Ring Interconversion Research Articles

Probing the role of proline in peptide hormones: NMR studies of bradykinin and related peptides

The use of NMR methods to study conformational and dynamic aspects of the proline residues in the nonapeptide bradykinin is reviewed. NMR analyses involve considerations of bistable equilibria which include the cis/trans conformational heterogeneity of the imide bond, the cis'/trans' regions of conformational stability which characterize rotation about the C α—CO bond (dihedral angle Ψ), and the interconversion of the pyrrolidine ring of proline between puckered C γ-endo and C γ-exo conformations. These conformational features are all characterized by different kinetic behavior, are interdependent with peptide bond conformation, and exhibit sensitivity to amino acid substitutions. Thus, the substitution of Gly 6 for Ser 6 increases the fractional cis probability of the sixth peptide bond from 0.1 to 0.35. Substitutions of α-aminoisobutyric acid (AIB) residues for proline introduce conformational constraints analogous to those in cis' proline. Correlations of pyrrolidine ring conformation and dynamics with the cis/trans ratio of the imide bond have also been observed in model systems. Conformational and activity analyses of [AIB 7]-bradykinin provided a stimulus for the development of the first bradykinin antagonist by Stewart and Vavrek (Vavrek RJ and Stewart JM, Competitive antagonists of bradykinin. Peptides 6: 161–164, 1985).

A dynamic NMR study of the nitrogen lone pair orientation in 2-benzoyl-5-methyl-5-aza-1,3-dithiacyclohexane

Nuclear Overhauser enhancement difference experiments and magnetization transfer experiments on 2-benzoyl-5-methyl-5-aza-1,3-dithiacyclohexane 1 at 186 K show conclusively that the N-methyl group adopts a preferred axial orientation. The result has implications for evaluation of the origin of the anomeric effect in this and related compounds. The free energy of activation for ring interconversion in 1 is estimated by spin saturation transfer experiments to be 10.7 ± 0.4 kcal mol−1. Keywords: D NMR, conformational analysis, nuclear Overhauser enhancement, saturation transfer.

Ring interconversion between a 7-membered ring (2,3-dihydro-1,4-benzodiazepine) and a 14-membered ring (2,3,9,10-dibenzo-1,5,8,12-tetra-azacyclotetradeca-4,11-diene)

Structure elucidation of the macrocyclic ligand 6 and interconversion to the benzodiazepine 4 is reported. Also, a versatile synthesis of the macrocyclic ligands 6 and 13 is described.

ChemInform Abstract: 3‐Azido‐1,2,4‐thiadiazoles from a New Ring Interconversion: The Reaction of Thionyl Chloride with Some 1‐Alkyl‐5‐aminotetrazoles.

ChemInformVolume 19, Issue 44 Heterocyclic Compounds ChemInform Abstract: 3-Azido-1,2,4-thiadiazoles from a New Ring Interconversion: The Reaction of Thionyl Chloride with Some 1-Alkyl-5-aminotetrazoles. R. N. BUTLER, R. N. BUTLER Chem. Dep., Univ. Coll., Galway, Ire.Search for more papers by this authorG. A. O'HALLORAN, G. A. O'HALLORAN Chem. Dep., Univ. Coll., Galway, Ire.Search for more papers by this authorD. A. O'DONOGHUE, D. A. O'DONOGHUE Chem. Dep., Univ. Coll., Galway, Ire.Search for more papers by this author R. N. BUTLER, R. N. BUTLER Chem. Dep., Univ. Coll., Galway, Ire.Search for more papers by this authorG. A. O'HALLORAN, G. A. O'HALLORAN Chem. Dep., Univ. Coll., Galway, Ire.Search for more papers by this authorD. A. O'DONOGHUE, D. A. O'DONOGHUE Chem. Dep., Univ. Coll., Galway, Ire.Search for more papers by this author First published: November 1, 1988 https://doi.org/10.1002/chin.198844171Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue44November 1, 1988 RelatedInformation

EPR and ENDOR investigation of daunomycin and adriamycin semiquinones

AbstractElectron spin resonance and ENDOR spectra of semiquinones from daunomycin, adriamycin, their derviatives and model compounds are reported. Hyperfine coupling constants were assigned with the help of TRIPLE resonance and partial deuteration. In contrast to published results, the data obtained were interpreted on the basis of a rapid conformational interconversion of ring A with participation of half chair and boat conformers.

ChemInform Abstract: Investigation of the Hindered Interconversion of the Central Ring in Substituted 9,10‐Dihydroazasilaanthracenes by Dynamic NMR.

ChemInformVolume 19, Issue 23 Organoelement Compounds ChemInform Abstract: Investigation of the Hindered Interconversion of the Central Ring in Substituted 9,10-Dihydroazasilaanthracenes by Dynamic NMR. A. E. ALIEV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this authorA. A. FOMICHEV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this authorA. V. VARLAMOV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this authorN. S. PROSTAKOV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this author A. E. ALIEV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this authorA. A. FOMICHEV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this authorA. V. VARLAMOV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this authorN. S. PROSTAKOV, Univ. druzhby narodov im. Lumumby, Moskva 117923Search for more papers by this author First published: June 7, 1988 https://doi.org/10.1002/chin.198823272AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue23June 7, 1988 RelatedInformation

Dynamic NMR study of the restricted interconversion of the central ring in 9,10-dihydrosilaazaanthracenes

Dynamic NMR study of the restricted interconversion of the central ring in 9,10-dihydrosilaazaanthracenes

A new ring interconversion: 3-azido-1,2,4-thiadiazoles from the reaction of thionyl chloride with 1-alkyl-5-aminotetrazoles

Heating of some 1-alkyl-5-aminotetrazoles with thionyl chloride gave 3-azido-1,2,4-thiadiazoles in a reaction involving 5-N-sulphinylaminotetrazoles as intermediates.

ENDOR Studies of Vitamin E Model Radical. The Solution Structure and Dynamic Behavior of Chromanyloxyl Ring

Abstract ENDOR technique has been used to elucidate the solution structure and dynamic behavior of chromanyloxyl ring in vitamin E radical. We have measured the ENDOR spectrum of a stable vitamin E model radical (7-t-butyl-2,2,5-trimethyl-6-chromanyloxyl (1)) in toluene in the temperature range −30°–−100°C. From detailed analysis of the temperature dependence of hyperfine coupling of β-methylene protons in the heterocyclic ring, the equilibrium conformation of the β-methylene group and activation energy, enthalpy and entropy for the conformational interconversion of the heterocyclic ring have been determined. The observed positive temperature dependence of the hyperfine coupling constants (a5CH3 and a8H) may be explained as a consequence of the restricted motion about the C8a–O1 bond in the chromanyloxyl ring, based on the McLachlan MO calculation.

Thermal Polymerization and Depolymerization Reactions of 10 Sulfur Allotropes Studied by HPLC and DSC [1

AbstractThe thermal decomposition (polymerization, depolymerization, ring interconversion) of a number of sulfur allotropes (S6, S7, S8, S10, S12, S13, S20, polymeric sulfur) has been investigated theoretically (on the basis of Gee's theory) and experimentally by differential scanning calorimetry (DSC) and high‐pressure liquid chromatography (HPLC) in the temperature region of 30–250°C. While the polymerization of liquid S8 is endothermic and endentropic (ΔS > 0), liquid S7 polymerizes exothermically and endentropically, and liquid S6 exothermically but exentropically (ΔS > 0). Therefore, a floor temperature exists for the polymerization of S8 and a hypothetical very high ceiling temperature for the polymerization of S6, while S7 is unstable with respect to polymerization over the whole temperature region. Excepting S8, all investigated cyclic sulfur allotropes yield polymeric sulfur on heating to 60–150°C followed by depolymerization to the equilibrium sulfur melt consisting mainly of S8, some S7, and traces of S6, S9, S12 and other rings.Polymeric sulfur (Sμ) slowly dissolves in CS2 at 20°C to give S8, S7 and traces of other rings (mainly S6, S9, S12). On heating of the Sμ/CS2 mixture in sealed ampoules to 80–100°C complete dissolution takes place within several hours or days and the rings S8 and S7 are the main products.

Further studies on the interconversion of large ring and cyclometallated complexes of rhodium, with the diphosphines But2P(CH2)5PBut2and But2PCH2CHCHCH2PBut2

Improved routes to the fluxional cyclometallated hydride [[graphic omitted]But2)] are reported. Treatment of this hydride with carbon monoxide and sodium tetraphenylborate in methanol gives the fluxional salt [[graphic omitted]But2)][Bph4], together with a small amount of the 16-atom ring complex, trans-[Rh2Cl2(CO)2{But2P(CH2)5PBut2)2], more readily prepared by treating [Rh2Cl2(CO)4] with the diphosphine. This 16-atom ring complex exists as two rotamers in solution at 25 °C. Although [[graphic omitted]But2)] gives [[graphic omitted]But2)] with sodium propan-2-oxide and carbon monoxide on the other hand the corresponding complex [[graphic omitted]But2)] on similar treatment gives a complex mixture (probably containing rotamers of large-ring chelates). Treatment of [[graphic omitted]But2)] with MeNC and sodium propan-2-oxide also gives mixtures, probably containing large-ring chelates. Treatment of [[graphic omitted]But2)] with MeNC or ButNC in the presence of sodium tetraphenylborate or ammonium hexafluorophosphate gives 16-atom ring chelate salts [Rh2(CNR)4{But2P(CH2)5PBut2}2][anion]2 which can also be made by treating [Rh(CNR)4][anion] with the diphosphine. Rotation of trans-MeNC–Rh–CNMe moieties around P–Rh–P bonds has been studied by variable-temperature n.m.r. spectroscopy. The complex [Rh2(CNBut)4(But2PCH2CHCHCHCH2PBut2)2][PF6]2 has also been prepared. Treatment of the cyclooctene complex [Rh2Cl2(C8H14)4] with But2P(CH2)5PBut2 and MeNC or ButNC (1 mol per rhodium atom) gives 16-atom ring complexes of type [Rh2Cl2(CNR)2{But2P(CH2)5PBut2}2]. The complex [Rh2Cl2(CNMe)2{But2P(CH2)5PBut2}2] gives only one rotamer in solution in which the two rhodiums are chemically non-equivalent. The diphosphine But2PCH2CHCHCH2PBut2 reacts similarly with [Rh2Cl2(C8H14)4] and MeNC but also gives a small amount of another (unidentified) product. Infrared and 1H, 31P, and 103Rh n.m.r. data are given.

Conformational studies of dithiastannolanes by dynamic nuclear magnetic resonance spectroscopy

The barriers to conformational interconversion of the five-membered rings of the title compounds of general type SnRR′(SCH2CHR″S)(R, R′= Me or Ph; R″= H or Me) have been measured for the first time by low-temperature n.m.r. studies. Room-temperature measurements indicate that the chelate rings exist as half-chair conformations with the –CH2CHR″– moiety in a fully staggered configuration, as in the solid state. These findings are at variance with a previous n.m.r. study of this type of system. The ΔG‡ values for the interconversion of the two half-chair conformations lie in the range 30–32 kJ mol–1 and are essentially independent of the substituents on the SnIV atom and on the five-membered ring.

Empirical Force Field Calculations XIII. The Ring Interconversion Modes of cis‐1, 2, 3, 4, 4a, 5, 8, 8a‐Octahydronaphthalene and its 1α, 4α‐Dimethyl Derivative

AbstractThe inversion of the (half‐chair) chair conformers of cis‐1, 2, 3, 4, 4a, 5, 8, 8a‐octahydronaphthalene (1) and of its 1α, 4α‐dimethyl derivative (2) are studied with molecular mechanics using the white and Bovill empirical force field. It is a multi‐stage process: first the chair form of the saturated ring transforms into a twist conformation, then the (half‐chair) twist form can follow several pseudorotational paths on which the one half‐chair form of the unsaturated ring passes into the other via a boat form, and finally the twisted saturated ring converts into the inverted chair conformation. In 1 the first part of this process is of higher energy (ΔH≠ = 34.4 kJ mol−1) than the lowest pseudorotational path (30.8 kJ mol−1), in 2 it is the pseudorotational part of the inversion that is of somewhat higher energy (34.0 kJ mol−1) than the chair‐to‐twist stage (32.9 kJ mol−1). The methyl substituents cut off low energy pseudorotational paths available to 1 and direct the pseudorotation in 2 to regions of higher energy. The experimental determination of the inversion barrier of 1 yields ΔG≠ = 41.4 kJ mol−1.

Syn–anti equilibrium of purine bases in dinucleoside monophosphates as studied by proton longitudinal relaxation

AbstractThe preferential orientations of the purine bases in dinucleoside monophosphates such as ApA, ApG, and GpA in 10−2M neutral aqueous solutions have been investigated by proton relaxation at 250 MHz. These orientations are deduced from computer simulations of the magnetization recovery curves following a 180° nonselective pulse. The distances between the H(8) proton of a base and the ribose ring protons which are used in these calculations are obtained by minimization as a function of the glycosyl torsion angle ϒ of the standard deviation between the isotropic reorientation correlation times τR derived from the relaxation rates of these protons. The average H(1′) – H(8) distance obtained by this procedure may be readily verified from the reduction of the H(1′) relaxation rate when H(8) is substituted by a deuteron. The limits of validity of the assumption of a single correlation time τR governing the proton relaxation have been estimated, taking into account several possible internal motions, e.g., the rotation of the base, of the methylene exocyclic group and the N ⇄ S interconversion of the ribose ring. For 10−10 < τR < 2 × 10−10 sec, it appears that the influence of these motions on the proton relaxation becomes perceptible when the jump rates among equilibrium positions exceed ca. 109 sec−1.The whole of the experimental results show that for the ribose ring N conformer, the orientation of the bases is found in the ranges 60° < ϒ < 80° (syn) and 180° < ϒ < 210° (anti). For ribose S conformer, it is observed that this orientation is mainly syn with 5° < ϒ < 90°. The average H(1′) – H(8) distance provides semiquantitative information on the overall syn or anti orientations of the base in each nucleoside moiety. At 298 K the population of the anti conformer is found to increase in the order A‐ pG < Ap‐G ∼ Gp‐A < Ap‐A < A‐pA < G‐pA. A more detailed analysis of relaxation data shows that the maximum possible fraction of the stacked form of dinucleotides, due to the occurrence of N‐anti conformers in both nucleoside moieties, is in the order ApG < GpA < ApA, in agreement with previous works, with however smaller values.Lastly the deuteron linewidth in position 8 of the bases indicates a syn–anti transition rate of the order of 109 sec−1 at room temperature, without noticeable effects therefore on the proton relaxation.

Mechanism of the Pyrylium/Pyridinium Ring Interconversion. Mild Preparative Conditions for Conversion of Amines into Pyridinium Ions

Successive base and acid catalysis in the transformation of pyrylium (1) into pyridinium ions (2) permits drastic reduction of reaction time (depending upon R) and/or of the temperature.

Recherches en série triazépine‐1,2,4 XIII. Hydrazinolyses de thioxo‐3 oxo(thioxo)‐5 triazépines‐1,2,4

AbstractThe ring interconversion of 2,7‐dimethyl‐3‐thioxo‐5‐oxo(thioxo)‐1,2,4‐triazepines into pyrazolones, 3‐hydrazinopyrazoles or tetrazocyne by hydrazinolysis are described.The hydrazine and methylhydrazine reactions afforded 2‐methyl thiosemicarbazide and 3(5)‐pyrazolones by breaking of the two N(1)‐C(7) and N(4)‐C(5) bonds in the triazepinone ring. The reaction with phenylhydrazine is different. In this case three reaction centres must be taken into account: 3, 5 and 7 positions.Hydrazinolysis of 5‐thioxo‐1,2,4‐triazepine is more complicated and depends on the experimental conditions. The mechanism suggested is addition of two molecules of hydrazines in the 5 position followed by a transannular reaction to the 7 position for hydrazine and to the 3 and 7 position for phenylhydrazine.

Relaxation effects in glassy selenium

Thermal relaxation phenomena were measured in samples of both melt-quenched and evaporated selenium. On the basis of earlier studies, the two methods of preparation produced samples with polymeric chain concentrations of 30–50% and 0% respectively; the rest of the material was in the form of eight member rings. The relaxation peak occurred between 320 and 330 K, and had an activation energy of ≈22.5 kcal/mole for the melt-quenched sample. A decrease of 1 K in the glass relaxation temperature and 0.5 kcal (a at) −1 in the activation energy was observed in samples which had been initially evaporated. No change was observed as a result of melting and quenching these evaporated samples. It is postulated that there was no change when the evaporated sample was melt-quenched be because rings and chains can interconvert and equilibrate relatively readily at temperatures as low as T g (50° C), and consequently the samples all had the same structure after once being heated above T g. The differences observed are probably due to accidental impurities in the evaporated samples which help catalyze the interconversion of rings and chains. Further, since the equilibrium concentration of polymeric chains is temperature dependent, it is postulated that the large relaxation effects seen at T < T g are due to the equilibration of these chains with the rings. The observed activation energy for the relaxation supports this view. It is about the same energy as has been previously measured for Se 8 ring breaking in liquid selenium. Two consequences of this postulate are that the selenium analog to the sulfur polymerization transition must occur well below room temperature if it exists, and therefore, that the equilibrium ring-chain ratio can be smoothly extrapolated down to room temperature from the published high-temperature data.

Nuclear Magnetic Resonance Evidence for High Barrier of Conformational Inversion in Hexahydro-3,3,7,7-tetramethyl-1,2-oxazepine-5-one

Variable temperature proton n.m.r. spectra indicate an activation energy of 19.0 ± 0.5 kcal/mol for conformational equilibration in hexahydro-3,3,7,7-tetramethyl-1,2-oxazepine-5-one. It is suggested that the rate process involves slow conformational interconversion of the seven-membered ring and not slow inversion at the nitrogen atom. The synthesis of several related 1,2-oxazepines is described.

Chemical studies of carbohydrates. Part I. Conversion of derivatives of glucose and allose into pyrazoles and pyridazines

AbstractOn reaction of 1,2:5,6‐di‐O‐isopropylidenc‐3‐O‐(p‐tolylsulfonyl)‐α‐D‐glueofuranose (1) with hydrazine hydrate at 140° besides formation of 3‐deoxy‐3‐hydrazino‐1,2:5,6‐di‐O‐isopropylidene‐α‐D‐allofuranose (2) and 3‐dcoxy‐1,2:5,6‐di‐O‐isopropylidene‐α‐D‐erythro‐hex‐3‐enofuranose (3), ring transformation into 3‐[4′‐(2′,2′‐dimethyl‐1′,3′‐dioxolanyl)]pyridazine (4) takes place. At 170°, however, only 2 and 4 are formed, indicating that 3 is the precursor of 4. Treatment of 3 with hydrazine hydrate at 170° indeed gives a nearly quantitative ring expansion into 4. Treatment of 3‐dcoxy‐3‐hydrazino‐1,2:5,6‐di‐O‐isopropylidenc‐α‐D‐glucofuranose (8) as well as the stereoisomeric allofuranose 2 with concentrated hydrochloric acid gives a nearly quantitative ring interconversion into 3‐(D‐erythro‐trihydroxypropyl)pyrazole (9).

Conformational analysis with lanthanide shift reagents. A new determination of the cyclohexanol a-valoe

selective 1,3-cis-hydrogen abstraction observed upon oxidation of cyclohexanol with ferrous ion-hydrogen peroxide proceeds through a bound iron-oxy species as in (1j.l This proposal necessitates a reasonable abundance of the axial cyclohexanol-metal solvate complex since the rate of hydrogen abstraction by this reactive intermediate is likely to be rapid compared to chair-chair ring interconversion. This consideration has led us to examine possibly disadvantageous effects of metal complexation on the equilibrium (1) and to search for independent evidence that the cis proton on carbon-3 can be in close proximity to the metal oxidant.