Additional Q7 binding sites drive protein aggregation in solution and statistical disorder in the crystalline biohybrid suggest new possibilities for protein-based materials.

Here, we provide the first structural characterization of host-guest complexation between cucurbit[7]uril (Q7) and dimethyllysine (KMe ) in a model protein. Binding was dominated by complete encapsulation of the dimethylammonium functional group. While selectivity for the most sterically accessible dimethyllysine was observed both in solution and in the solid state, three different modes of Q7-KMe complexation were revealed by X-ray crystallography. The crystal structures revealed also entrapped water molecules that solvated the ammonium group within the Q7 cavity. Remarkable Q7-protein assemblies, including inter-locked octahedral cages that comprise 24 protein trimers, occurred in the solid state. Cucurbituril clusters appear to be responsible for these assemblies, suggesting a strategy to generate controlled protein architectures.

Controlled protein assembly is an enabling technology, for example, in the bottom-up fabrication of biomaterials. This paper describes the assembly of a β-propeller protein using two orthogonal interaction modes. Previously, protein assembly was directed by metal coordination or macrocycle complexation. Here, we demonstrate the combination of metal coordination and macrocycle complexation for controlled assembly. An established protein−cucurbit[7]uril (Q7) assembly, which relies on trimeric Q7 clusters, was modified by the inclusion of metal-binding sites in the protein. The application of zinc−histidine coordination to tune the Q7-induced assembly resulted in metallo-bioorganic crystalline architectures. The relative arrangement of the protein−Q7 layers was reorganized by the zinc bridging ions. One structure resulted in a different type of protein−Q7 packing that involves Q7 dimers. Apparently, Q7 is a versatile molecular glue that can be combined with metal-mediated protein assembly. This dual strategy expands significantly the toolkit for engineered assembly.

The eligibility of tetraquinoxaline cavitands (QxCav) as molecular grippers relies on their unique conformational mobility between a closed (vase) and an open (kite) form, triggered in solution by conventional stimuli like pH, temperature and ion concentration. In the present paper, the mechanochemical conformational switching of ad hoc functionalized QxCav covalently embedded in an elastomeric polydimethylsiloxane and in a more rigid polyurethane matrix is investigated. The rigid polymer matrix is more effective in converting mechanical force into a conformational switch at the molecular level, provided that all four quinoxaline wings are covalently connected to the polymer.

Water-soluble, anionic calix[ n ]arenes are useful receptors for protein recognition and assembly. For example, sulfonato-calix[8]arene ( sclx 8 ) can encapsulate proteins and direct their assembly into porous frameworks. In this work, we turned our attention to an “extended arm” calixarene with 16 phenyl rings. We hypothesized that this larger receptor would have increased capacity for protein masking/encapsulation. A cocrystal structure of p -benzyl-sulfonato-calix[8]arene ( b-sclx 8 ) and cytochrome c (cyt c ) revealed a surprising assembly. A pseudorotaxane comprising a stack of three b-sclx 8 molecules threaded by polyethylene glycol (PEG) was bound to the protein. The trimeric b-sclx 8 stack, a tubelike structure with a highly charged surface, mediated assembly via a new mode of protein recognition. The calixarene stack presents four hydrophobic grooves, each of which binds to one cyt c by accommodating the N-terminal α-helix. This unprecedented binding mode suggests new possibilities for supramolecular protein chemistry.

No abstract

One approach to protein assembly involves watersoluble supramolecular receptors that act like glues. Bionanoarchitectures directed by these scaffolds are often systemspecific, with few studies investigating their customization. Herein, the modulation of cucurbituril-mediated protein assemblies through the inclusion of peptide tectons is described. Three peptides of varying length and structural order were N-terminally appended to RSL, a β-propeller building block. Each fusion protein was incorporated into crystalline architectures mediated by cucurbit[7]uril (Q7). A trimeric coiled-coil served as a spacer within a Q7-directed sheet assembly of RSL, giving rise to a layered material of varying porosity. Within the spacer layers, the coiled-coils were dynamic. This result prompted consideration of intrinsi-cally disordered peptides (IDPs) as modulatory tectons. Similar to the coiled-coil, a mussel adhesion peptide (Mefp) also acted as a spacer between protein-Q7 sheets. In contrast, the fusion of a nucleoporin peptide (Nup) to RSL did not recapitulate the sheet assembly. Instead, a Q7-directed cage was adopted, within which disordered Nup peptides were partially "captured" by Q7 receptors. IDP capture occurred by macrocycle recognition of an intrapeptide Phe-Gly motif in which the benzyl group was encapsulated by Q7. The modularity of these protein-cucurbituril architectures adds a new dimension to macrocycle-mediated protein assembly. Segregated protein crystals, with alternating layers of high and low porosity, could provide a basis for new types of materials.

Mechanochemical synthesis is an attractive preparative method that combines a green approach with versatility, efficiency, and rapidity of reaction. However, it often yields microcrystalline materials, and their small crystal size is a major hindrance to structure elucidation with conventional single-crystal or powder X-ray diffraction methods. This work presents the novel approach of combining mechanochemistry with electron diffraction techniques to elucidate the crystal structure of metal–organic compounds of zinc­(II) and copper­(II) with 2,6-pyridinedicarboxylic acid and 4,4′-bipyridine.