Spin-induced electron transmission through metal-organic chiral crystals.

Metal-organic Co(II)-phenylalanine crystals were studied and were found to possess magnetic properties and long-range spin transport. Magnetic measurements confirmed that in the crystals there are antiferromagnetic interactions between Co(II) and the lattice. The metal-organic crystals (MOCs) also present the chirality-induced spin selectivity (CISS) effect at room temperature. A long-range spin polarization is observed using a magnetic conductive-probe atomic force microscope. The spin polarization is found to be in the range of 35-45%.

Single amino acid bionanozyme for environmental remediation.

Enzymes are extremely complex catalytic structures with immense biological and technological importance. Nevertheless, their widespread environmental implementation faces several challenges, including high production costs, low operational stability, and intricate recovery and reusability. Therefore, the de novo design of minimalistic biomolecular nanomaterials that can efficiently mimic the biocatalytic function (bionanozymes) and overcome the limitations of natural enzymes is a critical goal in biomolecular engineering. Here, we report an exceptionally simple yet highly active and robust single amino acid bionanozyme that can catalyze the rapid oxidation of environmentally toxic phenolic contaminates and serves as an ultrasensitive tool to detect biologically important neurotransmitters similar to the laccase enzyme. While inspired by the laccase catalytic site, the substantially simpler copper-coordinated bionanozyme is ∼5400 times more cost-effective, four orders more efficient, and 36 times more sensitive compared to the natural protein. Furthermore, the designed mimic is stable under extreme conditions (pH, ionic strength, temperature, storage time), markedly reusable for several cycles, and displays broad substrate specificity. These findings hold great promise in developing efficient bionanozymes for analytical chemistry, environmental protection, and biotechnology.

Expanding the Structural Diversity and Functional Scope of Diphenylalanine-Based Peptide Architectures by Hierarchical Coassembly.

Modulation of the structural diversity of diphenylalanine-based assemblies by molecular modification and solvent alteration has been extensively explored for bio- and nanotechnology. However, regulation of the structural transition of assemblies based on this minimal building block into tunable supramolecular nanostructures and further construction of smart supramolecular materials with multiple responsiveness are still an unmet need. Coassembly, the tactic employed by natural systems to expand the architectural space, has been rarely explored. Herein, we present a coassembly approach to investigate the morphology manipulation of assemblies formed by N-terminally capped diphenylalanine by mixing with various bipyridine derivatives through intermolecular hydrogen bonding. The coassembly-induced structural diversity is fully studied by a set of biophysical techniques and computational simulations. Moreover, multiple-responsive two-component supramolecular gels are constructed through the incorporation of functional bipyridine molecules into the coassemblies. This study not only depicts the coassembly strategy to manipulate the hierarchical nanoarchitecture and morphology transition of diphenylalanine-based assemblies by supramolecular interactions but also promotes the rational design and development of smart hydrogel-based biomaterials responsive to various external stimuli.

On-off transition and ultrafast decay of amino acid luminescence driven by modulation of supramolecular packing.

Luminescence of biomolecules in the visible range of the spectrum has been experimentally observed upon aggregation, contrary to their monomeric state. However, the physical basis for this phenomenon is still elusive. Here, we systematically examine all coded amino acids to provide non-biased empirical insights. Several amino acids, including non-aromatic, show intense visible luminescence. Lysine crystals display the highest signal, whereas the very chemically similar non-coded ornithine does not, implying a role for molecular packing rather than the chemical characteristics. Furthermore, cysteine shows luminescence that is indeed crystal packing dependent as repeated rearrangements between two crystal structures result in a reversible on-off optical transition. In addition, ultrafast lifetime decay is experimentally validated, corroborating a recently raised hypothesis regarding the governing role of nπ∗ states in the emission formation. Collectively, our study supports that electronic interactions between non-fluorescent, non-absorbing molecules at the monomeric state may result in reversible optically active states by the formation of supramolecular fluorophores.

Self-Assembled Peptide Nano-Superstructure towards Enzyme Mimicking Hydrolysis.

The structural arrangement of amino acid residues in native enzymes underlies their remarkable catalytic properties, thus providing a notable point of reference for designing potent yet simple biomimetic catalysts. Herein, we describe a minimalistic approach to construct a dipeptide-based nano-superstructure with enzyme-like activity. The self-assembled biocatalyst comprises one peptide as a single building block, readily synthesized from histidine. Through coordination with zinc ion, the peptide self-assembly procedure allows the formation of supramolecular ß-sheet ordered nanocrystals, which can be used as basic units to further construct higher-order superstructure. As a result, remarkable hydrolysis activity and enduring stability are demonstrated. Our work exemplifies the use of a bioinspired supramolecular assembly approach to develop next-generation biocatalysts for biotechnological applications.

Long-Range Spin-Selective Transport in Chiral Metal-Organic Crystals with Temperature-Activated Magnetization.

Room-temperature, long-range (300 nm), chirality-induced spin-selective electron conduction is found in chiral metal-organic Cu(II) phenylalanine crystals, using magnetic conductive-probe atomic force microscopy. These crystals are found to be also weakly ferromagnetic and ferroelectric. Notably, the observed ferromagnetism is thermally activated, so that the crystals are antiferromagnetic at low temperatures and become ferromagnetic above ∼50 K. Electron paramagnetic resonance measurements and density functional theory calculations suggest that these unusual magnetic properties result from indirect exchange interaction of the Cu(II) ions through the chiral lattice.

Coassembly-Induced Transformation of Dipeptide Amyloid-Like Structures into Stimuli-Responsive Supramolecular Materials.

Conformational transition of proteins and peptides into highly stable, ß-sheet-rich structures is observed in many amyloid-associated neurodegenerative disorders, yet the precise mechanism of amyloid formation at the molecular level remains poorly understood due to the complex molecular structures. Short peptides provide simplified models for studying the molecular basis of the assembly mechanism that governs ß-sheet fibrillation processes underlying the formation and inhibition of amyloid-like structures. Herein, we report a supramolecular coassembly strategy for the inhibition and transformation of stable ß-sheet-rich amyloid-derived dipeptide self-assemblies into adaptable secondary structural fibrillar assemblies by mixing with bipyridine derivatives. The interplay between the type and mixing ratio of bipyridine derivatives allowed the variable coassembly process with stimuli-responsive functional properties, studied by various experimental characterizations and computational methods. Furthermore, the resulting coassemblies showed functional redox- and photoresponsive properties, making them promising candidates for controllable drug release and fluorescent imprint. This work presents a coassembly strategy not only to explore the mechanism of amyloid-like structure formation and inhibition at the molecular level but also to manipulate amyloid-like structures into responsive supramolecular coassemblies for material science and biotechnology applications.

Enhanced Fluorescence for Bioassembly by Environment-Switching Doping of Metal Ions.

The self-assembly of cyclodipeptides composed of natural aromatic amino acids into supramolecular structures of diverse morphologies with intrinsic emissions in the visible light region is demonstrated. The assembly process can be halted at the initial oligomerization by coordination with zinc ions, with the most prominent effect observed for cyclo-dihistidine (cyclo-HH). This process is mediated by attracting and pulling of the metal ions from the solvent into the peptide environment, rather than by direct interaction in the solvent as commonly accepted, thus forming an "environment-switching" doping mechanism. The doping induces a change of cyclo-HH molecular configurations and leads to the formation of pseudo "core/shell" clusters, comprising peptides and zinc ions organized in ordered conformations partially surrounded by relatively amorphous layers, thus significantly enhancing the emissions and allowing the application of the assemblies for ecofriendly color-converted light emitting diodes. These findings shed light into the very initial coordination procedure and elucidate an alternative mechanism of metal ions doping on biomolecules, thus presenting a promising avenue for integration of the bioorganic world and the optoelectronic field.

Nanomechanical Properties and Phase Behavior of Phenylalanine Amyloid Ribbon Assemblies and Amorphous Self-Healing Hydrogels.

Phenylalanine was the minimalistic and first of numerous nonproteinaceous building blocks to be demonstrated to form amyloid-like fibrils. This unexpected organization of such a simple building block into canonical architecture, which was previously observed only with proteins and peptides, has numerous implications for medicine and supramolecular chemistry. However, the morphology of phenylalanine fibrils and their mechanical properties was never characterized in solutions. Here, using electron and atomic force microscopy, we analyze the morphological and mechanical properties of phenylalanine fibrils in both air and fluids. The fibrils demonstrate an exceptionally high Young's modulus (up to 30 GPa) and are found to be composed of intertwined protofilaments in a helical or twisted ribbon morphology. In addition, X-ray scattering experiments provide convincing evidence of an amyloidal cross-ß-like secondary structure within the nanoassemblies. Furthermore, increasing the phenylalanine concentration results in the formation of highly homogenous, noncrystalline, self-healing hydrogels that display storage and loss moduli significantly higher than similar noncovalently cross-linked biomolecular nanofibrillar scaffolds. These remarkably stiff nanofibrillar hydrogels can be harnessed for various technological and biomedical applications, such as self-healing, printable, structural, load-bearing 3D scaffolds. The properties of this simple but quite remarkable hydrogel open a possibility to utilize it in the biomaterial industry.

Self-Assembly of Cyclic Dipeptides: Platforms for Functional Materials.

Supramolecular self-assembled functional materials comprised of cyclic dipeptide building blocks have excellent prospects for biotechnology applications due to their exceptional structural rigidity, morphological flexibility, ease of preparation and modification. Although the pharmacological uses of many natural cyclic dipeptides have been studied in detail, relatively little is reported on the engineering of these supramolecular architectures for the fabrication of functional materials. In this review, we discuss the progress in the design, synthesis, and characterization of cyclic dipeptide supramolecular nanomaterials over the past few decades, highlighting applications in biotechnology and optoelectronics engineering.

Stable and optoelectronic dipeptide assemblies for power harvesting.

Low biocompatibility or engineerability of conventional inorganic materials limits their extensive application for power harvesting in biological systems or at bio-machine interfaces. In contrast, intrinsically biocompatible peptide self-assemblies have shown promising potential as a new type of ideal components for eco-friendly optoelectronic energy-harvesting devices. However, the structural instability, weak mechanical strength, and inefficient optical or electrical properties severely impede their extensive application. Here, we demonstrate tryptophan-based aromatic dipeptide supramolecular structures to be direct wide-gap semiconductors. The molecular packings can be effectively modulated by changing the peptide sequence. The extensive and directional hydrogen bonding and aromatic interactions endow the structures with unique rigidity and thermal stability, as well as a wide-spectrum photoluminescence covering nearly the entire visible region, optical waveguiding, temperature/irradiation-dependent conductivity, and the ability to sustain quite high external electric fields. Furthermore, the assemblies display high piezoelectric properties, with a measured open-circuit voltage of up to 1.4 V. Our work provides insights into using aromatic short peptide self-assemblies for the fabrication of biocompatible, miniaturized electronics for power generation with tailored semiconducting optoelectronic properties and improved structural stability.

Non-proteinaceous hydrolase comprised of a phenylalanine metallo-supramolecular amyloid-like structure.

Enzymatic activity is crucial for various technological applications, yet the complex structures and limited stability of enzymes often hinder their use. Hence, de novo design of robust biocatalysts that are much simpler than their natural counterparts and possess enhanced catalytic activity has long been a goal in biotechnology. Here, we present evidence for the ability of a single amino acid to self-assemble into a potent and stable catalytic structural entity. Spontaneously, phenylalanine (F) molecules coordinate with zinc ions to form a robust, layered, supramolecular amyloid-like ordered architecture (F-Zn(ii)) and exhibit remarkable carbonic anhydrase-like catalytic activity. Notably, amongst the reported artificial biomolecular hydrolases, F-Zn(ii) displays the lowest molecular mass and highest catalytic efficiency, in addition to reusability, thermal stability, substrate specificity, stereoselectivity and rapid catalytic CO2 hydration ability. Thus, this report provides a rational path towards future de novo design of minimalistic biocatalysts for biotechnological and industrial applications.

l-Dopa and dopamine conjugated naphthalenediimides modulate amyloid ß toxicity.

The process of protein misfolding and aggregation to form neurotoxic species is strongly implicated in most of the neurodegenerative disorders. In particular, amyloid beta (Aß) misfolding and aggregation is central to pathophysiological processes of Alzheimer's disease. The development of aggregation modulators has enormous implications in the discovery of effective therapeutic agents for Alzheimer's disease. Herein, we report the design and synthesis of a series of natural amino acid, l-dopa and dopamine appended derivatives of naphthalenediimide (NDI) to identify efficient aggregation modulators. Furthermore, the molecular docking studies revealed the possible binding sites and binding mode of NDI-conjugates to Aß aggregates. Among the designed NDI-conjugates, l-dopa and dopamine derivatives (NLD and NDP, respectively) showed excellent aggregation modulation efficiency (inhibition and dissolution), as shown by the thioflavin T (ThT) binding assays, dot blot analysis and in cellulo studies. The docking results from in silico studies are in good agreement with the experimental data. In addition to their significant modulation efficiency towards Aß aggregation, NLD and NDP possess antioxidant activity conducive to the development of disease-modifying therapeutic agents for the treatment of Alzheimer's disease.

Quantum confined peptide assemblies with tunable visible to near-infrared spectral range.

Quantum confined materials have been extensively studied for photoluminescent applications. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio-imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for these nanostructures, and their utilization for in vivo imaging and as phosphors for light-emitting diodes is demonstrated. The data reveal that the morphologies and optical properties of the aromatic cyclo-dipeptide self-assemblies can be tuned, making them potential candidates for supramolecular quantum confined materials providing biocompatible alternatives for broad biomedical and opto-electric applications.

Minimalistic peptide supramolecular co-assembly: expanding the conformational space for nanotechnology.

Molecular self-assembly is a ubiquitous process in nature and central to bottom-up nanotechnology. In particular, the organization of peptide building blocks into ordered supramolecular structures has gained much interest due to the unique properties of the products, including biocompatibility, chemical and structural diversity, robustness and ease of large-scale synthesis. In addition, peptides, as short as dipeptides, contain all the molecular information needed to spontaneously form well-ordered structures at both the nano- and the micro-scale. Therefore, peptide supramolecular assembly has been effectively utilized to produce novel materials with tailored properties for various applications in the fields of material science, engineering, medicine, and biology. To further expand the conformational space of peptide assemblies in terms of structural and functional complexity, multicomponent (two or more) peptide supramolecular co-assembly has recently evolved as a promising extended approach, similar to the structural diversity of natural sequence-defined biopolymers (proteins) as well as of synthetic covalent co-polymers. The use of this methodology was recently demonstrated in various applications, such as nanostructure physical dimension control, the creation of non-canonical complex topologies, mechanical strength modulation, the design of light harvesting soft materials, fabrication of electrically conducting devices, induced fluorescence, enzymatic catalysis and tissue engineering. In light of these significant advancements in the field of peptide supramolecular co-assembly in the last few years, in this tutorial review, we provide an updated overview and future prospects of this emerging subject.

Bicomponent ß-sheet assembly of dipeptide fluorophores of opposite polarity and sensitive detection of nitro-explosives.

Fluorescent hydrogels of two dipeptide-pyrene amphiphiles of opposite polarity are developed via bicomponent antiparallel ß-sheet co-assembly. The helical molecular assembly resulted in the formation of fluorescent nanofibers. The sandwich-like interaction of nitroaromatics within the hydrogel matrix enabled selective and sensitive detection of toxic nitro-explosives.

SERS and fluorescence-based ultrasensitive detection of mercury in water.

The development of reliable and ultrasensitive detection marker for mercury ions (Hg2+) in drinking water is of great interest for toxicology assessment, environmental protection and human health. Although many Hg2+ detection methods have been developed, only few offer sensitivities below 1pM. Herein, we describe a simple histidine (H) conjugated perylene diimide (PDI) bolaamphiphile (HPH) as a dual-responsive optical marker to develop highly selective and sensitive probe as visible (sol-to-gel transformation), fluorescence and SERS-based Hg2+sensor platform in the water. Remarkably, HPH as a SERS marker supported on Au deposited monodispersed nanospheres monolayers (Au-MNM) of polystyrene offers an unprecedented selectivity and the best ever reported detection limit (LOD) of 60 attomolar (aM, 0.01 parts-per-quadrillion (ppq)) for Hg2+ in water. This is ten orders of magnitude lower than the United States Environmental Protection Agency (USEPA) tolerance limit of Hg2+ in drinking water (10nM, 2 ppb). This simple and effective design principle of host-guest interactions driven fluorescence and SERS-based detection may inspire the future molecular engineering strategies for the development of ultrasensitive toxic analyte sensor platforms.

Self-assembling peptide semiconductors.

Semiconductors are central to the modern electronics and optics industries. Conventional semiconductive materials bear inherent limitations, especially in emerging fields such as interfacing with biological systems and bottom-up fabrication. A promising candidate for bioinspired and durable nanoscale semiconductors is the family of self-assembled nanostructures comprising short peptides. The highly ordered and directional intermolecular π-π interactions and hydrogen-bonding network allow the formation of quantum confined structures within the peptide self-assemblies, thus decreasing the band gaps of the superstructures into semiconductor regions. As a result of the diverse architectures and ease of modification of peptide self-assemblies, their semiconductivity can be readily tuned, doped, and functionalized. Therefore, this family of electroactive supramolecular materials may bridge the gap between the inorganic semiconductor world and biological systems.