Showing papers on "Conformational isomerism published in 1996"

The magnitude of the backbone conformational entropy change in protein folding.

Abstract: The magnitude of the conformational entropy change experienced by the peptide backbone upon protein folding was investigated experimentally and by computational analysis. Experimentally, two different pairs of mutants of a 33 amino acid peptide corresponding to the leucine zipper region of GCN4 were used for high-sensitivity microcalorimetric analysis. Each pair of mutants differed only by having alanine or glycine at a specific solvent-exposed position under conditions in which the differences in stability could be attributed to differences in the conformational entropy of the unfolded state. The mutants studied were characterized by different stabilities but had identical heat capacity changes of unfolding (ΔCp), identical solvent-related entropies of unfolding (ΔSsolv), and identical enthalpies of unfolding (ΔH) at equivalent temperatures. Accordingly, the differences in stability between the different mutants could be attributed to differences in conformational entropy. The computational studies were aimed at generating the energy profile of backbone conformations as a function of the main chain dihedral angles ϕ and ϱ. The energy profiles permit a direct calculation of the probability distribution of different conformers and therefore of the conformational entropy of the backbone. The experimental results presented in this paper indicate that the presence of the methyl group in alanine reduces the conformational entropy of the peptide backbone by 2.46 ± 0.2 cal/K · mol with respect to that of glycine, consistent with a 3.4-fold reduction in the number of allowed conformations in the alanine-containing peptides. Similar results were obtained from the energy profiles. The computational analysis also indicates that the addition of further carbon atoms to the side chain had only a small effect as long as the side chains were unbranched at position β. A further reduction with respect to Ala of only 0.61 and 0.81 cal/K · mol in the backbone entropy was obtained for leucine and lysine, respectively. β-branching (Val) produces the largest decrease in conformational entropy (1.92 cal/K · mol less than Ala). Finally, the backbone entropy change associated with the unfolding of an α-helix is 6.51 cal/K · mol for glycine. These and previous results have allowed a complete estimation of the conformational entropy changes associated with protein folding. © 1996 Wiley-Liss, Inc.

Photoinduced Inter- and Intramolecular Proton Transfer in Aqueous and Ethanolic Solutions of 2-(2‘-Hydroxyphenyl)benzimidazole: Evidence for Tautomeric and Conformational Equilibria in the Ground State†

Abstract: Excited-state proton transfer in aqueous and ethanolic solutions of 2-(2‘-hydroxyphenyl)benzimidazole (HBI) was investigated by means of UV−vis absorption and fluorescence spectroscopy. The behavior of HBI in water differed from its behavior in ethanol, and in both solvents fluorescence behavior depended on acidity. In both neutral water and neutral ethanol, ground-state HBI exhibits conformational equilibrium between a cis-enol form with an intramolecular hydrogen bond and a trans-enol form that is hydrogen-bonded to the solvent; the ground-state keto tautomer is also present in water but was not detected in ethanol. The excited cis-enol conformer always undergoes ultrafast intramolecular proton transfer to afford the excited keto tautomer. The excited trans-enol form fluoresces in both solvents, and in water it also loses its hydroxyl proton to the solvent, leaving the excited anion. In both acidic aqueous solution and acidic ethanol, excited protonated HBI loses its hydroxyl proton to give the excited ...

MTPA vs MPA in the Determination of the Absolute Configuration of Chiral Alcohols by 1H NMR

Abstract: Molecular mechanics, semiempirical (AM1), and aromatic shielding effect calculations and DNMR experiments show that MTPA esters are constituted by three main conformers in close populations due to restricted rotation around the Cα−CO and Cα−Ph bonds. The small predominance of one conformer and the simultaneous operation of aromatic shielding and deshielding effects on the alcohol part, due to the orientation of the Ph ring, explains the small ΔδRS values observed. A graphical description of the aromatic magnetic field distribution in the conformers of MTPA and MPA esters and its use to correlate the average chemical shifts with the absolute stereochemistry is presented. Comparison of MTPA with MPA (two conformers) as reagents for determination by NMR of absolute stereochemistry indicates that MTPA esters are intrinsically limited by the greater complexity of their conformational composition, yield very small ΔδRS values, and are consequently less reliable for configurations assignment of chiral alcohols t...

Quantum Chemistry Study of Conformational Energies and Rotational Energy Barriers in n-Alkanes

Abstract: The gauche energy, the t-g barrier, and the cis barrier in n-butane and n-hexane have been investigated using high-level ab initio electronic structure calculations. CCSD(T)/cc-pVTZ//MP2/6-311G(2df,p) calculations yield a gauche energy in n-butane of 0.59 kcal/mol, which after correction for zero-point and thermal vibrational effects is within 0.05 kcal/mol of the values obtained from recent experiments. Calculations at the same level yield t-g and cis barrier energies in n-butane of 3.31 and 5.48 kcal/mol, respectively, supporting the traditional view that the cis barrier in n-butane is much higher than the t-g barrier. We found that torsional potential functions previously parametrized to reproduce the measured low-lying torsional vibrational transitions in the trans and gauche conformers of n-butane and which yield only a small energy difference between the barriers can be modified to reproduce both the spectroscopic data and the large quantum chemistry energy difference between barriers. For the centr...

Conformers, Energetics, and Basicity of 2,2‘-Bipyridine

Abstract: The proton affinities of the cis and trans conformers of 2,2‘-bipyridine have been determined at the MP2/6−31G**//HF/6−31G** level of theory. The neutral molecule and its protonated cation are both...

Syntheses and conformational analyses of glutamate analogs: 2-(2-carboxy-3-substituted-cyclopropyl)glycines as useful probes for excitatory amino acid receptors.

Abstract: An hypothesis that each subtype of glutamate receptors requires a specific conformation of l-glutamate for its selective activation was examined using the conformationally constrained analogs of l-glutamate, l-2-(2-carboxycyclopropyl)glycines (CCGs), and l-2-[2-carboxy-3-(methoxymethyl)cyclopropyl]glycines (MCGs). All MCG isomers were newly synthesized in a stereoselective manner via the common synthetic intermediate 5a starting with the oxazolidine aldehyde 1. The synthesis of the four MCG isomers was characterized by a stereoselective inversion of α-cyclopropyl acyl anion (e.g., from 10 to 11). The spectroscopic studies, in particular, pH vs J correlation experiments of CCGs and MCGs using 1H NMR and their molecular mechanics calculations, revealed that these analogs possessed an antiperiplanar conformation regarding the H−C2−C1‘−H bond as a majority among the other possible rotamers in aqueous solution. The fact that each CCG and MCG exhibited potent and selective activities to the distinct types of gl...

Comparison of conformer distributions in the crystalline state with conformational energies calculated by ab initio techniques

Abstract: The conformational preferences of 12 molecular substructures in the crystalline state have been determined and compared with those predicted for relevant model compounds by ab initio molecular orbital calculations. Least-squares regression shows that there is a statistically significant correlation between the crystal-structure conformer distributions and the calculated potential-energy differences, even though the calculations relate to a gas-phase environment. Torsion angles associated with high strain energy (>1 kcal mol-1) appear to be very unusual in crystal structures and, in general, high-energy conformers are underrepresented in crystal structures compared with a gas-phase, room-temperature Boltzmann distribution. It is concluded that crystal packing effects rarely have a strong systematic effect on molecular conformations. Therefore, the conformational distribution of a molecular substructure in a series of related crystal structures is likely to be a good guide to the corresponding gas-phase potential energy surface.

Diastereoselective Photochromism of an (R)-Binaphthol-Condensed Indolylfulgide

Abstract: Two new thermally irreversible photochromic (R)-binaphthol-condensed indolylfulgides (with a 1-(1,2-dimethyl-3-indolyl)-2-methylpropylidene group and with a 1-(1,2-dimethyl-3-indolyl)butylidene group, 6 and 7, respectively) were synthesized. Because of rapid thermal equilibration between the conformational isomers of 7E at room temperature, photocyclization of a substantial portion of 7E occurred through (P)-7Eα to give (9aS)-7C selectively. On the other hand, as thermal equilibration requires a long time for 6E at room temperature, its photochromic interconversion occurs only between (P)-6Eα and (9aS)-6C, and the photocyclization-inert 6E remained unchanged. The thermal stability and fatigue resistivity toward the iterative photochromic interconversion of 7 have been proved to be excellent among the fulgide derivatives. The photochromic reactions were accompanied by large changes of specific rotation values. The X-ray crystallographic analysis of a visible-light-sensitive colored form, (9aS)-6C, was carr...

Representation of Nonplanar Structures of Nickel(II) 5,15-Disubstituted Porphyrins in Terms of Displacements along the Lowest-Frequency Normal Coordinates of the Macrocycle

Abstract: The influence of substituents with increasing steric demands on the structure of nickel(II) 5,15-disubstituted porphyrins has been investigated with X-ray crystallography, UV−visible absorption spectroscopy, resonance Raman spectroscopy, molecular energy optimization calculations, and INDO/s molecular orbital calculations. Nickel 5,15-diphenylporphyrin is predicted by molecular mechanics calculations to be a mixture of planar and nonplanar conformers. All of the nickel dialkylporphyrins (where the alkyl group is propyl, isopropyl, and tert-butyl) are calculated to be in a predominantly gabled (gab) conformation resulting from an αα orientation of the substituents with respect to the macrocycle. This nonplanar gab distortion is made up of a linear combination of distortions along the lowest-frequency out-of-plane macrocycle normal coordinates of A2u (doming) and B1u (ruffling) symmetry types. A higher energy stable αβ conformer is also predicted for dialkylporphyrins, and its nonplanar structure can be rep...

H-Atom Transfer and Rotational Processes in the Ground and First Singlet Excited Electronic States of 2-(2‘-Hydroxyphenyl)oxazole Derivatives: Experimental and Theoretical Studies†

Abstract: The H-atom transfer and the rotational processes of 2-(2‘-hydroxyphenyl)oxazole derivatives in both ground (S0) and first singlet (S1) excited electronic states have been respectively studied from experimental and theoretical points of view. Experiment and theory support the coexistence of two ground state rotamers, E and ER, with OH···N and OH···O hydrogen bonds, respectively, rotamer E being the most stable and the only one that experiences a photoinduced H-atom motion in the S1 state. The fluorescence of 2-(2‘-hydroxyphenyl)-4-methyloxazole in a rigid polymeric medium suggests that in fluid media the phototautomer of the excited enol rotamer suffers a twisting motion around the C−C bond linking both moieties of the molecule. Ab initio calculations at the Hartree−Fock and CI-all-singles levels reveal (a) the existence of a high-energy barrier to the H-atom transfer in the S0 state, whereas in the S1 state this transfer has a small or null energy barrier, (b) a coupling between a charge transfer and the ...

Conformers of Saturated Chains: Matrix Isolation, Structure, IR and UV Spectra of n‐Si4Me10

Abstract: Infrared and ultraviolet spectra of the gauche and anti conformers of matrix-isolated permethyl-n-tetrasilane have been obtained separately by taking advantage of thermally induced gauche-to-anti conversion and of wavelength-selective photochemical destruction of either conformer. The resolved UV spectrum of the gauche conformer provides the first piece of experimental evidence in favor of the recently proposed reinterpretation of conformational effects on tetrasilane electronic states. According to this, it is not the energy but the intensity of the lowest singlet excitation that changes dramatically as the SiSiSiSi dihedral angle is varied, as a result of an avoided crossing between sigma sigma* and sigma pi* states. Implications for the general understanding of sigma conjugation in simple terms are discussed. Unconstrained MP2/6-31G* optimization predicts the existence of a third backbone conformer (ortho), with a dihedral angle of about 90 degrees. Its predicted (HF/3-21G*) mid-IR spectrum is indistinguishable from that of the gauche conformer, and the matrix-isolation spectra thus provide no evidence for or against its presence.

Tetramethoxy Calix[4]arenes Revisited: Conformational Control through Self-Assembly

Abstract: The concept of preorganization in molecular assembly has been well established, and its impact on synthetic supramolecular chemistry is profound.1 Many natural systems thrive on the ability of inherently flexible molecules to self-organize. This process is promoted by a well-defined surrounding architecture and culminates in self-assembly.2 The ability of a protein to find its thermodynamically most stable tertiary structure from a linear sequence of amino acids is an example. Also related is the ability of two flexible, complementary polynucleotide strands to form a double helix. In this paper we demonstrate how flexible molecules can reversibly self-assemble to give a well-defined receptor caVity. The calix[4]arene skeleton3 was chosen as a vehicle for modeling such phenomena. The calixarene platform has recently been exploited for assembly by several laboratories.4,5 Research in our group has explored a unique dimeric binding mode for the calix[4]arene framework which provides for the encapsulation of small molecule guests.5,6 Specifically, urea functions placed on the upper rim of the calix[4]arene permit dimerization to occur through a head-to-tail hydrogen bonding pattern (Figure 1). It is well-known that the calix[4]arenes interconvert between four discrete conformations in solution.3,7 This conformational flexibility can be controlled by alkylation of the phenolic oxygens with substituents larger than ethyl, i.e. reaction of the parent phenol with n-PrBr to give the tetrapropoxy derivative allows the isolation of three stable conformations: the cone (42%), partial cone (55%), and 1,3-alternate (3%).7b We have recently explored derivative 1-1, which uses benzyl ether substituents for such control. In calixarene derivative 1-2 much smaller lower rim substituents are present. The tetramethoxy calix[4]arene has been wellstudied and is defined as a “flexible” system.7,8 It freely interconverts between all four conformations, but the partial cone is the thermodynamically most favorable one.8 Specifically, in the parent tert-butyl system the difference in energy between the partial cone/cone isomers is ∼1.5 kcal/mol, and the barrier to interconversion is on the order of 13 kcal.8c We have found that intermolecular hydrogen bonding through dimerization can be used to driVe the conformational equilibrium exclusiVely to the cone conformer. Since substitution on the upper rim of the calixarene is not known to substantially bias the conformational equilibria,3 the observed conformational selection (self-organization) can be attributed solely to hydrogen bonding effects.

Theoretical Study of the Structure and Rotational Flexibility of Diacylhydrazines: Implications for the Structure of Nonsteroidal Ecdysone Agonists and Azapeptides

Abstract: High-level ab initio calculations have been used to determine the minimum energy structures of N,N‘-diformylhydrazine, N-methyl-N,N‘-diformylhydrazine, and N,N‘-dimethyl-N,N‘-diformylhydrazine. These calculations show that the global minimum is a nonplanar structure in which the nitrogen lone pairs are essentially perpendicular to one another. However, the energy required for (Z,Z)-diformylhydrazine to adopt a planar structure is less than 1 kcal/mol (MP2/6-31+G**). This is due to attractive intramolecular hydrogen bonds between the N-hydrogens and the carbonyl oxygens in the planar geometry. When one or both amide configurations are inverted (Z,E; E,E), or when the nitrogens are substituted, with methyl for example, these hydrogen bonds are lost and the planar structure becomes much less stable relative to the twisted rotamer. Thus, we conclude from these calculations that diacylhydrazines are intrinsically nonplanar with respect to the CO−N−N−CO torsion, and that with the exception of (Z,Z)-diformylhydr...

Probing the Stereochemical Requirements for Receptor Recognition of δ Opioid Agonists through Topographic Modifications in Position 1

Abstract: A series of side-chain constrained tyrosine derivatives, 2‘,6‘-dimethyl-β-methyltyrosines (TMT), has been designed and incorporated into position 1 of the highly selective δ opioid agonists DPDPE (Tyr-d-Pen2-Gly-Phe-d-Pen5-OH) and deltorphin I (DELT I, Tyr-d-Ala-Phe-Asp-Val-Val-Gly-NH2). Molecular mechanics calculations on isolated TMT residues and nuclear magnetic resonance (NMR) studies of the TMT1-containing peptides in DMSO showed that each of the four stereoisomers of TMT favors one particular rotamer of the side-chain χ1 torsional angle. Therefore, substitution of four TMT isomers for Tyr1 allows us to perform a systematic conformational scan through three staggered rotamers of the aromatic side chain, gauche (−), trans, and gauche (+), and to explore specific binding requirements of the receptor in relation to the side chain conformation. The potency and selectivity of four isomers of [TMT1]DPDPE and four isomers of [TMT1]DELT I were evaluated by radioreceptor binding assays in the rat brain using ...

The effects of physical ageing on conformational changes of poly(ethylene terephthalate) in the glass transition region

Abstract: In-situ FTIR studies on the conformational changes of poly(ethylene terephthalate) (PET) films with different thermal histories, i. e., quenched from the melt and sub-Tg annealed at different temperatures, were carried out while increasing the temperature through the glass transition region. The temperature dependencies of the infra-red spectra showed that incremental changes of the population of trans conformers in the quenched sample are gradual, while rather abrupt changes occur in the sub-Tg annealed samples. The magnitude and temperature of the abrupt changes of trans conformers were related with the temperature of sub-Tg annealing. An energy difference of 28.6 J/g between the trans and gauche conformational states was measured by the infra-red spectroscopic method. The energy absorbed during the abrupt conformational change represents only part of the energy of the endothermic peak observed by differential scanning calorimetry. The results are explained in terms of the formation of new cohesional entanglements during sub-Tg annealing.

Anti, ortho, and gauche conformers of perfluoro-n-butane : matrix-isolation ir spectra and calculations

Abstract: Nitrogen matrix-isolation IR spectra have been obtained for each of the three conformers of n-C4F10 (gauche, ortho, and anti) by trapping a hot conformer mixture on a cold CsI window and subsequent matrix annealing and spectral differencing. They were assigned by comparison with results of HF/6-31G* calculations, and the nature of the normal modes has been analyzed using the total energy distribution procedure. At the fully optimized MP2/6-31G* (frozen core) level, the CCCC dihedral angles and relative energies (kcal/mol) are 54.2 degrees and 0.68 (gauche), 94.8 degrees and 1.63 (ortho), and 165.5 degrees and 0 (anti). Single-point MP2/6-311G* (frozen core) relative energies at these geometries are 0.85, 2.12, and 0 kcal/mol, respectively. Only a minute amount of the ortho conformer is trapped in nitrogen matrix, and none in other matrices that were tried. A variation of the relative intensities of IR peaks of the gauche and anti conformers as a function of the temperature of the gas before deposition yields an ''average'' Delta H value of about 0.9 kcal/mol, with the anti conformer more stable. The temperature range covered was too small to reveal the expected bilinear nature of the van't Hoff plot.

Theoretical investigations on 1,2-ethanediol: The problem of intramolecular hydrogen bonds

Abstract: The conformational space of 1,2-ethanediol is studied on the basis of ab initio and semiempirical calculations. All possible conformers are treated. The relative energies of the conformers are systematically studied using various basis sets up to 6–311 + G(3df, 3pd) in order to perform calculations as accurate as possible within a reasonable amount of computer time. Electron correlation is included using Moller-Plesset perturbation theory. We propose two methods to evaluate the basis set superposition error associated with the intramolecular hydrogen bond appearing in some of the conformers. The results of semiempirical calculations are compared with these ab initio calculations. © 1996 by John Wiley & Sons, Inc.

Conformers of saturated chains : matrix isolation, structure, ir and uv spectra of n-si4me10

Abstract: Infrared and ultraviolet spectra of the gauche and anti conformers of matrix-isolated permethyl-n-tetrasilane have been obtained separately by taking advantage of thermally induced gauche-to-anti conversion and of wavelength-selective photochemical destruction of either conformer. The resolved UV spectrum of the gauche conformer provides the first piece of experimental evidence in favor of the recently proposed reinterpretation of conformational effects on tetrasilane electronic states. According to this, it is not the energy but the intensity of the lowest singlet excitation that changes dramatically as the SiSiSiSi dihedral angle is varied, as a result of an avoided crossing between sigma sigma* and sigma pi* states. Implications for the general understanding of sigma conjugation in simple terms are discussed. Unconstrained MP2/6-31G* optimization predicts the existence of a third backbone conformer (ortho), with a dihedral angle of about 90 degrees. Its predicted (HF/3-21G*) mid-IR spectrum is indistinguishable from that of the gauche conformer, and the matrix-isolation spectra thus provide no evidence for or against its presence.

MTPA (Mosher) amides of cyclic secondary amines: Conformational aspects and a useful method for assignment of amine configuration

Abstract: Mosher's MTPA (methoxy(trifluoromethyl)phenylacetyl) technology is a well-known tool used to determine the absolute configuration of chiral alcohols and primary amines. The technique now has been extended to include secondary amines. A number of MTPA amide derivatives have been prepared from cyclic amines. Both piperidines and pyrrolidines have been studied. A detailed discussion of the conformational issues associated with both amide bond rotation and ring flipping is presented. The observed 1H NMR chemical shifts are correlated into a model that allows unambiguous determination of absolute configuration of cyclic secondary amines. While the presence of amide rotamers must be accounted for in the analysis, this is a relatively straightforward process that follows from detailed evaluation of coupling constant data and is often aided by COSY. The exceptionally large Δδ values observed for these MTPA amides make this a valuable and reliable method for assigning amine configuration.

π-Stacking as a Control Element in the (2-PhInd)2Zr Elastomeric Polypropylene Catalyst

Abstract: The crystal structure of the Coates-Waymouth catalyst precursor, bis(2-phenylindenyl)zirconium dichloride ((2-PhInd)-ZrCl{sub 2}, 1) contained two distinct conformers in the unit cell. In one conformer the indenyl ligands were syn to one another (a meso stereochemistry), while in the other cnoformer the indenyl ligands were anti to one another (a rac stereochemistry). To understand why the catalyst formed from 1 produces blocks of isotactic and atactic polymer, a UFF force field conformational study on the catalyst precursor 1 and a model polymer system, (2-PhInd)Zr(CH{sub 3})(C{sub 7}H{sub 15}), was undertaken. A computational model is presented, which contains four main features. (1) The rac and meso conformations of the metallocene system observed by Coates and Waymouth are nearly isoenergetic (within 0.6 kcal/mol of each other). (2) The barrier between the rac and meso conformations is comparable to observed insertion barriers. (3) The shape of the rac conformation is consistent with the established stereochemical model of metallocene polymerizations. (4) Both the rac and meso conformations display {pi}-stacking interactions. Because of these features, the catalyst is able to produce blocks of atactic and isotactic polypropylene. {pi}-Stacking clearly influences the confirmations that the catalyst adopts during the polymerization process. By adding substituents to the phenyl groups more » or changing the solvent, one can alter the {pi}-stacking effects to favor one conformation or the other. 18 refs., 2 figs. « less

Peptide models. 18. Hydroxymethyl side-chain induced backbone conformational shifts of L-serine amide. All ab initio conformers of For-L-Ser-NH2

Abstract: Using ab initio conformational energy mapping (HF/3-21G) a maximum of nine characteristic backbone conformation clusters (αl, αd, βl, γl, γd, δl, δd, el, and ed) were previously established for dif...

Conformational Analysis of 1,4-Disilabutane and 1,5-Disilapentane by Combined Application of Gas-Phase Electron Diffraction and ab Initio Calculations and the Crystal Structure of 1,5-Disilapentane at Low Temperatures

Abstract: The gas-phase structures of the conformers of 1,4-disilabutane and 1,5-disilapentane have been analyzed from electron-diffraction data augmented by flexible restraints derived from ab initio calculations. This allowed the simultaneous refinement of 22 and 29 parameters for 1,4-disilabutane and 1,5-disilapentane, respectively. 1,4-Disilabutane has been found to be present in the vapour predominantly in the anti (A) form (76(2)% from the experiment, 83% predicted by theory). Consistency in the geometries is found between theoretical predictions and experimental findings, except for the torsion angle ∠(SiCCSi) of the gauche (G) conformer [exptl 78.5(21)°, theor 68.0°]. The AA conformer of 1,5-disilapentane was always found to be the lowest energy structure, while some doubt still remains about the ordering of the AG and G(+)G(−) conformers. The AA conformer is found to be the sole form present in the crystal [C2/c, a = 15.585(8), b = 4.704(3), c = 9.895(6) A, β = 95.77(4)°, Z = 4]. Good agreement is found fo...

Spectral and Photophysical Properties of Ethylene-Bridged Side-to-Side Porphyrin Dimers. 1. Ground-State Absorption and Fluorescence Study and Calculation of Electronic Structure of trans-1,2-Bis(meso-octaethylporphyrinyl)ethene

Abstract: We have studied a double-bond bridged porphyrin dimer, trans-1,2-bis(meso-octaethylporphyrinyl)ethene (tbisOEP), which in solutions exhibits new spectral properties: (i) pronounced absorption bands in addition to the monomer ones are observed in the 480−500 and 600−900 nm regions; (ii) a broad-band fluorescence with a viscosity-dependent intensity and spectral position is detected in the near-IR region (750−1100 nm). An investigation of fluorescence excitation spectra, combined with semiempirical quantum chemical calculations and geometry optimizations suggest that in solution tbisOEP exists in two main conformations, which we name conformers P and U. The ratio of their concentrations was estimated to be approximately 5:1 in toluene at room temperature. The P conformer was found to be responsible for the “usual” monomer-type absorption bands (Soret and Q) in the tbisOEP absorption spectrum, whereas the U conformer is responsible for the additional absorptions in the 480−500 and 600−900 nm regions. The un...

Structural requirements for the association of native and partially folded conformations of alpha-lactalbumin with model membranes.

Abstract: The effect of the structure and stability of several conformers of α-lactalbumin in aqueous solution on their association to negatively charged large unilamellar vesicles has been studied by circular dichroism, infrared spectroscopy, differential scanning calorimetry, and by content leakage experiments. Our results indicate that the affinity of αLA for negatively charged vesicles strongly depends on its conformational properties in solution. Analysis of the pH dependence of the interaction for the different conformers reveals that native-like, calcium-bound, ordered conformations become bilayer-associated through electrostatic forces. However, partially folded conformers are able to interact with negatively charged membranes at pHs higher than the protein isoelectric point, suggesting that hydrophobic interactions brought about by the exposure of hydrophobic residues at the protein surface are able to overcome the unfavorable electrostatic repulsion. Calorimetric and spectroscopic data in solution also in...

Substituent Effects on the Stability of Arene−Arene Complexes: An AM1 Study of the Conformational Equilibria of cis-1,3-Diphenylcyclohexanes

Abstract: Molecular orbital calculations at the AM1 level have been performed on cis-1,3-diarylcyclohexane systems (1, 2) in order to provide a theoretical model and suggest novel experimental models for the investigation of arene−arene π-stacking. Energy minima were located for diaxial conformers (a) in which aryl rings are coplanar and π-stacked and (b) in which aryl rings adopt an edge-to-face or intermediate conformation. The average face-to-face distance varies from 4.1 to 4.4 A, outside the van der Waals contact distance of 3.4 A, and the minimum inter-ring distance varies from 3.1 to 3.5 A. The diaxial−diequatorial conformational equilibria (ΔEax-eq) were calculated for a large series of para-substituted and meta-substituted 1,3-diarylcyclohexanes and plotted against Σσp, Δσp, and EHOMO − ELUMO. The best correlation was observed using electrostatic potentials calculated at the electron density surface on the π-face of individual arenes. Similar correlations were observed for conformational equilibria associa...