A Monte Carlo simulation study of branched polymers

Monte Carlo simulations are presented for the static properties of highly branched polymer molecules. The molecules consist of a semiflexible backbone of hard-sphere monomers with semiflexible side chains, also composed of hard-sphere monomers, attached to either every backbone bead or every other backbone bead. The conformational properties and structure factor of this model are investigated as a function of the stiffness of the backbone and side chains. The average conformations of the side chains are similar to self-avoiding random walks. The simulations show that there is a stiffening of the backbone as degree of crowding is increased, for example, if the branch spacing is decreased or side chain length is increased. The persistence length of the backbone is relatively insensitive to the stiffness of the side chains over the range investigated. The simulations reproduce most of the qualitative features of the structure factor observed in experiment, although the magnitude of the stiffening of the backbone is smaller than in experiment.     

A Peptide Backbone Stapling Strategy Enabled by the Multicomponent Incorporation of Amide N-Substituents

The multicomponent backbone N-modification of peptides on solid-phase is presented as a powerful and general method to enable peptide stapling at the backbone instead of the side chains. This work shows that a variety of functionalized N-substituents suitable for backbone stapling can be readily introduced by means of on-resin Ugi multicomponent reactions conducted during solid-phase peptide synthesis. Diverse macrocyclization chemistries were implemented with such backbone N-substituents, including the ring-closing metathesis, lactamization, and thiol alkylation. The backbone N-modification method was also applied to the synthesis of α-helical peptides by linking N-substituents to the peptide N-terminus, thus featuring hydrogen-bond surrogate structures. Overall, the strategy proves useful for peptide backbone macrocyclization approaches that show promise in peptide drug discovery.     

Influence of Rigid Side Chain Attraction on Stiffness and Conformations of Comb Copolymer Brushes Strongly Adsorbed on a Flat Surface

The influence of side‐chain attraction on the conformational properties of two‐dimensional polymer brushes with rigid side chains is investigated using Monte Carlo simulations. Using a rigid backbone, a characteristic interaction strength is determined by investigating the critical interaction energy for the collapse of the side chains onto the backbone. For a flexible backbone, the persistence length of the backbone is found to decrease with increasing attraction, irrespective of whether side‐chain flipping is allowed or not. This result is in good agreement with the theoretical modeling presented before. If side‐chain flipping is allowed, the attraction between the side chains leads to aggregation of successive side chains at one side of the backbone resulting in a characteristic local spiraling of the backbone.     

Inherent Conformational Preferences of Ac‐Gln‐Gln‐NHBn: Sidechain Hydrogen Bonding Supports a β‐Turn in the Gas Phase

Gas‐phase single‐conformation spectroscopy is used to study Ac‐Gln‐Gln‐NHBn in order to probe the interplay between sidechain hydrogen bonding and backbone conformational preferences. This small, amide‐rich peptide offers many possibilities for backbone–backbone, sidechain–backbone, and sidechain–sidechain interactions. The major conformer observed experimentally features a type‐I β‐turn with a canonical 10‐membered ring C=O—H?N hydrogen bond between backbone amide groups. In addition, the C=O group of each Gln sidechain participates in a seven‐membered ring hydrogen bond with the backbone NH of the same residue. Thus, sidechain hydrogen‐bonding potential is satisfied in a manner that is consistent with and stabilizes the β‐turn secondary structure. This turn‐forming propensity may be relevant to pathogenic amyloid formation by polyglutamine segments in human proteins.     

Size and persistence length of molecular bottle-brushes by Monte Carlo simulations

Single-chain simulations of densely branched comb polymers, or "molecular bottle-brushes" with side-chains attached to every (or every second) backbone monomer, were carried out by off-lattice Monte Carlo technique. A coarse-grained model, described by hard spheres connected by harmonic springs, was employed. Backbone lengths of up to 100 units were considered, and compared with the corresponding linear chains. The backbone molecular size was investigated as a function of its length at fixed arm size, and as a function of the arm size at fixed backbone length. The apparent swelling exponents obtained by a power-law fit were found to be larger than those for the corresponding linear polymers, indicative of stiffening of the comb backbone. The probability distribution function for the backbone end-to-end distance was also investigated for different backbone lengths and arm sizes. Analysis of this function yielded the critical exponents, which revealed an increase in the swelling exponent consistent with values found from the molecular size. The apparent persistence length of the backbone was also determined, and was found to increase with increasing branching density. Finally, the static structure factors of the whole bottle-brushes and of their backbones are discussed, which provides another consistent estimate of the swelling exponents.     

Reactions of living polystyrene with difunctional nitriles to produce specifically placed grafting sites

Graft polymers have been synthesized with two equal length branches and one or two branches of a different length or composition. The first step was a coupling reaction of living polystyrene with a difunctional nitrile. The product was hydrolyzed to form a ketone-containing backbone. Subsequently another sample of living polystyrene or of poly-2-vinylpyridine was added to the backbone to form the graft. Anionic polymerization was used for the synthesis of backbone and side chains, so all of the products are well defined. The products and reaction sequences also serve as models for a general synthesis of well-defined comb-shaped polymers, in which the length of the backbone, and the number, length, and spacing of the side chains may be controlled.     

Synthesis and thermal properties of side chain-type liquid crystalline polyurethanes

The synthesis of side chain-type polyurethanes is described. Their thermal properties were investigated by differential scanning calorimetry and polarizing microscopy and are discussed in terms of the dependence of the polymer backbone on temperature as shown by FT-infrared spectroscopy. The hydrogen bonding which arises from the rather flexible polymer backbone plays a more important role in determining the thermal stability than does the rigid polymer backbone.     

Backbone cleavages of [M - H](-) anions derived from caerin 1 peptides and some synthetic modifications. Molecular recognition initiating internal cyclisation of Glu23

The collision induced spectra of [M - H](-) anions from of caerin 1 peptides and some synthetic modifications show the usual alpha, beta and beta' backbone cleavages together with Ser (epsilon,gamma) and Glu (gamma) cleavages which break the peptide backbone in the vicinity of those residues. All of these cleavages require the peptide backbone to be flexible. There is also a backbone cleavage of a type not observed before. This cleavage involves nucleophilic attack of the carboxylate anion of the Glu23 side chain at the backbone CH of Ile 21. We propose that this cleavage requires the caerin peptide to be in an alpha helical conformation (the 3D structure that this peptide adopts in solution) in order that the interacting groups are held in close proximity.     

Surface-energy characteristics of films of molecular brushes based on polyimide and poly(methyl methacrylate)

Surface characteristics of film samples of molecular brushes with a polyimide backbone and PMMA side chains, as well as of films of polyimide constituting the backbone and linear PMMA homopolymers obtained via the selective destruction of the polyimide backbone of these brushes, are investigated for the first time. The surface-energy characteristics of the films of molecular brushes are determined by the structure and conformational state of the PMMA side chains. The conformations of molecular brushes possessing a polyimide backbone well screened by side chains are preserved after the transition from solutions to “dry” copolymer films and are characterized by high stability. The observed surface activity of molecular brushes is due to adhesion interactions with functional groups of the substrate. The difference in surface activities is caused by small-scale conformational changes in the side chains of molecular brushes. A globular core of molecular brushes formed by the polyimide backbone remains practically spherical and probably does not change in volume.     

Aggregate morphologies of amphiphilic graft copolymers in dilute solution studied by self-consistent field theory

Microstructures assembled by amphiphilic graft copolymers in a selective solvent (poor for the backbone chain and good for graft chains or poor for graft chains and good for the backbone chain) were investigated on the basis of a real-space algorithm of self-consistent field theory in two-dimensions. Circle-like micelles, line-like micelles, large compound micelles, and vesicles are obtained by tailoring the architectural parameters and interaction parameter between the graft blocks and solvents. The aggregate morphology stability regions of graft copolymers as functions of the position of first graft point and the number of branches are constructed. It is found that the architectural parameters play a remarkable role in the complex microstructure formation. The interaction between the graft blocks and solvents is also shown to exert an effect on the morphology stability regions. The distributions of the free end and inner blocks of the backbone are found to be different in various aggregate structures. For the circle-like micelles assembled by graft copolymers with a hydrophobic backbone and vesicles assembled by graft copolymers with a hydrophilic backbone, the free end and inner blocks segregate and localize in different parts of the aggregates depending on their length. However, with respect to the large compound micelles and vesicles assembled by graft copolymers with a hydrophobic backbone, the free end and inner blocks uniformly mix in the clusters.     

On the structure and the chain conformation of side-chain liquid crystal polymers

Abstract

Backbone anisotropy and the structure of the mesophases of a series of side-chain liquid crystal polymers have been studied in the bulk by neutron scattering. The backbone conformation is obtained by small-angle neutron scattering on mixtures of hydrogenous polymers with deuteriated backbones. The components of the radius of gyration parallel, R _⊥ and perpendicular, R ∥ to the magnetic field are determined as a function of temperature for both the nematic phase and the smectic phase. It is shown that the polymer backbone is deformed in both phases. When the polymer exhibits only a nematic phase, it adopts a prolate conformation, where the average backbone direction is more or less parallel to the aligned mesogenic groups. Upon transition from the smectic phase to a nematic phase, the backbone in the nematic phase assumes a slightly oblate shape. This tendency towards oblate shape is due to the smectic fluctuations which are always present in such nematic phases. The exentricity of the oblate backbone conformation in the smectic phase is always larger than in the nematic phase. This is attributed to a periodic distribution of the backbone between the mesophase layers. Then, the backbone anisotropy depends not only on the smectic structure (S_A1, S_Ad), but also on the temperature dependence of the density of aligned mesogenic groups in the layers. On the other hand, it is shown that the isotopic mixtures are no longer ideal when polymers deuteriated in the mesogenic moieties are mixed with the corresponding hydrogenous polymers.     

Differential ordering of the protein backbone and side chains during protein folding revealed by site-specific recombinant infrared probes

The time scale for ordering of the polypeptide backbone relative to the side chains is a critical issue in protein folding. The interplay between ordering of the backbone and ordering of the side chains is particularly important for the formation of β-sheet structures, as the polypeptide chain searches for the native stabilizing cross-strand interactions. We have studied these issues in the N-terminal domain of protein L9 (NTL9), a model protein with mixed α/β structure. We have developed a general approach for introducing site-specific IR probes for the side chains (azide) and backbone ((13)C═(18)O) using recombinant protein expression. Temperature-jump time-resolved IR spectroscopy combined with site-specific labeling enables independent measurement of the respective backbone and side-chain dynamics with single residue resolution. We have found that side-chain ordering in a key region of the β-sheet structure occurs on a slower time scale than ordering of the backbone during the folding of NTL9, likely as a result of the transient formation of non-native side-chain interactions.     

An extremely stable and orthogonal DNA base pair with a simplified three-carbon backbone

A nucleotide C3HQ with a minimal three-carbon backbone displays unprecedented pairing strength and orthogonality in a homopair C3HQ:C3HQ in the presence of one equivalent of Cu2+. The pairing stability in DNA even exceeds the related base pair having the regular 2'-deoxyribose backbone. This discovery of a synergy between an artificial backbone and base-pairing scheme opens new avenues for the economical design of modified oligonucleotides with tailored properties.     

Electrospray tandem mass spectrometry of mixed-sequence RNA/DNA oligonucleotides

The fragmentation of electrospray-generated multiply deprotonated RNA and mixed-sequence RNA/DNA pentanucleotides upon low-energy collision-induced dissociation (CID) in a hybrid quadrupole time-of-flight mass spectrometer was investigated. The goal of unambiguous sequence identification of mixed-sequence RNA/DNA oligonucleotides requires detailed understanding of the gas-phase dissociation of this class of compounds. The two major dissociation events, base loss and backbone fragmentation, are discussed and the unique fragmentation behavior of oligoribonucleotides is demonstrated. Backbone fragmentation of the all-RNA pentanucleotides is characterized by abundant c-ions and their complementary y-ions as the major sequence-defining fragment ion series. In contrast to the dissociation of oligodeoxyribonucleotides, where backbone fragmentation is initiated by the loss of a nucleobase which subsequently leads to the formation of the w- and [a-base]-ions, backbone dissociation of oligoribonucleotides is essentially decoupled from base loss. The different behavior of RNA and DNA oligonucleotides is related to the presence of the 2'-hydroxyl substituent, which is the only structural alteration between the DNA and RNA pentanucleotides studied. CID of mixed-sequence RNA/DNA pentanucleotides results in a combination of the nucleotide-typical backbone fragmentation products, with abundant w-fragment ions generated by cleavage of the phosphodiester backbone adjacent to the deoxy building blocks, whereas backbone cleavage adjacent to ribonucleotides induces the formation of c- and y-ions.     

Synthesis and thermal properties of side chain-type liquid crystalline polyurethanes

Abstract

The synthesis of side chain-type polyurethanes is described. Their thermal properties were investigated by differential scanning calorimetry and polarizing microscopy and are discussed in terms of the dependence of the polymer backbone on temperature as shown by FT-infrared spectroscopy. The hydrogen bonding which arises from the rather flexible polymer backbone plays a more important role in determining the thermal stability than does the rigid polymer backbone.     

Effects of the biological backbone on stacking interactions at DNA-protein interfaces: the interplay between the backbone···π and π···π components

The (gas-phase) MP2/6-31G*(0.25) π···π stacking interactions between the five natural bases and the aromatic amino acids calculated using (truncated) monomers composed of conjugated rings and/or (extended) monomers containing the biological backbone (either the protein backbone or deoxyribose sugar) were previously compared. Although preliminary energetic results indicated that the protein backbone strengthens, while the deoxyribose sugar either strengthens or weakens, the interaction calculated using truncated models, the reasons for these effects were unknown. The present work explains these observations by dissecting the interaction energy of the extended complexes into individual backbone···π and π···π components. Our calculations reveal that the total interaction energy of the extended complex can be predicted as a sum of the backbone···π and π···π components, which indicates that the biological backbone does not significantly affect the ring system through π-polarization. Instead, we find that the backbone can indirectly affect the magnitude of the π···π contribution by changing the relative ring orientations in extended dimers compared with truncated dimers. Furthermore, the strengths of the individual backbone···π contributions are determined to be significant (up to 18 kJ mol(-1)). Therefore, the origin of the energetic change upon model extension is found to result from a balance between an additional (attractive) backbone···π component and differences in the strength of the π···π interaction. In addition, to understand the effects of the biological backbone on the stacking interactions at DNA-protein interfaces in nature, we analyzed the stacking interactions found in select DNA-protein crystal structures, and verified that an additive approach can be used to examine the strength of these interactions in biological complexes. Interestingly, although the presence of attractive backbone···π contacts is qualitatively confirmed using the quantum theory of atoms in molecules (QTAIM), QTAIM electron density analysis is unable to quantitatively predict the additive relationship of these interactions. Most importantly, this work reveals that both the backbone···π and π···π components must be carefully considered to accurately determine the overall stability of DNA-protein assemblies.     

良溶剂中接枝型聚两性电解质单链构象的布朗动力学模拟

采用布朗动力学研究了在良溶剂中荷电平衡的接枝聚两性电解质(GPA)的单链构象转变行为,讨论了主链链长、支链数及电荷密度对GPA分子链构象转变的影响.研究发现,随着静电相互作用的增强,GPA分子链构象转变过程由线团、主链与支链间的折叠、链段塌缩和电荷配对形成偶极子与四极子等4个阶段构成.与线型聚两性电解质不同,GPA存在的额外支链间空间排斥与静电排斥作用随着分子结构的变化而改变,并影响构象转变行为.在强静电相互作用下,良溶剂中的GPA链由于溶剂化作用会再伸展,以保证偶极子完全配对成四极子.减小主链长度或电荷密度或增加支链数目都会增大体系的排斥力和主链的刚性,阻滞分子链的塌缩,并使得分子链再伸展的幅度增大.     

An NMR study of mobility in a crystalline side‐chain comblike polymer

Carbon‐13 spin–lattice relaxation times are measured for poly(octadecyl acrylate) above and below the melting point of the crystalline side chains. The chain backbone has long spin–lattice relaxation times below the melting point that shorten by more than an order of magnitude as the melting point range is traversed. Below the melting point, the backbone is nearly immobilized with spin–lattice relaxation changing very slowly with temperature. Above the melting point, the shorter spin–lattice relaxation times are typical of a rubber above the glass transition and decrease with increasing temperature. The methylene groups in the side chain are quite mobile well below the melting point, indicating fairly rapid anisotropic motion within the crystal. The methyl group at the end of the chain and the adjacent methylene group have longer spin–lattice relaxation times, indicating the greatest side‐chain mobility at the end, which is in the middle of the crystal structure. The side‐chain carbon adjacent to the carbonyl group is as mobile as the majority of the side‐chain carbon, indicating side‐chain mobility extends to all of the side‐chain CH₂ groups. The abrupt transition in the mobility of the backbone is not typical of the amorphous phase in a semicrystalline polymer where the backbone units can crystallize. The close proximity of every backbone segment to the crystalline domain locks backbone segmental motion below the melting point. Melting and crystallization of the side chains switch segmental motion of the backbone on and off. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 1548–1552, 2001     

Morphological studies of blends of conjugated polymers and acceptor molecules using langevin dynamics simulations

We use coarse‐grained Langevin dynamics simulations of blends of generic conjugated polymers and acceptor molecules to show how architecture (e.g., side chains, backbone flexibility of oligomers) and the pair‐wise interactions between the constituents of the blend affect morphology and phase transition. Alkyl side chains on the conjugated oligomer backbones shift the liquid crystal (LC) transition temperature from that of bare conjugated backbones and the direction of the shift depends on backbone–backbone interactions. Rigid backbones and constrained side chains cause a layer‐by‐layer morphology of conjugated polymers and amorphous acceptors, whereas flexible backbones and unconstrained side chains facilitate highly ordered acceptor arrangement. Strong backbone–backbone attraction shifts LC transition to higher temperatures than weak backbone–backbone attraction, and strong acceptor–acceptor attraction increases acceptor aggregation. Pure macro‐phase separated domains form when all pair‐wise interactions in the blend are strongly attractive, whereas interconnected domains form at intermediate acceptor–acceptor attraction and strong polymer–polymer attractions. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013     

Triazine‐Based Sequence‐Defined Polymers with Side‐Chain Diversity and Backbone–Backbone Interaction Motifs

Sequence control in polymers, well‐known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence‐defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H‐bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence‐defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen‐bonding motifs, and will thus enable new macromolecules and materials with useful functions.