Compactization of rigid-chain amphiphilic macromolecules with local helical structure

Conformational characteristics of amphiphilic macromolecules with secondary local helical structuring are studied by the method of molecular dynamics for different properties of a helix (bending angles between neighboring vectors of the bond and internal rotation angle) and different rigidities of its fixation. Extended helices with high distances between helical turns and dense helices in which neighboring turns directly adjoin each other are studied. As the quality of a solvent deteriorates, extended helices experience a well-pronounced coil-globule transition, whose amplitude increases with an increase in chain rigidity, while the dimensions of dense helices gradually change. In a poor solvent, extended helices formed “collagen-like” structures, flexible chains of dense helices produce hairpin structures, and rigid macromolecules of dense helices form rodlike globules with an almost ideal local helical order. Independently of helix parameters, a deterioration in solvent quality leads to stabilization of the local secondary structure.     

Viscoelasticity of a stretched polymer chain with ends exposed to a constant force

The viscoelasticity of a stretched polymer chain with its end particles exposed to oppositely acting forces is studied via collisional molecular dynamics and analytically. A simple model according to which a polymer molecule is a chain of particles linked through freely jointed elastic bonds is adopted. The analytical theory is in good agreement with the results of the computer simulation of time correlation functions in the range of large-scale motions of a polymer molecule. It is found that the decay of correlation functions K _αβμν of fluctuations of the microscopic stress tensor of a chain, K _zzzz, K _zαzα , = K _zαzα , (α = x, y; z is the axis along which the forces act), is slowed down, and their value increases relative to the respective correlation functions of a chain with fixed ends. The greater the force, the higher this difference. The correlation functions that are transverse with respect to the z axis do not differ from those for chains with fixed ends. The results show that, in the calculation of time correlation functions of strongly stretched polymer chains, different statistical ensembles are not equivalent; this must be taken into account in the dynamic theories of heavily deformed polymers.     

Helix formation in the polymer brush

This work considers the physics of a brush formed by polymers capable of undergoing a helix-coil transition. A self-consistent field approximation for strongly stretched polymer chains is used in combination with a lattice model of the interaction energy in helix-coil mixtures. Crowding-induced chain stretching stabilizes helix formation at moderate tethering densities while high tethering density causes sufficiently strong stretching to unravel segments of the helix, resulting in distinct layers of monomer density and helical content. Compared to a random-coil brush at low-to-moderate tethering density, a helicogenic brush is less resistant to compression in the direction perpendicular to stretching due to easy alignment of helices and fewer unfavorable interactions between helical segments. At higher tethering density, the abovementioned stretch-induced decrease in helical content resists further compression. The proposed model is useful for understanding an emerging class of biomaterials that utilize helix-forming polymer brushes to induce shape changes or to stabilize biofunctional helical peptide sequences.     

Influence of temperature on molecular regroupings and chain rupture under stretching deformation of high‐oriented linear polyethylene

Conformational regrouping and rupture of macromolecular chains at different stretching deformation temperatures of highly oriented linear polyethylene samples (monofilaments) were studied. Measurements of the relative concentration of rotational isomers and chain rupture were determined by IR spectroscopy. Regroupings occur in the highly oriented polymer when elastic stretching of the sample exceeds a threshold value, irrespective of deformation temperature; this is assumed to be due to steric conditions that influence the cooperative transition of coiled‐chain isomers in the extended isomeric conformational state. Polymer stretching at elevated temperatures, in comparison with room temperature, occurred at considerably lower loads and showed increases in elastic deformation, extent of conformational regroupings of molecular segments and reduction in the number of macromolecular ruptures. Deformation at identical values was accompanied by a smaller decrease in concentration of coiled‐chain rotational isomers. The number of molecular chain ruptures, which is proportional to stress load, appeared to be unaffected by temperature. It is proposed that the small decreases observed in the content of coiled‐chain isomers and of chain rupture with deformation are facilitated by macromolecular slippage processes that occur through polymer crystallites.     

The molecular basis of the adsorption of xylans on cellulose surface

In order to model the adsorption of xylan on cellulose, we have simulated, at the atomic level, the gas phase adsorption of small xylan fragments having 5 skeletal β (1 → 4) xylosyl residues (X₅), using molecular dynamics simulations. A first regime was considered, corresponding to a low surface coverage, with the adsorption of isolated X₅ in various initial orientations. In this regime, the simulation indicated that X₅ moved toward extended conformations, some of them being helical, with the possibility of either 2₁ or left-handed 3₁ helices. During the simulation, the X₅ fragments became preferentially oriented, parallel or anti parallel with respect to the cellulose chain axis. Substitution of the X₅ backbone by either GlcA and/or Araf side chains had no major influence on either the conformation or the efficiency of the interaction. However, the presence of side chains favored orientations of the X₅ backbone inclined with respect to the cellulose chain axis. In a second regime corresponding to monolayer coverage, the geometrical features of the adsorption of the xylan fragments on cellulose was roughly the same as that in the individual coverage situation. In this case, the monolayer became equilibrated at 0.14 g of xylan fragments for each g of cellulose, a figure that compared favourably with the values obtained in experimental adsorption of xylan on bacterial cellulose.     

Separation of single-stranded DNA fragments at a 10-nucleotide resolution by stretching in microfluidic channels

We report a novel DNA separation method by tethering DNA chains to a solid surface and then stretching the DNA chains with an electric field. The anchor is such designed that the critical force to detach a DNA chain is independent of its size. Because the stretching force is proportional to the DNA net charge, a gradual increase of the electric field leads to size-based removal of the DNA strands from the surface and thus DNA separation. Here we show that this method, originally proposed for separation of long double-stranded DNA chains (>10,000 base pairs), is also applicable to single-stranded (ss) DNA fragments with less than 100 nucleotides (nt). Theoretical analysis indicates that the separation resolution is limited by the fluctuation forces on tethered DNA chains. By employing a microfluidic platform with narrow channels filled with a buffer of low ionic conductivity, we are able to apply a strong electric field to the DNA fragments with negligible Joule heating. Upon stepwise increments of the electric field, we demonstrate efficient separation of short ssDNA fragments at a 10-nt resolution.     

Peptoid oligomers with alpha-chiral, aromatic side chains: sequence requirements for the formation of stable peptoid helices.

The achiral backbone of oligo-N-substituted glycines or "peptoids" lacks hydrogen-bond donors, effectively preventing formation of the regular, intrachain hydrogen bonds that stabilize peptide alpha-helical structures. Yet, when peptoids are N-substituted with alpha-chiral, aromatic side chains, oligomers with as few as five residues form stable, chiral, polyproline-like helices in either organic or aqueous solution. The adoption of chiral secondary structure in peptoid oligomers is primarily driven by the steric influence of these bulky, chiral side chains. Interestingly, peptoid helices of this class exhibit intense circular dichroism (CD) spectra that closely resemble those of peptide alpha-helices. Here, we have taken advantage of this distinctive spectroscopic signature to investigate sequence-related factors that favor and disfavor stable formation of peptoid helices of this class, through a comparison of more than 30 different heterooligomers with mixed chiral and achiral side chains. For this family of peptoids, we observe that a composition of at least 50% alpha-chiral, aromatic residues is necessary for the formation of stable helical structure in hexameric sequences. Moreover, both CD and 1H-13C HSQC NMR studies reveal that these short peptoid helices are stabilized by the placement of an alpha-chiral, aromatic residue on the carboxy terminus. Additional stabilization can be provided by the presence of an "aromatic face" on the helix, which can be patterned by positioning aromatic residues with three-fold periodicity in the sequence. Extending heterooligomer chain length beyond 12-15 residues minimizes the impact of the placement, but not the percentage, of alpha-chiral aromatic side chains on overall helical stability. In light of these new data, we discuss implications for the design of helical, biomimetic peptoids based on this structural motif.     

Gaussian fluctuations in tethered DNA chains

In a recent work [Gao et al., Appl. Phys. Lett. 134, 113902 (2007)], we reported a novel DNA separation method by tethering DNA chains to a solid surface and then stretching the DNA chains with an electric field. The anchor is such designed that the critical force to detach a DNA chain is independent of its length. Because the stretching force is proportional to the DNA net charge, a gradual increase of the electric field leads to size-based removal of the DNA strands from the surface and thus DNA separation. Originally proposed for separation of long double-stranded DNA chains (>10 000 bps), this method has been proven useful also for short single-stranded DNA fragments (<100 bases) for which the fluctuation force induced by the solvent becomes significant. Here we show that the fluctuation force can be approximately represented by a gaussian model for tethered DNA chains. Analytical expressions have been derived to account for the dependence of the fluctuation force on the surface confinement, the polymer chain length, and the DNA tethering potential. The theoretical predictions are found to coincide with experiment.     

The Important Roles of Water in Protein Folding: an Approach by Single Molecule Force Spectroscopy

The single-chain elasticity of a completely unfolded protein ((I27)8,modules of human cardiac titin) is studied in different liquid environments by the atomic force microscopy (AFM)-based single molecule force spectroscopy (SMFS).The experimental results show that there is a clear deviation between the force curves obtained in the aqueous and nonaqueous environments.Such a deviation can be attributed to the additional energy consumed by the rearrangement of the bound water molecules around the chain of the completely unfolded (I27)8 chain upon stretching in aqueous solution,which is very similar to the partial dehydration process from a denatured/unfolded to a native/folded protein.Through the analysis of the free energy changes involved in protein folding,we conclude that it is due to the weak disturbance of water molecules and the special backbone structures of proteins that the self-assembly of proteins can be achieved in physiological conditions.We speculate that water is likely to be an important criterion for the selection of self-assembling macromolecules in the prebiotic chemical evolution.     

An investigation of the photo-reactive and unreactive polymorphs of o -ethoxy cinnamic acid and of its photodimer

Detailed X-ray crystallographic investigation of the reactive α- and the unreactive γ-polymorphs ofo-ethoxy cinnamic acid has been carried out along with that of the photodimer, α-truxillic acid. The molecule is quite planar in the α-form, but in the γ-form, the side groups deviate significantly from the plane of the benzene ring. The carboxylic groups form normal cyclic hydrogen bonds in the α-form and near-symmetric hydrogen bonds in the γ-form. The infrared spectrum of the α-form shows the characteristic features of the cyclic dimer, but that of the γ-form is entirely different, marked by the absence of the O-H stretching band in the 3000 cm^-1 region. Charge density analysis throws some light on the structure and reactivity of the molecule in the two forms. The near-symmetric hydrogen bond in the γ-form is ionic and appears to restrict conjugation by way of distorting the molecule. This unusual feature keeps the cinnamoyl double bonds away from each other, rendering it photochemically unreactive. In the α-form, however, the double bonds have a closer approach. The cyclobutyl ring of the photodimer consists of weak single bonds, with the new pair being slightly longer.     

Deformation,Stretching, and Relaxation of Single‐Polymer Chains: Fundamentals and Examples#

Abstract

We review the basic theory for the static and dynamic properties of ideal and real chains. We describe the stretching of single ideal chains in both the strain and the stress ensembles, give scaling arguments for the deformation of real chains, and also consider the impact of chain rigidity by discussing the stretching of worm-like chains. We complement this theoretical outlook with specific examples that highlight the relevance of the single-molecule deformation in a practical perspective: the translocation of a macromolecule over a potential barrier, the collision of a single chain with fixed obstacles or other chains, the dynamics of a thethered chain in a strong shear flow, and some remarkable predictions concerning the deformation of composite chain molecules during free-solution electrophoresis.     

Binding Delocalization in Polymer Inclusion Complexes of Ring Molecules: Pseudopolyrotaxanes of α-Cyclodextrin and Poly(ethylene glycol)

With polymer substrates, the continuous variation method based on monomer unit concentration underestimates the number of monomer units covered by a low-molecular-weight ligand. Accordingly, gel permeation chromatography confirms that an α-cyclodextrin (α-CD) molecule occupies more than previously claimed two ethylene glycol units in solid α-CD/poly(ethylene glycol) inclusion complexes. Consequently, the poly(ethylene glycol) chain cannot be modeled as an array of distinct binding sites corresponding to two monomer units and no preferred positions, i.e., no distinct binding sites probably exist on the chain for α-CD threading. The effect of such binding delocalization can be assessed using the theory of binding large ligands to a finite one-dimensional lattice [I.R. Epstein: Biophys. Chem. 8, 327 (1978)]. Binding delocalization slightly decreases the average occupancy with highly occupied chains but strongly promotes the occupancy in the case of weak binding. This may be an additional reason for observed high yields of precipitated CD/polymer complexes.     

Quasiharmonic treatment of infrared and raman vibrational frequency shifts induced by tensile deformation of polymer chains. II. Application to the polyoxymethylene and isotactic polypropylene single chains and the three-dimensional orthorhombic polyethylene crystal

Quasiharmonic equations are derived for stress-induced vibrational frequency shifts in the infrared and Raman spectra of polymer chains subjected to a tensile stress. The expressions are applied to the helical chains of polyoxymethylene and isotactic polypropylene. Observed frequency shifts can be reproduced well by using reasonable anharmonic force constants. A semiquantitative interpretation is given for the close relationship between stress-induced vibrational frequency shifts and the deformation mechanism of the polymer chains. Stress-induced frequency shifts are also calculated for an orthorhombic polyethylene crystal subjected to uniaxial tension along the chain axis or to hydrostatic pressure. The results consistently and reasonably reproduce observed data, not only for the intramolecular vibrational modes but also for the external lattice modes. © 1992 John Wiley & Sons, Inc.     

α,ω-Bis(3,6-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)alkanes and products of their cyclization, pyrimidinophanes: intra- and intermolecular interaction in crystals and in solutions

Reaction of α,ω-bis(3,6-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)alkanes with paraformaldehyde leads to pyrimidinophanes, which contain four 3,6-dimethyluracil fragments, connected to each other by the methylene chains. A comparative study of intra- and intermolecular interactions of “open” and macrocyclic uracil derivatives in the crystal state and in solution was performed. According to the NMR spectroscopy data, there is no self-association of “open” and macrocyclic compounds in chloroform solutions, whereas the X-ray data revealed the intermolecular π-π contacts between the 3,6-dimethyluracil fragments in the crystals of these compounds. Conclusions on the presence of intramolecular interactions in chloroform solutions of α,ω-bis(3,6-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)alkanes and pyrimidinophanes were made based on the UV spectra, which were interpreted in terms of hypo- and hyperchromic effects relatively to the model uracil derivative. These conclusions correlate with the X-ray data: there are no intramolecular π-π contacts between the 3,6-dimethyluracil fragments both in the crystals and in solutions of “open” compounds, positions of these fragments relatively to each other in the molecules of pyrimidinophanes are defined by the lengths of the polymethylene bridges. The intramolecular stacking effect between the opposite uracil rings is observed for the macrocycles with trimethylene and hexamethylene chains, whereas there is no such interactions in pyrimidinophanes with tetramethylene chains. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 119–131, January, 2008.     

Spectral and fluorescent properties of cross-conjugated polyene ketones with terminalN-methylpyrrole residues

The spectral and fluorescent properties of a number of cross-conjugated ketones with one or two terminalN-methylpyrrole residues and those of polyene bis-ω, ω′-dimethylamino ketones with methyl substituents in the polyene chain and of some related compounds were studied. The photophysical properties of cross-conjugated ketones with terminalN-methylpyrrole residues are similar to those of the corresponding polyene bis-ω, ω′-dimethylamino ketones studied in detail previously. In both series of compounds, the absorption and fluorescence spectra undergo a bathochromic shift following an increase in the length of the polyene chains or introduction of α,α′-trimethylene or α,α′-dimethylene bridges into these chains; the same trend is observed on passing from less polar solvents to more polar solvents (positive solvatochromism). Thermochromism (long-wavelength shift of the absorption spectra upon cooling the solutions) is observed in both series of compounds. The introduction of methyl substituents into the polyene chains of bis-ω,ω′-dimethylamino ketones results in a decrease in the fluorescence quantum yield. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1293–1298, July, 1999.     

Experimental study of a diffusion-controlled reaction involving a chain molecule with terminal reactive sites

Diffusion-controlled reaction of electron transfer from diphenylsilane radical anions to the series of α- and α,ω-bromoalkanes with alkane chain length up to 18 atoms has been studied in n-dodecane solutions. At room temperature, reaction rate constants have been determined and corresponding reaction radii have been evaluated. It has been shown that a not-too-long chain molecule, which contains two terminal reaction sites and participates in the diffusion-controlled reaction, may be considered as a rapidly rotating pair of reacting sinks with a distance between their centers equal to the mean-square end-to-end distance of the molecule.     

Synthesis of triterpene acids conjugates with α-tocopherol synthetic analogs

Heterodimers were synthesized of pharmacologically important α-tocopherol synthetic analogs with triterpene acids(betulonic, betulinic), potential polyfunctionsl drugs possessing antioxidant activity. The combination of the fragments of biologically active substances was performed through linkers (residues of succinic acid, hydrazine, glycine, tetramethylenediamine) binding the side chain of the antioxidant molecule with atoms C³ or C²⁸ of the terpenoid.     

Folding Behavior of Polypeptides. A Monte Carlo Study of Simplified Models

Summary. A simple model of polypeptide chains was designed and studied. The chains were constructed on a flexible [310] lattice and consisted of united atoms located at the position of alpha carbons. Each united atom represented amino acid residues of two kinds: hydrophilic and hydrophobic. The sequence of the residues was assumed to be characteristic for α- and β-type of proteins. The force field used consisted of the long-range contact potential between polymer segments, the short range repulsion, and the local potential preferring conformational states characteristic for α-helices and β-strands. The Monte Carlo simulations of this model were carried out using the replica exchange technique coupled with the histogram method. The influence of temperature and the local potential on the size and internal structure of collapsed low temperature chains were studied. Thermodynamics of these systems consisting mainly of α and β secondary structures were determined. The properties of the coil-to-globule transition were presented and compared with other theoretical predictions and simulation results.     

Folding Behavior of Polypeptides. A Monte Carlo Study of Simplified Models

A simple model of polypeptide chains was designed and studied. The chains were constructed on a flexible [310] lattice and consisted of united atoms located at the position of alpha carbons. Each united atom represented amino acid residues of two kinds: hydrophilic and hydrophobic. The sequence of the residues was assumed to be characteristic for α- and β-type of proteins. The force field used consisted of the long-range contact potential between polymer segments, the short range repulsion, and the local potential preferring conformational states characteristic for α-helices and β-strands. The Monte Carlo simulations of this model were carried out using the replica exchange technique coupled with the histogram method. The influence of temperature and the local potential on the size and internal structure of collapsed low temperature chains were studied. Thermodynamics of these systems consisting mainly of α and β secondary structures were determined. The properties of the coil-to-globule transition were presented and compared with other theoretical predictions and simulation results.     

Synthesis and characterization of a persistent paramagnetic rotaxane based on α-cyclodextrin and α,ω-alkyl disulfides

A new synthetic strategy for the preparation of persistent paramagnetic cyclodextrin-based rotaxanes is described. The method consists in the formation of inclusion complexes between α-cyclodextrin (α-CD) and α,ω-dithiols containing an octamethylene chain covalently trapped by bulky stoppers composed of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) radical fragments. Interaction of α-CD (the bead) and 1,8-octanedithiol (the thread) occurs in aqueous alkaline media and encapsulation is obtained by nucleophilic substitution at both termini of the linear component with a bulky paramagnetic iodide [2,2,6,6-tetramethyl-4-(2-iodoacetamide)piperidine-N-oxyl]. Structure determination of the new [2]rotaxane by ¹H NMR is reported and the spectroscopic data are discussed.