Showing papers on "Conformational isomerism published in 1986"

Vibrational spectroscopic studies of conformation of poly(oxyethylene). II. Conformation–spectrum correlations

Abstract: Detailed normal-coordinate analysis has been carried out on a large number of conformers of model molecules of poly(oxyethylene); the model molecules treated are CH3(OCH2CH2)nOCH3 with n = 2,3, and 6. The systematic treatment provides well-defined correlations between conformation and vibrational spectra of poly(oxyethylene). The vibrations in the region 1050–800 cm−1, which are associated with the CO and CC stretching and CH2 rocking modes, are highly dependent on the conformation of the polymer chain. On the basis of these correlations, the infrared and Raman spectra of the molten state and of the aqueous solution are interpreted in terms of the conformational states. The analysis indicates that the following conformational fragments are present in these phases: GT-TG (T: trans; G: gauche), TT-TG, GT-GG, TT-TT, and TT-GG for the CH2CH2OCH2CH2 group, and TGT and TGG for the OCH2CH2O group. Conformational fragments GT-TG′ and GT-G′G′ are also possible in the analogy to GT-TG and GT-GG.

Structural heterogeneity in protein crystals

Abstract: Extensive conformational heterogeneity is reported in highly refined crystallographic models for the proteins crambin, erabutoxin, myohemerythrin, and lamprey hemoglobin. From 6% to 13% of the amino acid side chains of these four proteins are seen in multiple, discrete conformations. Most common are flexible side chains on the molecular surface, but structural heterogeneity occasionally extends to buried side chains or to the polypeptide backbone. A few instances of sequence heterogeneity are also very clear. Numerous solvent sites are multiplets, and at high resolution, multiple, mutually exclusive solvent networks are observed. The proteins have been studied with X-ray diffraction data extending to spacings of from 0.945 to 2.0 A. The extensive heterogeneity observed here provides detailed, accurate structures for conformational substates of these molecules and sets a lower bound on the number of substates accessible to each protein molecule in solution. Electron density is missing or very weak for only a few side chains in these protein crystals, revealing a strong preference for discrete over continuous conformational perturbations. The results at very high resolution further suggest that even rather small conformational fluctuations produce discrete substates and that unresolved conformers are accommodated in increased atomic thermal parameters.

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

Abstract: 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.

Ab initio studies of structural features not easily amenable to experiment: Part 49. Conformational analysis and molecular structures of ethylenediamine and aminoethanol

Abstract: The structures of eleven conformations of aminoethanol and of ten conformations of ethylenediamine were determined by ab initio gradient geometry optimization on the 4–21G level. The calculations show that many energetically different conformers exist for the gauche and trans forms (NCCO or NCCN torsions) of both systems. The results indicate that structural effects on NH bond distances associated with aliphatic N⋯N or NH⋯O type hydrogen bonding are less noticeable than those obtained previously for other XH⋯Y interactions. In the same way as CH and CC bonds in aliphatic compounds studied previously, NH bonds in the same NH2-group anti-periplanar to CH are found here to be slightly longer (∼0.001 A) than NH bonds antiperiplanar to CC. The most stable 4–21G conformations of ethylenediamine (NCCN ≅ 58° and 62°) are identical with the main conformer identified by others in the gas electron diffraction data of this compound (NCCN = 64° ± 4), but the calculations afford a more detailed description of the NH2 arrangements (NC torsions) than that obtained by the gas phase experimental data. Structural effects of electron lone-pair orientation are discussed. A small but potentially significant discrepancy exists between the electron diffraction rg average CC bond distance (1.545 A ± 0.008) and the calculated rg value (1.528 A ± 0.003; 4–21G average value empirically corrected as described previously). Experimental and calculated average rg CN bond distances are 1.469 A ± 0.004 and 1.463 A ± 0.006, respectively. Some aspects of the CC bond discrepancy are discussed in detail.

Structural studies on bioactive compounds. 4. A structure-antitumor activity study on analogs of N-methylformamide

Abstract: A series of derivatives of N-methylformamide (NMF), an experimental antitumor agent, has been prepared, having the general formula R3C(X)NR1R2 where R1 = H, CH3, CD3, CH2CF3, CH2CH2Cl, cyclopropyl, C2H5, CH2OH, CH2OR, CH2N(CH3)2; R2 = H, CH3; R3 = H, CF3, CCl3, CH3, Ph, NHCH3, N(CH3)2; and X = O, S, NH A further short series of "push-pull" olefins of the general formula R1R2C = CHNR3R4 has been synthesized where R1 = H, CH3 and R2 = H, NO2, CN, CHO, CH3 and R3 = H and R4 = H, CH3, morpholino These compounds have been tested for activity against the M5076 ovarian sarcoma and the TLX5 lymphoma in mice NMF was by far the most potent agent of both series with activity against both tumors Some other compounds showed weak activity, but there is a rigorous structural requirement for activity and most analogues were inactive Certain members of the series exist as equilibrium mixtures of rotamers about the amide or pro-amide bonds as shown by NMR

Isomerization and unimolecular dissociation channels of the oxalic acid monomer

Abstract: The results of molecular orbital calculations performed for the oxalic acid monomer using the 6‐31G, 6‐31G*(5d), 6‐31G**(5d), and MP2/6‐31G*(5d) levels are reported. At the latter three levels of approximation the geometry with intramolecular hydrogen bonds is calculated to have the lowest energy, and the energies calculated for planar rotational conformers fall within about 2 kcal/mol of one another. The barrier hindering internal rotation of the carboxyl groups about the C–C bond for the nonhydrogen bonded conformer is calculated to be less than 1 kcal/mol, and secondary potential energy wells for gauche, rather than for the expected cis, carbonyl orientation are found about 300 cal/mol above the trans conformer at the 6‐31G level. Vibrational frequencies calculated at the 6‐31G level for the H‐bonded conformer average about 9% higher than the observed values. On including electron correlation at the MP2 level the barrier calculated for the concerted, symmetrical, transfer of two protons between equivalent potential energy minima is 31.9 kcal/mol. This value is probably an upper bound. When electron correlation is ignored, calculations for the transfer of a single proton lead to a potential energy well that stabilizes an (HO)2CCO2 configuration with C2v symmetry at an energy 26–28 kcal/mol above that of the H‐bonded ground state conformer. When electron‐correlation is included at the MP2 level there is a saddle point in the PES instead. This is the transition state for proton exchange by successive transfers, and a search for its position at the MP2 level was not made. However, energy values of 25.7 and 36.6 kcal/mol are calculated using MP2/6‐31G*(5d) at optimized 6‐31G critical point geometries, and these values are taken as temporary estimates for the MP2 level transition state energies for two‐step proton exchange and for decarboxylation, respectively. It remains to be determined whether the stepwise proton exchange channel will be present for higher level calculations. The results of these MO calculations are consistent with the experimental observations of Lapidus, Barton, and Yankwichyielding first order kinetics, a low activation energy (31.5 kcal/mol), and complex kinetic isotope effects for the thermal decarboxylation of the oxalic acid monomer. Because of its importance in this reaction, calculations of the 1,2 H atom shift of dihydroxycarbene are also reported.

pH dependence of hydrogen exchange from backbone peptide amides in apamin.

Abstract: The kinetics of hydrogen exchange of the 11 most protected backbone amides of bee venom apamin have been measured between pH 1 and pH 8.5 by using time-resolved and saturation-transfer NMR spectroscopy. The five amides most protected from base-catalyzed exchange, those of residues 5 and 12-15, show highly correlated exchange behavior in the base-catalyzed regime. It is proposed that the intramolecular hydrogen bonds stabilizing these amides define a stable cooperative unit of secondary structure in apamin (a C-terminal helix and an N-terminal beta-turn). This conformational unit is further stabilized (by 5-6 kJ mol-1) on titration of the Glu-7 side-chain carboxyl group. The relative contributions of specific intramolecular interactions to this conformational stabilization are estimated. The pHminima in the pH-dependent single amide exchange curves are compared with values predicted by correcting for sequence-dependent contributions to amide exchange rates [Molday, R. S., Englander, S. W., & Kallen, R. G. (1972) Biochemistry 11, 150-158]. The lack of correlation suggests that the "open" conformers from which amide exchange occurs are nonrandom. This conclusion is dependent on the assumption that acid-catalyzed exchange occurs via N-protonation so that residual conformational effects on exchange rates in the open conformers will affect acid- and base-catalyzed rates in approximately equal and opposite ways. A strong correlation between the measured pHminima and the amide proton chemical shifts is observed, however, and this may be most easily accommodated if acid-catalyzed exchange occurs by the imidic acid mechanism (via amide O-protonation).

Infrared C–D Stretching and 2H NMR Spectra of Isopropyl-2-d 1-(p-Substituted Phenyl)ethyl Ketones. Evidence for the Hydrogen Bond-Like Interaction between C–D Group and Aromatic π-Electrons

Abstract: Isopropyl-2-d 1-(p-X-phenyl)ethyl ketones (where, X=H, NO2, Br, Cl, C2H5, CH3, and NH2) were shown to have two absorption bands in the C–D stretching region. The absorption band at the higher frequency (ca. 2177 cm−1) is assigned to the C–D···π approached conformer, and the high frequency shift is ascribed to the effect of steric compression. Weak C–D···π hydrogen bond was shown to occur by the measurement of the substituent effect on the formation constant and the relative enthalpy of the C–D···π approached conformer.

Spectra and structure of organophosphorus compounds. XXV. Raman and infrared spectra and conformational stability of ethyldimethylphosphine.

Abstract: The Raman (10–3500 cm−1) and infrared (50–3500 cm−1) spectra have been recorded for gaseous and solid ethyldimethylphosphine, CH3CH2P(CH3)2. Additionally, the Raman spectrum of the liquid has been recorded and qualitative depolarization values have been obtained. From the fact that several distinct Raman lines disappear on going from the fluid phases to the solid state, it is concluded that the molecule exists as a mixture of the gauche and trans conformers in the fluid phase with the gauche conformer being more stable and the only one present in the spectrum of the solid. From a temperature study of the Raman spectrum of the liquid, the enthalpy difference between the gauche and trans conformers was determined to be 134 ± 32 cm−1 (383 ± 92 cal mol−1). Relying on group frequencies and relative intensities of the infrared and Raman bands, and in some cases infrared band contours, a complete vibrational assignment is proposed for the gauche conformer. The assignment is supported by a normal coordinate calculation which was carried out utilizing a modified valence force field to obtain the frequencies of the normal modes and the potential energy distribution. The CH3-P torsions have been observed at 208 and 185 cm−1 in the gas phase and from these frequencies the periodic barriers to internal rotation have been calculated to be 905 ± 95 cm−1 (2.56 kcal mol−1). The CH3-C torsion was also observed in the gas phase at 217 cm−1 from which a periodic barrier of 1134 cm−1 (3.22 kcal mol−1) was calculated. The asymmetric torsional mode has been observed for the gauche conformer in both the infrared and Raman spectra of the gas at 91 cm−1 with evidence of ‘hot bands’ at lower frequencies. All of these results are compared with corresponding quantities for several other organophosphines.

Conformational analysis of DL‐, L‐ and D‐methionine by solid‐state 13C NMR spectroscopy

Abstract: The conformational analysis of DL-, L- and D-methionine was studied by solid-state 13C NMR with the help of cross-polarization and magic-angle spinning techniques. The spectrum of commercial crystalline DL-methionine showed two chemical shifts (18.7 and 15.8 ppm) for the methyl carbon. Crystallization from water or water-ethanol (95 : 5) allowed the separation of two crystalline forms (α and β), of which one had δ (CH3) 18.7 ppm and the other δ (CH3) 15.8 ppm. Therefore, each crystalline form of DL-methionine consists of a single conformer, a result in agreement with x-ray diffraction data. This conformational difference of the two crystalline forms was also reflected in the carbon resonances of C-β and C-γ. When L- and D-methionine were crystallized from water-ethanol (3 : 2), the solid-state 13C NMR spectra showed that each isomer displayed two methyl carbon peaks at 18.1 and 16.2 ppm of equal intensities, while the α-carbon resonances showed a broad peak due to two unresolved doublets. These results suggest that the L- or D-methionine crystal contains two different conformers in one unit cell, a conclusion that is also supported by the x-ray data.

Dynamic Liquid State NMR and IR Study of Tautomerism and Conformations of Tetraphenyloxalamidine, a Novel Small Intramolecular Double Hydrogen Transfer System

Abstract: Using Dynamic NMR Spectroscopy we have detected a novel intramolecular double hydrogen transfer in the oxalamidine (OA) system. OA is, therefore, so far the smallest known molecular unit capable of such a transfer. Because of solubility problems, experiments were performed on tetraphenyloxalamidine (TPOA, Ia) and the isotopically labeled compound TPOA-15N4-d20 (Ib) dissolved in CD2CI2. At low temperatures TPOA exists in a number of different conformations, of which only one conformation with two intramolecular hydrogen bonds is capable of an intramolecular hydrogen transfer which shows up in the 1H-15N signal of this conformer. At low temperatures a 1H-15N doublet (88 Hz coupling constant) is observed which changes into a triplet (44 Hz coupling constant) as the temperature is raised. The position of this signal is independent of temperature and concentration. Two further conformations were detected, of which one formed strong intermolecular hydrogen bonds and underwent fast intermolecular proton exchange. Above room temperature all NH signals coalesce into an exchange-broadened singlet. 13C experiments prove that this effect is due to a fast internal conversion of all conformers. IR experiments on TPOA in CCl4 did not reveal the complicated conformational behavior of TPOA. By lineshape analysis we obtained the rate constants of the HH migration, which are given by kHH = 1010.8 exp(−43 kJ mol−1/RT). An upper limit for the HD exchange rates were found for a sample deuterated to 90% in the labile proton sites: kHD = exp(−53 kJ mol −1/RT), i.e. kHH/kHD = 2.1 at 298 K. The data are compared to previous results on the azophenine rearrangement.

Conformational Energies and Structural Relaxation in Singly Bonded Silicon, Phosphorus and Sulfur-Compounds

Abstract: Conformational energy differences, structural relaxation and changes in bonding between different rotamers of silicon, phosphorus and sulfur compounds have been calculated by ab initio molecular orbital methods to permit systematic comparison between the compounds of first and second row elements. The results were obtained with polarized 3-21G and 4-31G basis sets on the series SiH3X, PH2X and SHX (X = BH2, CH3, NH2 and OH) and also on the rotamers of the second row hydrides Si2H6, P2H4 and S2H2. Bond length and bond angle relaxation and conformational energy differences for the Si -, P- and S-containing molecules are 30-50% smaller than in the compounds of the first row elements.

Proposals for the mu-active conformation of the enkephalin analog Tyr-cyclol(-N gamma-D-A2-bu-Gly-Phe-Leu-).

Abstract: The conformational behavior of the sterically restricted cyclic peptide Tyr-cyclo(-N gamma-D-A2-bu-Gly-Phe-Leu-), proposed recently as an enkephalin analog with high opiate activity, is examined by theoretical investigations. The method used allows the search of conformational energy minima associated with cyclic structures fitting a hypothetical opiate pharmacophore. The results obtained show that, despite the fact that many cyclic structures of low conformational energy can be found for this compound, only one of them can be retained as a conformer presenting the characteristic features of the imposed pharmacophore. This conformation is stabilized by an intramolecular H-bond between the D-A2bu-carbonyl and the Leu NH group so that a beta-turn is formed. This structure also presents a high mobility of the Tyr1 side-chain which can fit the tyramine moiety of rigid opiates with minor loss of conformational energy. A two-step binding mechanism is proposed for the interactions of this cyclic peptide with its receptor which could be an intermediate between the "zipper" model proposed for flexible linear peptides and the "lock-and-key" model adapted to rigid molecules. The selectivity of enkephalin analogs for mu and delta opioid receptors is discussed in light of the present theoretical investigations.

Fluorescence of conformational isomers of trans 2-styryl-naphthalene. Further evidence for different radiative decay parameters of the two rotamers

Abstract: The fluorescence properties of the conformer mixture of trans 2-styrylnaphthalene in inert solvents have been reinvestigated. The temperature, excitation wavelength and oxygen quenching effects on fluorescence spectra, quantum yields and decay profiles have been carefully examined. The results obtained give further confirmation to our previous fluorescence analysis thus supporting the assignment of different radiative decay parameters to the two conformers.