Showing papers on "Conformational isomerism published in 2000"

Thermochemistry and Conformational Polymorphism of a Hexamorphic Crystal System

Abstract: 5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile has been crystallized as six solvent-free polymorphs, which differ in the mode of packing and in molecular conformation. The conformational difference results principally from the thiophene torsion relative to the o-nitroaniline fragment, which leads to different crystal colors (red, orange, and yellow). Thermodynamic stability relationships between polymorphs have been determined from solid-state conversions and calorimetric data of melting and eutectic melting. Vibrational spectroscopy and ab initio calculations showed that most conformers in solution feature perpendicularly arranged thiophene and o-nitroaniline fragments, although a minor population of more planar conformers also exist. Crystallization has a stabilizing effect for more planar and higher dipole conformers over perpendicular ones by 3−6 kJ/mol. The only exception to this pattern is the one polymorph containing weak intermolecular hydrogen bonds.

Crystal structures of spin labeled T4 lysozyme mutants: implications for the interpretation of EPR spectra in terms of structure.

Abstract: High resolution (1.43-1.8 A) crystal structures and the corresponding electron paramagnetic resonance (EPR) spectra were determined for T4 lysozyme derivatives with a disulfide-linked nitroxide side chain [-CH(2)-S-S-CH(2)-(3-[2,2,5,5-tetramethyl pyrroline-1-oxyl]) identical with R1] substituted at solvent-exposed helix surface sites (Lys65, Arg80, Arg119) or a tertiary contact site (Val75). In each case, electron density is clearly resolved for the disulfide group, revealing distinct rotamers of the side chain, defined by the dihedral angles X(1) and X(2). The electron density associated with the nitroxide ring in the different mutants is inversely correlated with its mobility determined from the EPR spectrum. Residue 80R1 assumes a single g(+)()g(+)() conformation (Chi(1) = 286, X(2) = 294). Residue 119R1 has two EPR spectral components, apparently corresponding to two rotamers, one similar to that for 80R1 and the other in a tg(-)() conformation (Chi(1) = 175, X(2) = 54). The latter state is apparently stabilized by interaction of the disulfide with a Gln at i + 4, a situation also observed at 65R1. R1 residues at helix surface site 65 and tertiary contact site 75 make intra- as well as intermolecular contacts in the crystal and serve to identify the kind of molecular interactions possible for the R1 side chain. A single conformation of the entire 75R1 side chain is stabilized by a variety of interactions with the nitroxide ring, including hydrophobic contacts and two unconventional C-H.O hydrogen bonds, one in which the nitroxide acts as a donor (with tyrosine) and the other in which it acts as an acceptor (with phenylalanine). The interactions revealed in these structures provide an important link between the dynamics of the R1 side chain, reflected in the EPR spectrum, and local protein structure. A library of such interactions will provide a basis for the quantitative interpretation of EPR spectra in terms of protein structure and dynamics.

Complexation of Na+ and K+ to Aromatic Amino Acids: A Density Functional Computational Study of Cation-π Interactions

Abstract: Binding energies were calculated for the complexes of Na+ and K+ with phenylalanine (Phe), tyrosine (Tyr), and tryptophane (Trp), along with energies of low-energy conformers of the neutral amino acids. Structures were optimized and energies determined by density functional theory (DFT) with the B3LYP functional, using a basis set of 6-31+g(d) on all, or nearly all, heavy atoms. For all but one cation/ligand system, the most energetically favorable binding geometry was the tridentate N/O/Ring chelate. For K+/Trp, however, the advantage of placing the metal ion over the phenyl region of the indole side chain was dominant, leading to a most favored bidentate O/Ring binding geometry. All of the systems, and particularly the Trp systems, have multiple conformers with stabilities within a few kcal mol-1 of the most stable. Zwitterion forms of the complexes were not unreasonable, but were less stable than the normal forms by ∼5 kcal mol-1. To assess the importance of cation−π interactions, conformers were exami...

The Infrared and Ultraviolet Spectra of Individual Conformational Isomers of Biomolecules: Tryptamine

Abstract: Resonant ion-dip infrared (RIDIR) and UV−UV hole-burning spectroscopies are used to record the hydride stretch infrared spectra and S1←S0 ultraviolet spectra of each of seven conformational isomers of tryptamine free from interference from one another. The different conformations of the ethylamine side chain produce unique S1←S0 vibronic spectra, which can serve as the basis for RIDIR spectroscopy. The seven conformers possess unique spectral signatures in the alkyl CH stretch region of the infrared, which aid in the assignment of the observed transitions in the ultraviolet. Density functional theory (DFT) calculations of the structures, relative energies, and harmonic vibrational frequencies of nine low-energy minima are compared with the present and previous experimental data on tryptamine to assign the spectra of all seven conformers, all of which point the α carbon out of the plane of the indole ring. The nine conformers consist of all combinations of the three minimum-energy amino group positions (an...

Intra- and Intermolecular π-Type Hydrogen Bonding in Aryl Alcohols: UV and IR-UV Ion Dip Spectroscopy

Abstract: The structures of benzyl alcohol, its 1:1 water complex, and its dimer have been investigated by R2PI spectroscopy and IR−UV ion dip spectroscopy, combined with ab initio computation. The sole molecular conformer observed in the jet has a gauche arrangement of the gauche arrangement of the OH group relative to the C1−Cα bond, but the extent of π-type intramolecular H-bonding is small. Analysis of its rotational band contours suggests the incidence of vibronic coupling involving motion of the side chain and also leads to an estimate for the dihedral angle τ1(OCCC) lying in the range 35°−60°, in good agreement with the values (50°−60°) indicated by high-level ab initio calculations. The 1:1 water complex is assigned to a structure in which water binds as a proton acceptor to the alcohol group, and as a weak proton donor to the π-system of the aromatic ring. The arrangement of H-bonds is similar within the dimer: the OH of one molecule acts as both acceptor to the alcohol group and as donor to the π-system ...

Assignment of 1H and 13C spectra and investigation of hindered side‐chain rotation in lupeol derivatives†

Abstract: Complete 1H and 13C spectral assignments are reported for lupeol (1a) and two derivatives where the C-30 methyl group is replaced by CH2OH (1b) and HC O (1c). Compound 1c shows conformationally dependent substituent effects on 1H chemical shifts. It also shows line broadening of some 13C signals at 25 °C, suggesting hindered rotation of the side-chain group. This is confirmed by low-temperature spectra which show splitting of broadened peaks into pairs in a ca 2 : 1 area ratio. The free energy of activation of hindered rotation is estimated as 13.5 kcal mol−1. By contrast, 1a shows no evidence of hindered rotation down to −40 °C although NOE data suggest the presence of two conformers. Spartan molecular mechanics calculations confirm the presence of two stable conformers for 1a and 1c but overestimate the rotational barrier in 1a. The additional barrier in 1c probably reflects loss of conjugative stabilization during rotation. Copyright © 2000 John Wiley & Sons, Ltd.

The interaction of oligo(ethylene oxide) with water: a quantum mechanical study

Abstract: Using density functional theory with nonlocal corrections we have performed a systematic study of the molecular conformation and energetics of methoxy terminated oligo(ethylene oxide) (EG)n molecules. For n=3 we have calculated 31 conformers without and with adsorbed water, and made some comparisons with n=1, 2 and selected n=4 conformers. We find that solvated EG moieties with non-uniform gauche rotations are by far the most stable in the solvated state. We also examine rotational barriers around the C–O and C–C bonds. In addition, using the calculated energies and vibrational spectra of the dry and solvated EG strands and the tabulated thermodymamical functions of water we can estimate the enthalpy and entropy contribution to the free energy of solvation.

Synthesis and Alkali Metal Ion Binding Properties of Two Rigid Sterochemical Isomers of Calix[6]arene Bis-crown-4

Abstract: Cone and 1,2,3-alternate stereochemical isomers of 37,40-diallyloxy-(38,42),(39,41)-bis-crown-4 calix[6]arene, 3 and 4 were isolated in moderate yields by bridging the dialkylated calix[6]arene 2 with triethylene glycol di-p-tosylate. The alkali metal complex stoichiometries, association constants, and ion selectivities of 3 and 4 were studied by 1H NMR titration experiments, liquid−liquid extraction, electrospray ionization mass spectroscopy, and X-ray crystallography. Good agreement between the gas-phase and solution-phase studies regarding these metal binding properties was observed. Both conformers formed 1:1 complexes with all alkali metal ions but were structurally preorganized such that each exhibited a strong preference for the larger cesium ion as evidenced by the “deep-cavity” cesium complex of host 4, wherein π-metal interactions helped to stabilize the complex. The Cs+/Na+ selectivity factor for 4 was found to be 1500, while that of 3 was only 140.

Population, acid-base, and redox properties of N-acetylcysteine conformers.

Abstract: Rotamers of N-acetyl-L-cysteine (NAC, the most popular mucolytic drug) are characterized in terms of populations, site- and conformer-specific acid-base properties, reducing strength, and molecular pharmacology. A new, general relationship between the bulk- and rotamer-specific basicities is introduced. NAC at high pH predominantly exists in a trans thiolate-carboxylate rotameric form, whereas protonation promotes the occurrence of intramolecular hydrogen bond-forming isomers. Distribution curves of the rotamers are depicted as a function of pH. Rotamer-dependent thiolate basicities differ by up to 0.5 log k units. Carboxylate basicities show slight conformation-dependence only. The membrane-penetrating capabilities from various compartments of the body are assessed on the basis of the pH-dependent charge of the molecule. The thiol-disulfide half-cell potential is calculated, using the correlation between the thiolate basicity and oxidizability. The oxidation-reduction properties of NAC are compared to those of other biological thiols in their definite microscopic forms. The pharmacokinetic behavior is interpreted in terms of the physicochemical parameters, providing molecular/submolecular explanation for several therapeutic properties of NAC.

Photoelectron Spectroscopy and Circular Dichroism in Chiral Biomolecules: l-Alanine

Abstract: A theoretical treatment of the photoionization of the chiral amino acid l-alanine is presented. Particular attention is paid to a previously unobserved circular dichroism which should be detectable in the photoelectron angular distribution (CDAD) from randomly oriented molecules. Numerical estimates of this difference in the differential cross-sections for left- and right-circularly polarized light range as large as 40% of the mean cross-section. Three different low-energy conformational structures are considered. Further comparisons with the experimental photoelectron spectrum suggest, however, that only one dominates in the gas phase. This concurs with other experimental data but disagrees with conclusions drawn from previous molecular orbital calculations. The magnitude of the predicted CDAD effect, especially when ionizing skeletal bonding orbitals, is sufficient to suggest that it may provide an experimental means for successfully distinguishing optical and conformational isomers.

High pressure NMR reveals active-site hinge motion of folate-bound Escherichia coli dihydrofolate reductase.

Abstract: A high-pressure (15)N/(1)H two-dimensional NMR study has been carried out on folate-bound dihydrofolate reductase (DHFR) from Escherichia coli in the pressure range between 30 and 2000 bar. Several cross-peaks in the (15)N/(1)H HSQC spectrum are split into two with increasing pressure, showing the presence of a second conformer in equilibrium with the first. Thermodynamic analysis of the pressure and temperature dependencies indicates that the second conformer is characterized by a smaller partial molar volume (DeltaV = -25 mL/mol at 15 degrees C) and smaller enthalpy and entropy values, suggesting that the second conformer is more open and hydrated than the first. The splittings of the cross-peaks (by approximately 1 ppm on (15)N axis at 2000 bar) arise from the hinges of the M20 loop, the C-helix, and the F-helix, all of which constitute the major binding site for the cofactor NADPH, suggesting that major differences in conformation occur in the orientations of the NADPH binding units. The Gibbs free energy of the second, open conformer is 5.2 kJ/mol above that of the first at 1 bar, giving an equilibrium population of about 10%. The second, open conformer is considered to be crucial for NADPH binding, and the NMR line width indicates that the upper limit for the rate of opening is 20 s(-)(1) at 2000 bar. These experiments show that high pressure NMR is a generally useful tool for detecting and analyzing "open" structures of a protein that may be directly involved in function.

Resonant ion-dip infrared spectroscopy of benzene–(water)9: Expanding the cube

Abstract: The techniques of resonant two-photon ionization (R2PI), UV-UV hole-burning, and resonant ion-dip infrared (RIDIR) spectroscopy have been employed along with density functional theory (DFT) calculations to characterize the hydrogen-bonding topologies of three isomers of benzene–(water)9. Isomers I and II, with R2PI transitions shifted, respectively, by +77 and +63 cm−1 from the benzene monomer, have similar intensities in the R2PI spectrum. The signal from the third isomer (isomer III, shifted +60 cm−1) is present at about one-fourth the intensity of the other two. The experimental RIDIR spectrum of isomer I bears a strong resemblance to the spectrum of the benzene–(water)8 D2d-symmetry cubic structure identified in earlier work, but possessing an extra single-donor transition associated with the ninth water molecule. Using the S4 and D2d symmetry forms of the water octamer as base structures to which the ninth water molecule can be added, a total of nine “expanded-cube” structures are identified for W9 arising from two distinct insertion points in the W8(D2d) cube (D1,D2) and three such points in the W8(S4) cube (S1-S3). DFT calculations predict these to be spread over an energy range of less than 1 kcal/mol. Given that each of the nine “expanded-cube” (water)9 structures contains five symmetry-inequivalent free OH groups, a total of 45 “expanded-cube” benzene–(water)9 conformational isomers are predicted. Structural and vibrational frequency calculations have been performed on seven of these to determine how the (water)9 structural type and the attachment point of benzene to the structure affect the total energy and vibrational frequencies of the cluster. Based on a comparison of the experimental RIDIR spectrum with the calculated vibrational frequencies and infrared intensities, isomer I is attributed to the BW9(D1) structure in which benzene attaches to W9(D1) at the free OH of the water molecule which donates a H-bond to the ninth water. This structure has a calculated binding energy that is about 0.13 kcal/mol greater in magnitude than any other benzene–(water)9 isomer studied. The experimental spectra of isomers II and III are of insufficient quality to assign them to specific BW9 structures with confidence. However, isomer II is most consistent with an S4-derived expanded cube structure (either S1 or S2), while isomer III shows characteristics consistent with a second D1-derived BW9 structure in which benzene is attached at a position on the expanded cube remote from the ninth water.

Conformational studies in the cyclohexane series. 2. Phenylcyclohexane and 1-methyl-1-phenylcyclohexane

Abstract: The structures and relative energies of the conformers of phenylcyclohexane, and 1-methyl-1-phenylcyclohexane have been calculated at theoretical levels including HF/6-31G, B3LYP/6-311G, MP2/6-311G, MP2/6-311(2df,p), QCISD/6-311G, and QCISD/6-311G(2df,p). The latter gives conformational enthalpy (DeltaH degrees ), entropy (DeltaS degrees ), and free energy (DeltaG degrees ) values for phenylcyclohexane that are in excellent agreement with the experimental data. The calculations for 1-methyl-1-phenylcyclohexane find a free energy difference of 1.0 kcal/mol at -100 degrees C, favoring the conformation having an axial phenyl group, that is in only modest agreement with the experimental value of 0.32 +/- 0.04 kcal/mol. The origin of the phenyl rotational profiles for the conformers of phenylcyclohexane and 1-methyl-1-phenylcyclohexane is discussed.

Computational Studies on Carbohydrates: I. Density Functional Ab Initio Geometry Optimization on Maltose Conformations

Abstract: Ab initio geometry optimization was carried out on 10 selected conformations of maltose and two 2-methoxytetrahydropyran conformations using the density functional denoted B3LYP combined with two basis sets. The 6-31G and 6-311CCG basis sets make up the B3LYP/6-31G and B3LYP/6-311CCG procedures. Internal coordinates were fully relaxed, and structures were gradient optimized at both levels of theory. Ten conformations were studied at the B3LYP/6-31G level, and five of these were continued with full gradient optimization at the B3LYP/6-311CCG level of theory. The details of the ab initio optimized geometries are presented here, with particular attention given to the positions of the atoms around the anomeric center and the effect of the particular anomer and hydrogen bonding pattern on the maltose ring structures and relative conformational energies. The size and complexity of the hydrogen-bonding network prevented a rigorous search of conformational space by ab initio calculations. However, using empirical force fields, low-energy conformers of maltose were found that were subsequently gradient optimized at the two ab initio levels of theory. Three classes of conformations were studied, as defined by the clockwise or counterclockwise direction of the hydroxyl groups, or a flipped conformer in which the -dihedral is rotated by180 .D ifferent combinations of! side-chain rotations gave energy differences of more than 6 kcal/mol above the lowest energy structure found. The lowest energy structures bear remarkably close resemblance to the neutron and X-ray diffraction crystal structures. c 2000 John Wiley & Sons, Inc. JC omput Chem 21: 1204-1219, 2000

A Computational Study of Nicotine Conformations in the Gas Phase and in Water

Abstract: The conformational preferences of nicotine in three protonation states and in the gas phase as well as aqueous solution are investigated using several computational procedures. Conformational aspects emphasized are N-methyl stereochemistry, relative rotation of the pyridine and pyrrolidine rings, and pyrrolidine ring conformation. All methods consistently predicted that the N-methyl trans species are most stable for all protonation states in both gas phase and in water. However, the cis/trans energy gap is significantly reduced in water. Additionally, the two pyridine ring rotamers, which are energetically equivalent in the gas phase, experience different solvation energies in water.

Density Functional Calculation of Structural and Vibrational Properties of Glycerol

Abstract: The conformational distribution of glycerol is still an open question both in gas and in liquid phase. Density functional calculations on different conformers of glycerol are reported and compared to the experimental infrared spectra of the gas and of the liquid. The experimental infrared spectra of gas and liquid glycerol are fitted by a linear combination of the single conformer ab initio spectra, obtaining the relative conformer concentrations. For the gas the results are in agreement with electron diffraction experiments and with molecular dynamics simulation data. The conformational distribution of glycerol in liquid phase is less accurate but always indicative. Some results about the role of the intramolecular hydrogen bonding in stabilization and in structural features of the conformers are discussed.

Anharmonic treatment of the lowest-energy conformers of glycine: A theoretical study

Abstract: The structure and energetics of the four lowest-energy conformers of glycine were determined at the MP2/aug-cc-pVDZ level of theory. The optimized structural parameters for these conformers agree with previous theoretical results obtained by highly correlated ab initio methods and with available experimental data. The only structure with planar heavy atom arrangement is conformer I (global minimum), the other conformers have nonplanar heavy atom arrangements. In accordance with temperature dependence studies of the vibrational spectra in various rare gas environments, conformers III and IV have small interconversion barriers to conformer I (940 and 740 cm−1). Our calculations have shown that full-dimensional anharmonic treatment is required for an accurate description of the vibrational modes in various glycine conformers. The most pronounced effect has been observed for conformer II with the intramolecular O–H⋅⋅⋅N bond. The theoretical results obtained at the MP2/aug-cc-pVDZ level reproduce quantitatively the argon matrix experiments. The calculation uses the quartic force field approximation in the framework of second-order perturbation theory. An estimate of the higher-order correction is also given.

DFT conformational study of cysteine in gas phase and aqueous solution

Abstract: Different conformers of cysteine in gas phase are investigated at the DFT B3LYP/6-31G* and B3LYP/6-311 + +G** levels. The effect of the solvent is simulated by using the Onsager and polarizable continuum (PCM) models within the self-consistent reaction field method (SCRF) at the B3LYP/6-31G* level. Specifically, five neutral forms, two anions and one zwitterion were analysed. Both, in gas phase and solution the most stable normal form has the carboxyl group directed toward the amino group. In accord with the experiment, the PCM model predicts that the most stable structure in solution is a zwitterion, a species that does not exist or has a very small stability in gas phase. A major stabilization in solution is also predicted for the zwitterionic form of anionic cysteine. Thus the PCM model renders correct stability order of the different conformers in solution, while the Onsager model does not, which is due to the underestimation of the electrostatic contributions to the solute-solvent interaction for the zwitterions. (C) 2000 Elsevier Science B.V.

Rotational Spectra of Seven Conformational Isomers of 1-Hexene

Abstract: The rotational spectra of 7 of the expected 13 conformational isomers of 1-hexene have been measured and assigned at a rotational temperature of <2 K using a pulsed-molecular-beam Fourier transform microwave spectrometer. The rotational assignments were guided by predictions from the MM3 molecular mechanics force field of Allinger et al. and by ab initio electronic-structure calculations (MP2/6-31G*). Six of the seven observed conformers have C1 symmetry, as verified by the observation of a-, b-, and c-type electric-dipole transitions. The remaining conformer has Cs symmetry, consistent with its small inertial defect, Δ ≡ Icc − Ibb − Iaa = −12.65 uA2, and the observation of only a and b-type transitions. Here, Iαα is the moment of inertia of the conformer about its α-principal axis. The inertial defects determined for the seven conformers range from −12.65 to −51.29 uA2. Both the molecular mechanics and ab initio calculations indicate the observed conformers are associated with the seven lowest-energy con...

Infrared-Induced Rotamerization of Oxalic Acid Monomer in Argon Matrix

Abstract: Infrared-induced conformational isomerization of oxalic acid monomer isolated in an argon matrix at 7.5 K was studied by infrared spectroscopy. For the first time, three conformational states of this molecule were identified experimentally and their vibrational spectra are assigned. In good agreement with density functional theory predictions, all the observed conformers exhibit a trans OC−CO axis, differing in the relative conformation of their O−C−O−H axes. In the most stable conformer (belonging to the C2h symmetry point group), two intramolecular OH···O hydrogen bonds are present. The second (Cs) most stable conformer shows a single OH···O bond, and the third one (C2h) does not exhibit any intramolecular hydrogen bond. Using narrowband tunable irradiation in the near-infrared region it was possible to promote very efficiently conformer interconversions, which was followed spectroscopically.

Theoretical investigation on the conformational preferences of sulfinimines

Abstract: The potential energy surfaces of sulfinimine, H2CNS(O)H, 1, and methylsulfinimine, MeHCNS(O)H, 2, have been searched, using the ab initio MO and Density Functional Methods, to study the conformational preferences. Complete optimizations at HF/6-31G*, HF/6-31+G*, MP2/6-31+G* and B3LYP/6-31+G* levels on 1 showed that there are three minima on the path of rotation around N–S bond in 1. A conformer with synperiplanar arrangement, with the C–N–S–O torsional angle close to 13°, has been found to be the most preferred. Repulsions between the lone pairs of electrons present on N, S and O atoms are responsible for the observed conformational preferences of 1. The N–S bond rotational barrier in 1 is 9.16 kcal mol−1 at the B3LYP/6-31+G*(+ZPE) level. This high energy barrier can be attributed to the nN → σ*SO negative hyperconjugation and to the repulsive interactions between the lone pairs of electrons. The planar N-inversion barrier in 2Z is 18.72 kcal mol−1 at the B3LYP/6-31+G* (+ZPE) level, comparable to experimental values.

Structures of protonated arginine dimer and bradykinin investigated by density functional theory: further support for stable gas-phase salt bridges.

Abstract: The gas-phase structures and energetics of both protonated arginine dimer and protonated bradykinin were investigated using a combination of molecular mechanics with conformational searching to identify candidate low-energy structures, and density functional theory for subsequent minimization and energy calculations. For protonated arginine dimer, a good correlation (R = 0.88) was obtained between the molecular mechanics and EDF1 6-31+G* energies, indicating that mechanics with MMFF is suitable for finding low-energy conformers. For this ion, the salt-bridge or ion-zwitterion form was found to be 5.7 and 7.2 kcal/mol more stable than the simple protonated or ion-molecule form at the EDF1 6-31++G** and B3LYP 6-311++G** levels. For bradykinin, the correlation between the molecular mechanics and DFT energies was poor (R = 0.28), indicating that many low-energy structures are likely passed over in the mechanics conformational searching. This result suggests that structures of this larger peptide ion obtained using mechanics calculations alone are not necessarily reliable. The lowest energy structure of the salt-bridge form of bradykinin is 10.6 kcal/mol lower in energy (EDF1) than the lowest energy simple protonated form at the 6-311G* level. Similarly, the average energy of all salt-bridge structures investigated is 13.6 kcal/mol lower than the average of all the protonated forms investigated. To the extent that a sufficient number of structures are investigated, these results provide some additional support for the salt-bridge form of bradykinin in the gas phase.

Cyclopentapeptides as Flexible Conformational Templates

Abstract: Studies of 3D models for cyclopentapeptides (CPP's) employing only NMR spectroscopy encounter a serious problem. Because of conformer averaging, 3D structure(s) derived directly from NMR data may n...

Assignment of the absolute configuration of alpha-chiral carboxylic acids by 1H NMR spectroscopy

Abstract: The prediction of the absolute configuration of α-chiral carboxylic acids from the 1H NMR spectra of their esters with (R)- and (S)-ethyl 2-hydroxy-2-(9-anthryl) acetate [(R)- and (S)-9-AHA, 5] is discussed. Low-temperature NMR experiments, MM, semiempirical, and aromatic shielding effect calculations allowed the identification of the main conformers and showed that, in all esters studied, conformer ap is the most stable. A simple model for the assignment of the absolute configuration from NMR data is presented, and its reliability is corroborated with acids 6−31 of known absolute configuration. In addition to 5, other auxiliary reagents with open (32−38) and cyclic (39−42) structures have also been studied. trans-(+)- and (−)-2-phenyl-1-cyclohexanol (41) was found to be particularly efficient and produced ΔδRS values similar to those of 5.

Calix[4]arene based monophosphites, identification of three conformations and their use in the rhodium-catalysed hydroformylation of 1-octene

Abstract: Eight monodentate phosphites (2–9) based on the calix[4]arene backbone were synthesised following two synthetic routes. Out of six conformations only three were actually formed under the applied reaction conditions. X-Ray analysis of two conformers (4 and 5) provided insight into the 3-dimensional structure of two of these conformations. The three conformations were characterised by 1H, 13C and 31P NMR spectroscopy. NMR experiments showed that several of the phosphites are flexible showing fluxional behaviour of the molecular backbone in solution, but no interconversion between the different conformers was observed. The conformation of the product in the phosphite synthesis is determined at the point where the phosphorus atom is linked to two hydroxyl groups of the calix[4]arene (phosphorus amidite). Such an intermediate phosphorus amidite (12) was isolated in the synthesis of 4 and 5. Phosphites 3–6, 8 and 9 were tested in rhodium-catalysed hydroformylation. Differences in rate can be correlated to the conformation of the ligand.

Ab initio DFT study of the hydrogen bridges in hexafluoro-acetylacetone, trifluoro-acetylacetone and some 3-substituted derivatives

Abstract: All the theoretically possible keto and enol conformations of hexafluoro-acetylacetone (HFAA) as well as those of 2-trifluoro- (2TFAA) and 4-trifluoro-acetylacetone (4TFAA), have been investigated at ab initio level by using the 6-31G∗∗ basis. The correlation energy was evaluated by means of the Becke functional following the Density Functional Theory. It was found that the most stable conformers are always those stabilized by hydrogen bridges and characterized by Cs symmetry, as the parent acetylacetone. 4TFAA is about 4 kJ/mol favored with respect to 2TFAA. The withdrawing effect of the trifluoromethyl group(s) produces a decrease in the hydrogen bond strength (EHB) with respect to that of acetylacetone; in any case such strength is enhanced when 3-substituent groups are able to increase the conjugation of the system or to cause strong steric effects. In several open conformations the formation of a F⋯H–O bridge is observed, whose energy was estimated as 10 kJ/mol, at the most.

Solution structure of oxidized microsomal rabbit cytochrome b5. Factors determining the heterogeneous binding of the heme.

Abstract: Cytochrome b5 is heterogeneous in solution because of the presence of two isomers (A and B), differing in the rotation of the heme plane around the axis defined by the α and γ meso protons. For rabbit cytochrome b5, the A/B ratio is 5 : 1. The solution structure of the major form of the oxidized soluble fragment of rabbit microsomal cytochrome b5 (94 amino acids) is here solved through NMR spectroscopy. From 1908 NOEs, of which 1469 were meaningful, there were 246 pseudocontact shifts and 18 3J couplings, a family of 40 energy-minimized conformers were obtained with average backbone rmsd (for residues 4–84) of 0.060 ± 0.016 nm and average target function of 0.0078 nm2, no distance violations being larger than 0.03 nm. The structure was compared with the solution structures of the A (major) and B (minor) isomers of the rat cytochrome in the oxidized form. The A/B ratio for the rat cytochrome is 1.5 : 1, despite the very high sequence similarity (93%) to the rabbit protein. This comparison has provided insights into the factors determining the distribution in solution of the two isomers differing with respect to heme orientation. It appears that residues 23 and 74 are both important in determining this distribution, through interaction of their side chains with the prosthetic group. Hydrophobic and steric interactions are the key factors in determining the relative stability of one isomer with respect to the other.