Showing papers on "Conformational isomerism published in 1971"

The Conformational Properties of the Basic Pancreatic Trypsin-Inhibitor

Abstract: The conformational properties of the basic pancreatic trypsin-inhibitor have been studied using both physical and chemical techniques. The structural properties of this mini-protein are quite unusual. The folded conformation remains unaltered at 77 °C and pH 2.1 or in 6 M guanidine-HC] at pH 7.5. The selective cleavage [22] of the disulfide bridge Cys14-Cys38 reduces considerably the stability of the inhibitor towards heat or guanidine-HCl. A conformational study of the carboxamidomethyl, carboxymethyl, and aminoethyl derivatives of the inhibitor has been carried out after partial reduction and modification of Cys14 and Cys38 by iodoacetamide, iodoacetic acid, and ethyleneimine. There exist three folded isomeric forms of the inhibitor between pH 1 and 11. Form I is the most stable form; it exists near neutral pH. It is extremely thermostable and remains folded in 6 M guanidine-HCl. Form II is stable below pH 1.5–2; its transition temperature is 81 °C. Form III is predominant at pH 10–11 at 20 °C. A detailed analysis of the conformational isomers I, II and III has been carried out with the carboxamidomethylated inhibitor. Both physico-chemical and chemical data indicate that the acidic conformational change I ⇌ II is dependent upon the ionisation of a buried carboxylate which may be the side-chain of Glu7. The alkaline isomerisation I ⇌ III is induced by the unmasking of the α-ammonium of the N-terminal arginine residue. The apparent pK of the group is 9.4 at 25 °C. Acetylation of the α-amino group stabilizes a form very similar to III and prevents the formation of form I at neutral pH.

Protonenresonanz-Untersuchungen zur inneren Rotation, VIII. Konformationsanalyse α.α.o.o′-tetrasubstituierter Toluole mittels magnetischer Kernresonanz und halbempirischer Energieberechnung

Abstract: 1H n.m.r. spectra and semi-empirical calculations of strain energies have shown that the ground state of the toluene derivative 3 is represented by conformation a (R CH3), the α-methine proton of which eclipses one of the o-methyl groups. Accordingly, the existence of two rotamers, e.g.15E and 15Z, was demonstrated in the case of the toluenes 15, 16, 17, 18, and 19 synthesized with two unequal o- or m-substituents. The measured equilibrium ratios of rotamers (Table 2) are in good agreement with the results of the calculations for 15 and 16. - The free enthalpies of activation ΔGmath image for rotation about the Cαaryl bond vary from < 7.5 to 15 kcal/mole (Tables 1 and 2). Barriers of this kind were reproduced with sufficient accuracy by calculations for 3, 15, and 16 if the Cαaryl bond length and the bond angles were assumed to be flexible, i.e., if they were optimized for each rotational arrangement. The transition state turned out to be a conformation of type d, the CαH bond of which is arranged perpendicular to the benzene ring; potential energy curves for Cαaryl rotation are given in Fig. 3 and 4. Calculations presupposing a rigid molecular geometry erroneously result in conformation c as the transition state and yield barriers which are much higher than the measured ones.

Structure and Rotational Isomerism of Ethylenediamine as Studied by Gas Electron Diffraction

Abstract: The structure and the rotational isomerism of ethylenediamine have been investigated by means of gas electron diffraction. Evidence has been given for the presence of one conformer (gauche) in the vapor phase (at 50–120°C); the N–C–C–N dihedral angle measured from the cis position is 64·0±4°, and the fraction of any other isomer, if present, is estimated to be less than 5%. A theoretical prediction based on the SCF-CNDO/2 method has essentially accounted for this finding. The rg distances and the angles based on the ra structure determined by a least-squares analysis on molecular intensities, with estimated limits of error, are as follows: C–C=1.545±0.008 A, C–N=1.469±0.004 A, ∠C–C–N=110.2±0.7°, C–H=1.109±0.01 A, ∠C–C–H=111·9±5°, and ∠H–C–H=112·7±8°.

Conformations of the Esters. IV. The Conformations of Carbamates

Abstract: In alkyl or aryl carbonates, the presence of conformational isomers (s-cis and s-trans) has been confirmed by infrared and nuclear magnetic resonance spectroscopic techniques. The dipole-moment measurements also support the conclusions obtained from the spectroscopic data.

The effect of adjacent charges on the kinetics of rotation of the peptide bond.

Abstract: The kinetics of rotation of the peptide (amide) bond in dimethylacetamide, glycine dimethylamide, N-acetylsarcosine, and glycylsarcosine have been studied in basic, neutral, and acidic aqueous solutions by proton magnetic resonance spectroscopy. The data indicate that the presence of nearby negative or positive charges do not greatly perturb the energetics of conformational equilibration about the amide carbon-nitrogen bond. In N-acetylsarcosine and glycylsarcosine two distinguishabe conformers are present; their relative abundance is essentially 50%/50% except at low pH. It is suggested that intramolecular hydrogen bonding is responsible for deviations from this population ratio. The activation enthalpies (ΔH‡) for rotation appear to be linearly related to the corresponding activation entropies (ΔS‡) leading to an isokinetic temperature of about 400°K.

Rotational isomerism. Part XI. The nuclear magnetic resonance spectra and rotational isomerism of 1,2-difluoro- and 1,1,2-trifluoroethane

Abstract: The 1H and 19F spectra of 1,2-difluoroethane (I) and 1,1,2-trifluoroethane (II) are given and analysed.The solvent dependence of the coupling constants enables the rotamer energies and coupling constants to be obtained. In this process, the intrinsic solvent dependence of the vicinal HF and FF couplings (given by a control study of 1,1,1,2-tetrafluoroethane) was explicitly considered.The rotamer energies ΔE(Eg–Et) are for (I), ΔEv– 0·6, ΔE1– 2·6 and for (II)ΔEv 1·4, ΔE1 0·0 kcal/mol.The couplings in the rotamers of (I), (II), and 1,1,2,2-tetrafluoroethane are considered in detail. Increasing fluorine substitution gives a progressive but very nonlinear decrease in JtHH and JtHF which is much larger, for the latter, if the fluorine is introduced on the CH end of the CH·CF fragment.In (I), JgHH varies from 0 to 6·2 Hz depending on the orientation of the F nuclei, but increasing fluorine substitution evens out these effects to give JgHH 1·5—2·0 Hz. J t FF Is very dependent on the fluorine substitution, varying from –30 to 0 Hz but in contrast JgFF shows no dependence at all and is relatively constant at –13 to –5 Hz.

Peptide Conformations. I. Nuclear Magnetic Resonance Study of the Carbamate Reaction of Amino Acids and Peptides

Abstract: Nuclear magnetic resonance spectroscopy has been applied to the study of carbamate formation in solutions of amino acids and peptides in a carbonate-bicarbonate system. The possible conformations of these carbamates are discussed in terms of the n.m.r. data obtained. The n.m.r. parameters are reported for the diastereomers L-alanyl-L or D-phenylalanine and L-phenylalanyl-L or D-alanine and for the dipeptide glycyl-L-phenylalanine and their carbamates. The results are interpreted in terms of preferred rotamers about the Cα—Cβ bond of the phenylalanine residue and a β-type conformation of the peptide chain, wherein the two α-protons lie in the plane of the amide bond. All observations are in agreement with a shorter end to end distance in L,D- compared with L,L-dipeptides.

Equilibres conformationnels de glucides au niveau de liaisons σ sp2-sp3 C-C. III Dérivés d'oximes d'aldéhydo-sucres utilisation de tris-dipivaloylméthanato-europium†

Abstract: A series of sugar oximes and O-methyloximes of the general formula RCHNOR′ (R′ H, CH3) have been studied by PMR. spectroscopy. These compounds exist in solution as a mixture of the syn and anti isomers. The conformational equilibrium of the syn isomers seems to consist exclusively of the eclipsed rotamers, whereas for the anti isomers there appears to be a significant contribution from bisecting rotamers. Using tris-dipivaloylmethanato-europium it is found that the α proton of the anti oximes is much more deshielded than the corresponding proton of the syn isomers, which means that the downfield shift of a particular proton does not depend exclusively on its distance from the oxygen of the oxyimino group.

Evaluation of the thermodynamic parameters for the interconversion of the conformational isomers of two N-acyl-prolines by nuclear magnetic resonance spectroscopy

Abstract: Study of the 1H n.m.r. spectra of the N-acyl-prolines (I) and (II) in deuteriochloroform over a range of temperature has enabled the thermodynamic parameters for the interconversion of such conformers by rotation about the N–CO bond to be evaluated for the first time.

A Proton Magnetic Resonance Study of the Molecular Conformation of a Modified Nucleoside from Transfer RNA. Dihydrouridine

Abstract: The 220 MHz nuclear magnetic resonance (N.M.R.) spectra of dihydrouridine at 23 °C and 60 °C have been analyzed. From the N.M.R. data a conformational model is derived. The ribose moiety indicates a slight preference for the C3′exo and C2′endo conformations, although rapid interconversion between ring-puckered conformers is taking place. At high temperature the preference for C3′exo and C2′endo is less. The conformation of the exocyclic hydroxymethyl group is a rapid time average of all possible conformers with a preference for the gauche-gauche rotamer. By comparison with β-cyanuric acid riboside the chemical shifts of the ribose moiety in dihydrouridine are not influenced by the diamagnetic anisotropy of the keto group on the base, demonstrating that the base has the anti conformation with respect to the ribose ring. The dihydrouracil base does not exist in any of the classical puckered conformations, but manifests an average torsional angle of approximately 30° apparently due to rapid interconversion b...

Preparation and spectroscopic properties of methylamino derivatives of some difluoro- and bis(trifluoromethyl)phosphorus compounds

Abstract: : The preparation and characterization of four new compounds of the type (CF3)2P(E)N(H)CH3 and F2P(E)N(H)CH3(E = O,S) by aminolysis of the appropriate chlorophosphorus compound is described. Infrared and nmr spectra of the compounds indicate that no conformational preference is adopted on the latter time scale although the presence of conformational isomers may be indicated by infrared. Some hydrogen bonding is indicated by infrared studies especially for the compound F2P(O)N(H)CH3, which appears to be strongly hydrogen bonded in all states. The nmr spectral behavior indicates the presence of coupling of the N-H proton to the methyl proton. Second-order intensity variations are observed when the N-H chemical shift is close to that of the CH3 group. The nmr spectra of the phosphines X2PN(H)CH3(X = F,CF3) show the same features. (Author)

Structure and conformational analysis of co-ordination complexes. Part II. X-Ray crystal structure of cis-[carbonatobis(trimethylenediamine)cobalt(III)] perchlorate and conformational analysis of trimethylenediamine complexes

Abstract: The crystal structure of cis-[carbonatobis(trimethylenediamine)cobalt(III)] perchlorate, cis-[Co(tn)2CO3]ClO4(tn = trimethylenediamine), has been determined by X-ray structure analysis. The crystals are monoclinic space group P21/c, with a= 9·51, b= 13·22, c= 12·03 A and β= 111·17°. The structure was solved by Patterson and Fourier methods and refined by least squares to R 0·092 for 1347 observed reflections. The cobalt-tn rings are not related by molecular symmetry and have different and slightly distorted chair conformations. These distortions are well reproduced by a conformational strain energy minimization calculation using a comprehensive force-field. This conformational isomer of the cis-complex is not the one of least strain energy. Two other cis-isomers in which the ligands are related by a two-fold axis are possible; one has a lower and the other a higher strain energy, but neither of the forms could be detected in several preparations of the complex. The strain energy minimization of the tris-chair, tris-lel-skew-boat, and tris-ob-skew-boat forms of Co(tn)3+3 reveals an energy difference of 5·06 kcal mol–1 between the tris-ob-boat and tris-chair conformers, the tris-chair being the energetically more favourable. However the tris-lel-skew-boat was found to be 0·77 kcal mol–1 lower in energy than the trischair isomer.

31 P nuclear magnetic resonance study of conformers of trans-[MCl(CO)(PBu2tR)2](M = Rh or Ir; R = Me, Et, or Prn)

Abstract: The low temperature 31P n.m.r. spectra of the complexes trans-[MCl(CO)(PRBut2)2](M = Rh or Ir; R = Me, Et, or Prn) show the presence of three rotamers with very different chemical shifts.

Effect of Solvent Upon the Vicinal Proton Coupling Constants of Complex Substituted Ethanes. II. Anomalous Results for 1-Phenyl-1,2,2-trihaloethanes

Abstract: The n.m.r. spectra of 11 tetra-substituted ethanes have been obtained in a number of solvents. Changes in the vicinal coupling constants of 1-phenyl-1,2,2-trihaloethanes with solvent do not fit the electrostatic model for solvent effects. It is concluded that the theory breaks down because solute–solvent hydrogen bonding specifically favors the trans rotamers of these compounds. The conditions under which the theory would be expected to break down are also discussed in more general terms.

Interconversion of the cyclohexane conformers

Abstract: It is important to develop the understanding of conformations of cyclohexane and the role it has played in understanding the conformation of saturated carbon compounds.

Untersuchungen an Siebenring-Systemen, VIII. Darstellung und Reaktivität konformationsisomerer Tetraphenyl-tribenzocycloheptatriene (1.2.3.4-Tetraphenyl-9 H-tribenzo-[a.c.e]cycloheptene)

Abstract: Die Darstellung, Spektren und Reaktionen von konformationsisomeren Tetraphenyl-tribenzocycloheptatrienen (1.2.3.4-Tetraphenyl-9H-tribenzo[a.c.e]cycloheptenen. 1–3, 5–7) werden beschrieben. Aufgrund der hohen Energiebarriere fur die Ringinversion des zentralen Siebenringes (ΔG≠ ≧ 31 kcal Mol) ist es moglich, Konformere A und B mit quasi-aquatorialen und quasi-axialen Substituenten zu isolieren. Derivate des Typs A erweisen sich bei Solvolyse-Versuchen als -reaktionstrage, was z. B. die Isolierung des Chlorosulfits 2A ermoglicht. Andererseits gehen die Konformeren B leicht nucleophile Substitutionen unter bevorzugter Konformationserhaltung ein. Die konformativ bedingten Reaktivitatsunterschiede sowie die Struktur des „Tetraphenyl-tribenzotropylium-Ions 10” werden an Hand von Modellbetrachtungen diskutiert. Studies on Seven-Membered Ring Systems, VIII. Preparation and Reactivity of the Conformational Isomers in the Tetraphenyl-tribenzocycloheptatriene (1.2.3.4-Tetraphenyl-9H-tribenzo[a.c.e]cycloheptene) Series The synthesis, spectra and reactions of conformational isomers in the tetraphenyl-tribenzocycloheptatriene (1.2.3.4-tetraphenyl-9H-tribenzo[a.c.e]cycloheptene) series (1–3, 5–7) are described. It is possible to isolate the conformational isomers A and B with quasi-equatorial and quasi-axial substituents, because the central seven-membered ring system shows a very high energy barrier for ring inversion (ΔG≠ ≧ 31 kcal/Mol). Compounds of the type A are remarkably stable under solvolysis conditions; as a consequence the chlorosulfite 2A can be isolated. On the other hand, conformers of the type B readily undergo nucleophilic substitutions with high retention of conformation. These remarkable reactivity differences between the conformational isomers and the structure of the tetraphenyl-tribenzotropylium ion 10 are discussed on the basis of model considerations.

Hindered rotation in thioamides—II

Abstract: The NMR spectra for a series of amides and thioamides of type where R = CH3, C6H5 and C6H5CH2, were investigated from −60° to 150°C. The Arrhenius activation energies, Ea, for the normal amide equilibration were determined by the W½ method and the values range from 15.4 to 20.9 Kcal/mole. The three thioamides, compounds (2), (4) and (6) yield spectra showing a second, low temperature, equilibration. This exchange was first studied by Siddall and co-workers and they interpreted the spectral changes in terms of population changes of the conformational isomers about the NCH bonds. They assumed strong interaction of nitrogen alkyl groups which gave rise to three low energy dl pairs of isomers. Their results, however, as well as those obtained for similar compounds reported herein, show only two sets of patterns at low temperatures. These spectra suggest a first order, A⇄B, type equilibration where PA≠PB. An alternative assignment based upon the following classification of steric effects of S, R, R′ and R″, is suggested; (1) a strong interaction of the sulfur atom with the adjacent alkyl group on the nitrogen atom, R′, (2) a somewhat weaker interaction of R with the adjacent nitrogen alkyl group R″ and (3) a still weaker interaction of the two nitrogen alkyl groups, R′ and R″. This leads to four isomers, two dl pairs, C1T4, C6T3 and C1T6, C6T3, which are expected to have a lower energy than the rest and the first pair is preferred. The W½ method of measuring exchange rates was extended to cover A⇄B equilibrations, where PA≠PB. The results indicate an accuracy that is not significantly lower than that obtained by the more elaborate total line shape analysis.

Equilibres conformationnels de glucides au niveau de liaisons s̀ sp2‐sp3 CC. II Dérivés d'hydrozones d'aldéhydo‐sucres

Abstract: A series of alkyl-and aryl-hydrazones of different types of aldehydo-sugars with blocked hydroxy groups have been studied, mainly by PMR. spectroscopy. No traces of the azoalkane or ene-hydrazine forms were detected; the hydrazones were found to exist only in the syn form, except for the cases where an intramolecular hydrogen bond between the ‘amino’ hydrogen of the hydazono group and an oxygen o the glycosyl group provides an extra-stabilization to the anti isomer. Most of these syn hydrazones seem to exist as an equilibrium of the ‘classical’ eclipsed rotamers. The influence of solvent polarity both on configurational and conformational equilibria has been examined. The factors which determine the relative stability of the conformers about a sp2-sp3 s bond, particularly some kind of non-bonded attraction, are discussed.