Conformational properties of the macrocyclic trichothecene mycotoxin verrucarin A in solution

Phase-sensitive nuclear Overhauser enhancement spectroscopy (NOESY) experiments, (3)J couplings and computational molecular modeling (MM2* and MMFF force fields) were employed to examine the conformational properties of verrucarin A in chloroform solutions. The MMFF force field calculations resulted in a family of 12 low-energy structures along with their populations, the latter being determined by the NMR analysis of molecular flexibility in solution(NAMFIS) deconvolution analysis. The concluded model was capable of reproducing successfully the experimental NOESY cross-peak volumes and the proton-coupling constants. Among the 12 conformers, the one which was similar to the structure of verrucarin A in the solid state was the predominant accounting for 75% of the total relative population, although other low-energy conformations contributed to a lesser degree in order to explain the experimental data.     

Formation of allyl-substituted allene episulfide S-oxides and their thermal and acid-catalyzed rearrangements

Oxidation of allyl-substituted allene episulfides with a peracid gave the corresponding allene episulfide S-oxides which were found to undergo ready isomerization to bicyclo[2.1.1]thiahexane S-oxide derivatives on thermolysis or under acid-catalyzed reaction conditions.     

Conformational properties of macromolecular pyramoids and their potential use as nano-containers

We study the macroscopic behavior of a pyramid-like nano-construct made of linear macromolecular chains. The average mean square end-to-end distances of the six edges of the pyramoid are evaluated by means of the Gaussian chain model and are found smaller than those of free chains because of architecture confinement. We also evaluate the average areas of the four faces which give a first estimate of the open windows towards the interior space of the macromolecular construct and its loading capacity. The average volume of the polymeric nano-container, which provides a measure of its interior emptiness and carrying ability, is estimated as well. The density of monomers at each point of the construct shows the three-dimensional character of the nano-cage and the location of its entrances and voids.     

Conformational analysis of oligosaccharides in solution

A complete understanding of the role of carbohydrates in biological systems is to a large extent dependent on the information available about the equilibrium mixture and about the preferred conformation of the carbohydrate molecules in solution. The conformational analysis offers a tool which can determine all possible conformations which influence the solution behavior of carbohydrates. This paper attempts to survey the progress in the theoretical conformational analysis of saccharides in solution. The conformational analysis will be discussed in detail both with respect to the strategy for the investigation of conformational properties but also with regard to the quality of the method used for calculations of the energy of the isolated molecule and free energy of solvation. Finally, examples will be given to illustrate how the methods of conformational analysis can be used to estimate the solution behavior of cyclic model compounds of carbohydrates 2-methoxytetrahydropyran, monosaccharide D -glucopyranose, and two disaccharides; β-maltose and β-cellobiose.     

Conformational and electronic properties of a microperoxidase in aqueous solution: a computational study.

A theoretical study of the conformational properties of a small heme peptide in aqueous solution is carried out by classical, long-timescale molecular dynamics simulations. The electronic properties of this species, that is, the relative energies of its excited electronic states and the redox potential, are reproduced and related to the conformational behavior using the perturbed matrix method and basic statistical mechanics. Our results show an interesting coupling between the conformational transitions and the electronic properties. These investigations, beyond the biophysically relevant results addressing the long-standing question of the actual role of the enzyme structure on the enzyme activity, are also of some methodological interest since they offer a further computational perspective for including the electronic degrees of freedom into the modeling of rather complex molecular systems.     

N-Oxides and S-oxides of ellipticine analogs

Oxidation with perbenzoic acid derivatives in neutral organic solvents of 11-desmethylellipticine (at the pyrido-N) and oxa-ellipticine afforded the corresponding N-Oxides. Thia-ellipticine afforded the sulfone N-oxide, which underwent N-deoxygenation with triphenylphosphine to yield thia-ellipticine sulfone.     

Conformational analysis of random copolymers and influence of their compositions on physical properties

Considering four aromatic copolymers as an example, it was shown that the Kuhn segment of those random copolymers calculated by Monte Carlo method had a nonlinear dependence on the copolymer’s composition. It was also shown that the behavior of glass transition temperature, free volume, and dielectric permittivity versus conformational rigidity was similar to the behavior of aromatic homopolymers.     

Enantioselective synthesis,chiroptical properties and absolute configuration of 3-aminosubstituted isothiazole S-oxides

Herein we report a mild and efficient method to synthesize chiral 3-aminosubstituted isothiazole sulfoxides taking advantage of (+)- and (?)-((8,8-dichlorocamphoryl)sulfonyl)oxaziridine under microwave irradiation. The determination of the absolute configuration of the chiral sulfoxide was achieved by theoretical calculation of the CD spectra. The reason for the observed stereoselectivity was enlightened by means of analysis of our data using DFT calculations.     

Conformational equilibria of ethanolamine and its hydrochloride in solution

The conformational preferences of ethanolamine and its hydrochloride in solution were estimated by comparing experimental NMR vicinal proton-proton coupling constants to semiemprical coupling constants for each staggered rotamer, derived by the Haasnoot-Altona method. Strong gauche preferences are observed for both ethanolamine and its hydrochloride over a wide range of solvent polarities. Concentration was not observed to significantly affect the position of the conformer equilibria.     

Conformational properties ofn-alkanes

Values of the conformational entropy contributionΔS _c to the melting entropyΔS _m are calculated from a recently reported equation of state (Jain and Simha), and compared with theoretical valuesS _c derived from the rotational isomeric state approximation. For the shortern-alkanesΔS _c is considerably larger thanS _c , whereas for the longern-alkanes the conformational entropy contribution can approximately be described with the rotational isomeric state model. Equations are presented for the calculation of specific volumes at the melting temperature as a function of chain length.     

Conformational properties of polyhydroxyethers

The conformation of four types of polyhydroxyethers and one amine-cured triglycidyl isocyanurate resin were studied. Static and dynamic light scattering as well as small angle neutron scattering revealed a scarcely detectable influence of branching on the overall dimensions. The branching density has, however, a very pronounced effect on the intrinsic viscosity. The behavior of the latter results from the inverse proportionality of the intrinsic viscosity to the segment density. Estimation of this apparent density gave swelling ratios of only 2 to 5. The cured epoxy resins showed no swelling up to molecular weights of 10 000; in the higher molecular weight region the swelling ratios increase continuously up to a factor of 9.     

Conformational properties of azapeptides

The conformation of several model compounds for azapeptides was systematically examined on the basis of ab initio MO theory at various approximation levels. The calculations show the azapeptide conformation essentially determined by the hydrazine and urea constituents along the sequence. This leads to a characteristic conformer pattern which excludes the possibility of β sheet conformations, but indicates a high potency for the formation of helix and β turn structures. The N atom may change between planar and pyramid structures. The peculiar conformation properties make azaamino acids an attractive tool for secondary structure design in peptides and proteins.     

Conformational properties of pyrethroids

Summary X-ray database searches and theoretical potential-energy calculations indicate that the acid moieties of pyrethroid cyclopropanecarboxylate esters adopt a well-defined, relatively inflexible conformation. In contrast, the alcohol moieties can exist in many low-energy geometries. One of the least conformationally flexible pyrethroid alcohols is 4-phenylindan-2-ol. The approximate overall conformation adopted at the biological binding site by insecticidal esters of this alcohol can be deduced with reasonable confidence by molecular modelling. Graphics superposition of a variety of pyrethroid acids suggests the existence of a large but rather narrow pocket at the binding site, in which substituents at the 3-position of the cyclopropane ring can be accommodated. This pocket is asymmetric with respect to the plane of the cyclopropane ring, extending further on the side remote from the ester group. The effects of -substitution on the insecticidal activity of pyrethroid esters may be due to the influence of substituents on the preferred conformations of the molecules. This hypothesis rationalises the paradoxical dependence on absolute stereochemistry of the activities of various allylbenzyl and cinnamyl alcohol derivatives.Supplementary material available from the authors: Five pages with Cartesian coordinates of hypothesised active conformations of compounds 1, 4, 7, 22–27, 34, 42 and 45.Zeneca Agrochemicals in the U.K. is part of Zeneca Limited.     

Conformational fluctuations and electronic properties in myoglobin

In this article we use the recently developed perturbed matrix method (PMM) to investigate the effect of conformational fluctuations on the electronic properties of heme in Myoglobin. This widely studied biomolecule has been chosen as a benchmark for evaluating the accuracy of PMM in a large and complex system. Using a long, 80-ns, molecular dynamics simulation and unperturbed Configuration Interaction (CISD) calculations in PMM, we reproduced the main spectroscopic features of deoxy-Myoglobin. Moreover, in line with our previous results on a photosensitive protein, this study reveals a clear dynamical coupling between electronic properties and conformational fluctuations, suggesting that this correlation could be a general feature of proteins.     

Conformational transition and aggregation of ϰ-carrageenan macromolecules in solution

Summary Consideration has been given to the processes of conformational transition and aggregation in the aqueous solutions of -carrageenan depending on its concentration, the temperature of the system as a whole and the content of the potassium ions by the methods of polarimetry and spectroturbidimetry. It has been established that one and the same degree of mutarotation can be attained on variation of the concentration of both -carrageenan and potassium ions. The aggregation of the -carrageenan macromolecules occurs under the action of the potasssium ions and is independent of temperature.With 8 figures and 1 table     

Synthesis of linear and angular anthraquinonoisothiazol-3-ones,their S-oxides,and S,S-dioxides

2-Methyltetrahydroanthra[2,3-d]isothiazole-3,5,10-trione and 2-R-tetrahydroanthra[2,1-d]isothiazole-3,6,11-triones were synthesized by the reactions of 3-chloro-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide and 1-nitro-9,10-dioxo-9,10-dihydroanthracene-2-carboxamide with alkanethiols followed by cyclization of the resulting alkylthioamides into isothiazolones under the action of SO₂Cl₂. The products were oxidized to give the corresponding S-oxides and S,S-dioxides.     

Conformational properties of thiophene oligomers

The molecular geometries and the torsional potentials about the inter‐ring C‐C bond in α‐oligothiophenes (α‐nTh, n=2–4) have been calculated by means of conventional ab initio and density functional theory (DFT) calculations employing the hybrid B3LYP and BH&HLYP functionals. The position and the energetics of the critical points in the potential energy curve generated by rotation about the inter‐ring C? C bond are shown to be dependent on the computational method. DFT calculations, in comparison with MP2 calculations, favour conjugative interactions, while steric and coulombic interactions are equally treated by both methods. On oligomerization the electron delocalisation increases slightly, the p‐charge being preferentially confined within the rings, although it is sufficient to move the molecular structure towards co‐planarization and to increase the barrier through the perpendicular conformation. The IR and Raman spectra on the relevant rotamers of α‐2Th have been computed at HF/6–31G* and B3LYP/6–31G* levels. The comparison with the experiment is excellent. It has been found that small twisting from the planar conformation has no apparent effects, while 90° twisting and isomerization to the syn‐gauche form produce significant frequency and intensity variations which could be useful probes in conformational studies. The simulated IR and Raman spectra of the α‐2Th rotamers are consistent with a smallπ‐electron delocalisation between the rings.     

Conformational properties of O-alkylated benzamides

In this article, we report the synthesis, solid-state and solution-state conformational studies of O-alkylated aromatic benzamides based on two scaffolds. Intramolecular hydrogen bonding provides conformational pre-organization and side chains can interact with each other within a molecule. In the solid-state three-dimensional arrangement, the molecules further interact with each other through non-covalent interactions. Given, the demonstrated potential of this class of scaffolds to act as helix mimetics for the inhibition of protein–protein interactions (PPIs), these results provide key insight for future inhibitor design.     

Conformational preference of polyglycine in solution to elongated structure

Do polypeptide chains ever behave like a random coil? In this report we demonstrate that glycine, the residue with the fewest backbone restrictions, exhibits a strong preference for an extended conformation in solution when polymerized in short segments of polyglycine. A model peptide system comprised of two unique tripeptide units, between which 1 to 18 glycine residues are inserted, is characterized by NMR and by small-angle X-ray scattering (SAXS). The residual dipolar coupling (RDC) values of the two tripeptide units are insensitive to changes in number of intervening glycines, suggesting that extension of the linker does not alter the average angular relationship between the tripeptides. Polyglycine segments longer than nine residues form insoluble aggregates. SAXS measurements using synchrotron radiation provide direct evidence that polyglycine peptides adopt elongated conformations. In particular, the construct with a linker with six glycines showed a scattering profile indicative of a monomeric state with a radius of gyration and the maximum dimension of 9.1 A and approximately 34 A, respectively. The ensemble averaged global structure of this 12-mer peptide can best be approximated by a cylinder with a radius of 4 A and a length of approximately 33 A, making it intermediate in extension between a beta strand and an alpha helix.