Nanoarchitectonics beyond Self‐Assembly: Challenges to Create Bio‐Like Hierarchic Organization

Incorporation of non‐equilibrium actions in the sequence of self‐assembly processes would be an effective means to establish bio‐like high functionality hierarchical assemblies. As a novel methodology beyond self‐assembly, nanoarchitectonics, which has as its aim the fabrication of functional materials systems from nanoscopic units through the methodological fusion of nanotechnology with other scientific disciplines including organic synthesis, supramolecular chemistry, microfabrication, and bio‐process, has been applied to this strategy. The application of non‐equilibrium factors to conventional self‐assembly processes is discussed on the basis of examples of directed assembly, Langmuir–Blodgett assembly, and layer‐by‐layer assembly. In particular, examples of the fabrication of hierarchical functional structures using bio‐active components such as proteins or by the combination of bio‐components and two‐dimensional nanomaterials, are described. Methodologies described in this review article highlight possible approaches using the nanoarchitectonics concept beyond self‐assembly for creation of bio‐like higher functionalities and hierarchical structural organization.     

Pigmentation Chemistry and Radical‐Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage

Alkaptonuria (AKU) is a rare disease characterized by high levels of homogentisic acid (HGA); patients suffer from tissue ochronosis: dark brown pigmentation, especially of joint cartilage, leading to severe early osteoarthropathy. No molecular mechanism links elevated HGA to ochronosis; the pigment's chemical identity is still not known, nor how it induces joint cartilage degradation. Here we give key insight on HGA‐derived pigment composition and collagen disruption in AKU cartilage. Synthetic pigment and pigmented human cartilage tissue both showed hydroquinone‐resembling NMR signals. EPR spectroscopy showed that the synthetic pigment contains radicals. Moreover, we observed intrastrand disruption of collagen triple helix in pigmented AKU human cartilage, and in cartilage from patients with osteoarthritis. We propose that collagen degradation can occur via transient glycyl radicals, the formation of which is enhanced in AKU due to the redox environment generated by pigmentation.     

De Novo Construction of Catenanes with Dissymmetric Cages by Space‐Discriminative Post‐Assembly Modification

Considerable efforts have been made to increase the topological complexity of mechanically interlocked molecules over the years. Three‐dimensional catenated structures composed of two or several (usually symmetrical) cages are one representative example. However, owing to the lack of an efficient universal synthetic strategy, interlocked structures made up of dissymmetric cages are relatively rare. Since the space volume of the inner cavity of an interlocked structure is smaller than that outside it, we developed a novel synthetic approach with the voluminous reductant NaBH(OAc)₃ that discriminates this space difference, and therefore selectively reduces the outer surface of a catenated dimer composed of two symmetric cages, thus yielding the corresponding catenane with dissymmetric cages. Insight into the template effect that facilitates the catenation of cages was provided by computational and experimental techniques.     

Controllable Si−C Bond Activation Enables Stereocontrol in the Palladium‐Catalyzed [4+2] Annulation of Cyclopropenes with Benzosilacyclobutanes

A novel and unusual palladium‐catalyzed [4+2] annulation of cyclopropenes with benzosilacyclobutanes is reported. This reaction occurred through chemoselective Si?C(sp²) bond activation in synergy with ring expansion/insertion of cyclopropenes to form new C(sp²)?C(sp³) and Si?C(sp³) bonds. An array of previously elusive bicyclic skeleton with high strain, silabicyclo[4.1.0]heptanes, were formed in good yields with excellent diastereoselectivity under mild conditions. An asymmetric version of the reaction with a chiral phosphoramidite ligand furnished a variety of chiral bicyclic silaheterocycle derivatives with good enantioselectivity (up to 95.5:4.5 er). Owing to the mild reaction conditions, the good stereoselectivity profile, and the ready availability of the functionalized precursors, this process constitutes a useful and straightforward strategy for the synthesis of densely functionalized silacycles.     

Electrochemical Difunctionalization of Alkenes by a Four‐Component Reaction Cascade Mumm Rearrangement: Rapid Access to Functionalized Imides

An electrochemical four‐component reaction cascade Mumm rearrangement was developed. It is a rare example of in situ generation of O‐acyl isoamides for 1,3‐(O→N) acyl transfer. Inexpensive, commercially available arylethylenes, aryl or heterocyclic acids, acetonitrile, and alcohols were used as substrates. A wide range of aryl acids and alcohols were tolerated and provided imides in satisfactory yields. Subsequent hydrolysis of imides could be utilized to synthesize valuable amides and β‐amino alcohol derivatives.     

A Hydrolytically Stable Vanadium(IV) Metal–Organic Framework with Photocatalytic Bacteriostatic Activity for Autonomous Indoor Humidity Control

Metal–organic frameworks (MOFs) with long‐term stability and reversible high water uptake properties can be ideal candidates for water harvesting and indoor humidity control. Now, a mesoporous and highly stable MOF, BIT‐66 is presented that has indoor humidity control capability and a photocatalytic bacteriostatic effect. BIT‐66 (V₃(O)₃(H₂O)(BTB)₂), possesses prominent moisture tunability in the range of 45–60 % RH and a water uptake and working capacity of 71 and 55 wt %, respectively, showing good recyclability and excellent performance in water adsorption–desorption cycles. Importantly, this MOF demonstrates a unique photocatalytic bacteriostatic behavior under visible light, which can effectively ameliorate the bacteria and/or mold breeding problem in water adsorbing materials.     

An Fe2+‐ and α‐Ketoglutarate‐Dependent Halogenase Acts on Nucleotide Substrates

While halogenated nucleosides are used as common anticancer and antiviral drugs, naturally occurring halogenated nucleosides are rare. Adechlorin (ade) is a 2′‐chloro nucleoside natural product first identified from Actinomadura sp. ATCC 39365. However, the installation of chlorine in the ade biosynthetic pathway remains elusive. Reported herein is a Fe²⁺‐α‐ketoglutarate halogenase AdeV that can install a chlorine atom at the C2′ position of 2′‐deoxyadenosine monophosphate to afford 2′‐chloro‐2′‐deoxyadenosine monophosphate. Furthermore, 2′,3′‐dideoxyadenosine‐5′‐monophosphate and 2′‐deoxyinosine‐5′‐monophosphate can also be converted, albeit 20‐fold and 2‐fold, respectively, less efficiently relative to the conversion of 2′‐deoxyadenosine monophosphate. AdeV represents the first example of a Fe²⁺‐α‐ketoglutarate‐dependent halogenase that converts nucleotides into chlorinated analogues.     

A Coordinative Dendrimer Achieves Excellent Efficiency in Cytosolic Protein and Peptide Delivery

Cytosolic protein delivery is a prerequisite for the development of protein therapeutics that act on intracellular targets. Proteins are generally membrane‐impermeable and thus need a carrier such as a polymer to facilitate their internalization. However, the efficient binding of proteins with different isoelectric points to polymeric carriers is challenging. In this study, we designed a coordinative dendrimer to solve this problem. The dendrimers modified with dipicolylamine/zinc(II) complex were capable of binding proteins through a combination of ionic and coordination interactions. The best polymer efficiently delivered 30 cargo proteins and peptides into the cytosol, while maintaining their bioactivity after intracellular release. The removal or replacement of zinc ions in the polymer with other transition‐metal ions lead to significantly decreased efficiency in cytosolic protein delivery. This study provides a new strategy to develop robust and efficient polymers for cytosolic protein delivery.