Method Of Conformational Analysis Research Articles

Conformational theory applied to polysaccharide structure

Theoretical methods of conformational analysis have been applied to the biopolymers with beneficial consequences for the elucidation of structure–function relationships in these molecules. The methodology of theoretical conformational analysis and the fruits of its application to the biopolymers, particularly the polypeptides, have been the subject of numerous reviews (Ramachandran & Sasisekharan, 1968; Scheraga, 1968; Venkatachalam & Ramachandran, 1969; Scheraga, 1971; Brant, 1972; Hopflnger, 1973). A critical evaluation of these techniques as applied to the polynucleotides has recently appeared (Olson, 1975 a, b).

Towards a molecular orbital method for the conformational analysis of very large biomolecules

A quantum chemical method is proposed for the conformational analysis of very large biomolecules. The total wave function is constructed of localized bond fragments each determined on the basis of chemical intuition and model calculations on small molecules. The transferability of bond orbitals, localized strictly onto a few atoms of the molecule is discussed. The Lowdin procedure is applied to obtain orthogonalized molecular orbitals. The energy expression is calculated using the ZDO assumption. Simplified formulas for the Coulombic-type electronic interaction integrals are introduced. This approximation is similar to the assumption of the CNDO-method made in order to maintain rotational invariance. To obtain an energy expression, containing a number of terms proportional toN2, (N is the number of occupied orbitals) the overlap of non-adjacent bond orbitals is neglected. At last a simple point-charge interaction is assumed to act between atoms lying far from each other. Thus the calculation of the energy involves the evaluation of a number of integrals proportional to the first power ofN. Numerical results for H2, Li2 and LiH are given.

Conformational analysis of aminoacyladenylates II. EHT study of glycyladenylate

The lowest energy conformations for the glycyladenylate molecule are predicted for the first time by a quantum mechanical method of conformational analysis (Extended Hückel Theory). This paper is the continuation of our previous work on the common skeleton of all the aminoacyladenylates; it treats the simultaneous study of the two rotations around the phosphate group. These studies have shown that glycyladenylate presents a flexibility correlated with both the 5′ AMP and the glycine conformations. The number of energy minima, equal to seven when 5′ AMP is in ANTI gt conformation, is restricted when the conformation becomes ANTI gg; this fact is due, for this last 5′ AMP conformation, to a steric obstacle between the adenine base and the sugarphosphate-glycine chain. The knowledge of the possible configurations can constitute a first step towards the understanding of the recognition process between the glycyladenylate molecule and the glycyladenylate t-RNA synthetase.

Effect of 4-t-butyl and other 4-substituents on rate constants for reactions of 1,1-disubstituted cyclohexanes and piperidines. 4-t-Butyl derivatives as valid reactivity models in the kinetic method of conformational analysis of cyclohexanes

A 4-t-butyl group (or a 4-methyl group) has no effect on the rate constant for ethoxy-exchange in diethyl cyclohexane-1,1-dicarboxylates; a 4-phenyl group, however, increases the rate constant by more than 50%. By contrast, both 4-alkyl and 4-phenyl groups increase the overall rate constants for nucleophilic displacement by thiopholate anion at the benzyl methylene groups in 1-benzylpiperidine benzobromides, a 4-t-butyl group approximately doubling the value. The significance of these results in relation to the validity of the usual kinetic method for conformational analysis of cyclohexanes is discussed.

The significance of a methyl group in the stereoselectivity of cobalt(lII) complexes

This paper represents the first attempt to apply methods of conformational analysis to problems of stereochemistry in metal complexes.

Conformational analysis by kinetic methods: A critique : Theory and experimental development of procedures based on very fast chemical reactions

Two general methods of conformational analysis by kinetic methods are distinguished, and some definitive experiments are described concerning the validity of the reactivity-model method as employed for cyclohexanes. The fast chemical reaction method is analysed in detail, and potential applications to conformational equilibria of N-alkylpiperidines are discussed. The selectivity of electrophilic addition of some photogenerated carbenes and nitrenes to organic sulphides is examined.

Relative rates of ethoxy exchange in 4-substituted diethylcyclohexane-1,1-dicarboxylates. Validation of the use of 4-t-butyl derivatives as reactivity models in the kinetic method of conformational analysis of cyclohexanes

A 4-t-butyl group has no effect on the observed rate of ethoxy exchange in diethylcyclohexane-1,1-dicarboxylates, a significant result in relation to the validity of the usual kinetic method for conformational analysis of cyclohexanes.

Investigation of the stereochemistry of the radical telomerization of propylene with 1,1,1,3-tetrachlorobutane by the method of conformational PMR analysis

1. The stereochemistry of the radical telomerization of propylene by 1,1,1,3-tetrachlorobutane, catalyzed by Fe(CO)5 with additions of i-C3H7OH or dimethylformamide at 95°, was investigated by the method of conformational PME analysis. 2. To evaluate the diastereomeric composition of the lower member of the telomer homolog series of 2,4,4,6-tetrachloroheptane, we studied the distribution of the rotational isomers of the molecule in several solvents of different types and assigned the configurations of two racemic forms, on the basis of a comparison of the conformational composition and differences in shielding constants of the methylene protons. 3. A total lack of stereodirection of the substitution reaction with the participation of the intermediate acyclic radical, probably determined by the absence of induction of the asymmetrical atom at a 1,5-distance from the reaction center, was detected.

Investigation of the stereochemistry of the radical telomerization of propylene by polyhalomethanes by the method of conformational PMR analysis

1. The stereochemical radical telomerization of propylene with CCl4 and CBrCl3 was investigated by the method of conformational PMR analysis at 60°. The relative configurations of diastereomeric racemic forms of the telomer CCl3CH2CH(CH3)CH2CHBrCH3 were established according to conformational data, considering the previous independent assignments for CCl3CH2CH(CH3)CH2CHCICH3 and structurally close chiral polychloroalkanes. 2. The reactions of chain transfer to CCl4 and CBrCl3 forα, γ-disubstituted aliphatic radicals have the same stereodirection. The approach of the telogen to the radical from the side opposite to the position of the substituent in the next-to-last monomer unit proved to be the preferential direction of attack. 3. Differences in the parameters of the PMR spectra of diastereomeric forms of nonsymmetrical polyhalosubstituted aliphatic hydrocarbons with two chiral centers from the similar dissymmetrical compounds retaining certain elements of symmetry, important for the assignment of the configurations, were detected.

The infrared spectra and symmetry of fluorocompounds adsorbed on lanthanide halides: The fluorine bond

When covalent fluorine-containing compounds are brought in contact with rare earth metal halides they adhere strongly to the surface. We have studied the i.r. spectra of the following compounds adsorbed on rare earth metal halides: CF 4CF 3Cl,CF 2Cl 2, HCF 2Cl,C 2F 4Cl 2, and C 2F 2H 2. In all cases the spectra of the adsorbed species resemble quite closely those of their gaseous analogs. The fundamental stretching modes remain essentially unaltered, but the bending modes are usually not observed; neither are the combination and overtone bands. We have seen no previous reports of this kind of bonding in the literature. We shall refer to it as fluorine bonding. Fluorine containing molecules would be expected to sit on the surface of rare earth metal halides in a manner which permits the maximum number of fluorine atoms to contact the surface consistent with the most probable structure. This requirement stabilizes the adsorbed molecule in a definite conformation, thus permitting the i.r. spectrum of that conformation to be measured. This prediction led us to conclude that our experimental observations could lead to a method of conformational analysis. We verified this conclusion by measuring the spectrum of C 2F 4Cl 2 on the surface of ErCl 3 and ErF 3. The molecule would be expected to sit on the surface in either the cis or gauche form. By comparison with published data we ascertained that the gauche form of the molecule is stabilized on adsorption. In the discussion below we have drawn many conclusions about the adsorbed molecules listed above. In the future we shall test other molecules and attempt to verify the suitability of the method for conformational analysis. Of particular interest was the failure of C 2F 2H 2 to be adsorbed. We hope to examine similar compounds and see if this is a peculiarity of unsaturated compounds.

Conformational comparison of aromatic molecules and their ions. III N-(Diphenylmethylene)-aniline and benzil by NMR and EPR

Utilizing methods of conformational analysis developed from Johnson-Bovey tables and the Fraenkel electron density-chemical shift relation, the dihedral angle of the A ring of N-(diphenylmethylene)-aniline I is found to have its average position near that of benzalaniline, i.e., nearly vertical. Due to a complex spectrum, the geometries of the other rings are difficult to assess. The dianion I−2 shows a large chemical shift from I owing to the high negative charge. The average positions of the phenyl rings of benzil (II) are confirmed by NMR to be perpendicular to each other and those of II−2 to be nearly parallel to each other, but perpendicular to the plane of the cis chelate.

An approach to conformational analysis of peptides and proteins in solution based on a combination of nuclear magnetic resonance spectroscopy and conformational energy calculations.

Simple criteria, based on the combined use of nmr spectral parameters and potential energy maps, are proposed for the conformational analysis of polypeptides and proteins. Experimentally determined coupling constants (3)J(NC) for the N-C(alpha) bond are consistent with the Karplus-Bystrov relationship. It is proposed therefore that (3)J(NC) can be used to distinguish (a) between right-and left-handed alpha-helices, (b) between alpha-helical, beta-pleated sheet, and randomly coiled forms of peptides. The average (3)J(NC) for the random coil is predicted. The criteria proposed are valid for both L- and D-amino acids. Correlation between the Karplus-Bystrov relationship for (3)J(NC) and the peptide conformational potential energy map limits the possible values of the N-C(alpha) dihedral angle varphi of each amino acid residue in a polypeptide and protein, and therefore presents a method of conformational analysis in solution superior to the use of either nmr or conformational maps alone. Nmr studies of hydrogen bonding or neighboring-group diamagnetic anisotropy reduce the number of possibilities consistent with the above criteria. A suggestion for evaluating the dihedral angle is presented. These criteria are useful provided the coupling constant is not obscured by line broadening.

The conformational analysis of saturated heterocycles. Part XXVIII. 5-Alkoxy-1,3-dioxans

cis–trans-Equilibrium constants have been determined for a series of 5-alkoxy-2-aryl-1,3-dioxans. The rotamer populations of the cis-derivatives have been investigated by dipole moments. The relative stabilities of the individual rotamers of the various conformers are discussed in terms of specific intramolecular interactions. The range of applicability of the semiquantitative method of conformational analysis by assignment of constant energies to specific intramolecular interactions is surveyed by reference to literature data.

Failure of the chemical shift method of conformational analysis in quaternary salts from 4-alkylpiperidines

Conformational free-energy values for 4-substituents (or 4,4-geminal pairs) in 1-benzylpiperidine benzobromides cannot be derived from the chemical-shift differences between ax- and eq-1-benzyl methylene protons.

Shortcomings in the infrared spectroscopic method of conformational analysis of cyclohexanols

Shortcomings in the infrared spectroscopic method of conformational analysis of cyclohexanols

The effect of substituents on geminal proton–proton coupling constants

A series of 2-benzyloxytetrahydropyrans bearing substituents at the ortho, meta, and para positions of the benzene ring have been synthesized. From the nuclear magnetic resonance spectrum of each compound, the geminal coupling constant (J) between the non-equivalent protons of the benzylic methylene group was determined. The geminal coupling constant for the methylene group of several benzyl sulfoxides was also measured. In the ether series it was found that J varied from 11.1 to 13.3 c.p.s. and was directly proportional to the Hammett σ value for the meta and para substituents. In the sulfoxides, however, J was unaffected by the substituent. On the basis of the molecular orbital theory of geminal coupling constants and steric considerations, it is proposed that the sensitivity of J to the substituent effect is dependent upon the conformation of the molecules with respect to the Ar—CH2 bond. The potential utility of this relation as a method of conformational analysis is discussed.

The effect of substituents on geminal proton–proton coupling constants

A series of 2-benzyloxytetrahydropyrans bearing substituents at the ortho, meta, and para positions of the benzene ring have been synthesized. From the nuclear magnetic resonance spectrum of each compound, the geminal coupling constant (J) between the non-equivalent protons of the benzylic methylene group was determined. The geminal coupling constant for the methylene group of several benzyl sulfoxides was also measured. In the ether series it was found that J varied from 11.1 to 13.3 c.p.s. and was directly proportional to the Hammett σ value for the meta and para substituents. In the sulfoxides, however, J was unaffected by the substituent. On the basis of the molecular orbital theory of geminal coupling constants and steric considerations, it is proposed that the sensitivity of J to the substituent effect is dependent upon the conformation of the molecules with respect to the Ar—CH2 bond. The potential utility of this relation as a method of conformational analysis is discussed.

Direct evidence of limitations in the applicability of the kinetic method of conformational analysis

Direct evidence of limitations in the applicability of the kinetic method of conformational analysis