The electrostatic potential of yeast tRNAPhe. II. The potentials of the phosphate groups in their various conformational states

The range of conformational states of the phosphate groups observed in the published crystal structure of tRNA^Phe is used as the basis for theoretical studies on the effect of conformation on the electrostatic potentials of these moieties. Deductions concerning the influence of these effects on the potential of a complete tRNA^Phe macromolecule are presented.     

The conformational properties of glycosidic linkages

The developments in stereochemistry which have made possible our present appreciation of the preferred orientation of the aglycon for a glycopyranoside are briefly reviewed. Recent studies in this laboratory are presented wherein, for model compounds, measurements were made of the coupling constant between the ¹³C-aglyconic carbons and anomeric hydrogens as an estimate of the torsion angles, of ¹³C-chemical shifts as a measure of relative steric compressions at the anomeric centers, and of contributions to the molecular rotations by units of conformational asymmetry defined by atoms about the glycosidic bond. These measurements are compared to the results of hard-sphere calculations. It is concluded that the exo-anomeric effect offers an important resistance to rotation about the anomeric carbon to glycosidic bond (φ angles) and that the preferred conformation for a glycopyranoside arise mainly from rotation about the aglyconic carbon to glycosidic oxygen bond (ψ angles).     

The conformational analysis of tetrahydro-1,4,2-dioxazines

A conformational study of some tetrahydro-1,4,2-dioxazines by use of ¹H and ¹³C NMR spectroscopy is reported. The conformational characteristics of this ring are compared to those of the related systems, tetrahydro-1,2- and 1,3-oxazine. A study of model compounds allows the assignment of ring and nitrogen inversion processes in the variable temperature NMR spectra. Ring inversion is found to be a lower energy process than nitrogen inversion. The barriers to these processes are measured in several derivatives and the implications of the results for studies of nitrogen inversion in other 6-membered rings are pointed out. The conformational free energy differences of N-Me and N-Et groups are measured and discussed. It is somewhat easier to put an N-Et group axial than N-Me (ca.0.25 kcal mole^?1). It also appears than an Et group at C-6 goes axial more readily than does a Me.     

The synthesis and conformational analysis of tetrahydro-1,2,4-oxadiazines

The synthesis and variable temperature ¹H and ¹³C NMR spectra of three tetrahydro-1,2,4-oxadiazines are reported. The N(4)-Me inversion barriers are 6.8–7.0 (ax→ts) and 7.4–7.9 kcal mol^?1 (eq→ts) with ΔG° 0.6–0.9 kcal mol^?1. The N(2)-Me inversion barriers are 10.4–11.4 (ax→ts) and 11.6–13.1 kcal mol^?1 (eq→ts) with ΔGδ 1.2–1.7 kcal mol^?1. The barrier to ring inversion is ca. 12.7 kcal mol^?1. “R value” analysis shows the ring to have a 56.5±2δ dihedral angle about the C(5)-(6) bond, indicative of the expected chair conformation.     

Hormone-receptor interactions. Synthesis and conformational study of cyclo-L-cystathionine.

The purpose of this work was to see whether the replacement of a sulfur atom in a cystine disulfide bridge by a methylene group is an only superficial ‘isosteric’ substitution, i.e. with regard to size, hydrophobia, bond angles, etc., or whether it would also encompass such parameters as preferred conformations in solution (M- or P-helicity of the bridge). The methods involved the synthesis of a model compound, cyclo-L -cystathionine (cyclo-L -carbacystine), and its investigation by ¹H- and ¹³C-NMR. It is concluded that the conformations of the CH₂(β)? CH₂(γ)? S? CH₂(β') bridge, and of the diketopiperazine ring are closely similar to the analogous elements in cyclo-L -cystine (DMSO as solvent). This knowledge might help to explain the fact that carba analogs of heterodetic-cyclic polypeptide hormones are often biologically very active.     

The conformational equilibrium of 1,3-dichloro-5-methylcyclohexane

Two of the stereoisomers of the title compound were prepared and their dipole moments were measured. For the r-1,c-3-dichloro-t-5-methylcyclohexane, the free energy difference between conformers with axial-axial (aa) and equatorial-equatorial (ee) chlorines was measured by a variable temperature NMR method, and the value found was 1.3 ± 0.2 Kcal/mol^-1 (in acetone) favoring the latter. Molecular mechanics studies show that the solvation energy and the electrostatics are of major importance in understanding this equilibrium. Calculations show the effect of the methyl group is essentially additive, and give for cis-1,3-dichlorocyclohexane itself ee?aa DH+ 3.0 kcal mol^-1 (acetone).     

The synthesis and conformational behaviour of 2,11-dithia[3,3]metacyclophanes with internal phenyl substituents.

The synthesis of syn- and anti-9-methyl-18-phenyl- and anti-9, 18-diphenyl 2, 11 dithia[3,3]metacyclophanes is described, together with their variable temperature ¹Hmr spectra. Only partial rotation of the phenyl substituents (gD^≠_c ?50 kJ. mol^?1) is believed to occur.     

The influence of the solvent on the conformational energy differences due to the anomeric effect

The solvation free energy ΔG^sol of molecules exhibiting the anomeric effect is computed in an approach that considers a continuous distribution for the solvent. A partition of ΔG^sol into separately evaluated contributions confirms that changes in the energy of the systems due to changes in conformation of the solute are ruled by the electrostatic contribution. A comparison with the “exact” values indicates that the approximate expression for the electrostatic contribution to ΔG^sol are not accurate enough to permit a proper modeling of the solvent influence on the anomeric effect. The systems are composed of methanediol, methoxymethanol, dimethoxymethane, and 2-methoxytetrahydropyran in carbon tetrachloride, chloroform, acetone, and water. The calculations have been performed at the SCF level with the STO -3G and 4–31G basis sets.     

Carbon-13 NMR studies of thyroid hormones and model compounds. The conformational analysis of diphenyl ethers

The ¹³C spectra of a series of thyroid hormones and derivatives including thyroxine (T₄) sodium salt, T₄-N-acetyl methyl ester, triiodothyronine (T₃), T₃-sodium salt, T₃-methyl ester hydrochloride, sodium triiodothyroacetate and ethyl triiodothyropropionate were assigned using chemical shift trends from model compounds, coupling constants and relaxation times. The ¹³C spectra of a series of diphenyl ethers were assigned and the chemical shift trends observed were analyzed on the basis of conformational changes engendered by mesomeric or steric effects.     

High-molecular-weight hydrolyzed polyacrylamides. I. Characterization. Effect of salts on the conformational properties

The effect of ionization (α) and added salts (NaCl, CaCl₂, MgCl₂) on the dimensions of commercially available high-molecular-weight polyacrylamides (M _w ? 4 × 10⁶), hydrolyzed at various extents (0.04 < τ < 0.49) and which have been characterized, was investigated by viscosity and light-scattering measurements performed at 25°C. The data point with evidence to the strong dependence of the chain dimensions on the charge density (ατ) and the effect of the nature and concentration of added salts. From a practical point of view it is shown that there is no advantage to using too highly hydrolyzed samples (τ > 0.45) in media containing large amounts of salts that lead to precipitation of polymers, especially in the presence of divalent ions.     

Dithiosalicylides and trithiosalicylides. Their conformational behaviour in solution

The trithiosalicylide derivatives ($\text{11}$) - ($\text{14}$) have been synthesised and shown to exist in solution as ring inverting ($\text{15}$?$\text{15}$^*) enantiomeric helical conformations.     

Molecular mechanics of peroxides. I. Parametrization and conformational analysis of linear compounds

A force field has been developed for use in MM2 calculations of geometric and energy data for linear peroxides R₁? O? O? R₂ and tested in some of them (R₁, R₂ = H, Me, Et, Prⁱ, Bu^t). The field obtained yield results that agree considerably better with experimental and ab initio data than those afforded by the only set of estimated parameters hitherto available.     

A force-field study of the conformational characteristics of the iduronate ring

Methods of molecular mechanics were applied to investigate the conformation of the (methyl 2-O-sulfate-4-methyl-α-L-idopyranose) uronic acid (DMIS), in order to correlate the peculiar vicinal proton coupling constants observed in polysaccharides containing the iduronate ring to the conformational characteristics of this sugar ring. We found three conformers with comparable energies, namely the two chair forms ¹C₄ and ⁴C₁ and the skew-boat form ²S₀(L); the latter is separated from each chair form by a barrier of about 9 kcal/mol. Along the pseudorotational path three additional minima (³S₁, ¹S₃, and ¹S₅) were found, yet at least 4 kcal/mol higher than ²S₀. The results obtained for the relative energies of the three conformers and the conformation of the side groups were affected by the inclusion of the electrostatic term and, in particular, by the charge assigned to the ionic groups of DMIS. However, the conformational properties of the idopyranosidic ring in DMIS (and in related compounds) should still be interpreted in terms of equilibrium among these three conformers only.     

The 13C NMR conformational analysis of 9,10-dihydroanthracene monoanions

The ¹³C NMR chemical shifts and coupling constants for the parent and $\text{t}$-butyl 9,10-dihydroanthraceneyl lithiums indicate sp² hybridization and flattened geometries.     

Oxazepines and thiazepines. XIII—conformational analysis of 2,3-dihydrobenzothiazepine derivatives

The conformation and relative configuration of various condensed heterocycles possessing a 2,3-dihydro-1,5-benzothiazepine moiety and their synthetic intermediates were determined by ¹H and ¹³C NMR spectroscopy. It was found that epimerization takes place during the ring closure reaction.     

The multiple minimum problem in molecular modeling. Tree searching internal coordinate conformational space

A general algorithm is described which exhaustively searches conformational space using an internal coordinate tree search. Using only geometrical operations and a set of criteria for eliminating chemically unreasonable structures, the algorithm generates starting geometries for optimization by molecular mechanics. An implementation of this algorithm is exceedingly fast and finds all known minima, as well as several new ones, for four test alkanes. This method makes feasible global conformational searches for molecules with up to 10⁹ conformational possibilities.     

Structural and conformational study of ortopramides derived of the tropane system

Several 3(substituted benzamido)N-substituted-nortropane compounds have been synthesized and their molecular structures determined by IR, ¹H NMR and ¹³C NMR methods. From the IR data a molecular association was deduced for these compounds in the solid state. From the ¹H NMR and ¹³C NMR, the following general features were deduced: All compounds studied adopt a slightly flattened chair conformation in CDCl₃ or DMSO solution. In all cases, only the epimer with the amido group in the exo position was isolated.     

Angular dependence of the vicinal interproton spin–spin coupling in silacyclohexanes. The conformational energy term of the methyl group in 1-methyl-1-silacyclohexane

An approximate Karplus-Conroy relationship between the vicinal coupling constants J(H SiCH ) in a silaethane fragment and the corresponding torsional angles τ in silacyclohexanes is proposed. The relationship ³J(H SiCH ) VS τ is asymmetric. The ¹H NMR parameters and conformational features of cis- and trans-3,5-dimethyl-1-silacyclonexane and 3-silabicyclo[3.2.1]octane are discussed, and the conformational energy term for the methyl group in 1-methyl-1-silacyclohexane is found to be approximately 1.45 kJ mole^?1 in favour of the axial position for the methyl group, in good agreement with previously calculated values.