Noncovalent Assembly Research Articles

Noncovalent assembly of non-metallic porphyrin on graphene oxide nanosheets and its application for simultaneous determination of Cu2+ and Pb2+ in real water

A newly developed electrochemical sensor for simultaneous detection of Cu2+ and Pb2+ in polluted water using the non-metallic porphyrin functioned graphene oxide (GO) by π-π noncovalent interactions is demonstrated. Introduction of 5,10,15,20-tetra(4-hydroxyphenyl)-21H, 23H-porphine (THPP) on GO nanosheets resulted in enhanced electron transfer due to the high electron mobility of GO and the excellent electron-feeding properties of THPP. Due to the synergistic effect between THPP and GO, the prepared sensors showed remarkable electrocatalytic activity for the reduction of Cu2+ and Pb2+. It exhibited two-segmentinear response over the concentration range from 5 − 300 μM and 300–––900 μM with a detection limit of 1.5 μM for Cu2+ and two-segment corresponding linear range of 5–––250 μM and 250–––900 μM with a detection limit of 1.6 μM for Pb2+. In addition, the proposed sensor has excellent anti-interference ability for some common cations and anions. The technique can be used successfully for simultaneously detection of residual Cu2+ and Pb2+ in real water, thus demonstrating its high utility for conventional sensing applications in real environments.

Solvent dependency of catalyst-substrate aggregation through π-πstacking in photoredox catalysis.

Assemblies of photoredox catalysts and their target substrates prior to photoexcitation is a phenomenon na\"ively overlooked by the majority of synthetic chemists, but can have profound influences on reactivity and selectivity in photocatalytic reactions. In this study, we determine the aggregation states of triarylamine radical cationic photocatalysts with various target arene substrates in different solvents by specifically parameterized polarizable molecular dynamics simulations. A $\pi$-stacking interaction previously implicated by more expensive, less-representative quantum calculations is confirmed. Critically, this study presents new insights on: i) the ability of solvents (MeCN vs DMF) to make or break a photocatalytic reaction by promoting (MeCN) or demoting (DMF) its catalyst-substrate assemblies, which is a determining factor for reactivity, ii) the average "lifetimes" of assemblies in solution from a dynamic simulation. We find that both in the ground state and photoexcited cationic radical state, the lifetimes of these assemblies all molecules remain relatively in tact for relatively large time periods, often higher than 60 ps, making them ideal to undergo reactions upon photoexcitation. Such aspects have not addressed by previous studies on synthetic photocatalytic reactions involving non-covalent assemblies.

Non-Covalent Assembly of Multiple Fluorophores in Edible Protein/Lipid Hydrogels for Applications in Multi-Step Light Harvesting and White-Light Emission.

The design and production of biodegradable and sustainable non-toxic materials for solar-energy harvesting and conversion is a significant challenge. Here, our goal was to report the preparation of novel protein/lipid hydrogels and demonstrate their utility in two orthogonal fundamental studies-light harvesting and white-light emission. Our hydrogels contained up to 90% water, while also being self-standing and injectable with a syringe. In one application, we loaded these hydrogels with suitable organic donor-acceptor dyes and demonstrated the energy-transfer cascade among four different dyes, with the most red-emitting dye as the energy destination. We hypothesized that the dyes were embedded in the protein/lipid phase away from the water pools as monomeric entities and that the excitation of any of the four dyes resulted in intense emission from the lowest-energy acceptor. In contrast to the energy-transfer cascade, we demonstrate the use of these gels to form a white-light-emitting hydrogel dye assembly, in which excitation migration is severely constrained. By restricting the dye-to-dye energy transfer, the blue, green, and red dyes emit at their respective wavelengths, thereby producing the composite white-light emission. The CIE color coordinates of the emission were 0.336 and 0.339-nearly pure white-light emission. Thus, two related studies with opposite requirements could be accommodated in the same hydrogel, which was made from edible ingredients by a simple method. These gels are biodegradable when released into the environment, sustainable, and may be of interest for energy applications.

Orbitrap-Based Mass and Charge Analysis of Single Molecules.

Native mass spectrometry is nowadays widely used for determining the mass of intact proteins and their noncovalent biomolecular assemblies. While this technology performs well in the mass determination of monodisperse protein assemblies, more real-life heterogeneous protein complexes can pose a significant challenge. Factors such as co-occurring stoichiometries, subcomplexes, and/or post-translational modifications, may especially hamper mass analysis by obfuscating the charge state inferencing that is fundamental to the technique. Moreover, these mass analyses typically require measurement of several million molecules to generate an analyzable mass spectrum, limiting its sensitivity. In 2012, we introduced an Orbitrap-based mass analyzer with extended mass range (EMR) and demonstrated that it could be used to obtain not only high-resolution mass spectra of large protein macromolecular assemblies, but we also showed that single ions generated from these assemblies provided sufficient image current to induce a measurable charge-related signal. Based on these observations, we and others further optimized the experimental conditions necessary for single ion measurements, which led in 2020 to the introduction of single-molecule Orbitrap-based charge detection mass spectrometry (Orbitrap-based CDMS). The introduction of these single molecule approaches has led to the fruition of various innovative lines of research. For example, tracking the behavior of individual macromolecular ions inside the Orbitrap mass analyzer provides unique, fundamental insights into mechanisms of ion dephasing and demonstrated the (astonishingly high) stability of high mass ions. Such fundamental information will help to further optimize the Orbitrap mass analyzer. As another example, the circumvention of traditional charge state inferencing enables Orbitrap-based CDMS to extract mass information from even extremely heterogeneous proteins and protein assemblies (e.g., glycoprotein assemblies, cargo-containing nanoparticles) via single molecule detection, reaching beyond the capabilities of earlier approaches. We so far demonstrated the power of Orbitrap-based CDMS applied to a variety of fascinating systems, assessing for instance the cargo load of recombinant AAV-based gene delivery vectors, the buildup of immune-complexes involved in complement activation, and quite accurate masses of highly glycosylated proteins, such as the SARS-CoV-2 spike trimer proteins. With such widespread applications, the next objective is to make Orbitrap-based CDMS more mainstream, whereby we still will seek to further advance the boundaries in sensitivity and mass resolving power.

Genetic Fusion of Thermoresponsive Polypeptides with UCST-type Behavior Mediates 1D Assembly of Coiled-Coil Bundlemers.

Thermoresponsive resilin-like polypeptides (RLPs) of various lengths were genetically fused to two different computationally designed coiled coil-forming peptides with distinct thermal stability, to develop new strategies to assemble coiled coil peptides via temperature-triggered phase separation of the RLP units. Their successful production in bacterial expression hosts was verified via gel electrophoresis, mass spectrometry, and amino acid analysis. Circular dichroism (CD) spectroscopy, ultraviolet-visible (UV/Vis) turbidimetry, and dynamic light scattering (DLS) measurements confirmed the stability of the coiled coils and showed that the thermosensitive phase behavior of the RLPs was preserved in the genetically fused hybrid polypeptides. Cryogenic-transmission electron microscopy and coarse-grained modeling revealed that functionalizing the coiled coils with thermoresponsive RLPs leads to their thermally triggered noncovalent assembly into nanofibrillar assemblies.

Genetic Fusion of Thermoresponsive Polypeptides with UCST‐type Behavior Mediates 1D Assembly of Coiled‐Coil Bundlemers

AbstractThermoresponsive resilin‐like polypeptides (RLPs) of various lengths were genetically fused to two different computationally designed coiled coil‐forming peptides with distinct thermal stability, to develop new strategies to assemble coiled coil peptides via temperature‐triggered phase separation of the RLP units. Their successful production in bacterial expression hosts was verified via gel electrophoresis, mass spectrometry, and amino acid analysis. Circular dichroism (CD) spectroscopy, ultraviolet‐visible (UV/Vis) turbidimetry, and dynamic light scattering (DLS) measurements confirmed the stability of the coiled coils and showed that the thermosensitive phase behavior of the RLPs was preserved in the genetically fused hybrid polypeptides. Cryogenic‐transmission electron microscopy and coarse‐grained modeling revealed that functionalizing the coiled coils with thermoresponsive RLPs leads to their thermally triggered noncovalent assembly into nanofibrillar assemblies.

A pillar[5]arene noncovalent assembly boosts a full-color lanthanide supramolecular light switch.

A photo-responsive full-color lanthanide supramolecular switch was constructed from a synthetic 2,6-pyridine dicarboxylic acid (DPA)-modified pillar[5]arene (H) complexing with lanthanide ion (Ln3+ = Tb3+ and Eu3+) and dicationic diarylethene derivative (G1) through a noncovalent supramolecular assembly. Benefiting from the strong complexation between DPA and Ln3+ with a 3 : 1 stoichiometric ratio, the supramolecular complex H/Ln3+ presented an emerging lanthanide emission in the aqueous and organic phase. Subsequently, a network supramolecular polymer was formed by H/Ln3+ further encapsulating dicationic G1via the hydrophobic cavity of pillar[5]arene, which greatly contributed to the increased emission intensity and lifetime, and also resulted in the formation of a lanthanide supramolecular light switch. Moreover, full-color luminescence, especially white light emission, was achieved in aqueous (CIE: 0.31, 0.32) and dichloromethane (CIE: 0.31, 0.33) solutions by the adjustment of different ratios of Tb3+ and Eu3+. Notably, the photo-reversible luminescence properties of the assembly were tuned via alternant UV/vis light irradiation due to the conformation-dependent photochromic energy transfer between the lanthanide and the open/closed-ring of diarylethene. Ultimately, the prepared lanthanide supramolecular switch was successfully applied to anti-counterfeiting through the use of intelligent multicolored writing inks, and presents new opportunities for the design of advanced stimuli-responsive on-demand color tuning with lanthanide luminescent materials.

A hydrogen-bonded organic framework of rigidly branched fluorophore: guest-adaptive cavity and phase-dependent light emission

A non-covalent assembly of a highly branched molecule produces porous crystals supported only by weak interactions. This flexible network shows reversible morphological changes and displays fluorescence responses to external stimuli and guest uptake.

Covalent post-assembly modification of π-conjugated supramolecular polymers delivers structurally robust light-harvesting nanoscale objects.

A two-component stapling strategy is used to covalently tether a new class of water-soluble supramolecular polymers built from bay-functionalized perylene bisimide (PBI) units. By leveraging a novel combined strategy where excitonic coupling and fluorescence data are exploited as spectroscopic reporters, structural design principles are established to form light-harvesting superstructures whose ground-state electronic properties are not sensitive to solvation environments. Moreover, we interrogate the structural properties of stapled superstructures by capitalizing on the drastic changes in fluorescence quantum yields against parent supramolecular assemblies. In essence, our work shows that the combination of excitonic coupling measurements and photoluminescence experiments delineates a more accurate understanding of the design principles required to limit the degree of structural defects and magnify short- and long-range electronic couplings between redox-active units in this new class of solvated nanoscale objects. These results highlight that the fragile conformation of non-covalent assemblies, which are regulated by weak secondary interactions, can be preserved by post-assembly modification of preformed supramolecular polymers. These synthetic and spectroscopic principles can in turn be codified as experimental handles to parameterize the optoelectronic properties of light-harvesting nanoscale objects.

Combinatorial non-covalent assembly of graphene oxide and chromophores into hybrid nanofilms for organic electronics

Functionally different 2D hybrids were assembled by using the same starting set of components comprising graphene oxide, perylene chromophore, polydiacetylene surfactant and divalent ions to modulate the properties of resulting systems.

Unraveling the mechanism of the supramolecular self-assembly during the in vivo metabolism of geniposide from Chinese medicine

Unraveling the detailed mechanism of Chinese medicine in curing diseases is of vital importance for the development of such long-standing traditional medicine. Here, we investigated the exposed form in vivo and bioactivity of Chinese medicine from an aspect of supramolecular chemistry. We demonstrated that the genipin (GP), an aglycone of geniposide (GE) transformed by β-glucosidase, can react with methylamine (MA), a harmful metabolite in the gut, to produce gardenia blue in vivo, which leads to a significant decrease of MA. The gardenia blue is supramolecular assemblies (SA), which can alleviate the interference with intestinal bacteria. Moreover, the formation mechanism of SA was revealed, in which genimethylamine reacted from GP and MA, was covalently polymerized into dimers and then non-covalently self-assembled into the SA. This study provides evidence that the supramolecular pigments can be formed in vivo during the metabolism of Chinese medicine through simultaneously covalent and non-covalent assembly, which may play key roles in their pharmacological activity.

Atomistic Pictures of Self-Assembled Helical Peptide Nanofibers.

Spontaneous self-assembly of peptides has been at the forefront of supramolecular chemistry and materials science research over the last two decades. Despite the wealth of information on the morphology of the assembled objects, atomic resolution details of molecular arrangements inside them are largely unknown. In this paper, we investigated non-covalent assemblies of zwitterionic l-phenylalanine tripeptides in water using all-atom explicit-solvent molecular dynamics computer simulations. Our studies produced atomistic pictures of spontaneously assembled nanofibers composed of hundreds of peptide molecules. The dimensions of the nanofibers varied from 10 to 18 nm, with irregular helical twists along the long axes. Previously published experimental data, acquired under similar conditions, provided direct validation of the fibrous morphology and indirect support for the non-trivial helicity observed in our simulations. Quantitative analyses of peptide-water and peptide-peptide interactions revealed heterogeneous local environments of molecules across the nanometer length scales. The combination of electrostatic, hydrogen bonding, van der Waals, and hydrophobic interactions, adopted by a single molecule, was dependent on its relative position inside the fiber. Despite the presence of three hydrophobic phenyl groups, very few molecules were found to be completely shielded from the surrounding water, indicating a subtle role of the hydrophobic effect. Limited conformational flexibility of the tripeptide, along with bare electrostatic interactions, appeared to play a crucial role in the emergence of fibrous morphology of the nanostructures. Our analyses led us to formulate plausible qualitative explanations of the assembly behavior in terms of thermodynamic driving forces and kinetic considerations. We established a clear relationship between details of chemical interactions operating within few molecules and characteristics of the self-assembled states at much longer length scales.

Noncovalent Enzyme Nanogels via a Photocleavable Linkage.

Enzyme nanogels (ENGs) offer a convenient method to protect therapeutic proteins from in vivo stressors. Current methodologies to prepare ENGs rely on either covalent modification of surface residues or the noncovalent assembly of monomers at the protein surface. In this study, we report a new method for the preparation of noncovalent ENGs that utilizes a heterobifunctional, photocleavable monomer as a hybrid approach. Initial covalent modification with this monomer established a polymerizable handle at the protein surface, followed by radical polymerization with poly(ethylene glycol) methacrylate monomer and ethylene glycol dimethacrylate crosslinker in solution. Final photoirradiation cleaved the linkage between the polymer and protein to afford the noncovalent ENGs. The enzyme phenylalanine ammonia lyase (PAL) was utilized as a model protein yielding well-defined nanogels 80 nm in size by dynamic light scattering (DLS) and 76 nm by atomic force microscopy. The stability of PAL after exposure to trypsin or low pH was assessed and was found to be more stable in the noncovalent nanogel compared to PAL alone. This approach may be useful for the stabilization of active enzymes.

Noncovalent minimal assembly of exogenous histamine with hemin cofactor as a peroxidase-mimicking cooperative catalyst

SummaryBy mimicking the synergistic interplay of primary and secondary coordination spheres within native peroxidases, we demonstrate a scaffold-free, yet highly effective molecular-level cooperation between an iron(III)-containing hemin cofactor and exogenous histamine in accelerating a peroxidase-like reaction. Density functional theory computations predict that, among structurally similar molecules, the histamine is the most interactive partner of hemin to elicit a spontaneous peroxidation by electrostatically attracting the proton of hydrogen peroxide to its own imidazole and thermodynamically stabilizing a transition-state intermediate. Although the molecular weight of hemin-histamine pair is 763, 1.7% of the horseradish peroxidase, cooperative catalysis of two natural molecules exhibits 17.3 times greater catalytic efficiency (17.93 M−1s−1) and 57.8 times larger specific activity (36.45 μmol/min·mg) than the hemin alone (1.04 M−1s−1 and 0.63 μmol/min·mg). Despite no scaffold or covalent linkage, the self-assembly with hemin is highly histamine-specific in complex environments, leading rapid color changes by substrate oxidation within 10 s.

Different phosphoric triamide [HN]3-nP(O)[N]n (n = 1, 2) skeletons lead to identical non-covalent interactions assemblies: X-ray crystallography investigation, Hirshfeld surface analysis and molecular docking study against SARS-CoV-2

In this work, we describe the crystal structures of two new phosphoramides containing the same [(3-Cl)C6H4NH]P(O) = Y segment (Y[N(CH3)CH2C6H5]2 (1) and Y[NC4H8O]2 (2)) and an improved model of [C6H11(CH3)N]P(O)[NHC(CH3)3]2 (compound 3). The structures are experimentally investigated by single crystal X-ray diffraction using two types of refinements with spherical (S) and aspherical (AS) [Hirshfeld atomic refinements (HARs)] form factors, FT-IR and 1H, 13C, 31P NMR spectroscopy. A biological molecular docking investigation gives hints to suggest an appropriate inhibitory activity against MPro of SARS-COV-2 (6M03 and 6LU7) especially for 1 with a binding energy around −6 (6M03)/−7 (6LU7) kcal/mol. In the present work, the docking simulations are carried out for the first time for three series of ligand (L)-protein (P) complexes: L (with S form)-P (6M03), L (with AS form)-P (6M03) and L (AS)-P (6M03-N, with hydrogen atoms at their theoretical neutron values), where the binding energies are approximately proved to be 0.8 kcal/mol lower for simulations with 6M03-N than those for 6M03. Moreover, the structural study illustrates that the hydrogen bond patterns of all three structures consist of one-dimensional zigzag chains formed by classical NH…O hydrogen bond interactions. Further stabilization is provided by weak interactions such as CH…Cl (for 1 and 2), Cl…π (for 1 and 2) and CH…O (for 2 and 3). Furthermore, the intermolecular interactions are analyzed by three-dimensional (3D) Hirshfeld surfaces, 2D fingerprint plots and enrichment ratios. The favored contacts identified by Hirshfeld surface analysis are H…O/O…H interactions covering the NH…O hydrogen bonds for all three structures. For 1 and 2, Cl…C/C…Cl contacts covering Cl…π interactions are recognized as the most enriched contacts.

Investigation of Dopamine Release on Self-assembled Monolayers by Scanning Electrochemical Microscopy

Dopamine, a neurotransmitter, controls many psychological and behavioral activities of the mammalian central nervous system. Over secretion of dopamine can make the body overexcited and lead to mental disorders. Whereas, less secretion can develop Parkinson’s symptoms. Therefore, achieving controlled release of dopamine plays a vital role in life sciences. In this work, two kinds of self-assembled monolayers were prepared by non-covalent and covalent assembly, respectively, to reach the function of dopamine controllable release. After characterization of the two self-assembled monolayers, the release function was well monitored and analyzed by scanning electrochemical microscopy. The result showed that ion pair effect, as well as acids and alkali, would stimulate a steady-state release of dopamine on the non-covalent monolayers. The combined effect of alkali and positive potential would stimulate a steady-state release of dopamine on the covalent monolayers. This work successfully reaches the controllable release of dopamine in vitro, and offers some reference value for this function in vivo.

Noncovalent Assembly Enabled Strong yet Tough Materials with Room-Temperature Malleability and Healability.

The manufacturing of both metals and polymer materials strongly relies on melt processing at relatively high temperatures which needs complex shaping-cooling equipment, long molding time, and considerable energy consumption. Reducing the processing temperature to achieve room-temperature malleability is heavily desired for low-carbon demands but continues to be a great challenge. Here, we demonstrate a noncovalent assembly strategy to fabricate room-temperature malleable composites embedded by liquid metals with excellent toughness (105.88 MJ m-3, higher than most traditional plastics and metallic aluminum) and strong mechanical strength (35.49 MPa). The dissociation-reconstruction of supramolecular bonding interactions between assembled nanoparticles and polymer matrix allow the malleable composite with two interchangeable supramolecular states to achieve programming at room temperature stimulated by water vapor and give it self-healing ability (self-healing efficiency of ∼100%; the healed sample can lift about 52,300 times its own weight). Furthermore, the composite also exhibits metallic luster and prospective application in thermal dissipation. This strategy might be an efficient way for the development of a method for strong and tough materials structurally designed to achieve programming at moderate conditions.

Noncovalent Assembly and Catalytic Activity of Hybrid Materials Based on Pd Complexes Adsorbed on Multiwalled Carbon Nanotubes, Graphene, and Graphene Nanoplatelets.

Green catalysts with excellent performance in Cu-free Sonogashira coupling reactions can be prepared by the supramolecular decoration of graphene surfaces with Pd(II) complexes. Here we report the synthesis, characterization, and catalytic properties of new catalysts obtained by the surface decoration of multiwalled carbon nanotubes (MWCNTs), graphene (G), and graphene nanoplatelets (GNPTs) with Pd(II) complexes of tetraaza-macrocyclic ligands bearing one or two anchor functionalities. The decoration of these carbon surfaces takes place under environmentally friendly conditions (water, room temperature, aerobic) in two steps: (i) π–π stacking attachment of the ligand via electron-poor anchor group 6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxo-pyrimidine and (ii) Pd(II) coordination from PdCl42–. Ligands are more efficiently adsorbed on the flat surfaces of G and GNPTs than on the curved surfaces of MWCNTs. All catalysts work very efficiently under mild conditions (50 °C, aerobic, 7 h), giving a similar high yield (90% or greater) in the coupling of iodobenzene with phenylacetylene to form diphenylacetylene in one catalytic cycle, but catalysts based on G and GNPTs (especially on GNPTs) provide greater catalytic efficiency in reuse (four cycles). The study also revealed that the active centers of the ligand-Pd type decorating the support surfaces are much more efficient than the Pd(0) and PdCl42– centers sharing the same surfaces. All of the results allow a better understanding of the structural factors to be controlled in order to obtain an optimal efficiency from similar catalysts based on graphene supports.

Understanding structure–properties relationships of porphyrin linked to graphene oxide through π–π-stacking or covalent amide bonds

Two graphene oxide nanoassemblies using 5-(4-(aminophenyl)-10,15,20-triphenylporphyrin (TPPNH2) were fabricated by two synthetic methods: covalent (GO-CONHTPP) and noncovalent bonding. GO-CONHTPP was achieved through amide formation at the periphery of GO sheets and the hybrid material was fully characterized by FTIR, XPS, Raman spectroscopy, and SEM. Spectroscopic measurements together with theoretical calculations demonstrated that assembling TPPNH2 on the GO surface in DMF-H2O (1:2, v/v) via non-covalent interactions causes changes in the absorption spectra of porphyrin, as well as efficient quenching of its emission. Interestingly, covalent binding to GO does not affect notably neither the porphyrin absorption nor its fluorescence. Theoretical calculations indicates that close proximity and π–π-stacking of the porphyrin molecule with the GO sheet is possible only for the non-covalent functionalization. Femtosecond pump–probe experiments revealed that only the non-covalent assembly of TPPNH2 and GO enhances the efficiency of the photoinduced electron transfer from porphyrin to GO. In contrast to the non-covalent hybrid, the covalent GO-CONHTPP material can generate singlet oxygen with quantum yields efficiency (ΦΔ = 0.20) comparable to that of free TPPNH2 (ΦΔ = 0.26), indicating the possible use of covalent hybrid materials in photodynamic/photothermal therapy. The spectroscopic studies combined with detailed quantum-chemical analysis provide invaluable information that can guide the fabrication of hybrid materials with desired properties for specific applications.

Highly Ordered Supramolecular Assembled Networks Tailored by Bioinspired H-Bonding Confinement for Recyclable Ion-Transport Materials

Highly Ordered Supramolecular Assembled Networks Tailored by Bioinspired H-Bonding Confinement for Recyclable Ion-Transport Materials