Metal-driven folding and assembly of a minimal ß-sheet into a 3D-porous honeycomb framework.

In contrast to short helical peptides, constrained peptides, and foldamers, the design and fabrication of crystalline 3D frameworks from the ß-sheet peptides are rare because of their high self-aggregation propensity to form 1D architectures. Herein, we demonstrate the formation of a 3D porous honeycomb framework through the silver coordination of a minimal ß-sheet forming a peptide having terminal metal coordinated 4- and 3-pyridyl ligands.

Helitwistacenes-Combining Lateral and Longitudinal Helicity Results in Solvent-Induced Inversion of Circularly Polarized Light.

Helicity is expressed differently in ortho- and para-fused acenes-helicenes and twistacenes, respectively. While the extent of helicity is constant in helicenes, it can be tuned in twistacenes, and the handedness of flexible twistacenes is often determined by more rigid helicenes. Here, we combine helicenes with rigid twistacenes consisting of a tunable degree of twisting, forming helitwistacenes. While the X-ray structures reveal that the connection does not affect the helicity of each moiety, their electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) spectra are strongly affected by the helicity of the twistacene unit, resulting in solvent-induced sign inversion. ROESY NMR and TD-DFT calculations support this observation, which is explained by differences in the relative orientation of the helicene and twistacene moieties.

Molecular Engineering of Ordered Piezoelectric Sulfonic Acid-Containing Assemblies.

Sulfonic acid-containing bioorganic monomers with wide molecular designability and abundant hydrogen bonding sites hold great potential to design diverse functional biocrystals but have so far not been explored for piezoelectric energy harvesting applications due to the lack of strategies to break the centrosymmetry of their assemblies. Here, a significant molecular packing transformation from centrosymmetric into non-centrosymmetric conformation by the addition of an amide terminus in the sulfonic acid-containing bioorganic molecule is demonstrated, allowing a high electromechanical response. The amide-functionalized molecule self-assembles into a polar supramolecular parallel ß-sheet-like structure with a high longitudinal piezoelectric coefficient d11 = 15.9 pm V-1 that produces the maximal open-circuit voltage of >1 V and the maximal power of 18 nW in nanogenerator devices pioneered. By contrast, molecules containing an amino or a cyclohexyl terminus assemble into highly symmetric 3D hydrogen bonding diamondoid-like networks or 2D double layer structures that show tunable morphologies, thermostability, and mechanical properties but non-piezoelectricity. This work not only presents a facile approach to achieving symmetry transformation of bioorganic assemblies but also demonstrates the terminal group and the property correlation for tailor-made design of high-performance piezoelectric biomaterials.

Factors Controlling Complex Morphologies of Isomorphous Metal-Organic Frameworks.

We demonstrate here how nitrate salts of bivalent copper, nickel, cobalt, and manganese, along with an achiral organic ligand, assemble into various structures such as symmetrical double-decker flowers, smooth elongated hexagonal bipyramids, and hexagonal prisms. Large morphological changes occur in these structures because of different metal cations, although they maintain isomorphous hexagonal crystallographic structures. Metal cations with stronger coordination to ligands (Cu and Ni) tend to form uniform crystals with unusual shapes, whereas weaker coordinating metal cations (Mn and Co) produce crystals with more regular hexagonal morphologies. The unusual flower-like crystals formed with copper nitrate have two pairs of six symmetrical petals with hexagonal convex centers. The texture of the petals indicates dendritic growth. Two different types of morphologies were formed by using different copper nitrate-to-ligand ratios. An excess of the metal salt results in uniform and hexagonal crystals having a narrow size distribution, whereas the use of an excess of ligand results in double-decker morphologies. Mechanistically, an intermediate structure was observed with slightly concave facets and a domed center. Such structures most likely play a key role in the formation of double-decker crystals that can be formed by fusion processes. The coordination chemistry results in isostructural chiral frameworks consisting of two types of continuous helical channels. Four pyridine units from four separate ligands are coordinated to the metal center in a plane having a chiral (propeller-type) arrangement. The individual double-decker flower crystals are homochiral and a batch consists of crystals having both handedness.

Entropically-Driven Co-assembly of l-Histidine and l-Phenylalanine to Form Supramolecular Materials.

Molecular self- and co-assembly allow the formation of diverse and well-defined supramolecular structures with notable physical properties. Among the associating molecules, amino acids are especially attractive due to their inherent biocompatibility and simplicity. The biologically active enantiomer of l-histidine (l-His) plays structural and functional roles in proteins but does not self-assemble to form discrete nanostructures. In order to expand the structural space to include l-His-containing materials, we explored the co-assembly of l-His with all aromatic amino acids, including phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp), all in both enantiomeric forms. In contrast to pristine l-His, the combination of this building block with all aromatic amino acids resulted in distinct morphologies including fibers, rods, and flake-like structures. Electrospray ionization mass spectrometry (ESI-MS) indicated the formation of supramolecular co-assemblies in all six combinations, but time-of-flight secondary-ion mass spectrometry (ToF-SIMS) indicated the best seamless co-assembly occurs between l-His and l-Phe while in the other cases, different degrees of phase separation could be observed. Indeed, isothermal titration calorimetry (ITC) suggested the highest affinity between l-His and l-Phe where the formation of co-assembled structures was driven by entropy. In accordance, among all the combinations, the co-assembly of l-His and l-Phe produced single crystals. The structure revealed the formation of a 3D network with nanocavities stabilized by hydrogen bonding between -N (l-His) and -NH (l-Phe). Taken together, using the co-assembly approach we expanded the field of amino acid nanomaterials and showed the ability to obtain discrete supramolecular nanostructures containing l-His based on its specific interactions with l-Phe.

Energy Transport in Dichroic Metallo-organic Crystals: Selective Inclusion of Spatially Resolved Arrays of Donor and Acceptor Dyes in Different Nanochannels.

In this study, the precise positioning and alignment of arrays of two different guest molecules in a crystalline host matrix has been engineered and resulted in new optically active materials. Sub-nm differences in the diameters of two types of 1D channels are sufficient for size-selective inclusion of dyes. Energy transport occurs between the arrays of different dyes that are included in parallel-positioned nanochannels by Förster resonance energy transfer (FRET). The color of individual micro-sized crystals are dependent on their relative position under polarized light. This angular-dependent behavior is a result of the geometrically constrained orientation of the dyes by the crystallographic packing of the host matrix and is concentration dependent.

Crystallographic-Morphological Connections in Star Shaped Metal-Organic Frameworks.

The symmetry of a crystal's morphology usually reflects the symmetry of the crystallographic packing. For single crystals, the space and point groups allow only a limited number of mathematical descriptions of the morphology (forms), all of which are convex polyhedrons. In contrast, concave polyhedrons are a hallmark of twinning and polycrystallinity and are typically inconsistent with single crystallinity. Here we report a new type of structure: a concave polyhedron shape single crystal having a multidomain appearance and a rare space group (P622). Despite these unusual structural features, the hexagonal symmetry is revealed at the morphological levels.

Modulating the Electromechanical Response of Bio-Inspired Amino Acid-Based Architectures through Supramolecular Co-Assembly.

Supramolecular packing dictates the physical properties of bio-inspired molecular assemblies in the solid state. Yet, modulating the stacking modes of bio-inspired supramolecular assemblies remains a challenge and the structure-property relationship is still not fully understood, which hampers the rational design of molecular structures to fabricate materials with desired properties. Herein, we present a co-assembly strategy to modulate the supramolecular packing of N-terminally capped alanine-based assemblies (Ac-Ala) by changing the amino acid chirality and mixing with a nonchiral bipyridine derivative (BPA). The co-assembly induced distinct solid-state stacking modes determined by X-ray crystallography, resulting in significantly enhanced electromechanical properties of the assembly architectures. The highest rigidity was observed after the co-assembly of racemic Ac-Ala with a bipyridine coformer (BPA/Ac-DL-Ala), which exhibited a measured Young's modulus of 38.8 GPa. Notably, BPA crystallizes in a centrosymmetric space group, a condition that is broken when co-crystallized with Ac-L-Ala and Ac-D-Ala to induce a piezoelectric response. Enantiopure co-assemblies of BPA/Ac-D-Ala and BPA/Ac-L-Ala showed density functional theory-predicted piezoelectric responses that are remarkably higher than the other assemblies due to the increased polarization of their supramolecular packing. This is the first report of a centrosymmetric-crystallizing coformer which increases the single-crystal piezoelectric response of an electrically active bio-inspired molecular assembly. The design rules that emerge from this investigation of chemically complex co-assemblies can facilitate the molecular design of high-performance functional materials comprised of bio-inspired building blocks.

Ternary host-guest complexes with rapid exchange kinetics and photoswitchable fluorescence.

Confinement within molecular cages can dramatically modify the physicochemical properties of the encapsulated guest molecules, but such host-guest complexes have mainly been studied in a static context. Combining confinement effects with fast guest exchange kinetics could pave the way toward stimuli-responsive supramolecular systems-and ultimately materials-whose desired properties could be tailored "on demand" rapidly and reversibly. Here, we demonstrate rapid guest exchange between inclusion complexes of an open-window coordination cage that can simultaneously accommodate two guest molecules. Working with two types of guests, anthracene derivatives and BODIPY dyes, we show that the former can substantially modify the optical properties of the latter upon noncovalent heterodimer formation. We also studied the light-induced covalent dimerization of encapsulated anthracenes and found large effects of confinement on reaction rates. By coupling the photodimerization with the rapid guest exchange, we developed a new way to modulate fluorescence using external irradiation.

Exploiting Minimalistic Backbone Engineered γ-Phenylalanine for the Formation of Supramolecular Co-Polymer.

Ordered supramolecular hydrogels assembled by modified aromatic amino acids often exhibit low mechanical rigidity. Aiming to stabilize the hydrogel and understand the impact of conformational freedom and hydrophobicity on the self-assembly process, two building blocks based on 9-fluorenyl-methoxycarbonyl-phenylalanine (Fmoc-Phe) gelator which contain two extra methylene units in the backbone, generating Fmoc-γPhe and Fmoc-(3-hydroxy)-γPhe are designed. Fmoc-γPhe spontaneously assembled in aqueous media forming a hydrogel with exceptional mechanical and thermal stability. Moreover, Fmoc-(3-hydroxy)-γPhe, with an extra backbone hydroxyl group decreasing its hydrophobicity while maintaining some molecular flexibility, self-assembled into a transient fibrillar hydrogel, that later formed microcrystalline aggregates through a phase transition. Molecular dynamics simulations and single crystal X-ray analyses reveal the mechanism underlying the two residues' distinct self-assembly behaviors. Finally, Fmoc-γPhe and Fmoc-(3-OH)-γPhe co-assembly to form a supramolecular hydrogel with notable mechanical properties are demonstrated. It has been believed that the understanding of the structure-assembly relationship will enable the design of new functional amino acid-based hydrogels.

Chiral Motifs in Highly Interpenetrated Metal-Organic Frameworks Formed from Achiral Tetrahedral Ligands.

Formation of highly interpenetrated frameworks is demonstrated. An interesting observation is the presence of very large adamantane-shaped cages in a single network, making these crystals new entries in the collection of diamondoid-type metal-organic frameworks (MOFs). The frameworks were constructed by assembling tetrahedral pyridine ligands and copper dichloride. Currently, the networks' degree of interpenetration is among the highest reported and increases when the size of the ligand is increased. Highly interpenetrated frameworks typically have low surface contact areas. In contrast, in our systems, the voids take up to 63 % of the unit cell volume. The MOFs have chiral features but are formed from achiral components. The chirality is manifested by the coordination chemistry around the metal center, the structure of the helicoidal channels, and the motifs of the individual networks. Channels of both handednesses are present within the unit cells. This phenomenon shapes the walls of the channels, which are composed of 10, 16, or 32 chains correlated with the degree of interpenetration 10-, 16-, and 32-fold, respectively. By changing the distance between the center of the ligand and the coordination moieties, we succeeded in tuning the diameter of the channels. Relatively large channels were formed, having diameters up to 31.0 Å×14.8 Å.

Atomic insight into short helical peptide comprised of consecutive multiple aromatic residues.

The occurrence of sequential multiple aromatic residues in a helical sequence is rare compared to the ß-sheet rich structure. Here, using helix promoting α-aminoisobutyric acid (Aib) residues, we unravel atomistic details of the helical secondary structure formation and the super helical assembly of two heptapeptides composed of sequential five and six phenylalanine (Phe) residues.

Directing the Morphology, Packing, and Properties of Chiral Metal-Organic Frameworks by Cation Exchange.

We show that metal-organic frameworks, based on tetrahedral pyridyl ligands, can be used as a morphological and structural template to form a series of isostructural crystals having different metal ions and properties. An iterative crystal-to-crystal conversion has been demonstrated by consecutive cation exchanges. The primary manganese-based crystals are characterized by an uncommon space group (P622). The packing includes chiral channels that can mediate the cation exchange, as indicated by energy-dispersive X-ray spectroscopy on microtome-sectioned crystals. The observed cation exchange is in excellent agreement with the Irving-Williams series (MnZn) associated with the relative stability of the resulting coordination nodes. Furthermore, we demonstrate how the metal cation controls the optical and magnetic properties. The crystals maintain their morphology, allowing a quantitative comparison of their properties at both the ensemble and single-crystal level.

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.

Co-Assembly Induced Solid-State Stacking Transformation in Amino Acid-Based Crystals with Enhanced Physical Properties.

The physical characteristics of supramolecular assemblies composed of small building blocks are dictated by molecular packing patterns in the solid-state. Yet, the structure-property correlation is still not fully understood. Herein, we report the unexpected cofacial to herringbone stacking transformation of a small aromatic bipyridine through co-assembly with acetylated glutamic acid. The unique solid-state structural transformation results in enhanced physical properties of the supramolecular organizations. The co-assembly methodology was further expanded to obtain diverse molecular packings by different bipyridine and acetylated amino acid derivatives. This study presents a feasible co-assembly approach to achieve the solid-state stacking transformation of supramolecular organization and opens up new opportunities to further explore the relationship between molecular arrangement and properties of supramolecular assemblies by crystal engineering.

Coexistence of 1 : 1 and 2 : 1 inclusion complexes of indigo carmine.

We show that the optical properties of indigo carmine can be modulated by encapsulation within a coordination cage. Depending on the host/guest molar ratio, the cage can predominantly encapsulate either one or two dye molecules. The 1 : 1 complex is fluorescent, unique for an indigo dye in an aqueous solution. We have also found that binding two dye molecules stabilizes a previously unknown conformation of the cage.

Guest Molecule-Mediated Energy Harvesting in a Conformationally Sensitive Peptide-Metal Organic Framework.

The apparent piezoelectricity of biological materials is not yet fully understood at the molecular level. In particular, dynamic noncovalent interactions, such as host-guest binding, are not included in the classical piezoelectric model, which limits the rational design of eco-friendly piezoelectric supramolecular materials. Here, inspired by the conformation-dependent mechanoresponse of the Piezo channel proteins, we show that guest-host interactions can amplify the electromechanical response of a conformationally mobile peptide metal-organic framework (MOF) based on the endogenous carnosine dipeptide, demonstrating a new type of adaptive piezoelectric supramolecular material. Density functional theory (DFT) predictions validated by piezoresponse force microscopy (PFM) measurements show that directional alignment of the guest molecules in the host carnosine-zinc peptide MOF channel determines the macroscopic electromechanical properties. We produce stable, robust 1.4 V open-circuit voltage under applied force of 25 N with a frequency of 0.1 Hz. Our findings demonstrate that the regulation of host-guest interactions could serve as an efficient method for engineering sustainable peptide-based power generators.

Inhibitor-Mediated Structural Transition in a Minimal Amyloid Model.

Despite the fundamental clinical importance of amyloid fibril formation, its mechanism is still enigmatic. Crystallography of minimal amyloid models was a milestone in the understanding of the architecture and biological activities of amyloid fibers. However, the crystal structure of ultimate dipeptide-based amyloids is not yet reported. Herein, we present the crystal structure of a typical amyloid-forming minimal dipeptide, Ac-Phe-Phe-NH2 (Ac-FF-NH2 ), showing a canonical ß-sheet structure at the atomic level. The simplicity of the structure helped in investigating amyloid-inhibition using crystallography, never previously reported for larger peptide models. Interestingly, in the presence of an inhibitor, the supramolecular packing of Ac-FF-NH2 molecules rearranged into a supramolecular 2-fold helix (21 helix). This study promotes our understanding of the mechanism of amyloid formation and of the structural transitions that occur during the inhibition process in a most fundamental model.

Ring Size Determines the Conformation, Global Aromaticity and Photophysical Properties of Macrocyclic Oligofurans.

In π-conjugated macrocycles, there is a trade-off between the global and local expression of effects such as aromaticity, with the outcome of the trade-off determined by the geometry and aromaticity of the constituent units. Compared with other aromatic rings, the aromatic character of furan is relatively small, and therefore global effects in macrocyclic furans are expected to be more pronounced. Following our introduction of macrocyclic oligofuran, we present the first synthesis of a series of π-conjugated bifuran macrocycles of various ring sizes, from trimer to hexamer, and characterize them using both computational and experimental methods. The properties of macrocyclic oligofurans change considerably with size: The smaller trimer is rigid, weakly emissive and planar as revealed by its single crystal structure, and displays global antiaromaticity. In contrast, the larger pentamer and hexamer are flexible, emissive, have non-planar structures, and exhibit local aromaticity. The results are supported by NICS and ACID calculations that indicate the global antiaromaticity of planar furan macrocycles, and by transient absorption measurements showing sharp absorption band for the trimer and only the internal conversion decay pathway.

Pathway-Dependent Coordination Networks: Crystals versus Films.

We demonstrate the formation of both metallo-organic crystals and nanoscale films that have entirely different compositions and structures despite using the same set of starting materials. This difference is the result of an unexpected cation exchange process. The reaction of an iron polypyridyl complex with a copper salt by diffusion of one solution into another resulted in iron-to-copper exchange, concurrent ligand rearrangement, and the formation of metal-organic frameworks (MOFs). This observation shows that polypyridyl complexes can be used as expendable precursors for the growth of MOFs. In contrast, alternative depositions of the iron polypyridyl complex with a copper salt by automated spin coating on conductive metal oxides resulted in the formation of electrochromic coatings, and the structure and redox properties of the iron complex were retained. The possibility to form such different networks from the same set of molecular building blocks by "in solution" versus "on surface" coordination chemistry broadens the synthetic space to design functional materials.