Folding-Controlled Assembly of Ortho-Phenylene-Based Macrocycles

2020 ◽  
Author(s):  
Viraj kirinda ◽  
Scott Hartley
Keyword(s):  
Self Assembly ◽  
Structural Control ◽  
Structural Changes ◽  
Condensation Product ◽  
Gel Permeation Chromatography ◽  
Emergent Behavior ◽  
Order Structure ◽  
High Level ◽  
Alkoxy Groups ◽  
Energy Surfaces

The self-assembly of foldamers into macrocycles is a simple approach to non-biological higher-order structure. Previous work on the co-assembly of ortho-phenylene foldamers with rod-shaped linkers has shown that folding and self-assembly affect each other; that is, the combination leads to new emergent behavior, such as access to otherwise unfavorable folding states. To this point this relationship has been passive. Here, we demonstrate control of self-assembly by manipulating the foldamers’ conformational energy surfaces. A series of o-phenylene decamers and octamers have been assembled into macrocycles using imine condensation. Product distributions were analyzed by gel-permeation chromatography and molecular geometries extracted from a combination of NMR spectroscopy and computational chemistry. The assembly of o-phenylene decamers functionalized with alkoxy groups or hydrogens gives both [2+2] and [3+3] macrocycles. The mixture results from a subtle balance of entropic and enthalpic effects in these systems: the smaller [2+2] macrocycles are entropically favored but require the oligomer to misfold, whereas a perfectly folded decamer fits well within the larger [3+3] macrocycle that is entropically disfavored. Changing the substituents to fluoro groups, however, shifts assembly quantitatively to the [3+3] macrocycle products, even though the structural changes are well-removed from the functional groups directly participating in bond formation. The electron-withdrawing groups favor folding in these systems by strengthening arene–arene stacking interactions, increasing the enthalpic penalty to misfolding. The architectural changes are substantial even though the chemical perturbation is small: analogous o-phenylene octamers do not fit within macrocycles when perfectly folded, and quantitatively misfold to give small macrocycles regardless of substitution. Taken together, these results represent both a high level of structural control in structurally complex foldamer systems and the demonstration of large-amplitude structural changes as a consequence of a small structural effects.

Folding-Controlled Assembly of Ortho-Phenylene-Based Macrocycles

2020 ◽  
Author(s):  
Viraj kirinda ◽  
Scott Hartley
Keyword(s):  
Self Assembly ◽  
Structural Control ◽  
Structural Changes ◽  
Condensation Product ◽  
Gel Permeation Chromatography ◽  
Emergent Behavior ◽  
Order Structure ◽  
High Level ◽  
Alkoxy Groups ◽  
Energy Surfaces

The self-assembly of foldamers into macrocycles is a simple approach to non-biological higher-order structure. Previous work on the co-assembly of ortho-phenylene foldamers with rod-shaped linkers has shown that folding and self-assembly affect each other; that is, the combination leads to new emergent behavior, such as access to otherwise unfavorable folding states. To this point this relationship has been passive. Here, we demonstrate control of self-assembly by manipulating the foldamers’ conformational energy surfaces. A series of o-phenylene decamers and octamers have been assembled into macrocycles using imine condensation. Product distributions were analyzed by gel-permeation chromatography and molecular geometries extracted from a combination of NMR spectroscopy and computational chemistry. The assembly of o-phenylene decamers functionalized with alkoxy groups or hydrogens gives both [2+2] and [3+3] macrocycles. The mixture results from a subtle balance of entropic and enthalpic effects in these systems: the smaller [2+2] macrocycles are entropically favored but require the oligomer to misfold, whereas a perfectly folded decamer fits well within the larger [3+3] macrocycle that is entropically disfavored. Changing the substituents to fluoro groups, however, shifts assembly quantitatively to the [3+3] macrocycle products, even though the structural changes are well-removed from the functional groups directly participating in bond formation. The electron-withdrawing groups favor folding in these systems by strengthening arene–arene stacking interactions, increasing the enthalpic penalty to misfolding. The architectural changes are substantial even though the chemical perturbation is small: analogous o-phenylene octamers do not fit within macrocycles when perfectly folded, and quantitatively misfold to give small macrocycles regardless of substitution. Taken together, these results represent both a high level of structural control in structurally complex foldamer systems and the demonstration of large-amplitude structural changes as a consequence of a small structural effects.

Biomimetic materials: An introduction

1992 ◽  
Vol 50 (2) ◽  
pp. 1020-1021 ◽  
Author(s):  
M. Sarikaya ◽  
J. T. Staley ◽  
I. A. Aksay
Keyword(s):  
Self Assembly ◽  
Structural Control ◽  
Hierarchical Structures ◽  
Ceramic Composites ◽  
Advanced Materials ◽  
Length Scale ◽  
Spider Webs ◽  
Biomimetic Materials ◽  
Synthetic Materials ◽  
All Ceramic

Biomimetics is an area of research in which the analysis of structures and functions of natural materials provide a source of inspiration for design and processing concepts for novel synthetic materials. Through biomimetics, it may be possible to establish structural control on a continuous length scale, resulting in superior structures able to withstand the requirements placed upon advanced materials. It is well recognized that biological systems efficiently produce complex and hierarchical structures on the molecular, micrometer, and macro scales with unique properties, and with greater structural control than is possible with synthetic materials. The dynamism of these systems allows the collection and transport of constituents; the nucleation, configuration, and growth of new structures by self-assembly; and the repair and replacement of old and damaged components. These materials include all-organic components such as spider webs and insect cuticles (Fig. 1); inorganic-organic composites, such as seashells (Fig. 2) and bones; all-ceramic composites, such as sea urchin teeth, spines, and other skeletal units (Fig. 3); and inorganic ultrafine magnetic and semiconducting particles produced by bacteria and algae, respectively (Fig. 4).

THE IMPACT OF UKRAINE'S EXCISE DUTY POLICY ON THE TRANSFORMATION PROCESSES OF THE TOBACCO MARKET

2020 ◽  
Vol 2020 (10) ◽  
pp. 19-33
Author(s):  
Nadiia NOVYTSKA ◽  
◽  
Inna KHLIEBNIKOVA ◽  
Keyword(s):  
Structural Changes ◽  
Tax Avoidance ◽  
Transformation Process ◽  
State Regulation ◽  
Tobacco Products ◽  
Excise Duty ◽  
Increasing Demand ◽  
High Level ◽  
The Impact ◽  
Transformation Processes

The market of tobacco products in Ukraine is one of the most dynamic and competitive. It develops under the influence of certain factors that cause structural changes, therefore, the aim of the article is to conduct a comprehensive analysis of transformation processes in the market of tobacco and their alternatives in Ukraine and identify the factors that cause them. The high level of tax burden and the proliferation of alternative products with a potentially lower risk to human health, including heating tobacco products and e-cigarettes, are key factors in the market’s transformation process. Their presence leads to an increase in illicit turnover of tobacco products, which accounts for 6.37% of the market, and the gradual replacement of cigarettes with alternative products, which account for 12.95%. The presence on the market of products that are not taxed or taxed at lower rates is one of the reasons for the reduction of excise duty revenues. According to the results of 2019, the planned indicators of revenues were not met by 23.5%. Other reasons for non-fulfillment of excise duty revenues include: declining dynamics of the tobacco products market; reduction in the number of smokers; reorientation of «cheap whites» cigarette flows from Ukraine to neighboring countries; tax avoidance. Prospects for further research are identified, namely the need to develop measures for state regulation and optimization of excise duty taxation of tobacco products and their alternatives, taking into account the risks to public health and increasing demand of illegal products.

Cooperative Self-Assembly of Pyridine-2,6-Diimine-Linked Macrocycles into Mechanically Robust Nanotubes

2019 ◽  
Author(s):  
Michael J. Strauss ◽  
Darya Asheghali ◽  
Austin Evans ◽  
Rebecca Li ◽  
Anton Chavez ◽  
...  
Keyword(s):  
Aspect Ratio ◽  
High Aspect Ratio ◽  
Self Assembly ◽  
Gel Permeation Chromatography ◽  
Synthetic Polymers ◽  
Young’S Moduli ◽  
Structural Rigidity ◽  
Assembly Mechanism ◽  
Low Dimensionality ◽  
Harsh Conditions

<p>Nanotubes assembled from macrocyclic precursors offer a unique combination of low dimensionality, structural rigidity, and distinct interior and exterior microenvironments. Usually the weak stacking energies of macrocycles limit the length or strength of the resultant nanotubes. Imine-linked macrocycles were recently found to assemble into high-aspect ratio (>10<sup>3</sup>), lyotropic nanotubes in the presence of excess acid. Yet these harsh conditions are incompatible with many functional groups and processing methods, and lower acid loadings instead catalyze macrocycle degradation. Here we report pyridine-2,6-diimine-linked macrocycles that assemble into high-aspect ratio nanotubes in the presence of less than 1 equiv of CF<sub>3</sub>CO<sub>2</sub>H per macrocycle. Analysis by gel permeation chromatography and fluorescence spectroscopy revealed a cooperative self-assembly mechanism. Nanofibers obtained by touch-spinning the pyridinium-based nanotubes exhibit Young’s moduli of 1.48 GPa, which exceeds that of many synthetic polymers and biological filaments. These findings will enable the design of structurally diverse nanotubes from synthetically accessible macrocycles. </p>

scholarly journals Computational Methods for Structure-to-Function Analysis of Diet-Derived Catechins-Mediated Targeting of In Vitro Vasculogenic Mimicry

2021 ◽  
Vol 20 ◽  
pp. 117693512110092
Author(s):  
Abicumaran Uthamacumaran ◽  
Narjara Gonzalez Suarez ◽  
Abdoulaye Baniré Diallo ◽  
Borhane Annabi
Keyword(s):  
Machine Learning ◽  
Cancer Cells ◽  
Structural Changes ◽  
Function Analysis ◽  
Vasculogenic Mimicry ◽  
Machine Learning Algorithms ◽  
Emergent Behavior ◽  
Molecular Signature ◽  
Ovarian Cancer Cells

Background: Vasculogenic mimicry (VM) is an adaptive biological phenomenon wherein cancer cells spontaneously self-organize into 3-dimensional (3D) branching network structures. This emergent behavior is considered central in promoting an invasive, metastatic, and therapy resistance molecular signature to cancer cells. The quantitative analysis of such complex phenotypic systems could require the use of computational approaches including machine learning algorithms originating from complexity science. Procedures: In vitro 3D VM was performed with SKOV3 and ES2 ovarian cancer cells cultured on Matrigel. Diet-derived catechins disruption of VM was monitored at 24 hours with pictures taken with an inverted microscope. Three computational algorithms for complex feature extraction relevant for 3D VM, including 2D wavelet analysis, fractal dimension, and percolation clustering scores were assessed coupled with machine learning classifiers. Results: These algorithms demonstrated the structure-to-function galloyl moiety impact on VM for each of the gallated catechin tested, and shown applicable in quantifying the drug-mediated structural changes in VM processes. Conclusions: Our study provides evidence of how appropriate 3D VM compression and feature extractors coupled with classification/regression methods could be efficient to study in vitro drug-induced perturbation of complex processes. Such approaches could be exploited in the development and characterization of drugs targeting VM.

Synthesis of poly(methyl methacrylate)-b-poly(acrylic acid) by DPE method

e-Polymers ◽  
2008 ◽  
Vol 8 (1) ◽  
Author(s):  
Dong Chen ◽  
Ruixue Liu ◽  
Zhifeng Fu ◽  
Yan Shi
Keyword(s):  
Molecular Weight ◽  
Acrylic Acid ◽  
Methyl Methacrylate ◽  
Diblock Copolymer ◽  
Self Assembly ◽  
Gel Permeation Chromatography ◽  
Amphiphilic Diblock Copolymer ◽  
Poly Methyl Methacrylate ◽  
Copolymer Poly ◽  
Poly Acrylic Acid

AbstractAmphiphilic diblock copolymer poly(methyl methacrylate)-b-poly(acrylic acid) (PMMA-b-PAA) was prepared by 1,1-diphenylethene (DPE) method. Firstly, free radical polymerization of methyl methacrylate was carried out with AIBN as initiator in the presence of DPE, giving a DPE-containing PMMA precursor with controlled molecular weight. tert-Butyl acrylate (tBA) was then polymerized in the presence of the PMMA precursor, and PMMA-b-PtBA diblock copolymer with controlled molecular weight was prepared. Finally, amphiphilic diblock copolymer PMMA-b-PAA was obtained by hydrolysis of PMMA-b-PtBA. The formation of PMMA-b-PAA was confirmed by 1H NMR spectrum and gel permeation chromatography. Transmission electron microscopy and dynamic light scattering were used to detect the self-assembly behavior of the amphiphilic diblock polymers in methanol.

scholarly journals Structural control of fibrin bioactivity by mechanical deformation

2020 ◽  
Author(s):  
Sachin Kumar ◽  
Yujen Wang ◽  
Manuel K. Rausch ◽  
Sapun H. Parekh
Keyword(s):  
Biological Activity ◽  
Conformational Changes ◽  
Structural Control ◽  
Structural Changes ◽  
Tensile Deformation ◽  
Mechanical Strain ◽  
Fibrous Protein ◽  
Binding Partners ◽  
Blood Clots ◽  
Β Sheet

AbstractFibrin is a fibrous protein network that entraps blood cells and platelets to form blood clots following vascular injury. As a biomaterial, fibrin acts a biochemical scaffold as well as a viscoelastic patch that resists mechanical insults. The biomechanics and biochemistry of fibrin have been well characterized independently, showing that fibrin is a hierarchical material with numerous binding partners. However, comparatively little is known about how fibrin biomechanics and biochemistry are coupled: how does fibrin deformation influence its biochemistry at the molecular level? In this study, we show how mechanically-induced molecular structural changes in fibrin affect fibrin biochemistry and fibrin-platelet interaction. We found that tensile deformation of fibrin lead to molecular structural transitions of α-helices to β-sheets, which reduced binding of tissue plasminogen activator (tPA), an enzyme that initiates fibrinolysis, at the network and single fiber level. Moreover, binding of tPA and Thioflavin T (ThT), a commonly used β-sheet marker, was primarily mutually exclusive such that tPA bound to native (helical) fibrin whereas ThT bound to strained fibrin. Finally, we demonstrate that conformational changes in fibrin suppressed the biological activity of platelets on mechanically strained fibrin due to attenuated αIIbβ3 integrin binding. Our work shows that mechanical strain regulates fibrin molecular structure and fibrin biological activity in an elegant mechano-chemical feedback loop, which likely influences fibrinolysis and wound healing kinetics.

scholarly journals Structural control for the coordinated assembly into functional pathogenic type-3 secretion systems

2019 ◽  
Author(s):  
Nikolaus Goessweiner-Mohr ◽  
Vadim Kotov ◽  
Matthias J. Brunner ◽  
Julia Mayr ◽  
Jiri Wald ◽  
...  
Keyword(s):  
Self Assembly ◽  
Structural Control ◽  
Helical Structure ◽  
Structural Basis ◽  
Protein Chain ◽  
Assembly Process ◽  
Secretion Systems ◽  
Ring Assembly ◽  
Serovar Typhimurium ◽  
Type 3

AbstractFunctional injectisomes of the type-3 secretion system assemble into highly defined and stoichiometric bacterial molecular machines essential for infecting human and other eukaryotic cells. However, the mechanism that governs the regulated step-wise assembly process from the nucleation-phase, to ring-assembly, and the filamentous phase into a membrane embedded needle complex is unclear. We here report that the formation of a megadalton-sized needle complexes from Salmonella enterica serovar Typhimurium (SPI-1, Salmonella pathogenicity island-1) with proper stoichiometries is highly structurally controlled competing against the self-assembly propensity of injectisome components, leading to a highly unusual structurally-pleiotropic phenotype. The structure of the entire needle complex from pathogenic injectisomes was solved by cryo electron microscopy, focused refinements (2.5-4 Å) and co-variation analysis revealing an overall asymmetric arrangement containing cyclic, helical, and asymmetric sub-structures. The centrally located export apparatus assembles into a conical, pseudo-helical structure and provides a structural template that guides the formation of a 24-mer cyclic, surrounding ring, which then serves as a docking interface comprising three different conformations for sixteen N-terminal InvG subunits of the outer secretin ring. Unexpectedly, the secretin ring excludes the 16th protein chain at the C-terminal outer ring, resulting in a pleiotropic 16/15-mer ring and consequently to an overall 24:16/15 basal body structure. Finally, we report how the transition from the pseudo-helical export apparatus into the helical filament is structurally resolved to generate the protein secretion channel, which provides the structural basis to restrict access of unfolded effector substrates. These results highlight the diverse molecular signatures required for a highly coordinated assembly process and provide the molecular basis for understanding triggering and transport of unfolded proteins through injectisomes.

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