Conformational study of the 1,2,3-propanetriol (glycerol) in the channel of the aquaglyceroporin GlpF

The X-ray structure of the aquaglyceroporin GlpF protein refined by Fu et al. [D. Fu, A. Libson, L.J.W. Miercke, C. Weitzman, P. Nollert, J. Krucinski, R.M. Stroud, Science 290 (2000) 481--486.] shows three glycerol molecules co-crystallized inside the channel. The conformations of these molecules have been used to study the relationship between conformation, energy balance and hydration in the hope that it will provide insight into the molecular transport mechanism in the channel. Initially, the position of the hydrogen atoms of the glycerol molecule in the three conformations was established. As the glycerol molecule progressively loses its hydration waters in its transport pathway inside the channel, the nature of the glycerol bonds changes: the geometry of the alkyl backbone adapts to the available space while the progressive dehydration is partially compensated by the formation of intramolecular hydrogen bonds. The nature of these hydrogen bonds has been established by DFT calculation of the rotation barriers of the hydroxyl groups. Finally, the influence of the intramolecular hydrogen bonds on the conformation of the alkyl backbone has been established by quantum calculations of potential energy surfaces by semi-empirical quantum calculations PM3/Zindo.     

Helical molecular programming: folding of oligopyridine-dicarboxamides into molecular single helices

Molecular strands composed of alternating 2,6-diaminopyridine and 2,6-pyridinedicarbonyl units have been designed to self-organize into single stranded helical structures upon forming intramolecular hydrogen bonds. Pentameric strands 11, 12, and 14, heptameric strands 1 and 20, and undecameric strand 15 have been synthesized using stepwise convergent strategies. Single helical conformations have been characterized in the solid state by single crystal X-ray diffraction analysis for four of these compounds. Helices from pentameric strands 12 and 14 extend over one turn, and helices from heptameric 20 and undecameric 15 species extend to one and a half and two and a half turns, respectively. Intramolecular hydrogen bonds are responsible for the strong bending of the strands. 1H NMR shifts both in polar and nonpolar organic solvents indicate intramolecular overlap between the peripheral aromatic groups. Thus, helical conformations also predominate in solution. Molecular stochastic dynamic simulations of strand folding starting from a high energy extended linear conformer show a rapid (600 ps at 300 K) conversion into a stable helical conformation.     

Oligo(p-phenylene-ethynylene)s with backbone conformation controlled by competitive intramolecular hydrogen bonds

A series of conjugated oligo(p-phenylene-ethynylene) (OPE) molecules with backbone conformations (that is, the relative orientations of the contained phenylene units) controlled by competitive intramolecular hydrogen bonds to be either co-planar or random were synthesised and studied. In these oligomers, carboxylate and amido substituents were attached to alternate phenylene units in the OPE backbone. These functional groups were able to form intramolecular hydrogen bonds between neighbouring phenylene units. Thereby, all phenylene units in the backbone were confined in a co-planar conformation. This planarised structure featured a more extended effective conjugation length than that of regular OPEs with phenylene units adopting random orientation due to a low rotational-energy barrier. However, if a tri(ethylene glycol) (Tg) side chain was appended to the amido group, it enabled another type of intramolecular hydrogen bond, formed by the Tg chain folding back and the contained ether oxygen atom competing with the ester carbonyl group as the hydrogen-bond acceptor. The outcome of this competition was proven to depend on the length of the alkylene linker joining the ether oxygen atom to the amido group. Specifically, if the Tg chain folded back to form a five-membered cyclic structure, this hydrogen-bonding motif was sufficiently robust to overrule the hydrogen bonds between adjacent phenylene units. Consequently, the oligomers assumed non-planar conformations. However, if the side chain formed a six-membered ring by hydrogen bonding with the amido NH group, such a motif was much less stable and yielded in the competition with the ester carbonyl group from the adjacent phenylene unit. Thus, the hydrogen bonds between the phenylene units remained, and the co-planar conformation was manifested. In our system, the hydrogen bonds formed by the back-folded Tg chain and amido NH group relied on a single oxygen atom as the hydrogen-bond acceptor. The additional oxygen atoms in the Tg chain made a negligible contribution. A bifurcated hydrogen-bond motif was unimportant. From our results, in combination with the results from an independent study by Meijer et al., it is evident that intramolecular hydrogen bonds involving back-folded oligo(ethylene glycol) moieties may differ in their structural details. Absorption spectroscopy served as a convenient yet sensitive technique for analysing hydrogen-bonding motifs in our study.     

Effect of hydrogen bonds on the amorphous phase of a polymer as determined by atomistic molecular modelling

Molecular simulations of poly(vinyl phenol) were performed to study the effect of hydrogen bonds. Three conformations were constructed and their structure was validated in terms of the solubility parameter and gyration radius. Amorphousness was confirmed by calculating the X-ray pattern and pair correlation function. Isotropy of the structure was verified using the bond-orientational correlation function for backbone, phenyl rings, and O–H groups forming hydrogen bonds. Glass transition temperature was calculated using a stepwise change on temperature at constant pressure. The values were found to be comparable to experimental data and were consistent with poly(styrene) simulations published in the literature. The percentage of hydrogen bonds found in the model, 63%, was in good agreement with previous semi-quantitative evaluation by FTIR spectroscopy.     

alpha and piDL helical states of alternating poly(gamma-benzyl D-L-glutamate) in solution.

As in solid state, strictly alternating poly(gamma-benzyl D-L-glutamate) in solution can adopt two different helical conformations. Besides the alpha helix, a second helical conformation is found at higher temperatures in dioxane and chloroform, the properties of which correspond to that of the piDL4 helix. As the molecules have a finite length a screw sense is favored for both helical forms thus giving rise to optical activity allowing the study of the transconformation by optical rotatory dispersion and circular dichroism besides infrared and dielectric measurements. Thus, as the temperature is raised the equilibria right-left handed alpha helices and alpha-piDL helical forms can be followed. The favored screw senses are determined by the number of interacting side chains for the alpha helix and by the number of hydrogen bonds which are formed in the piDL helical conformation. The side chain-side chain interactions in the alpha helix are experimentally shown to be attractive.     

Modeling the amorphous phase of comb‐like polymers

In this work, we apply a methodology recently developed by us to perform atomistic simulations of the amorphous phase of poly(α‐octadecyl β‐aspartate) and poly‐ (octadecyl acrylate). The simulation method, which is denoted SuSi/CB, combines the strength of an algorithm specially designed to generate atomistic models of dense amorphous polymers and the Configurational Bias Monte Carlo procedure. Modeling results reveal that poly(octadecyl acrylate) presents a tendency to adopt backbone helical conformations, while no trace of helicity was detected in the amorphous phase poly(α‐octadecyl β‐aspartate). Regarding the side chain organization, the paraffinic pool formed by the octadecyl side chains is slightly greater for the poly(acrylate) than for the poly(β‐aspartate). According to these features, it can be concluded that the small chemical differences between the two investigated polymers are enough to provide some distinctive structural features. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 953–966, 2006     

The tunability of the electronic structures for poly(carbosilylsilanes): a theoretical study

To tune purposefully the electronic structures of poly(carbosilylsilanes), a theory study has been investigated using the density functional theory combined with AM1 method. Attentions were paid to the dependence of molecular geometries and absorption spectra on the backbone conformation and the various substituting groups. The strong electronegative substituents can more effectively tune the geometries and spectra of the polysilanes than the alkyl ones. Their main-chain substitutions can induce the great red-shift of the absorption spectra, and the side-chain substitutions can induce the blue-shift. The length of methylene chain in the carbosilyl groups exerts the small effect on the absorption spectra, but with the lengthening of side chain, poly(carbosilylsilanes) have a preference for the all-trans conformation with the loose helix backbone. Different from the alkyl side chain in poly(alkylsilanes), the lengthening of carbosilyl chain leads to the decrease of the positive charges of silicon backbone.     

Helix-sense-selective polymerization of phenylacetylene having two hydroxy groups using a chiral catalytic system

We have found a simple and novel synthetic method for obtaining a chiral polymer from an achiral monomer by using a chiral catalytic system. The chirality of the polymer was caused only by a one-handed helical backbone, and the polymer had no other chiral structures in the side groups. In addition, the helical conformation was stable in solution by itself. This is the first example of helix-sense-selective polymerization of a substituted acetylene. The stability of the helicity was found to be caused by intramolecular hydrogen bonds.     

Efficient search for all low energy conformations of polypeptides by Monte Carlo methods

The Metropolis Monte Carlo method has been added to the program FANTOM for energy refinement of polypeptides and proteins using a Newton–Raphson minimizer in torsion angle space. With this extension, different strategies for global minimization of the semiempirical energy function ECEPP/2 by various temperature schedules and restriction of conformational space were tested for locating local minimum conformations with low energy of the pentapeptide Met-enkephalin. In total, 1881 conformations below ?10 kcal/mol were found. These conformations could be represented by 77 nonidentical conformations which were analysed for their pattern of hydrogen bonds, types of tight turn, pairwise root-mean-square-deviation (rmsd), Zimmermann codes and side chain conformations. All low energy conformations below ?10.4 kcal/mol show strong similarity to the global minimum conformation in the backbone structure.     

Syntheses and polymerizations of novel chiral poly(acrylamide) macromonomers and their chiral recognition abilities

Chiral poly(acrylamide) macromonomers (PMB‐1, PMB‐2, PPAE‐1, and PPAE‐2) were synthesized from 2‐methacryloyloxyethyl isocyanate and prepolymers, that is, poly[(S)‐methylbenzyl acrylamide] or poly(L ‐phenylalanine ethylester acrylamide with a terminal carboxylic acid or hydroxy group. Radical homopolymerizations of poly(acrylamide) macromonomers were carried out under several conditions to obtain the corresponding optically active polymers. A strong temperature dependence on the specific optical rotation was observed for poly(PPAE‐2) in comparison with that for the corresponding prepolymer. This might have resulted from a change in the conformation caused by hydrogen bonds between polymer‐graft branches in the polymacromonomer. Radical copolymerizations of poly(acrylamide) macromonomers with styrene and methyl methacrylate were performed with azobisisobutyronitrile in tetrahydrofuran at 60 °C. Chiroptical properties of the copolymers were slightly influenced by comonomer units. Chiral stationary phases were prepared by the radical polymerization of poly(acrylamide) macromonomers in the presence of silica gel containing vinyl groups on the surface. Some racemic compounds such as menthol and mandelic acid were resolved on the chiral stationary phases for high‐performance liquid chromatography. The conformation based on hydrogen bonds between polymer‐graft branches in the polymacromonomers may play an important role in chiral discrimination. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1726–1741, 2002     

梳状高分子烷基侧链构象和堆积结构的红外光谱研究

以正十九烷和两种接枝烷基链的梳状高分子N-十八烷基聚乙烯亚胺(PEI18C)、N-十八烷基聚对苯甲酰胺(PBA18C)为研究对象,利用红外光谱对处于受限和自由状态的烷基链的构象和堆积结构随温度的变化进行了对比研究.结果表明,处于受限和自由状态的烷基链的构象排列和堆积结构及其转变行为不同,且受限于柔性PEI主链和刚性PBA主链的烷基链也不相同.从主链刚性的角度,探讨了影响烷基侧链构象和堆积结构的原因.     

Remarkable Structure Effects on Chiroptical Properties of Polyisocyanides Carrying Proline Pendants

Chiral polymers with simple chemical structures and high helical conformation stabilities are important for their applications as chiral supports and asymmetrical catalysts. We report herein the synthesis of a series of aliphatic polyisocyanides carrying proline pendants of different chiralities, and an investigation of the effects of the chemical structures of these pendants on the chiroptical properties of the polymers. The configuration of the chiral center at the 4‐position of the proline pendants was changed from S to R to check its effect on the handedness of the helical conformation. To examine the effects of steric hindrance on the stabilities of the helical conformation for these aliphatic representatives, proline pendants with various substituents at both the carboxyl and amine terminals were designed. To further examine the steric effects of the proline pendants, aromatic counterparts were also prepared. In the latter case, the effects of hydrogen bonds between pendant units on the enhancement and stabilities of the helical conformation were investigated by switching from the ester to an amide linkage. The Cotton effects and signal intensities of both aliphatic and aromatic polyisocyanides from circular dichroism spectroscopy were compared based on the bulkiness of the pendant groups, solvent polarities, and solution temperatures. It was found that highly stable helical conformations of polyisocyanides could be imposed by small bulky monoproline pendants.     

A novel type of optically active helical polymers: Synthesis and characterization of poly(N‐propargylureas)

This article presents two novel artificial helical polymers, substituted polyacetylenes with urea groups in side chains. Poly( 4 ) and poly( 5 ) can be obtained in high yields (≥97%) and with moderate molecular weights (11,000–14,000). Poly( 4 ) contains chiral centers in side chains, and poly( 5 ) is an achiral polymer. Both of the two polymers adopted helical structures under certain conditions. More interestingly, poly( 4 ) exhibited large specific optical rotations, resulting from the predominant one‐handed screw sense. The helical conformation in poly( 5 ) was stable against heat, while poly( 4 ) underwent conformational transition from helix to random coil upon increasing temperature from 0 to 55 °C. Solvents had considerable influence on the stability of the helical conformation in poly( 4 ). The screw sense adopted by the helices was also largely affected by the nature of the solvent. Poly( 4 ‐co‐ 5 )s formed helical conformation and showed large optical rotations, following the Sergeants and Soldiers rule. By comparing the present two polymers (with one ? N? H groups) with the three polymers previously reported (with two ? N? H groups in side chains), the nature of the hydrogen bonds formed between the neighboring urea groups played big roles in the formation of stable helical conformation. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4112–4121, 2008     

Determination of the major solution conformation of tyrocidine A,using molecular mechanics energy minimization and NMR-derived distance and torsion angle constraints

Molecular mechanics energy calculations coupled with nuclear magnetic resonance-determined distance and torsion angle constraints have been used to determine the three-dimensional structure of tyrocidine A, a cyclic decapeptide which exists largely as a single conformation in solution. Two open-chain polyalanine models were used to represent separate halves of the peptide backbone and a combinatorial method of searching conformation space used to generate candidate structures consistent with experimental distance constraints. These structures were energy-minimized using the AMBER molecular mechanics forcefield and the resulting conformations classified by factor analysis of their Cartesian coordinates. Representative low-energy conformers of the two halves of the backbone were fused together and two candidate conformations of the completed backbone refined by further minimization using both distance and torsional constraints. Side chains were then added as their experimentally preferred rotamers and the whole molecule minimized without constraints to give the final model structure. This shows type II' and III ß turns at residues 4–5 and 9–10, respectively, coupled by twisted antiparallel strands which show hydrogen bonds between all four pairs of opposing peptide groups. The backbone conformation of residues 2–6 closely resembles that found in the crystal structure of gramicidin S.     

Quantum mechanical study of the conformational behavior of proline and 4R-hydroxyproline dipeptide analogues in vacuum and in aqueous solution

The conformational behavior of the title compounds has been investigated by Hartree-Fock, MP2, and DFT computations on the most significant structures related to variations of the backbone dihedral angles, cis/trans isomerism around the peptide bond, and diastereoisomeric puckering of the pyrrolidine ring. In vacuum the reversed gamma turn (gammal), characterized by an intramolecular hydrogen bridge, corresponds to the absolute energy minimum for both puckerings (up and down) of the pyrrolidine ring. An additional energy minimum is found in the helix region, but only for an up puckering of the pyrrolidine ring. When solvent effects are included by means of the polarizable continuum model the conformer observed experimentally in condensed phases becomes the absolute minimum. The down puckering is always favored over its up counterpart, albeit by different amounts (0.4-0.5 kcal/mol for helical structures and about 2 kcal/mol for gammal structures). In helical structures cis arrangements of the peptide bond are only slightly less stable than their trans counterparts. This is no longer true for gammal structures, because the formation of an intramolecular hydrogen bond is possible only for trans peptide bonds. In most cases, proline and hydroxyproline show the same general trends; however, the electronegative 4(R) substituent of hydroxyproline leads to a strong preference for up puckerings irrespective of the backbone conformation.     

Calix

Chiral calix[4]arene derivatives with four O-(N-acetyl-PhgOMe), (1), (Phg denotes R-phenylglycine), or O-(N-acetyl-LeuOMe) (2) strands have been synthesised. Both compounds exist in chloroform in stable cone conformations with a noncovalently organised cavity at the lower rim that is formed by circular interstrand amidic hydrogen bonds. Such organisation affects both the selectivity and extraction/transport properties of 1 and 2 toward metal cations. Calix[4]arene derivatives with one OCH2COPhgOMe strand (3), two OCH2COPhgOMe strands (5) and with 1,3-OMe-2,4-(O-CH2COPhgOMe) substituents (4) at the lower rim have also been prepared. For 3, a conformation stabilised by a circular hydrogen-bond arrangement is found in chloroform, while 4 exists as a time-averaged C2 conformation with two intramolecular NH ...OCH3 hydrogen bonds. Compound 5 has a unique hydrogen-bonding motif in solution and in the solid state with two three-centred NH-.. O and two OH...O hydrogen bonds at the lower rim. This motif keeps 5 in the flattened cone conformation in chloroform. The X-ray structure analysis of 1 revealed a molecular structure with C2 symmetry; this structure is organised in infinite chains by intra- and intermolecular H bonds. The solid-state and solution structures of the [1-Na]ClO4 complex are identical, C4 symmetric cone conformations.     

pH-responsive self-assembly and conformational transition of partially propyl-esterified poly(alpha,beta-L-aspartic acid) as amphiphilic biodegradable polyanion

Poly(alpha,beta-L-aspartate) (PAsp) was partially esterified to afford an amphiphilic biodegradable polyanion, poly(sodium aspartate-co-propyl aspartate) (PAsp-Na/PAsp-P). The synthesized polyanion could be assembled into the nano-scaled aggregates in aqueous medium. The aggregate morphologies were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) as a function of pH. It was demonstrated that micellization of this random copolymer occurred with stimulus of pH changes to form various morphological micelles. The copolymer existed as precipitate at low pH (pH<2). When pH increased to 4, the polymers were associated into spherical micelles with the core of poly(propyl aspartate) (PAsp-P) hydrophobic units and shell of some negatively charged poly(sodium aspartate) (PAsp-Na) units. At higher pH (pH>5), toroidal nanostructures of the micelles were formed because rigid polyamide chains directly assemble into the large hollow spheres. The CD study showed that the conformation underwent a transition between alpha-helix and random coil at pH 3-7. The cooperative transitions were regulated by the degree of ionization of carboxylic side chains. When they were protonated (neutralized), the molecular backbone was in favor of the regular helical structure; when deprotonated (ionized), the electrostatic repulsions among side chains destabilized the intramolecular hydrogen bonds, thus randomizing the regular conformation.     

间位聚苯及其衍生物的构象与电子结构的理论研究

用分子力学方法(MM)对间位聚苯(PMP)及其衍生物的势能随扭曲角(f)变化规律进行了研究.结果表明，势能曲线上出现四个能量最小值，分别对应于扭曲角f ≈－135°,－45°,45°,135°.进一步对以上构建的全部PMP及其衍生物用分子力场Drieding 2.11进行了分子力学能量优化.最终得到主要的四种构象，其中螺旋构象的能量最低，而且以螺旋构象为优势分布构象.在真实条件下，PMP及其衍生物长链可能采取以上四种构象的混合片段组成.用量子化学方法(GGA-DFT)研究了PMP及其衍生物的电子结构能隙随相邻苯环之间的扭曲角的变化趋势.用量子化学半经验方法(AM1)对四种构象分别进行几何优化，优化结果与分子力学优化结果基本一致，并运用混合密度泛函方法(DFT/B3LYP/6-31G)进一步对AM1优化的构象结构进行更精确的电子结构能隙计算.最终得出影响间位聚苯及其衍生物电子结构能隙的主要因素为连接苯环间扭曲角的大小.     

Molecular orientation in helical and all-trans oligo(ethylene glycol)-terminated assemblies on gold: results of ab initio modeling

The structural properties of self-assembled monolayers (SAMs) of oligo(ethylene glycol) (OEG)-terminated and amide-containing alkanethiols (HS(CH(2))(15)CONH(CH(2)CH(2)O)(6)H and related molecules with shorter alkyl or OEG portions) on gold are addressed. Optimized geometry of the molecular constituents, characteristic vibration frequencies, and transition dipole moments are obtained using density-functional theory methods with gradient corrections. These data are used to simulate IR reflection-absorption (RA) spectra associated with different OEG conformations. It is shown that the positions and relative intensities of all characteristic peaks in the fingerprint region are accurately reproduced by the model spectra within a narrow range of the tilt and rotation angles of the alkyl plane, which turns out to be nearly the same for the helical and all-trans OEG conformations. In contrast, the tilt of the OEG axis changes considerably under conformational transition from helical to all-trans OEG. By means of ab initio modeling, we also clarify other details of the molecular structure and orientation, including lateral hydrogen bonding, the latter of which is readily possessed by the SAMs in focus. These results are crucial for understanding phase and folding characteristics of OEG SAMs and other complex molecular assemblies. They are also expected to contribute to an improved understanding of the interaction with water, ions, and ultimately biological macromolecules.     

N,N'-linked oligoureas as foldamers: chain length requirements for helix formation in protic solvent investigated by circular dichroism, NMR spectroscopy, and molecular dynamics

N,N'-linked oligoureas with proteinogenic side chains are peptide backbone mimetics belonging to the gamma-peptide lineage. In pyridine, heptamer 4 adopts a stable helical fold reminiscent of the 2.6(14) helical structure proposed for gamma-peptide foldamers. In the present study, we have used a combination of CD and NMR spectroscopies to correlate far-UV chiroptical properties and conformational preferences of oligoureas as a function of chain length from tetramer to nonamer. Both the intensity of the CD spectra and NMR chemical shift differences between alphaCH2 diastereotopic protons experienced a marked increase for oligomers between four and seven residues. No major change in CD spectra occurred between seven and nine residues, thus suggesting that seven residues could be the minimum length required for stabilizing a dominant conformation. Unexpectedly, in-depth NMR conformational investigation of heptamer 4 in CD3OH revealed that the 2.5 helix probably coexists with partially (un)folded conformations and that Z-E urea isomerization occurs, to some degree, along the backbone. Removing unfavorable electrostatic interactions at the amino terminal end of 4 and adding one H-bond acceptor by acylation with alkyl isocyanate (4 --> 7) was found to reinforce the 2.5 helical population. The stability of the 2.5 helical fold in MeOH is further discussed in light of unrestrained molecular dynamics (MD) simulation. Taken together, these new data provide additional insight into the folding propensity of oligoureas in protic solvent and should be of practical value for the design of helical bioactive oligoureas.