Stacking Of Monomers Research Articles

The Aggregation Units of J-Aggregates: Transitioning from Monomers to Hydrogen-Bonded Dimers.

In recent years, J-aggregates, as supramolecular assembly structures, have increasingly attracted scientific interest. Currently, the prevailing consensus is that J-aggregates are formed through the interleaved stacking of monomers arranged in parallel. However, our findings suggest that the fundamental units constituting J-aggregates are not limited to monomers alone but also encompass molecular aggregates interconnected by noncovalent bonds, which we designate as aggregation units. We have synthesized three asymmetric pyrrolopyrrole cyanine (PPCy) dyes capable of forming hydrogen-bonded dimers and have verified that these hydrogen-bonded dimers can serve as aggregation units to generate J-aggregates. The detailed structural and optical properties revealed that the J-aggregates of these dyes exhibited a significantly red-shifted and narrowed emission in the near-infrared (NIR) fluorescence compared to the monomers.

Photostimuli Reach a Selective Intermediate in a Microflow: One‐Shot Transformation from a Supramolecular Co‐Polymer to a Micro‐Disk Structure

AbstractIn supramolecular chemistry, photostimulants are generally combined with a static solution under thermodynamic equilibrium with no time progression. After reaching the thermodynamic state, self‐assembly events contain various species–a mixture of component molecules, intermediate species, and completed assemblies–which light reaches uniformly. In this study, snapshot control of supramolecular polymerization was first combined with pinpoint photoirradiation using a microflow system. Employing the azobenzene derivative trans‐C3NO as a monomer, a snapshot moment of supramolecular polymerization along a microflow channel was selectively irradiated with UV light at 365 nm in a space‐resolved manner, so that the monomers, intermediates (oligomers), or extended supramolecular polymers were selectively exposed to light stimuli. We found that a pinpoint photostimulus to each snapshot moment had a pronounced effect on the kinetic pathway by tuning the timing at which the snapshot moment of cis‐C3NO was generated. Upon irradiation in the upstream region, in the very early stages before initiating polymerization, supramolecular polymerization was suppressed by generating a less reactive cis‐C3NO monomer. However, photoirradiation does not affect the supramolecular polymers in the downstream region because of their stiff nature. Remarkably, when irradiating the middle stream region involving a soft‐natured intermediate species, supramolecular copolymerization occurred through in situ conversion from trans‐ and cis‐C3NO inside the primitive supramolecular polymer. Loose monomer stacking in the primitive aggregate endows it with mechanoresponsiveness. Under the influence of shear force in a Hagen–Poiseuille flow, the resultant supramolecular copolymers containing geometrically different cis‐isomers were rolled up and transformed into a micrometer‐sized disk‐like structure. During the in situ supramolecular copolymerization and transformation to the disk structure, a liquid–liquid interface generated in the laminar flow acted as a template to fix the orientation of the monomers and supramolecular polymers, leading to the uniform disk formation. Furthermore, monomers’ orientation in the aligned supramolecular polymers are fixed on the interface, on which light is always irradiated in an anisotropic manner. This results in both complexity at the molecular level and long‐range structural order such as regular rolling up at the micrometer range over the molecular scale. By incorporating the photostimulus system, microflow extends its potential for supramolecular chemistry.

Macrocyclization-induce emission enhancement characteristics of benzothiadiazole-based macrocycles: A theoretical study

We present a comprehensive investigation into the molecular structures in the ground state and the first singlet excited state, intramolecular and intermolecular interactions, as well as the emission properties of monomers, dimers and macrocycles using density functional theory and time-dependent density functional theory. Our study aims to unveil the macrocyclization-induce emission enhancement principle for benzothiadiazole-based macrocycles. Compared with the typical π-π stacking of monomers, macrocycles exhibit the tighter stacking arrangement due to the presence of strong intramolecular and intermolecular hydrogen bond interactions and the rigid triangular geometry of macrocycle, which is conducive to the enhancement of emissions efficiency. The calculated oscillator strength of macrocycles in the first excited state is much higher than that of dimers composed of two monomers. Meanwhile, the large transition electric dipole moment is beneficial for enhancing the emission efficiency. Additionally, our study reveals an emission wavelength red-shift for macrocycles after “CH”/N substitution in the acceptor moiety, and the transition mode from LUMO to HOMO can be mainly attributed to intramolecular charge transition characters from acceptor to donor fragments. Our theoretical study might provide valuable insights for the design of innovative luminescent macrocycles with high emission efficiency.

Size-Selective Phagocytic Clearance of Fibrillar α-Synuclein through Conformational Activation of Complement Receptor 4.

Aggregation of α-synuclein (αSN) is an important histological feature of Parkinson disease. Recent studies showed that the release of misfolded αSN from human and rodent neurons is relevant to the progression and spread of αSN pathology. Little is known, however, about the mechanisms responsible for clearance of extracellular αSN. This study found that human complement receptor (CR) 4 selectively bound fibrillar αSN, but not monomeric species. αSN is an abundant protein in the CNS, which potentially could overwhelm clearance of cytotoxic αSN species. The selectivity of CR4 toward binding fibrillar αSN consequently adds an important αSN receptor function for maintenance of brain homeostasis. Based on the recently solved structures of αSN fibrils and the known ligand preference of CR4, we hypothesize that the parallel monomer stacking in fibrillar αSN creates a known danger-associated molecular pattern of stretches of anionic side chains strongly bound by CR4. Conformational change in the receptor regulated tightly clearance of fibrillar αSN by human monocytes. The induced change coupled concomitantly with phagolysosome formation. Data mining of the brain transcriptome in Parkinson disease patients supported CR4 as an active αSN clearance mechanism in this disease. Our results associate an important part of the innate immune system, namely complement receptors, with the central molecular mechanisms of CNS protein aggregation in neurodegenerative disorders.

Synthesis and phase transitions of monomers carrying a biphenyleneazobenzene or an azotolane group. Precursors of photo-responsive liquid crystal polymers

Four functional methacrylate monomers, two of them carrying a biphenyleneazobenzene group, and the other two an azotolane group, were synthesized. The synthetic route involved several reactions, among which are the Suzuki-Miyaura and Sonogashira cross-coupling reactions that allowed us to prepare long rigid rodlike azobenzene cores. The chemical structure of these new azo-monomers was confirmed by proton nuclear magnetic resonance (1H NMR) spectroscopy, and the thermotropic liquid-crystalline behavior was determined from differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (XRD) analyses. The four monomers showed a mesomorphic behavior that extends over a broad temperature range. The phase transitions of the monomers carrying a biphenyleneazobenzene core were much broader and weaker than those of monomers carrying an azotolane group. Also, the former showed no crystallization in cooling to room temperature. The four studied monomers displayed liquid crystal phases with lamellar order (SmA and SmC), but only those carrying an azotolane core developed an additional nematic phase. The lamellar stacking of monomers is discussed in terms of lateral interactions between the rigid rodlike cores. Both types of monomers showed a trans to cis photo-conversion of around 90% when irradiated with UV–light. These new monomers are precursors of photo-responsive liquid crystal polymers.

Effect of H-Bonding on Order Amplification in the Growth of a Supramolecular Polymer in Water.

While a great deal of knowledge on the roles of hydrogen bonding and hydrophobicity in proteins has resulted in the creation of rationally designed and functional peptidic structures, the roles of these forces on purely synthetic supramolecular architectures in water have proven difficult to ascertain. Focusing on a 1,3,5-benzenetricarboxamide (BTA)-based supramolecular polymer, we have designed a molecular modeling strategy to dissect the energetic contributions involved in the self-assembly (electrostatic, hydrophobic, etc.) upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this set of simulations, we have unraveled the cooperative mechanism for polymer growth, where a critical size must be reached in the aggregates before emergence and amplification of order into the experimentally observed fibers. Furthermore, we have found that the formation of ordered fibers is favored over disordered aggregates solely on the basis of electrostatic interactions. Detailed analysis of the simulation data suggests that H-bonding is a major source of this stabilization energy. Experimental and computational comparison with a newly synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to form the H-bonding network, demonstrated that this BTE variant is also capable of fiber formation, albeit at a reduced persistence length. This work provides unambiguous evidence for the key 1D driving force of hydrogen bonding in enhancing the persistency of monomer stacking and amplifying the level of order into the growing supramolecular polymer in water. Our computational approach provides an important relationship directly linking the structure of the monomer to the structure and properties of the supramolecular polymer.

Structural Transitions of Membrane-Bound Chiral Biopolymers

In vivo, structural biopolymers such as MreB, FtsZ and eukaryotic homologs such as F-actin can exist in a membrane bound state where they assist in and regulate many important cellular functions including cell division and cell wall growth and maintenance. Here we show that the interplay between the chirality of a filament, its elasticity and membrane interactions can have non-trivial consequences for the conformations that it can adopt, thus directly affecting its functional role. We study a continuum model that describes a filament that is bound to an attractive cylindrical (rigid) membrane which extends our analysis for filaments bound to flat substrates (ref-2012). In the model we explicitly treat the natural preferred twist that is inherent in most biopolymers due to monomer stacking and assume that binding domains along the filament follow this natural twist forming a sticky attractive helix. We also introduce two elastic parameters allowing for the mechanical compliance of the filament, where filament bending along the surface of cylinder is modeled as a Worm-Like Chain (WLC) that couples to the curvature of the cylinder, and elastic twist deformation along the axis of the filament. We find, for certain parameter regimes, there exists a transition from an absorbed straight filament to a mechanically stable conformation where a helix is preferred. We also find there are periodic surface bound discommensurate stable solutions for both of the bending and twist degrees of freedom, where filament conformations are described by the well studied Frenkel-Kontorova dynamics for absorbed atomic lattices. Our results provide insight into the relation between a filament's molecular properties and its macroscopic conformation in a functional context.

Synthesis of Polydiacetylenes with Pyridyl Groups Directly Bound to the Main Chain

N-Substituted carbamic acid esters of 8-pyridyl-5,7-octadiyn-1-ol were synthesized and all the monomers showed solid-state polymerizabilities by UV irradiation to give polydiacetylenes with pyridyl groups directly bound to the π-conjugated backbone. Hydrogen-bond complexes of these monomers with dodecanoic acid (DA) or perfluorododecanoic acid (PFDA), in which the pyridyl nitrogen atom formed a hydrogen bond with the hydrogen atom of the carboxyl group, were also prepared. Although complex formability of DA with the monomers in this study was not so high, many PFDA complexes were obtained because of the higher acidity. All complexes could be polymerized in the solid state and the conversion increased by complexation compared with the original monomers. More favorable monomer stacking for solid-state polymerization could be achieved by combination of intermolecular hydrogen bonds between urethane groups and alkyl (or perfluoroalkyl) chain packing.

Malaria Parasite Actin Polymerization and Filament Structure

A novel form of acto-myosin regulation has been proposed in which polymerization of new actin filaments regulates motility of parasites of the apicomplexan class of protozoa. In vivo and in vitro parasite F-actin is very short and unstable, but the structural basis and details of filament dynamics remain unknown. Here, we show that long actin filaments can be obtained by polymerizing unlabeled rabbit skeletal actin (RS-actin) onto both ends of the short rhodamine-phalloidin-stabilized Plasmodium falciparum actin I (Pf-actin) filaments. Following annealing, hybrid filaments of micron length and "zebra-striped" appearance are observed by fluorescence microscopy that are stable enough to move over myosin class II motors in a gliding filament assay. Using negative stain electron microscopy we find that pure Pf-actin stabilized by jasplakinolide (JAS) also forms long filaments, indistinguishable in length from RS-actin filaments, and long enough to be characterized structurally. To compare structures in near physiological conditions in aqueous solution we imaged Pf-actin and RS-actin filaments by atomic force microscopy (AFM). We found the monomer stacking to be distinctly different for Pf-actin compared with RS-actin, such that the pitch of the double helix of Pf-actin filaments was 10% larger. Our results can be explained by a rotational angle between subunits that is larger in the parasite compared with RS-actin. Modeling of the AFM data using high-resolution actin filament models supports our interpretation of the data. The structural differences reported here may be a consequence of weaker inter- and intra-strand contacts, and may be critical for differences in filament dynamics and for regulation of parasite motility.

Association Thermodynamics and Conformational Stability of β-Sheet Amyloid β(17-42) Oligomers: Effects of E22Q (Dutch) Mutation and Charge Neutralization

Amyloid fibrils are associated with many neurodegenerative diseases. It was found that amyloidogenic oligomers, not mature fibrils, are neurotoxic agents related to these diseases. Molecular mechanisms of infectivity, pathways of aggregation, and molecular structure of these oligomers remain elusive. Here, we use all-atom molecular dynamics, molecular mechanics combined with solvation analysis by statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D-RISM-KH) in a new MM-3D-RISM-KH method to study conformational stability, and association thermodynamics of small wild-type A β 17–42 oligomers with different protonation states of Glu 22, as well the E22Q (Dutch) mutants. The association free energy of small β-sheet oligomers shows near-linear trend with the dimers being thermodynamically more stable relative to the larger constructs. The linear (within statistical uncertainty) dependence of the association free energy on complex size is a consequence of the unilateral stacking of monomers in the β-sheet oligomers. The charge reduction of the wild-type A β 17–42 oligomers upon protonation of the solvent-exposed Glu 22 at acidic conditions results in lowering the association free energy compared to the wild-type oligomers at neutral pH and the E22Q mutants. The neutralization of the peptides because of the E22Q mutation only marginally affects the association free energy, with the reduction of the direct electrostatic interactions mostly compensated by the unfavorable electrostatic solvation effects. For the wild-type oligomers at acidic conditions such compensation is not complete, and the electrostatic interactions, along with the gas-phase nonpolar energetic and the overall entropic effects, contribute to the lowering of the association free energy. The differences in the association thermodynamics between the wild-type A β 17–42 oligomers at neutral pH and the Dutch mutants, on the one hand, and the A β 17–42 oligomers with protonated Glu 22, on the other, may be explained by destabilization of the inter- and intrapeptide salt bridges between Asp 23 and Lys 28. Peculiarities in the conformational stability and the association thermodynamics for the different models of the A β 17–42 oligomers are rationalized based on the analysis of the local physical interactions and the microscopic solvation structure.

Reaction Mechanism Based on X-ray Crystal Structure Analysis during the Solid-State Polymerization of Muconic Esters

We have investigated a change in the crystal structures of di(4-alkoxybenzyl) (E,E)- and (Z,Z)-muconates during the solid-state polymerization by X-ray crystal structure analyses and have discussed a reaction mechanism for the polymerization. The solid-state polymerization is divided into a homogeneous polymerization which proceeds in the solid solution of the remaining monomer and the resulting polymer and a heterogeneous polymerization in which a crystal phase separation occurs between the monomer and polymer crystal domains during the reaction. According to the former model, the monomer crystal phase continuously changes into the polymer crystal phase without any phase separation when the slightest movement of atoms induces less strain in the crystals. The molecular dynamics of the muconates in the solid state were monitored by in situ single and powder X-ray diffraction experiments. In fact, we succeeded in the direct observation of the expanding crystal lattices and cell volume at the initial stage of polymerization, followed by subsequent shrinking in the process of the homogeneous reaction. On the other hand, a phase separation was observed during the reaction according to the heterogeneous polymerization model, in which a considerable movement of atoms is required. The monomer stacking structure determines the reaction path during the solid-state polymerization.

Stereocontrol of diene polymers by topochemical polymerization of substituted benzyl muconates and their crystallization properties

AbstractWe report the stereocontrol of diene polymers by the topochemical polymerization of alkoxy‐substituted benzyl muconates in the solid state. A monomer stacking structure is controlled by the weak intermolecular interactions in the monomer crystals, depending on the structure and position of the alkoxy‐substituent. The translational and alternating types of molecular stacking structures in a column provide diisotactic and disyndiotactic polymers, respectively, by the solid‐state polymerization under UV and γ‐ray irradiation. On the other hand, the meso and racemo structures of the resulting polymers are determined by the molecular symmetry of the used muconate monomers. The various substituted benzyl ester polymers are transformed into the same ethyl ester polymers with the four types of tacticities. The structure and crystallization behavior of the substituted benzyl ester polymers as well as the ethyl ester polymers have been revealed in detail. We clarify the effects of the tacticity on the crystallization property of the stereoregular polymuconates. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4952–4965, 2006

Polymer Crystal Engineering for Control of Stereochemical Structure of Polymers: Stereospecific Monomer Synthesis and Stereospecific Solid-State Polymerization

ABSTRACT We have successfully synthesized diisotactic and disyndiotactic polymers of (Z,Z)- and (E,E)-muconates with various benzyl ester groups. Muconic acid was conveniently converted into its corresponding ester derivatives without EZ isomerization when reacted with benzyl bromides in the presence of potassium carbonate in hexamethylphosphoramide (HMPA) at room temperature. Several monomers undergo photopolymerization in the crystalline state to give stereoregular polymers according to the monomer configuration and the ester substituents. X-ray single crystal structure analysis of the monomer and polymer crystals has revealed the process of the topochemical polymerization. In the monomer crystals with 4-alkoxybenzyl groups as the ester substituents, a columnar structure is formed by the alternate stacking of monomer molecules with the aid of weak hydrogen bonds such as CH/π and CH/O intermolecular interactions. The alternate stacking is appropriate for syndiotactic polymerization, being different from the crystal structures of many other ester monomers which provide a diisotactic polymer due to the translational monomer stacking in a column, as is seen in the crystals of the 4-chloro-, 4-bromo-, and 4-nitro-substituted benzyl esters. Weak and flexible intermolecular interactions provide a variety of crystal structures and different type of molecular stacking leading to the different tacticity of the polymers.

Human amyloid-derived aßcontains tyrosine cross-linked oligomers

Amyloid fibrils are associated with many neurodegenerative diseases. It was found that amyloidogenic oligomers, not mature fibrils, are neurotoxic agents related to these diseases. Molecular mechanisms of infectivity, pathways of aggregation, and molecular structure of these oligomers remain elusive. Here, we use all-atom molecular dynamics, molecular mechanics combined with solvation analysis by statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D-RISM-KH) in a new MM-3D-RISM-KH method to study conformational stability, and association thermodynamics of small wild-type Aβ17–42 oligomers with different protonation states of Glu22, as well the E22Q (Dutch) mutants. The association free energy of small β-sheet oligomers shows near-linear trend with the dimers being thermodynamically more stable relative to the larger constructs. The linear (within statistical uncertainty) dependence of the association free energy on complex size is a consequence of the unilateral stacking of monomers in the β-sheet oligomers. The charge reduction of the wild-type Aβ17–42 oligomers upon protonation of the solvent-exposed Glu22 at acidic conditions results in lowering the association free energy compared to the wild-type oligomers at neutral pH and the E22Q mutants. The neutralization of the peptides because of the E22Q mutation only marginally affects the association free energy, with the reduction of the direct electrostatic interactions mostly compensated by the unfavorable electrostatic solvation effects. For the wild-type oligomers at acidic conditions such compensation is not complete, and the electrostatic interactions, along with the gas-phase nonpolar energetic and the overall entropic effects, contribute to the lowering of the association free energy. The differences in the association thermodynamics between the wild-type Aβ17–42 oligomers at neutral pH and the Dutch mutants, on the one hand, and the Aβ17–42 oligomers with protonated Glu22, on the other, may be explained by destabilization of the inter- and intrapeptide salt bridges between Asp23 and Lys28. Peculiarities in the conformational stability and the association thermodynamics for the different models of the Aβ17–42 oligomers are rationalized based on the analysis of the local physical interactions and the microscopic solvation structure.