Showing papers on "Conformational isomerism published in 2001"

Detection of Multiple Protein Conformational Ensembles in Solution via Deconvolution of Charge-State Distributions in ESI MS

Abstract: Monitoring the changes in charge-state distributions of protein ions in electrospray ionization (ESI) mass spectra has become one of the commonly accepted tools to detect large-scale conformational changes of proteins in solution. However, these experiments produce only qualitative, low-resolution information. Our goal is to develop a procedure that would produce quantitative data on protein conformational isomers coexisting in solution at equilibrium. To that end, we have examined the evolution of positive ion charge-state distributions in the

Conformational landscapes of aromatic amino acids in the gas phase : infrared and ultraviolet ion dip spectroscopy of tryptophan

Abstract: The conformational structures of tryptophan, isolated in the gas phase, have been assigned by combining the results of ultraviolet hole-burning and infrared ion dip spectroscopy with the predictions of ab initio calculations conducted at the MP2/6-311 + G(d,p)//B3LYP/6-31 + G(d) levels of theory. As in phenylalanine, the most strongly populated, and lowest energy conformer presents a folded alanyl side chain that is stabilised by a ‘daisy chain’ of hydrogen-bonded interactions. These link the acidic proton, the amino group and the indole ring. There is a further interaction between the carbonyl oxygen and the neighbouring CH group on the pyrrole ring. A quantitative evaluation of the dipole–dipole interactions between the alanyl side chain and the indole ring in the 1La and 1Lb electronic states does not support the suggestion of electronic state mixing. In particular it casts doubt on the assignment of the fluorescence of the most stable, ‘special’ conformer to emission from the 1La state.

The beta-peptide hairpin in solution: conformational study of a beta-hexapeptide in methanol by NMR spectroscopy and MD simulation.

Abstract: The structural and thermodn. properties of a 6-residue β-peptide I that was designed to form a hairpin conformation have been studied by NMR spectroscopy and mol. dynamics simulation in methanol soln. The predicted hairpin would be characterized by a 10-membered hydrogen-bonded turn involving residues 3 and 4, and two extended antiparallel strands. The interproton distances and backbone torsional dihedral angles derived from the NMR expts. at room temp. are in general terms compatible with the hairpin conformation. Two trajectories of system configurations from 100-ns mol.-dynamics simulations of the peptide in soln. at 298 and 340 K have been analyzed. In both simulations, reversible folding to the hairpin conformation is obsd. Interestingly, there is a significant conformational overlap between the unfolded state of the peptide at each of the temps. As already obsd. in previous studies of peptide folding, the unfolded state is composed of a (relatively) small no. of predominant conformers and in this case lacks any type of secondary-structure element. The trajectories provide an excellent ground for the interpretation of the NMR-derived data in terms of ensemble avs. and distributions as opposed to single-conformation interpretations. From this perspective, a relative population of the hairpin conformation of 20% to 30% would suffice to explain the NMR-derived data. Surprisingly, however, the ensemble of structures from the simulation at 340 K reproduces more accurately the NMR-derived data than the ensemble from the simulation at 298 K, and this point needs further investigation.

Conformation of Methylene Chains in an Intercalated Surfactant Bilayer

Abstract: Infrared and Raman spectroscopy have been used to establish the conformation and orientation of the methylene “tail” of cetyl trimethylammonium ions intercalated in an inorganic layered host, $CdPS_{3}$. Intercalation, effected by a two-step ion-exchange process leading to the formation of $Cd_{0.83}$$PS_{3}$ $(CTA)_{0.34}$, occurs with a lattice dilation of 26.5 \AA with the surfactant ions within the galleries adopting a bilayer structure. The frequencies of the conformationally sensitive methylene stretching modes in the infrared and Raman spectra indicate that a majority of the bonds in the methylene chain are in a trans conformation. The methylene chains are tilted with respect to the inorganic layer. The tilt angle as determined from orientation-dependent infrared spectra is \sim $35^0$. Although the population of gauche conformers is low, it has been possible to identify specific conformational sequences containing a gauche bond, in the interior and termini of the intercalated methylene chains, by their characteristic frequencies in the infrared spectrum. These high-energy conformers, except for the ones at the chain end, disappear on cooling, leaving on average all 15 methylene units of the intercalated cetyl trimethylammonium ion in trans conformational registry at 40 K. The terminal gauche defects are significant in preventing interdigitation of the low-density intercalated surfactant bilayer.

The conformational structures and dipole moments of ethyl sulfide in the gas phase

Abstract: The pure rotational spectrum of ethyl sulfide has been measured from 12 to 21 GHz in a 1 K jet-cooled expansion using a Fourier-transform microwave (FTMW) spectrometer. Prominent features in the spectrum are assigned to transitions from three conformational isomers. Additional assignments of the 13C and 34S isotopomer spectra of these conformers effectively account for all of the remaining transitions in the spectrum. Accurate “heavy-atom” substitution structures are obtained via a Kraitchman analysis of 14 rotational parameter sets, permitting definitive identification of the molecular structures of the three conformers. Two of the structures designated as the gauche–gauche (GG) and trans–trans (TT) conformers have symmetric forms with C2 and C2v symmetries, respectively, and the third trans–gauche (TG) configuration is asymmetric. The components of the electric dipole moment along the principal inertial axes have been determined from Stark measurements and are consistent with these structural assignment...

Computational analysis of the potential energy surfaces of glycerol in the gas and aqueous phases: effects of level of theory, basis set, and solvation on strongly intramolecularly hydrogen-bonded systems.

Abstract: The 126 possible conformations of 1,2,3-propanetriol (glycerol) have been studied by ab initio molecular orbital and density functional theory calculations in the gas and aqueous phases at multiple levels of theory and basis sets. The partial potential energy surface for glycerol as well as an analysis of the conformational properties and hydrogen-bonding trends in both phases have been obtained. In the gas phase at the G2(MP2) and CBS-QB3 levels of theory, the important, low-energy conformers are structures 100 and 95. In the aqueous phase at the SM5.42/HF/6-31G* level of theory, the lowest energy conformers are structures 95 and 46. Boltzmann distributions have been determined from these high-level calculations, and good agreement is observed when these distributions are compared to the available experimental data. These calculations indicate that the enthalpic and entropic contributions to the Gibbs free energy are important for an accurate determination of the conformational and energetic preferences of glycerol. Different levels of theory and basis sets were used in order to understand the effects of nonbonded interactions (i.e., intramolecular hydrogen bonding). The efficiency of basis set and level of theory in dealing with the issue of intramolecular hydrogen bonding and reproducing the correct energetic and geometrical trends is discussed, especially with relevance to practical computational methods for larger polyhydroxylated compounds, such as oligosaccharides.

Conformers of nonionized proline. matrix-isolation infrared and post-hartree - fock ab initio study

Abstract: Matrix-isolation IR spectroscopy and ab initio calculations performed at the DFT, MP2, MP4, and CCSD(T) levels of theory were employed to investigate the conformational topology of the nonionized amino acid proline and its deuterated derivative, N,O-dideuteroproline (proline-d2). In the calculations, equilibrium structures of 15 low-energy proline conformers were obtained using the DFT/B3LYP/aug-cc-pVDZ and MP2/aug-cc-pVDZ methods. The harmonic frequencies and IR intensities of the conformers were calculated for the DFT geometries, and these data was used to account for the zero-point vibration energy correction and to assist the analysis of the experimental matrix-isolation IR spectra. Two proline conformers were found to be present in the Ar matrix. They are the lowest energy conformer with a N···HO H bond (conformer IIa) and the second conformer with a NH···OC H bond (conformer Ia). We found that the DFT/B3LYP and MP2 methods are not capable of predicting the relative energies of the proline conformers...

Classical and Quantum-Mechanical Studies of Crystalline FOX-7 (1,1-Diamino-2,2-dinitroethylene)

Abstract: First principles molecular orbital and plane-wave ab initio calculations have been used to investigate the structural and vibrational properties of the highly efficient low sensitive explosive 1,1-diamino-2,2-dinitroethylene (FOX-7) in both the gas and solid phases The ab initio molecular orbital calculations performed at second-order (MP2) and fourth-order (MP4) Moller−Plesset levels and using density-functional theory (DFT) methods with B3LYP functional indicate that in the gas phase FOX-7 is the most stable conformer relative to its cis-1,2 and trans-1,2 isomers The calculated MP2 and DFT structures for the FOX-7 molecule agree well with the experimental X-ray configuration but with twists of the nitro and amino groups much larger than in the solid phase The calculated fundamental vibrational frequencies at the DFT level generally compare well with the MP2 results The IR spectra were computed for the three isomers The structural properties of the FOX-7 crystal have been studied by a plane-wave DFT

Combined FTIR Matrix Isolation and Ab Initio Studies of Pyruvic Acid: Proof for Existence of the Second Conformer

Abstract: The molecular structure of pyruvic acid was investigated by matrix isolation FTIR spectroscopy, density functional theory (DFT), and ab initio calculations performed at the RHF, MP2, MP4(SDQ), and CCSD(T) levels of theory with the aug-cc-pVDZ basis set. In these calculations, the geometries of the three lowest energy conformers of pyruvic acid were fully optimized at the DFT/B3LYP/aug-cc-pVDZ and MP2/aug-cc-pVDZ levels. Additionally, the relative energies of the conformers were calculated at the MP4, CCSD, and CCSD(T) levels. Harmonic frequencies and IR intensities were then calculated for these three conformers and were used to account for the zero point vibrational energy corrections and to assist the assignment of the observed bands to the different forms. We found that two conformers are present in the Ar matrix, and both forms exhibit a planar framework with the carbonyl bonds in a trans arrangement but differ in the orientation of the hydroxyl hydrogen. By varying the temperature of the pyruvic acid...

Conformational features and anion-binding properties of calix[4]pyrrole: A theoretical study

Abstract: The conformational preference of calix[4]pyrrole and its fluoride and chloride anion-binding properties have been investigated by density functional theory calculations. Geometries were optimized by the BLYP/3-21G and BLYP/6-31G* methods, and energies were evaluated with the BLYP/6-31+G** method. To model the effect of medium, the SCIPCM solvent model was also employed. Four typical conformations of the parent substituent-free calix[4]pyrrole were studied. Both in the gas phase and in CH2Cl2 solution, the stability sequence is predicted to be 1,3-alternate > partial cone > 1,2-alternate > cone. The cone conformation is predicted to be about 16.0 and 11.4 kcal/mol less stable in the gas phase and CH2Cl2 solution, respectively. This is mainly due to electrostatic repulsions arising from the all-syn pyrrole/pyrrole/pyrrole/pyrrole arrangement present in this conformer. The existence of possible 1:1 and 1:2 anion-binding modes were explored in the case of fluoride anion, and the factors favoring the 1:1 bindi...

Substrate conformational transitions in the active site of chorismate mutase: their role in the catalytic mechanism.

Abstract: Chorismate mutase acts at the first branch-point of aromatic amino acid biosynthesis and catalyzes the conversion of chorismate to prephenate. The results of molecular dynamics simulations of the substrate in solution and in the active site of chorismate mutase are reported. Two nonreactive conformers of chorismate are found to be more stable than the reactive pseudodiaxial chair conformer in solution. It is shown by QM/MM molecular dynamics simulations, which take into account the motions of the enzyme, that when these inactive conformers are bound to the active site, they are rapidly converted to the reactive chair conformer. This result suggests that one contribution of the enzyme is to bind the more prevalent nonreactive conformers and transform them into the active form in a step before the chemical reaction. The motion of the reactive chair conformer in the active site calculated by using the QM/MM potential generates transient structures that are closer to the transition state than is the stable CHAIR conformer.

Proton mobility in protonated glycylglycine and N-formylglycylglycinamide: A combined quantum chemical and RKKM study

Abstract: Theoretical model calculations were performed to investigate the degree of validity of the mobile proton model of protonated peptides. The structures and energies of the most important minima corresponding to different structural isomers of protonated diglycine and their conformers, as well as the barriers separating them, were determined by DFT calculations. The rate coefficients of the proton transfer reactions between the isomers were calculated using the RRKM method in order to obtain a quantitative measure of the time scale of these processes. The proton transfer reactions were found to be very fast already at and above the threshold to the lowest energy decomposition pathway. Two possible mechanisms of b2+-ion formation via water loss from the dipeptide are also discussed. The rate-determining step of the proton migration along a peptide chain is also investigated using the model compound N-formylglycylglycinamide. The investigations revealed that this process very possibly occurs via the protonation of the carbonyl oxygens of the amide bonds, and its rate-determining step is an internal rotation-type transition of the protonated C=O-H group between two adjacent C=O-H…O=C bridges. Copyright © 2001 John Wiley & Sons, Ltd.

Thermodynamic, spectroscopic, and computational evidence for the irreversible conversion of β- to α-endosulfan

Abstract: Previous studies have provided unequivocal evidence for the symmetry of beta-endosulfan and the corresponding asymmetry of alpha-endosulfan; the conversion of beta-endosulfan to alpha-endosulfan was identified. In this study, evidence from differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR) experiments combined with computational chemistry calculations was used to propose a molecular mechanism for the corresponding conformational changes that occur in this process. DSC and NMR data of mixtures indicated that both isomers can influence the conformer populations in the solid, solution, and vapor phase. Computational chemistry demonstrated that the relative S==O configuration between alpha- and beta-isomers can be the intermediate state through which the conformations of alpha- and beta-isomers affect each other. Furthermore, calculations for mixtures indicated that the asymmetrical conformation of the sulfite in alpha-endosulfan can induce asymmetry in beta-endosulfan, and conversion to alpha-endosulfan occurs from this transition state.

Study of the conformational transition of A beta(1-42) using D-amino acid replacement analogues.

Abstract: A critical event in Alzheimer's disease is the transition of Abeta peptides from their soluble forms into disease-associated beta-sheet-rich conformers. Structural analysis of a complete D-amino acid replacement set of Abeta(1-42) enabled us to localize in the full-length 42-mer peptide the region responsible for the conformational switch into a beta-sheet structure. Although NMR spectroscopy of trifluoroethanol-stabilized monomeric Abeta(1-42) delineated two separated helical domains, only the destabilization of helix I, comprising residues 11-24, caused a transition to a beta-sheet structure. This conformational alpha-to-beta switch was directly accompanied by an aggregation process leading to the formation of amyloid fibrils.

Conformational Preferences of Neurotransmitters: Ephedrine and Its Diastereoisomer, Pseudoephedrine

Abstract: The conformational preferences of the diastereomeric neurotransmitters (1R2S) ephedrine and (1S2S) pseudoephedrine have been studied in the gas phase, under free jet-expansion conditions, using ultraviolet spectroscopy (both R2PI and LIF) and infrared ion-dip and hole-burning spectroscopy in combination with ab initio calculation. This has led to the identification and assignment of two conformers in ephedrine and four in pseudoephedrine. Assignments have been made by comparing their experimental infrared and LIF spectra with ab initio vibrational frequencies and ultraviolet rotational band contours. The relative stabilities of the conformers are controlled by a delicate balance between intramolecular hydrogen bonding and dispersive interactions between the methyl groups of the side chain, both with each other and with the aromatic ring. The relative conformational stabilities calculated for ephedrine do not agree with the experimental results; two of its low-lying conformers were detected, but a third, l...

Two folded conformers of ubiquitin revealed by high-pressure NMR.

Abstract: High-pressure 15N/1H two-dimensional NMR spectroscopy has been utilized to study conformational fluctuation of a 76-residue protein ubiquitin at pH 4.5 at 20 degrees C. The on-line variable pressure cell technique is used in conjunction with a high-field NMR spectrometer operating at 750 MHz for 1H in the pressure range between 30 and 3500 bar. Large, continuous and reversible pressure-induced 1H and 15N chemical shifts were observed for 68 backbone amide groups, including the 7.52 ppm 15N shift of Val70 at 3500 bar, indicating a large-scale conformational change of ubiquitin with pressure. On the basis of the analysis of sigmoid-shaped pressure shifts, we conclude that ubiquitin exists as an equilibrium mixture of two major folded conformers mutually converting at a rate exceeding approximately 10(4) s(-1) at 20 degrees C at 2000 bar. The second conformer exists at a population of approximately 15% (DeltaG(0) = 4.2 kJ/mol) and is characterized with a significantly smaller partial molar volume (DeltaV(0) = -24 mL/mol) than that of the well-known basic native conformer. The analysis of 1H and 15N pressure shifts of individual amide groups indicates that the second conformer has a loosened core structure with weakened hydrogen bonds in the five-stranded beta-sheet. Furthermore, hydrogen bonds of residues 67-72 belonging to beta5 are substantially weakened or partially broken, giving increased freedom of motion for the C-terminal segment. The latter is confirmed by the significant decrease in 15N[1H] nuclear Overhauser effect for residues beyond 70 at high pressure. Since the C-terminal carboxyl group constitutes the reactive site for producing a multi-ubiquitin structure, the finding of the second folded conformer with a substantially altered conformation and mobility in the C-terminal region will shed new light on the reaction mechanism of ubiquitin.

A Matrix Isolation Spectroscopic and Quantum Chemical Study of Fumaric and Maleic Acid

Abstract: Relative energies and vibrational spectra of buthenedioic acid [(E)- and (Z)-HOOC−CHCH−COOH; fumaric and maleic acids] were calculated using Hartree−Fock (HF), Moller−Plesset to 2nd order (MP2), and B3LYP Density Functional Theory (DFT) levels of approximation. Computationally the lowest energy conformer of maleic acid has a nearly planar structure with an OH···OC intramolecular hydrogen bond closing a seven member ring. Second conformer of maleic acid adopts a cis arrangement around the C−O bonds and exhibits the two carbonyl bonds in a nearly orthogonal arrangement with one carboxylic group in the plane containing the carbon atoms. Fumaric acid has three planar conformers with relative energies within 5 kJ mol-1. These conformers exhibit a cis arrangement around the C−O bond and differ by the relative conformation of their OC−CC axes. The infrared spectra of the studied compounds isolated in a solid argon matrix feature the most stable conformers. Narrowband tunable irradiation in the near-infrared regi...

Conformational Preferences of Neurotransmitters: Norephedrine and the Adrenaline Analogue, 2-Methylamino-1-phenylethanol

Abstract: The conformational preferences of the neurotransmitters (1R2S) norephedrine and 2-methylamino-1-phenylethanol (MAPE) have been examined under free-jet expansion conditions using a combination of laser-induced fluorescence (LIF), mass-selected resonant 2-photon ionization (R2PI), and infrared ion-dip spectroscopy together with ab initio calculations. Comparison of experimental infrared spectra and rotational band contours with ab initio data has allowed a full structural assignment of three conformers in MAPE and two in norephedrine. All five conformers are stabilized by intramolecular hydrogen bonding between the functional groups of the ethanolamine side chain, with the OH group acting as a proton donor. Further stabilizing interactions are provided by NH···π hydrogen bonds and by dispersive interactions between the methyl group of the side chain and the aromatic ring. A delicate balance of these factors controls both the relative stabilities of the conformers and, through cooperative effects, the streng...

Structure and conformational equilibrium of thiacalix[4]arene by density functional theory

Abstract: Density functional theory calculations for the structure and conformational equilibrium of thiacalix[4]arene are reported. The conformational equilibrium of thiacalix[4]arene, a heterocalixarene in which the phenol groups are bridged by sulphur atoms is compared to the conformational equilibrium of calix[4]arene. Thiacalix[4]arene conformational energies relative to the cone conformer (ΔE's) are reduced in comparison with calix[4]arene. This conformational change is in qualitative agreement with recent NMR spectroscopy measurements of the conformational equilibrium for a tetraethylether of thiacalix[4]arene in a CDCl3 solution which indicates an enhanced chemical exchange of thiacalixarene conformers in comparison with similar methylene bridged structures. Density functional theory results for the structure of thiacalix[4]arene are in good agreement with recent X-ray diffraction measurements. The electrostatic potentials in the cone conformers of thiacalix[4]arene and calix[4]arene suggest that their complexation or recognition abilities can be significantly different. Dipole moments of the four thiacalix[4]arene conformers are in the order: cone>1,2-alternate>partial-cone>1,3-alternate.

Conformational isomerism and weak molecular and magnetic interactions in ternary copper(II) complexes of [Cu(AA)L']ClO4.nH2O, where AA = L-phenylalanine and L-histidine, L' = 1,10-phenanthroline and 2,2-bipyridine, and n = 1 or 1.5: synthesis, single-crystal X-ray structures, and magnetic resonance investigations.

Abstract: Weak molecular and magnetic exchange interactions in ternary copper(II) complexes, viz., [Cu(L-phe)(phen)(H(2)O)]ClO(4) (1), [Cu(L-phe)(bpy)(H(2)O)]ClO(4) (2), and [Cu(L-his)(bpy)]ClO(4).1.5H(2)O (3), where L-phe = L-phenylalanine, L-his = L-histidine, phen = 1,10-phenanthroline, and bpy = 2,2'-bipyridine, have been investigated. Single-crystal X-ray structures reveal that complex 2 crystallizes in a monoclinic space group P2(1), with unit cell parameters a = 7.422(7) A, b = 11.397(5) A, c = 12.610(2) A, beta = 102.10(5) degrees, V = 1043.0(11) A(3), Z = 2, R = 0.0574, and R(w) = 0.1657. Complex 3 crystallizes in a monoclinic space group C2, with a = 18.834(6) A, b = 10.563(4) A, c = 11.039(3) A, beta = 115.23(2) degrees, V = 1986.6(11) A(3), Z = 4, R = 0.0466, and R(w) = 0.1211. Molecules of 2, in the solid state, are self-assembled via weak intra- and intermolecular pi-pi stacking and H-bonding interactions. Molecules of 3 exhibit intermolecular dimeric association with the Cu.Cu separation being 3.811 A. X-ray structures and (1)H NMR studies reveal conformational isomerism in both solid and liquid states of complexes 1 and 2. The aromatic side chain of L-phe in 1 and 2 adopts either a "folded" (A) or an "extended" (B) conformation. Variable-temperature (1)H NMR and spin lattice relaxation measurements point out interconversion between conformations A and B at temperatures above 323 K. The change in molecular conformation induces a change in the electron density at the site of copper and band gap energy between HOMO and LUMO orbitals. Interestingly, in spite of paramagnetic nature, complexes 1 and 2 are amenable for both EPR and (1)H NMR spectroscopic studies. Single-crystal EPR spectra of 2 in three orthogonal planes are consistent with three-dimensional magnetic behavior. Intramolecular exchange dominates the dipolar interactions. The EPR spectra of 3 correspond to weak magnetic interactions between associated dimeric units. The structural and magnetic resonance investigations together reveal that the weak pi-pi stacking interactions are the electronic pathways for magnetic interactions in 1-3.

Kinetics and mechanism of the (-)-sparteine-mediated deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine.

Abstract: The (-)-sparteine-mediated asymmetric lithiation-substitution of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine ((E)-5) to afford gamma-substituted enantiomerically enriched products 6 is reported. The solution structure for the lithiated intermediate 8.1 in these reactions was determined by heteronuclear NMR to be a configurationally stable, alpha-lithio, eta(1)-coordinated monomer. This intermediate is proposed to exist as two rotamers that are rapidly equilibrating on the NMR time scale; competitive electrophilic substitution of each conformation results in the formation of Z or E products. Kinetic measurements of the lithiation by in situ infrared spectroscopy provide pseudo-first-order rate constants for reactions with a variety of concentrations of amine, (-)-sparteine, and n-BuLi. The reaction is first order in amine and zero order in 1:1 base--ligand complex. When the concentration of n-BuLi is varied independently of (-)-sparteine concentration, the reaction rate exhibits an inverse dependence on n-BuLi concentration. The deuterium isotope effect for the reaction was determined to be 86 at -75 degrees C, a result consistent with C--H bond breaking in the rate-determining step and indicative of tunneling. A reaction pathway involving a prelithiation complex is supported by kinetic simulations.