at the MP2/6-31G^*//HF/6-31G^* level.The proportion of correlated interation energies to their total interaction energies for all clusters was at least 29.3 percent,and the BSSE of ΔE(MP2) was at least 10.0kJ/mol.Dispersion and/or electrostatic force were dominant in all clusters.There exist cooperative effects in both the chain and the cyclic trimers.The vibrational frequencies associated with N-O stretches or wags exhibit slight red shifts,but the modes associated with the motion of hydrogen atoms of the methyl group show somewhat blue shifts with respect to those of monomer.Thermodynamic properties of dimethylnitroamine and its clusters at different temperatures have been calculated on the basis of vibrational analyses.The changes of the Gibbs free energies for the aggregation from monomer to the most stable dimer and trimer were predicted to be 14.37kJ/mol and 30.40kJ/mol,respectively,at 1 atm and 298.15K.     

FTIR studies of intermolecular hydrogen bonding in halogenated ethanols

The effect of halogen substitution on intermolecular hydrogen-bonding in ethanol is studied. Specifically, Fourier-transform infrared (FTIR) spectra of ethanol, 2,2,2-trifluoroethanol (TFE), and 2,2,2-trichloroethanol dissolved in carbon tetrachloride are reported as a function of temperature and concentration. The spectral intensities corresponding to monomer, dimer, and multimer formation are used to determine the effect of halogen substitution on intermolecular hydrogen-bonding. The enthalpy for dimerization was found to evolve from -4.2+/-0.3 kcal/mol in ethanol to -6.8+/-1.0 kcal/mol in TFE. An opposite trend was observed for multimer formation with enthalpies of -3.7+/-0.5 in ethanol and -2.1+/-1.4 kcal/mol in TFE. The majority of this evolution is assigned to the ability of ethanols to form intramolecular hydrogen bonds involving the hydoxyl proton and the halogen substituents.     

Cooperative and substitution effects in enhancing strengths of halogen bonds in FCl⋯CNX complexes

In this paper, the cooperative effect of halogen bond with hydrogen bond has been used to make a halogen bond in FCl-CNH dimer vary from a chlorine-shared one to an ion-pair one. The halogen bond is strengthened in FCl-CNH-CNH trimer and its maximal interaction energy equals to -76 kJ∕mol when the number of CNH in FCl-CNH-(CNH)(n) polymer approaches infinity. Once the free H atom in FCl-CNH-CNH trimer is replaced with alkali metals, the halogen bond becomes strong enough to be an ion-pair one in FCl-CNH-CNLi and FCl-CNH-CNNa trimers. An introduction of a Lewis acid in FCl-CNH dimer has a more prominent effect on the type of halogen bond. A prominent cooperative effect is found for the halogen bond and hydrogen bond in the trimers. FH-FCl-CNH-CNH and FH-FCl-CNH-CNLi tetramers have also been studied and the interaction energy of halogen bonding in FH-FCl-CNH-CNLi tetramer is about 12 times as much as that in the FCl-CNH dimer. The atoms in molecules and natural bond orbital analyses have been carried out for these complexes to understand the nature of halogen bond and the origin of the cooperativity.     

Stereo- and regiocontrol in ene-dimerisation and trimerisation of 1-trimethylsilyl-3-phenylcyclopropene

1-Trimethylsilyl-3-phenylcyclopropene and its 2D-analog undergo a highly stereocontrolled ene-reaction to give a single dimer. Further reaction leads to one or more trimers derived through two ene-reactions. The dimer formed easily undergoes cycloaddition with active dienes and nitrile oxides while the trimers do not react under the same conditions. The first enantioselective example of an ene-reaction of cyclopropene derivatives using optically active 1-trimethylsilyl-3S-phenylcyclopropene is also discussed.     

Analysis of non-covalent interactions in (bio)organic molecules using orbital-partitioned localized MP2

Localized molecular orbitals (LMO) are used as basis for an MP2 treatment (LMP2) of electron correlation energies. The major aim is an improved understanding of the non-covalent interactions in large molecules with an emphasis on intra-molecular dispersion effects. A partitioning of the inter-fragment electron correlation energy into electron pairs of different orbital type (i.e., sigma, pi, lone-pairs) is presented. The benzene dimer, 1,4-diphenylbutane conformations, and the tyrosine-glycine dipeptide are used as model systems. For the benzene dimer, comparisons with CCSD(T) data are made in order to analyse the MP2 problems for pi-pi stacking. A comparison of phenyl-phenyl interactions in the benzene dimer and for 1,4-diphenylbutane conformations reveals a very good transferability of dispersion-type contributions to binding from an inter-molecular to an intra-molecular situation. In both systems, the relative (percentage) contributions of sigma-sigma, sigma-pi, and pi-pi pairs to the total inter-fragment correlation energy is a clear signature for the binding mode (pi-stacked vs. T-shaped). For various benzene dimer conformations, we find a linear relation between the MP2 interaction energy error and the correlation contribution from pi-pi pairs. In the dipeptide, also dispersion-type electron correlations between the glycyl amino acid residue and the phenol group are most relevant for folding. This convincingly explains problems of DFT with such systems reported previously. Although in this case only one aromatic ring (and a glycyl moiety) is involved, the same sigma-sigma, sigma-pi, and pi-pi correlations seem to dominate the shape of the potential energy surface.     

Chirality Induction and Amplification in the 2,2,2‐Trifluoroethanol⋅⋅⋅Propylene Oxide Adduct

Chirality induction and amplification in a model system, that is, the 2,2,2‐trifluoroethanol (TFE)???propylene oxide (PO) adduct, were investigated using free‐space and cavity‐based Fourier transform microwave spectroscopy, complemented with high level ab initio calculations. Rotational spectra of four out of eight predicted TFE??PO adducts were assigned, and the remaining four were shown to relax to the geometries of the four observed in a jet expansion. The g+ TFE???S‐PO adduct was found to be favored over that of g? TFE???S‐PO by a factor of 2.8 at 60 K. This difference contrasts the TFE dimer for which an extreme case of chirality synchronization was previously reported. All TFE???PO conformers observed take on the open arrangement, in contrast to 2‐fluoroethanol???PO, which prefers the closed arrangement. Furthermore, perfluorination at CH₃ increases the hydrogen‐bonding energy by about 70 % over its ethanol counterpart.     

Energetics and mechanism of the decomposition of trifluoromethanol

The thermal instability of alpha-fluoroalcohols is generally attributed to a unimolecular 1,2-elimination of HF, but the barrier to intramolecular HF elimination from CF3OH is predicted to be 45.1 +/- 2 kcal/mol. The thermochemical parameters of trifluoromethanol were calculated using coupled-cluster theory (CCSD(T)) extrapolated to the complete basis set limit. High barriers of 42.9, 43.1, and 45.0 kcal/mol were predicted for the unimolecular decompositions of CH2FOH, CHF2OH, and CF3OH, respectively. These barriers are lowered substantially if cyclic H-bonded dimers of CF3OH with complexation energies of approximately 5 kcal/mol are involved. A six-membered ring dimer has an energy barrier of 28.7 kcal/mol and an eight-membered dimer has an energy barrier of 32.9 kcal/mol. Complexes of CF3OH with HF lead to strong H-bonded dimers, trimers and tetramers with complexation energies of approximately 6, 11, and 16 kcal/mol, respectively. The dimer, CH3OH:HF, and the trimers, CF3OH:2HF and (CH3OH)2:HF, have decomposition energy barriers of 26.7, 20.3, and 22.8 kcal/mol, respectively. The tetramer (CH3OH:HF)2 gives rise to elimination of two HF molecules with a barrier of 32.5 kcal/mol. Either CF3OH or HF can act as catalysts for HF-elimination via an H-transfer relay. Because HF is one of the decomposition products, the decomposition reactions become autocatalytic. If the energies due to complexation for the CF3OH-HF adducts are not dissipated, the effective barriers to HF elimination are lowered from approximately 20 to approximately 9 kcal/mol, which reconciles the computational results with the experimentally observed stabilities.     

Intramolecular and liquid structure of 2,2,2-trifluoroethanol by X-ray diffraction

Intramolecular and liquid structure of 2,2,2-trifluoroethanol (TFE) have been investigated by x-ray diffraction at 25°C. The structural parameters for the skeleton of the molecules in the liquid phase are similar to those in the gas phase. The conformers of TFE molecules in the liquid phase are discussed. The O...O distance at about 284 pm and additional F...O one at about 302 pm were found to be characteristic for the first neighbor interactions. Various models (dimers and trimers) have been examined for analyzing the first neighbor structure. The liquid structure was explained in terms of small clusters consisting of two to three molecules rather than of a more extended polymeric network.Central Research Institute for Chemistry of the Hungarian Academy of Sciences, Budapest, P. O. Box 17, H-1525, Hungary.     

London potential-energy surfaces for symmetrical alkali trimers

Semiempirical valence bond calculations have been performed on the symmetrical alkali trimers in order to obtain their potential-energy surface, binding energy, and equilibrium geometry. For these calculations original and generalized Rosen–Morse potentials for the ground state and two similar types of new potentials for the triplet state of alkali dimers have been used. At small internuclear distances the potential surfaces show a shallow well which extends into the entrance and exit valleys without an energy barrier. The trimers are found to be stable both in linear and bent configurations, but the most stable configuration in each case is linear and symmetric. The force constants corresponding to stretching and bending deformations of the trimers have been calculated for this configuration. It has been observed that unlike the stretching, the bending deformation does not sensitively affect the energy variation of the ground state of the trimers.     

Ionic liquids from Car-Parrinello simulations, part I: liquid AlCl3

The properties of isolated AlCl3 clusters and the bulk system are investigated by means of static and dynamic electronic structure methods. We find important structural motifs with the edge connectivity dominant in a dimer and the corner connectivity dominant in a trimer. Furthermore, the trimer cluster exhibits an interesting ring structure with large cooperative effects relative to the dimer. Comparing the found structural motifs in isolated molecule calculations with the structure of the liquid allows us to determine the dominance of edge connectivity in the liquid. The size of the clusters present in the liquid indicates indeed that the dimer is the most abundant species, but there are also trimers, tetramers, and pentamers present. From the local dipole analysis both for the isolated clusters as well as for the liquid, further proof for the edge connectivity is given. However, all results point to the fact that there is also some small percentage of corner connectivity present that might be attributed to the most stable corner-connected cluster, namely the trimer. Importantly, we find that energetic considerations of isolated (static) clusters only do not represent the findings in liquid phase. Instead, a quantum cluster equilibrium approach or simulations are needed.