Showing papers on "Conformational isomerism published in 1978"

Dynamic proton magnetic resonance studies on complex spin systems. Non‐mutual three‐spin exchange in four 1‐substituted cyclohexanes‐2,2,3,3,4,4,5,5‐d8 and mutual four‐spin exchange in cyclohexane‐1,1,2,2,3,3,4,4‐d8

Abstract: The intrinsic advantage proffered by coupled three-proton spin systems in the quantitative study of conformational equilibria and equilibrations, as elaborated and exemplified in the preceding publication, is exploited for the determination of precise thermodynamic and dynamic parameters for octadeuteriocyclohexanes containing a cyano, chloro, bromo or deuteriomethoxy substituent and hydrogen atoms on the substituted and on one contiguous carbon. Dynamic quantities for the ring reversal of cyclohexane-1,1,2,2,3,3,4,4-d8, obtained by bandshape analysis of the deuterium-decoupled proton NMR spectra broadened by mutual four-spin exchange, are also reported. The measured standard entropy differences between the axial and equatorial conformational isomers of the monosubstituted cyclohexanes show that, in addition to the rotational entropy, there must be a significant contribution from the vibrational partition functions. The experimental activation entropies for the cyclohexane chair-to-twist-boat conversion are at variance with conclusions drawn from naive symmetry considerations, but agree with the more sophisticated treatment of Pickett and Strauss; the data establish that there is virtually free pseudorotation in the transition states of the ring reversal for cyclohexane itself as well as for the monosubstituted derivatives studied in this investigation.

Azolides. Part 12. Carbon-13 nuclear magnetic resonance study of N-methyl and N-acetyl derivatives of azoles and benzazoles

Abstract: 13 C N.m.r. chemical shifts and C–H coupling constants of methyl- and acetyl-benzazoles have been derived from data for the corresponding uncondensed azoles by addition of increments which depend on the position and nature of the azole nitrogen atoms present. Use of 13C n.m.r. parameters by estimation of conformer distribution in acetylazoles or -benzazoles proved reliable only when the individual conformers were observable. In the absence of steric effects the composition of equilibrium mixtures of isomeric N-substituted azoles is independent of the nature of the N-substituent.

Molecular structure and conformation of ethyl methyl ether as studied by gas electron diffraction.

Abstract: The bond distances (rg) and angles (rα) in ethyl methyl ether have been determined by gas electron diffraction as follows: average of C(methyl)–O and C(methylene)–O=1.418±0.002 A, C–C=1.520±0.004 A, C–H=1.118±0.004 A, ∠C–O–C=111.9±0.5°, ∠O–C–C=109.4±0.3°, ∠H–C–H=109.0±0.4°, where uncertainties represent estimated limits of experimental error. The two rg(C–O) distances have been estimated independently with the aid of the rotational constants for the trans conformer reported by Hayashi et al.: C(methyl)–O=1.413±0.009 A and C(methylene)–O=1.422±0.007 A. The dihedral angle for the gauche conformer, 84±6°, and the relative abundance of the trans and gauche conformers in the gas phase at 20 °C, nt⁄(nt+ng)=0.80±0.08, have also been determined.

Experimental conformational study of two peptides containing α-aminoisobutyric acid. Crystal structure of N-acetyl-α-aminoisobutyric acid methylamide†

Abstract: Some theoretical studies have predicted that the conformational freedom of the α-aminoisobutyric acid (H-Aib-OH) residue is restricted to the α-helical region of the Ramachandran map. In order to obtain conformational experimental data, two model peptide derivatives, MeCO-Aib-NHMe 1 and ButCO-LPro-Aib-NHMe 2, have been investigated. The Aib dipeptide 1 crystallizes in the monoclinic system (a = 12.71 A, b = 10.19 A, c = 7.29 A, β = 110.02°, Cc space group) and its crystal structure was elucidated by x-ray diffraction analysis. The azimuthal angles depicting the molecular conformation (ϕ = −55.5°, ψ = −39.3°) fall in the α-helical region of the Ramachandran map and molecules are hydrogen-bonded in a three-dimensional network. In CCl4 solution, ir spectroscopy provides evidence for the occurrence of the so-called 5 and C7 conformers stabilized by the intramolecular i i and i + 2 i hydrogen bonds, respectively. The tripeptide 2 was studied in various solvents [CCl4, CD2Cl2, CDCl3, (CD3)2SO, and D2O] by ir and pmr spectroscopies. It was shown to accommodate predominantly the βII folded state stabilized by the i + 3 i hydrogen bond. All these experimental findings indicate that the Aib residue displays the same conformational behavior as the other natural chiral amino acid residues.

Crystal properties as indicators of conformational changes during ligand binding or interconversion of Mcg light chain isomers.

Abstract: Crystals were prepared from samples of nonjovalent and covalently linked dimers previously isolated as intermediates and end products in the interconversion of conformational isomers of immunoglobulin light chains from the patient Mcg. In ammonium sulfate these dimers crystallized in the trigonal form characteristic of the native Bence-Jones protein and in an abnormal needle form associated with conformational changes in the vicinity of the interchain disulfide bond. Trigonal forms were compared with the native covalent dimer by difference Fourier analysis at 3.5-A resolution. The packing of molecules in the trigonal crystal lattice was examined in detail to determine the steric limitations governing chemical modifications, chemical modifications within crystals or in solutions slated for crystallization. When the modifications involved only the cleavage and alkylation of the interchain disulfide bond, the difference Fourier maps indicated only local conformational changes mainly in the COOH-terminal pentapeptide segment of monomer 2 of the dimer. When light chains were dissociated from heavy chains and reassembled into a dimer, there were changes in segments which interact to stabilize the V domain dimer. These changes, as well as the more extensive changes in the needle forms, could be reversed by dissolving the crystals, cleaving the interchain disulfide bond, andmore » allowing it to reoxidize. The resulting proteins crystallized as trigonal forms indistinguishable from those of the native dimer. After the binding of two molecules of bis(dinitrophenyl)lysine and subsequent removal of the ligands by dialysis, the dimer crystallized only as needles.« less

Interconversion of conformational isomers of light chains in the Mcg immunoglobulins.

Abstract: Previous crystallographic studies in this laboratory demonstrated that immunoglobulin light chains with the same amino acid sequence can have at least two and probably three or more conformations, depending on whether the second member of an interacting pair is a light or heavy chain. If a heavy chain is not available in the assembly medium, a second light chain plays the structural role of the heavy chain in the formation of a dimer. In the present work, the lambda-type light chains were dissociated from the heavy chains of a serum IgG1 immunoglobulin from the patient Mcg and reassembled noncovalently into a dimer. The reassembly process was completed by allowing the penultimate half-cystine residues to form an interchain disulfide bond. The covalently linked dimer was compared with the Mcg urinary Bence-Jones dimer, for which an atomic model has been fitted to a 2.3-A electron density map. The assembled dimer and the native Bence-Jones protein were indistinguishable in their chromatographic and electrophoretic properties, as well as in their activity in the binding of bis(dinitrophenyl)lysine. These results indicate that the light chains can be converted into the two types of Bence-Jones conformational isomers. The procedure was also reversed: the two Bence-Jones isomers were dissociated and reassembled as the single type of isomer associating with each of two heavy chains in the IgG1 protein. The change in activity occurring when a light chain associates with a heavy chain instead of a second light chain is illustrated by the fact that the Mcg IgG1 immunoglobulin does not bind dis(dinitrophenyl)lysine in measurable amounts.

Conformation-reactivity relationship for pyridoxal Schiff's bases. Rates of racemization and alpha-hydrogen exchange of the pyridoxal Schiff's bases of amino acids.

Abstract: The role of stereoelectronic effects in controlhg the reaction specificity of biological reactions involving pyri- doxal phosphate-amino acid Schiff's bases was tested with nonenzymatic models. The rates of racemization and H,, ex- change of a series of pyridoxal-amino acid Schiff's bases were determined. The order of these rates does not parallel the predictions based solely on electronic or steric effect, but parallels the proportions of the reactive conformers (e.g., conformers with the C,-H, bond orthogonal to the a system) estimated by CPK models. The special reactivity of the phe- nylalanine Schiff' s base was consistent with a special confor- mation in which some type of a--a interaction increases the Pyridoxal phosphate--amino acid Schiff s bases are key in- termediates in many important biological reactions catalyzed by enzymes which require pyridoxal phosphate as a cofactor. These include transaminases, decarboxylases, synthetases, racemases, etc. (Snell & Dimari, 1970). All of these reactions are believed to proceed via cleavage of one of three bonds to C, of the amino acid. Dunathan (1966, 1971) postulated that these enzymes control the reaction specificity by controlling the conformation about the N-C, bond of the Schiff's base (SB)' intermediate. He suggested that the bond orthogonal to the a system of the SB is most easily broken due to the maximum 6-a overlap, and therefore in the enzyme active site the bond to be broken is aligned orthogonal to the P plane. Although this model was used to relate the N-C, bond conformation of the SB inter- mediates to the reaction specificity of a number of enzymes (Dunathan, 1966, 1971), it has not been adequately tested in nonenzymatic systems. However, the principle that bonds parallel to a orbitals are more labile than bonds not aligned with the a orbitals has been used to explain the 12-fold dif- ference in the rates of exchange of the axial and equatorial protons LY to a ketone group in 3/3-acetoxycholestan-7-one in the process of enolization (Corey & Sneen, 1956). This effect was attributed to stereoelectronic factors since the u electrons of the axial bond are more favorably located for overlap with the a orbital of the carbonyl group. This stereoelectronic effect has also been invoked by other workers (Hine et al., 1965) and is supported by calculations which predict maximum 6-a proportion of exchangeable conformers, thus further sub- stantiating the role of conformation in governing the reactivity of the C,,-H, bond. Furthermore, semiempirical calculations of the conformation about the C,-N bond were performed using the CAMSEA conformational analysis program. The results of conformational calculations are consistent with the results of conformational analysis by nuclear magnetic reso- nance. The order of reactivity of the C,-H, bond of the SB dianion, pH 12.0, predicted by calculation based on stereoe- lectronic effects, though not quantitatively parallel to the ob- served rate constants, is qualitatively in agreement with the experimental results.

Rotamers arising from restricted motions and electromc interactions of acetoxymethyl groups in carbohydrates

Abstract: The two dimensional conformational spaces available for acetoxymethyl groups in carbohydrates are reported. The studies were performed on two molecules differing in their C-4 configurations, i.e. gluco and galacto. The acetoxymethyl group was assigned a mean geometry derived from the computation of 19 equivalent groups as found in pertinent acetylated carbohydrates. The internal energy calculations were performed by including the partitioned contributions arising from the non-bonded energies, electrostatic interactions, and torsion energy. An instability rating of 3 kcal/mol was assigned to conformations involving peri interactions, i.e., trans–gauche and gauche–gauche forms in gluco and galacto carbohydrates, respectively. The results which are best described in term of topology show that several conformations corresponding to the trans and gauche states of the C—O single bond are preferred. However, significant shifts from perfect staggering are observed. The predicted regions of low energy are found to...

Conformational analysis of pyridoxal Schiff's bases. Nuclear magnetic resonance studies of the conformations about the C4-C4', Calpha-Cbeta, and N-Calpha bonds of the pyridoxal Schiff's bases of amino acids.

Abstract: The solution conformations of a series of pyri- doxal-amino acid Schiff s bases were analyzed using I3C and IH nuclear magnetic resonance techniques. The I3C-'H coupling constants were assigned based on model compounds and isotopic labeling. The predominant conformation of the (2444' bond was found to be "cis" based on nuclear Ov- erhauser effect (NOE) measurements and the "simultaneous" upfield shift of both H~J and HSf in the Schiff's bases of aro- matic amino acids. Going from the monoanion (pD 8.2) to the dianion (pD 12.3), changes in these two effects suggested an increasing contribution of the "trans" conformer. The con- Pyridoxal phosphate-amino acid Schiff s bases are key in- termediates in many important biological reactions (Snell & Dimari, 1970; Dunathan, 197 1 ), including transamination, decarboxylation, racemization, and /3 and y elimination and substitution reactions. These reactions of Schiff's bases involve a number of electron and hydrogen shifts and presumably are controlled by subtle conformational effects. Dunathan (1 966) has suggested that the bond perpendicular to the r system of the Schiff's base is most easily broken, and that the enzymes govern reaction specificity by controlling the conformation of the N-C, bond. Another important structural feature is the conformation of the C~-C~J bond, which can be cis or trans

Raman study of the rotational isomers of bicyclopropyl and vinylcyclopropane

Abstract: The Raman spectra of bicyclopropyl and vinylcyclopropane were studied in the solid, liquid and vapor phases in an attempt to identify their rotational isomers and to measure their enthalpy differences. For bicyclopropyl, the presence of the s-trans and gauche isomers in the liquid and vapor phases has been confirmed. The present measurements show that the gauche isomer is more stable in both the vapor and liquid, by 91±28 cal mol−1 in the vapor and by 188±10 cal mol−1 in the liquid. For vinylcyclopropane, features due to only two conformers could be identified in the liquid and vapor spectra. In the vapor the predominant isomer, previously identified as the s-trans rotamer,9 was found to be more stable by 1.1±0.1 kcal mol−1.

Proton magnetic resonance studies of 2′-deoxynucleosides and nucleotides in the syn conformation

Abstract: Proton magnetic resonance data for 6-methyl-2′-deoxyuridine and its 3′- and 5′-monophosphate derivatives are obtained in aqueous solution and compared with data for corresponding thymine derivatives. The data show that the derivatives of the 6-methyluracil base occupy the syn conformation. The presence of the syn base leads to a flattening of the sugar ring and destabilization of the g+ conformer about the C(4′)—C(5′) bond. This destabilization is particularly large at the 5′-nucleotide level and is discussed in terms of a repulsive interaction involving the 2-keto oxygen of the base and the negatively charged 5′-group.

Carbon-13 NMR spectra of monosulphones and disulphones: Substitution rules and conformational effects

Abstract: Carbon-13 NMR spectra have been obtained for 27 aliphatic monosulphones and 13 aliphatic disulphones. Substitution rules have been formulated which allow the prediction of chemical shifts when a CH2 group in a hydrocarbon is replaced by an SO2 group, or when an H atom in a sulphone is replaced by an alkyl group. Carbon atoms β to a sulphone group show a marked upfield shift effect which is sensitive to the conformation about the CS bond; atoms in the trans position experience an upfield shift (−9.39±1.64 ppm) compared with those in the gauche position. An assignment of the meso (m) and racemic (r) β-carbon peaks in di-sec-butyl sulphone was made by synthesis of the optically active compound. |δm–δLr| decreases with increasing temperature for both β–carbon atoms; this effect was interpreted in terms of two available conformers for each of the m and r compounds, those for the m form having the same energy and entropy, and those for the r form having ΔS=0.6 J K−1 mol−1 and ΔH=0.8 kJ mol−1. Observed chemical shifts for the disulphones were compared with those estimated by the application of the first set of substitution rules.

Nucleotide Torsional Flexibility in Solution and the Use of the Lanthanides as Nuclear‐Magnetic‐Resonance Conformational Probes

Abstract: In this article the single family of conformations of adenosine 5′-monophosphate (5′AMP) in aqueous solution previously obtained using the lanthanide ions as nuclear magnetic resonance (NMR) probes is shown to disagree with the conformational data available from independent NMR methods, such as coupling constants and nuclear Overhauser enhancement analysis. The original lanthanide experimental data is reinterpreted assuming the contribution of different conformers to the observed magnetic perturbations. The average conformation obtained for 5′ AMP agrees quite satisfactorily with the other independent conformational information.

Structures and populations of conformers of nucleoside monophosphates in aqueous solution. I. General methods of conformation search with lanthanide‐ion probes and spin‐coupling constants and application to uridine‐5′‐monophosphate

Abstract: The Ln(III)-induced shifts and Gd(III)-induced changes of the spin-lattice relaxation times were observed for the 1H and 13C resonances of uridine-5′-monophosphate (5′-UMP) in 2H2O solutions at pH 1.7–2.0. The vicinal spin-coupling constants changed little by the addition of lanthanide cations, indicating that the conformations of this mononucleotide remained almost the same upon complex formation. A general method was worked out for conformation studies of flexible molecules with lanthanide-ion probes and spin-coupling constants. This method was applied in an extensive computer search for 5′-UMP, and it was concluded that the observed Ln(III)-induced shifts, Gd(III)-induced changes of relaxation times, and vicinal spin-coupling constants could only be accounted for by a mixture of conformers. The populations of the major conformers, gg-3′-endo-anti, and gg-2′-endo-anti, amount to 46 ± 12% and 29 ± 11%, respectively. The correlation between local conformations are discussed on the basis of the present results.

Conformational characteristics of the RNA subunit ApA from energy minimization studies.

Abstract: In an attempt to better our understanding of the conformational stabilities in RNAs, an intensive theoraticl study has been carried out on one of its dimeric subunits, ApA, using an improved set of atom-atom interaction energy parameters and an improved version of energy-minimization technique. The C(3′)0endo and the C(2′)-endo sugar ApA units were sperately considered and 38 probable conformations have been analyzed in each case. The total potential energy, comprising nonbonded, electrostatic, and torsional contributions, was minimized by varying all seven relevant dihedral angles simumtaneously. The result reveal that 17 conformations in the case of C(3′)-endo sugar ApA and 7 confomations in the case of C(2′)-endo sugar ApA unit, the lowest energy conformation corresponds to a nonhelical structure and the A-RNA and the Watson-Crick-yype conformations lie at energy levels of about 0.5 and 1.0 Kcal/mo., respectively, above the lowest energy found. For ApA with the lops of different types in the backbone and they all differ in energies by about 3.5 Kcal/mol with refrence to the lowest energy founs. It is noted that the order ofmprefrence of the base stacking is observed in the A-RNA and the Watson-Crick type conformers. The ApA unit with C(2′)-endo sugar is forced to assume phosphodiester conformations with large deviations fom the expected staggered conformations compared to the ApA unit with C(3′)-endo sugar. The result obtained for ApA are discussed with refrence to those previously obtained for the dApdA unit. Te theoretical predictions are compared with the experimental data on the tRNAPhe crystal, as well as those on fibrous RNAs and RNa subunitlike crystal structures. This study brings out many important aspects of the conformational stability of ApA which have been missed by studies made by others on this system.