Effects of Aqueous and Organic Solvents on the Conformational Properties of the Helix-Forming alpha-Methyl-beta-L-aspartamyl Residue

The conformational preferences of N-acetyl-N'-methyl-alpha-methyl-beta-L-aspartamide, which is the model compound for helical poly(beta-L-aspartate)s, have been determined by ab initio SCF-MO computations. Two driving patterns have been found for the existing 13 minimum energy conformations: (i) intramolecular hydrogen bonding interactions of both amide-amide and amide-ester type; and (ii) repulsive interactions between the four oxygen atoms contained in the molecule. Self-consistent reaction-field (SCRF) calculations based on the method proposed by Miertus, Scrocco, and Tomasi have been performed in order to evaluate the effect of the solvent on the conformational preferences of the compound subject of study. Water and carbon tetrachloride were the solvents chosen for this purpose, and results have been discussed and interpreted on the basis of their electronic structures. The conclusions drawn from this study are of assistance to understand some features of the conformational transitions experimentally found in poly(beta-L-aspartate)s.     

The Structure of the Elusive Simplest Dipeptide Gly-Gly

Among the hundreds of peptide compounds for which conformations have been determined by using different spectroscopic techniques, the structure of the simplest dipeptide glycylglycine (Gly-Gly) is conspicuously absent. Herein, for the first time, solid samples of Gly-Gly have been vaporized by laser ablation and three different structures have been revealed in a supersonic expansion by Fourier transform microwave spectroscopy. The intramolecular hydrogen bonding interactions that stabilize the observed forms have been established based on the ¹⁴N nuclear quadrupole hyperfine structure. We have illustrated how conformer interconversion distorts the equilibrium conformational distribution, giving rise to missing conformers in the conformational landscape.     

Conformational and packing energy for the three crystalline forms of isotactic poly-α-butene

Calculations of the conformational and of the packing energy have been performed for the three main crystalline modifications of isotactic poly-α-butene. Calculations of the conformational energy have been performed first through minimizations of the energy of the isolated chains under the constraint of maintaining the experimental helical symmetry and periodicity for each modification. In this way accurate conformations have been determined for the helices corresponding to the three modifications. These conformations have been used for calculation of the packing energy of the three modifications of poly-α-butene. The considered space groups are those experimentally observed; for each modification also the possibility of statistical up and down positioning of the chains has been examined. The differences between the packing energies are greater than those between the conformational energies for the three different modifications. The relative stabilities of the three modifications of poly-α-butene, as obtained by our calculations, are discussed.     

Cyclohexene-sulfur bichloride adducts.: Stereochemical considerations.

The reaction of sulfur dichloride with cyclohexene produces two isomeric trans-adducts of meso and dl configurations. Derivatives of both series have been obtained and configurations have been assigned by means of pseudoasymmetry. General principles for the conformational analysis of systems which contain two inverting 6-membered rings have been discussed and the positions of conformational equilibria have been evaluated. The new conformational effect-stabilization of “heteroconformer”—has been found in the case of dl-bis(2-chlorocyclohexyl) sulfoxide.     

Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E. coli Cells

The β-barrel assembly machinery (BAM complex) is essential for outer membrane protein (OMP) folding in Gram-negative bacteria, and represents a promising antimicrobial target. Several conformational states of BAM have been reported, but all have been obtained under conditions which lack the unique features and complexity of the outer membrane (OM). Here, we use Pulsed Electron-Electron Double Resonance (PELDOR, or DEER) spectroscopy distance measurements to interrogate the conformational ensemble of the BAM complex in E. coli cells. We show that BAM adopts a broad ensemble of conformations in the OM, while in the presence of the antibiotic darobactin B (DAR-B), BAM′s conformational equilibrium shifts to a restricted ensemble consistent with the lateral closed state. Our in-cell PELDOR findings are supported by new cryoEM structures of BAM in the presence and absence of DAR-B. This work demonstrates the utility of PELDOR to map conformational changes in BAM within its native cellular environment.     

Random fluorinated copolymers of tetrafluoroethylene: a study of the inclusion/exclusion of defects from the crystal by conformational and packing energy calculations

A conformational analysis has been performed on the isolated chains of copolymers of tetrafluoroethylene with hexafluoropropene, chlorotrifluoroethylene or perfluoromethyl vinyl ether, in comparison with polytetrafluoroethylene. The lowest energy conformations in accordance with the chain repeating distance of polytetrafluoroethylene in the low temperature crystal phase have been used in packing energy calculations. The results of both conformational and packing energy calculations suggest that the  Cl group is easily tolerated in the crystal phase. The —CF₃ group could also be tolerated in the crystal phase but at the cost of conformational and crystal lattice deformations. On the contrary, it can be concluded that the —OCF₃ group is excluded from the crystal phase because its presence should require high energy values and wide deformations in the unit cell parameters.     

Theoretical justification of empirical additivity schemes for conformational energies

Additivity of conformational energy of saturated molecules has been studied using the perturbation theory for density matrix. Analytical expressions for both total and conformational energies have been obtained and analyzed up to the third‐order members. It is shown that the conformational energy of compounds under investigation can be presented as a sum of transferable increments corresponding to the energies of separate conformational segments and their sequences. The role of end groups in determination of energies of conformational segments is revealed. The influence of substitution has been investigated. The dependence of subtle conformational effects on common structural peculiarities of Hamiltonians of saturated molecules has been concluded. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003     

Ground-state conformational equilibrium of previtamin D and its E-isomer: Effect on the absorption characteristics

The ground-state conformational analysis of previtamin D, its E-isomer, tachysterol, their 10-desmethyl analogues and 1-methyl-1-hydroxy-previtamins have been performed by force-field calculations. Differences in the absorption characteristics of these compounds are discussed in view of the chromophore geometry and abundance (%) of the calculated conformers according to a Boltzmann distribution at 298 K. On the basis of present calculations, the red shift of previtamin D low-temperature UV and CD spectra determined earlier is attributed to the shift of conformational equilibrium in favour of more stable cZc geometries. The effect of complex formation with simplest model cluster of silica surface ((H₃SiO)₃SiOH), on previtamin D and tachysterol conformational equilibria and on UV-absorbance maxima has been evaluated.     

Vibrational Circular Dichroism Spectroscopy of Three Multidentate Nitrogen Donor Ligands: Conformational Flexibility and Solvent Effects

A series of multidentate nitrogen donor ligands have been synthesized and characterized and their conformational distributions in solution have been investigated. Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectroscopy, complemented with DFT calculations, have been used to probe the conformations of these important ligands in solution directly. These three ligands demonstrate very different conformational flexibility; the pyridine subunits and amine groups may adopt a number of different conformations. Experimental VA and VCD data measured in CDCl₃ have been compared to the theoretical spectra of all possible most stable conformers. Solvent effects have been taken into account by using the implicit polarizable continuum model and explicit solvation model. The explicit hydrogen‐bonding solvation model is important for explaining the VCD sign‐reverse phenomenon in the amide I region. Good agreement has been achieved between experimental and predicted spectra for all three ligands; thus allowing detailed examination of the related conformational structures and distributions in solution.     

The role of molecular mechanics in the prediction of the chain conformation of polymers in the crystalline state: Syndiotactic polymers

Molecular mechanics methods have been used in order to find the conformations of various syndiotactic polymers in crystals. Three different classes of polymers have been examined: i) polyolefins, such as poly(propylene), polystyrene, poly(1‐butene) and poly(1,2‐butadiene); ii) polydienes, such as cis‐1,4‐poly(1,3‐pentadiene); iii) alternating copolymers of carbon monoxide with styrene or styrene derivatives. The presence of conformational polymorphism in some of the studied polymers is predicted and explained by maps and minimizations of the conformational energy. The calculated internal parameters and chain axis repeats of all the considered polymers result in very good agreement with X‐ray experimental data reported in literature. The role of intramolecular nonbonded interactions in determining the conformations of the polymer chains is thoroughly discussed.     

Conformational properties of structurally rigid polyamides. I. Conformation of polyamides and model diamides derived from optically active cyclic 1,2-dicarboxylic acids

The conformational equilibria of piperidine diamides derived from five cyclic 1,2-dicarboxylic acids (I–V) have been investigated by dipole moment measurements and a priori conformational energy estimates. Since these diamides represent the building blocks of the polyamides derived from the above cyclic diacids and piperazine or trans-2,5-dimethylpiperazine, the results obtained in the study of the models have been used to investigate the conformation of the polymers. The overall evidence suggests that cyclopentane, cyclohexane, and bicyclooctane piperazine polymers behave as rigid rods in which the structural units possess approximately the same conformational preference exhibited by the respective model diamides.     

A theoretical analysis of the conformation of Ac-L-Ala-L-Pro-L-Ala-NHMe with intramolecular hydrogen bonds

Summary 1. The optimum conformations of Ac-L-Ala-L-Pro-L-Ala-NHMe with eight possible systems of intramolecular hydrogen bonds have been calculated by the method of theoretical conformational analysis.2. The structures found serve as canonical forms for the study of the conformational states of sections of peptide-protein systems with proline residues.3. It has been shown that the interaction of adjacent residues in the structure of the compound mentioned play the dominating role.M. M. Shemyakin Institute of Bioorganic Chemistry, Moscow. Translated from Khimiya Prirodynykh Soedinenii, No. 2, pp. 233–238, March–April, 1976.     

Structural Study and Conformational Behavior of the Two Different Lipopolysaccharide O‐Antigens Produced by the Cystic Fibrosis Pathogen Burkholderia multivorans

Lipopolysaccharides (LPSs) are virulence factors expressed by Gram‐negative bacteria; they are among those mainly responsible for bacterial virulence. In this work we define the primary structure and the conformational features of the O‐chain from the LPS produced by the highly virulent clinical isolate Burkholderia multivorans strain C1576, an opportunistic human pathogen isolated in a cystic fibrosis center and causative of an outbreak with lethal outcome. We demonstrate that the LPS from this clinical isolate consists of two O‐polysaccharide chains present in different amounts and made up of repeating units, both containing deoxy sugar. Additionally, conformational studies have been performed to establish and compare the spatial arrangements of the two polysaccharides and differences in their shape have been highlighted. The comprehension of the structural and conformational features of the two repeating units may help to explain their biological significance, the molecular shape of the bacterial external surface, and the comprehension at the molecular level of the recognition mechanisms of the antibodies.     

In situ FT-IR spectroscopic study on the conformational changes of isotactic polypropylene in the presence of supercritical CO2

The conformational changes of isotactic polypropylene (iPP) under supercritical CO₂ condition with different pressure and temperature have been carefully studied by in situ Fourier-transform infrared spectroscopy (FT-IR). Analysis of the corresponding spectra shows that the conformational ordering by supercritical CO₂ results in the intensity enhancement of the regularity bands of iPP. Due to the high CO₂ concentration and strong intermolecular interaction, iPP can reach an equilibrium state in a short time at high CO₂ pressure. The equilibrium time increases with soaking temperature. After supercritical CO₂ treatment, two mechanisms, the formation of short helix from amorphous phase and the extension of short helix into long one, happen simultaneously. The latter mechanism undergoes quickly at the beginning of induced conformational changes and then slows down, resulting in the slight increase of crystallinity. At the same time, the conformational ordering in amorphous phase happens continuously until a thermodynamic equilibrium. In summary, in the presence of supercritical CO₂, the conformational ordering of iPP chains occurs exclusively in the amorphous region, with no impact on the crystal part.     

Locking the Conformation of a Paddlewheel Rhodium Complex: Design,Synthesis, and Applications in Catalytic Nitrene Transfers

The exponential proliferation of conformers makes it impossible to examine the entire population in most systems. Controlling conformational ensembles is thus pivotal in many areas of chemistry. Rh₂(esp)₂, a dicarboxylate-derived paddlewheel rhodium complex, is one of the most effective catalysts for nitrene chemistry. Its enormous success has led to preparing many analogous complexes. However, there has been little consideration for the conformational dynamics of the parent catalyst. Herein, we report a new ligand modification principle that prevents conformer interconversion. The resulting complex comprises two isolable conformers, whose structures have been determined by X-ray diffraction. Combined experimental and computational data has revealed similarities and dissimilarities between the conformationally confined and parent complexes. Three model cases have demonstrated the utility of conformational fixation in the development of stereoselective catalysts for nitrene transfer reactions. The design principle described in this study can be combined with other established modification strategies, serving as a springboard for further advancement of the chemistry of paddlewheel metal complexes.     

Solvent and substituent effects on the conformational equilibria and intramolecular hydrogen bonding of 4-substituted-2-hydroxybenzaldehydes

By applying the B3LYP/6-31G(d) method with the SCIPCM model on seven 4X substituted 2-hydroxybenzaldehydes, some structural characteristics related with their conformational equilibria and intramolecular hydrogen bonds have been clarified. The compounds are almost completely under the planar conformation characterized by a strong intramolecular hydrogen bond, which decreases in those solvents that possess a higher hydrogen bond donating capability and polarity. The substituents exert a marked influence on the conformational equilibrium constants and the strength of the IHB. Moreover, the excellent Hammett-type equations obtained support the proposed conformational reactions to quantify the IHB in the o-hydroxybenzaldehydes studied.     

Conformation of glycomimetics in the free and protein-bound state: structural and binding features of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man

The conformational properties of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man in solution have been carefully analyzed by a combination of NMR spectroscopy and time-averaged restrained molecular dynamics. It has been found that both the alpha-1,3- and the alpha-1,6-glycosidic linkages show a major conformational averaging. Unusual Phi ca. 60 degrees orientations for both Phi torsion angles are found. Moreover, a major conformational distinction between the natural compound and the glycomimetic affects to the behavior of the omega(16) torsion angle around the alpha-1 --> 6-linkage. Despite this increased flexibility, the C-glycosyl analogue is recognized by three mannose binding lectins, as shown by NMR (line broadening, TR-NOE, and STD) and surface plasmon resonance (SPR) methods. Moreover, a process of conformational selection takes place, so that these lectins probably bind the glycomimetic similarly to the way they recognize the natural analogue. Depending upon the architecture and extension of the binding site of the lectin, loss or gain of binding affinity with respect to the natural analogue is found.     

Investigation of conformational transition in poly(cyclohexyl methacrylate)

The variations of intrinsic viscosity and refractive index increment with temperature for poly(cyclohexyl methacrylate) in isobutyl methyl ketone have been studied. A conformational transition has been found in the range 10–30°C. The influence of the molar volume of the side-group on the conformational transition temperature has also been discussed with respect to results for related polymers.     

Resonance assignments of diastereotopic CH2 protons in the anomeric side chain of selenoglycosides by means of 2J(Se,H) spin‐spin coupling constants

Unambiguous resonance assignments of diastereotopic CH₂ protons in the anomeric side chain of nine alkyl‐ and aralkylselenoglycosides have been carried out on the basis of experimental CPMG‐HSQMBC measurements and theoretical second order polarization propagator approach (SOPPA) calculations of geminal ⁷⁷Se‐¹H spin‐spin coupling constants involving diastereotopic pro‐R and pro‐S protons. Theoretical conformational analyses have been performed at the MP2/6‐311G** level. The conformational space of each of the selenoglycosides under study could be adequately described as a mixture of six interconverting conformers with the molar fractions depending on the nature of the side chain substituent at the selenium atom. The good agreement observed between measured and the weighted conformational averaged values of the calculated coupling constants provides a basis for reliable diastereotopic assignments in this type of carbohydrate structures. Copyright © 2012 John Wiley & Sons, Ltd.     

Spatial structures of natural sesquiterpenes of the humulene type

The spatial structures of the natural sesquiterpenes -,-, and -humulenes have been studied by the method of molecular mechanics (MM). The conformational states of the 11-membered macrocycle in the humulenes have been analyzed on the basis of calculated figures and x-ray structural results. It has been shown that four conformational states, differing by the mutual positions of the C14 and C15 methyl groups and the C7 and C8 atoms relative to the plane of the macrocycle are characteristic for all humulenes. These conformational states are denoted as₁₄U⁸ ₇,¹⁴U⁸ ₇,₁₄U⁷ ₈, and¹⁴U⁷ ₈. The conformational flexibility of the 11-membered ring in the humulenes has been evaluated.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (3712) 40 64 75. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 287–296, May–June, 1997.