Showing papers on "Conformational isomerism published in 1987"

Barriers to rotation adjacent to double bonds. 3. The carbon-oxygen barrier in formic acid, methyl formate, acetic acid, and methyl acetate. The origin of ester and amide resonance

Abstract: The structures of the rotamers about the C-O bonds of formic acid, methyl formate, acetic acid, and methyl acetate were calculated by using the 6-31G* basis set and complete geometrical relaxation Large basis sets (6-311+G**) and correction for electron correlation were needed in order to obtain calculated barriers that were in good agreement with the available experimental data The factors that control the geometry at a carbonyl group are considered, and it is shown that an analysis in terms of bond path angles leads to a direct connection with electronegativity The nature of the interaction between an amino group and a carbonyl, as in an amide, is examined and shown not to involve charge transfer from the nitrogen to the carbonyl oxygen, but rather it involves charge transfer between carbon and nitrogen The origin of the rotational barrier in esters and of the difference in energy between the E and Z conformers is discussed

Virtual and solution conformations of oligosaccharides.

Abstract: The possibility that observed nuclear Overhauser enhancements and bulk longitudinal relaxation times, parameters measured by 1H NMR and often employed in determining the preferred solution conformation of biologically important molecules, are the result of averaging over many conformational states is quantitatively evaluated. Of particular interest was to ascertain whether certain 1H NMR determined conformations are "virtual" in nature; i.e., the fraction of the population of molecules actually found at any time within the subset of conformational space defined as the "solution conformation" is vanishingly small. A statistical mechanics approach was utilized to calculate an ensemble average relaxation matrix from which (NOE)'s and (T1)'s are calculated. Model glycosidic linkages in four oligosaccharides were studied. The solution conformation at any glycosidic linkage is properly represented by a normalized, Boltzmann distribution of conformers generated from an appropriate potential energy surface. The nature of the resultant population distributions is such that 50% of the molecular population is found within 1% of available microstates, while 99% of the molecular population occupies about 10% of the ensemble microstates, a number roughly equal to that sterically allowed. From this analysis we conclude that in many cases quantitative interpretation of NMR relaxation data, which attempts to define a single set of allowable torsion angle values consistent with the observed data, will lead to solution conformations that are either virtual or reflect torsion angle values possessed by a minority of the molecular population. On the other hand, calculation of ensemble average NMR relaxation data yields values in agreement with experimental results. Observed values of NMR relaxation data are the result of the complex interdependence of the population distribution and NOE (or T1) surfaces in conformational space. In conformational analyses, NMR data can therefore be used to test different population distributions calculated from empirical potential energy functions.

Vibrational spectra and assignments, normal coordinate analyses, ab initio calculations, and conformational stability of the propenoyl halides

Abstract: The infrared and Raman (3500–30 cm−1) spectra of gaseous and solid propenoyl bromide, CH2 CHCBrO, have been recorded. The Raman spectrum of the liquid has been obtained and qualitative depolarization values have been measured. The fundamental asymmetric torsion for both the s‐trans and s‐cis conformers has been observed along with several hot transitions. From these transitions the potential function governing the internal rotation has been determined and the s‐trans to s‐cis barrier is 1861 cm−1 (5.32 kcal/mol), the trans conformer being more stable by 158±20 cm−1 (452±57 cal/mol). All normal modes have been assigned for the s‐trans conformer and many of those for the s‐cis conformer, based on band contours, depolarization values, and group frequencies. A normal coordinate calculation has been carried out by utilizing a modified valence force field to calculate the frequencies and the potential energy distribution for both conformers. Temperature studies of the Raman spectra of gaseous propenoyl fluoride...

Conformational analysis of synthetic heparin-like oligosaccharides containing α-L-idopyranosyluronic acid†

Abstract: High-field NMR spectroscopy of synthetic heparin-like di- and trisaccharides has afforded a complete set of inter-proton-coupling data on α-L-idopyranosyluronic acid, which have been used for conformational analysis. These data lead to the conclusion that α-L-iduronic acid may display considerable conformational freedom including 1C4, 4C1 and 2S0 (e.g. compound 1) conformers. The 2-O-sulphate substituent at iduronic acid tends to stabilize the 1C4 conformation (e.g. compounds 2 and 4). In addition carbohydrate substituents at position 4 hinder the 4C1 conformation (e.g. compound 3a,b versus 1). Furthermore, the conformation of α-L-idopyranosyluronic acid 2-sulphate is affected seriously by the substituent at position 2 of the non-reducing glucosamine residue. Thus the presence of an ammonium group (i.e. compound 7) leads to unexpected deformation of the 1C4 form of iduronic acid, whereas a sulphamino substituent at this position (e.g. compound 5a,b) brings about the 2S0 skew boat conformation. The iduronic acid moiety of a trisaccharide (compound 6), which represents a part of the anti-thrombin III-binding site of heparin, shows conformational preference for the 2S0 form in aqueous solution under low ionic conditions. However, increasing the ionic strength (e.g. 3 M NaCl) causes the conformational equilibrium to incline towards the 1C4 chair conformer. This feature may be indicative for the mechanism of conformational control as exerted by the AT-III protein upon heparin binding. Several molecular models of preferred conformers have been constructed; Nuclear Overhauser Enhancement data, exo-anomeric effect and Van der Waals interactions have been taken into account.

Reevaluation of rotamer populations for 1,6 linkages: reconciliation with potential energy calculations.

Abstract: Applications of ensemble averaging to the solution conformation of model compounds for N-linked glycans are further investigated. Specifically, the interpretation usually applied to observed values of J5,6', a parameter reflecting the rotameric distribution about C5-C6 bonds (torsion angle omega in 1,6 glycosidic linkages) in 6-O-substituted hexopyranosides, was found to be inconsistent with populations derived from potential energy calculations. However, agreement between observed and calculated, ensemble-averaged values of J5,6' was obtained and the distribution of omega rotamers reinterpreted. Values of J5,6' that were previously interpreted as indicative of equipartition between two rotamers in fact reflect a marked preference for one of them. Additional potential energy terms, previously absent from energy calculations, are introduced and shown to be without effect on interpretations of omega rotamer distributions. From comparisons with both NMR relaxation and scalar coupling constant data, it is concluded that a simple empirical algorithm, HSEA, calculating van der Waals, exo-anomeric, and (as appropriate) hydrogen-bonding terms, is best suited for describing the population distributions in solution for oligosaccharides and N-linked glycans.

15N,13C,6Li NMR spectroscopic studies and colligative measurements of lithiated cyclohexanone phenylimine solvated by tetrahydrofuran

Abstract: N, 6Li, and I3C NMR spectroscopic studies of lithiated cyclohexanone phenylimine (1) in tetrahydrofuran/hydrocarbon solutions detected three different species. 6Li and I5N NMR spectroscopic studies of (6Li,15N)-1 showed the two species observed at low THF concentrations to be a pair of stereoisomeric dimers and the single species appearing at high THF concentrations to be a contact ion paired monomer. Colligative measurements demonstrated the dimers to be bis-solvated at 0 OC. Measurements of the dimer-monomer equilibrium at -94 "C provided best fit to an equilibrium between tris-solvated monomers and bis or higher solvated dimers. We recently isolated a crystalline diisopropylamine solvate of lithiated cyclohexanone phenylimine that was shown to possess a bis-solved dimer structure in the solid state (Figure l).) Spectroscopic analyses showed the existence of a 2: 1 mixture of two rapidly interconverting species in hydrocarbon solution. Although previous studies of lithiated imines had uncovered similar resonance duplications," explanations hinging upon various spatial orientations of the imine carbon skeleton (Figure 2) failed to account for the specific case in question. For example, discrete rotamers around the N-Ci+, bond of lithiated isopropylimines described by Fraser2 seemed highly unlikely for an N-phenyl- substituted imine anion. It seemed equally improbable that both syn and anti isomers would be observable since e~perimental~~ and theoretical evidence5 supported a very large (4-5 kcal/mol) stabilization of the syn orientation. E/Z isomer mixtures observed for acyclic lithiated N-alkyl- and N-phenylimines would be geo- metrically impossible for the corresponding endocyclic imine anion^.^ To further understand the solution behavior of such a poorly precedented diisopropylamine solvate,6 we turned to a strategy for determining both aggregation and solvation states that has been little used in organolithium chemistry since its introduction7~* ~~

Conformational constraints of amino acid side chains in α‐helices

Abstract: The conformational freedom of amino acid side chains is strongly reduced when the side chains occur on an α-helix. A quantitative evaluation of this freedom has been carried out by means of conformational energy computations for all naturally occurring amino acids and for α-aminobutyric acid when they are placed in the middle of a right-handed poly(L-alanine) α-helix. One of the three possible rotameric states for rotation around the Cα Cβ bond (viz. g+) is excluded completely on the helix because of steric hindrance, and the relative populations of the other two rotamers (t and g−) are altered because of steric interactions and the reduction of hydrogen-bonding possibilities. The computed tendencies of the changes in distributions of rotamers, on going from an ensemble of all backbone conformations to the α-helix, agree with the observed tendencies in proteins. Minimum-energy side-chain conformations in an α-helix have been tabulated for use in conformational energy computations on polypeptides.

A High-Resolution Solid-State 13C NMR Study of the Secondary Structure of Branched (1→3)-β-D-Glucans from Fungi: Evidence of Two Kinds of Conformers, Curdlan-Type Single-Helix and Laminaran-Type Triple-Helix Forms, as Manifested from the Conformation-Dependent 13C Chemical Shifts

Abstract: The high-resolution 13C NMR spectra of a variety of fungal branched (1→3)-β-D-glucans were recorded in a DMSO solution and a lyophilized solid in order to gain an insight into the primary and secondary structures in relation to their gel-forming property We found that all the five lyophilized branched (1→3)-β-D-glucans examined so far, except lentinan, exhibit the laminaran-type triple-helix form, as established by the close resemblance of the 13C NMR spectra among them On the contrary, lentinan taking the curdlan-type singlehelix conformation was readily converted to the triple-helix form by lyophilization after having been dissolved in a 8M urea solution (1M=1 mol dm−3) and dialysis against distilled water This finding should be compared with the similar conformational change of curdlan: the conversion by this procedure was at most 50%; annealing at 150°C, followed by slow cooling, was essential for a complete conversion This treatment did not induce the reverse conformational change from the triple

Modeling chemical reactivity. 6. Comparison of conformational energy profiles and electrophilic reactivities and stereoselectivities of chiral allylic alcohols and ethers. Evidence against intramolecular hydrogen bonding in allylic alcohols

Abstract: Conformational energy profiles for 3-buten-2-ol and 2-methoxy-3-butene, obtained from a uniform level of nonempirical molecular orbital theory, are qualitatively similar; the differences between the two appear to arise primarily because of steric interactions. The lowest energy conformers for both position the OH (OR) group directly over the double bond, casting doubt on the previously advanced interpretation that the equilibrium conformation of the allylic alcohol is directed in part by hydrogen bonding between the hydroxylic hydrogen and the ..pi.. bond. It suggests instead that the conformational biases in both the alcohol and ether are influenced primarily by minimization of oxygen lone pair-..pi.. bond repulsion. Electrostatic potentials indicate a preference for electrophilic attack anti to the OR group in the high-abundance but low-reactivity conformers of 2-methoxy-3-butene and syn to OR in the less abundant but much more reactive conformers, the same preferences as have previously been noted in 3-buten-2-ol. Given that electrophilic addition to allylic alcohols and ethers generally occurs syn to the OH (OR) functionality, the results of the theory support a notion that the overall reaction stereochemistry in these systems is influenced more by relative conformer reactivity than by relative abundance.

Comparison by 1H-nmr spectroscopy of the conformation of the 2600 dalton antifreeze glycopeptide of polar cod with that of the high molecular weight antifreeze glycoprotein.

Abstract: The antifreeze glycopeptide (AFGP-8) from polar cod, B. saida, is a 14-amino acid polypeptide having alternating glycotripeptide sequences of Ala-[Gal(β1 3)GalNAc(β1 O)]-Thr-Pro and Ala-[Gal(β1 3)GalNAc(β1 O)]-Thr-Ala, with alanyl residues at amino and carboxy terminals. Conformational studies of AFGP-8 have been carried out by 1H-nmr and empirical energy calculations to investigate the difference in its antifreeze behavior from that of the more active high-molecular weight AFGP 1-4 of P. borchgrevinki. The 1H-nmr spectra, including the resonances of the exchangeable amide protons, were assigned by two-dimensional correlated spectroscopy (COSY), one-dimensional difference decoupling, and nuclear Overhauser effect (NOE) measurements. For the four threonyl residues, the amide proton coupling constants and the small coupling constants between Hα and Hβ indicate similar conformations, despite significant chemical shift differences. The strong NOE between the α protons and the amide protons of the residue following together with large temperature coefficients of chemical shifts, indicate an extended conformation not consisting of α-helix, turns or bends. Energy computations indicate several low-energy conformations consistent with the observed coupling constants for ϕ. Among these, a left-handed helical conformation with three repeating residues per turn has been proposed, which is in accordance with the observed NOE between the methyl group of the α-GalNAc and Ala Hβs. While the observed Overhauser effects in the threonyl side chain suggest a certain amount of conformational averaging, the effect involving the acetmido methyl of α-GalNAc and Hβs of Ala indicate that it as is a major conformer. In view of the close similarity between the conformations of AFGP-8 and the more active antifreeze polymer, AFGP 1-4, we propose that the difference in their activities is due to the length of the regular repeating structure with glycosylation at every third amino acid residue, and not due to any fundamental difference in their conformations.

Nuclear magnetic resonance analysis and conformational characterization of a cyclic decapeptide antagonist of gonadotropin-releasing hormone.

Abstract: Two-dimensional proton nuclear magnetic resonance spectroscopy at 500 MHz has been carried out on the cyclic decapeptide antagonist of gonadotropin-releasing hormone: cyclo-(delta 3-Pro1-D-pClPhe2-D-Trp3-Ser4-Tyr5-D-Trp6-NMeLeu7-Arg8- Pro9-beta-Ala 10). The antagonist exists in two slowly interconverting conformations. All data are consistent with the conclusion that one form has all-trans peptide bonds and the other has a cis beta-Ala10-delta3-Pro1 bond. With the use of sequential assignment methods, chemical shift assignments were obtained for all backbone and side-chain protons of both conformational isomers except for the serine and tyrosine hydroxyl groups and the C gamma, C delta, and guanidinium group protons of the arginine. Temperature dependence of spectral parameters and magnitudes of observed nuclear Overhauser effects support the interpretation that both conformers of the antagonist consist of two beta-turns (type II', D-Trp6-NMeLeu7; type II, delta 3-Pro1-D-pClPhe2) connected by extended antiparallel beta-like strands.

Coupling of the overall molecular motion with the conformational transitions. II. The full rotational problem

Abstract: The method proposed in the companion paper for analysing the coupling between overall and internal dynamics is applied to the study of the full rotational motion of a molecule with one internal degree of freedom. For systems characterized by a finite set of stable conformers determined by the minima of the intramolecular potential, a simplified time evolution operator of mixed type is derived, with the continuous diffusion equation and the generalized random walk operator representing the overall rotation and the internal dynamics, respectively. The dependence on the conformational state of the rotational diffusion tensor is one source of coupling between these two types of motion. Another source is represented by the recoil rotations acting on each subunit during a conformational transition. Both conformational-dependent rotational diffusion tensors and recoil rotations can be calculated from a model for the friction exerted by the solvent. Some applications of the theory are presented in relation to the butane molecule and the molecules having the structure of biphenyl, with particular emphasis on the calculation of the experimental observables in NMR and dielectric relaxation measurements.

Theoretical approach to the molecular conformation of nonfused biheterocycles. Bifurans and furylpyrroles

Abstract: The internal torsional potential for the three structural isomers of bifuran (2,2'-, 2,3'-, and 3,3'-) and the four furylpyrroles (2,2'-, 2,3'-, 3,2'-, and 3,3'-) have been derived from standards SCF STO-3G and 4-31G calculations. Important differences in the potential shapes arise from the two basis sets mainly concerning the planar or out-of-planar structure of equilibrium conformations and the torsional barrier heights. The more relevant results are as follows: (i) 2,2'-isomers show twofold potentials and planar equilibrium conformations. The significance of the greater stability of the cis conformer of 2,2'-furylpyrrole is discussed. (ii) For the rest of the isomers, STO-3G predicts twofold potentials in all cases, whereas 4-31G potentials are found to be greatly dependent on the structure of the interannular region. In particular, fourfold potentials implying gauche out-of-plane equilibrium conformations and strong decreasing barrier heights are found whenever four hydrogen atoms are present in that region.

Furanose ring conformation: the application of ab initio molecular orbital calculations to the structure and dynamics of erythrofuranose and threofuranose rings

Abstract: Ab initiao molecular orbital calculations have been conducted on four tetrofuranose anomers, ..cap alpha..- and ..beta..-D-erythrofuranose and ..cap alpha..- and ..beta..-D-threofuranose, to study the effect of ring conformation on molecular parameters (bond lengths, bond angles, bond torsions) and on total energies. Geometric optimizations of envelope and planar conformers were conducted using the STO-3G basis set; single-point calculations were also performed with the 3-21G basis set. Preferred solution conformations deduced from previous NMR studies are in good agreement with those predicted by calculation, indicating that the intrinsic structures of these furanoses dictate their preferred geometries, and that solvation by water (/sup 2/H/sub 2/O) does not appear to be a major conformational determinant. The ..beta..-D-erythro configuration, which is structurally related to the ..beta..-D-ribo configuration found in RNA, was found to have significantly different conformational behavior from the other three configurations.

NMR studies of indoles and their N-carboalkoxy derivatives

Abstract: The 13C NMR assignment of indoles and 5-methoxyindoles substituted at position 3, and some of their N-carboalkoxy derivatives, was achieved from one- and two-dimensional NMR experiments. Substituent chemical shifts and 1J(CH) values were evaluated. The dynamic processes of N-carboalkoxyindoles and N-carboalkoxyindoline observed by high-field 1H NMR show the existence of two preferred rotamers around the carbamate NC(O)OR bond, which was interpreted in terms of frequency/field strength-dependent phenomena.

Theoretical conformational analysis of a μ-selective cyclic opioid peptide analog

Abstract: The allowed conformations of the μ-receptor-selective cyclic opioid peptide analog were determined using a grid search through the entire conformational space. Energy minimization of the 13-membered ring structure lacking the exocyclic Tyr1 residue and the Phe3 side chain using the molecular mechanics program Maximin resulted in only four low-energy conformations. These four ring structures served as templates for a further energy minimization study with the Tyr1 residue and Phe3 side chain added to the molecule. The results indicated that the Tyr1 and Phe3 side chains enjoy considerable orientational freedom, but nevertheless, only a limited number of low-energy side-chain configurations were found. The obtained low-energy conformers are discussed in relation to various proposed models of the bioactive conformation of enkephalins and morphiceptin.

Conformation of eight-membered dioxathiasilocin heterocycles in solution

Abstract: The dibenzo[d,g][1,3,6,2]dioxathiasilocin derivatives 3a-f were prepared by the reaction of the thiobisphenols 1a-b with the corresponding dichlorosilanes 2a-e using triethylamine as an acid acceptor. The free energy of activation for ring inversion of the 2,4,8,10-tetra-tert-butyl-substituted 3a was determined by variable temperature 1H NMR to be 13.9 kcal/mol. The 1H NMR spectral data of 3a requires that the ring conformer possess a σ plane of symmetry passing through the silicon and bridging sulfur atoms. In the variable temperature 1H NMR spectra of the 2,4,8,10-tetramethyl-substituted 3b no evidence was observed for the slowing of ring inversion at-55oC, suggesting that the energy of activation for ring inversion is less than 10.9 kcal/mol. The 1H NMR spectral data of 3e-f indicates the presence of equilibrating conformational isomers. The results of this study supports the suggestion that steric factors are a major contributor to the barrier of ring inversion for the dibenzo-[d, g][1,3,6,2]...

Spectra and structure of small ring compounds. XLVIII. Conformational stability of methylcyclobutane from low frequency Raman data of the gas

Abstract: The low frequency (500–80 cm−1) Raman spectra of gaseous methylcyclobutane, c‐C4H7CH3, and methyl‐d3‐cyclobutane have been recorded. A series of Q branches beginning at 161 cm−1 for the light molecule and 154 cm−1 for the d3 compound with successive transitions falling to lower frequencies have been assigned to the ring puckering vibrations of both the low energy equatorial and high energy axial conformers. These data have been fitted to an asymmetric potential function of the form: V(cm−1)=(4.78±0.10)×105X4−(3.08±0.04)×104X2 +(2.18±0.1)×104X3 with an assumed reduced mass of 160 amu for the light compound. Utilizing this potential the difference between the puckering angles for the two conformers was calculated to be 4.3° with the equatorial conformer having the larger value of 20.7°. A similar potential was obtained for the d3 molecule. The energy difference between the equatorial and axial forms was found to be 247±20 cm−1 (706 cal/mol) and a barrier of 641±20 cm−1 (1.83 kcal/mol) was found for the inte...