Jing Sun

Non‐enzymatic RNA Copying: Enhanced non‐enzymatic ligation allows the rapid copying of long RNA template and short RNA splinted templates, thus suggesting a potential route to the assembly of artificial systems capable of evolution.

Abstract

The non‐enzymatic replication of the primordial genetic material is thought to have enabled the evolution of early forms of RNA‐based life. However, the replication of oligonucleotides long enough to encode catalytic functions is problematic due to the low efficiency of template copying with mononucleotides. We show that template‐directed ligation can assemble long RNAs from shorter oligonucleotides, which would be easier to replicate. The rate of ligation can be greatly enhanced by employing a 3′‐amino group at the 3′‐end of each oligonucleotide, in combination with an N‐alkyl imidazole organocatalyst. These modifications enable the copying of RNA templates by the multistep ligation of tetranucleotide building blocks, as well as the assembly of long oligonucleotides using short splint oligonucleotides. We also demonstrate the formation of long oligonucleotides inside model prebiotic vesicles, which suggests a potential route to the assembly of artificial cells capable of evolution.

A macrocyclic dinuclear Pd^II complex was developed as a novel doubly threaded [3]rotaxane scaffold and applied as a rotaxane cross‐linker. Radical polymerization of vinyl monomers in the presence of the cross‐linker afforded rotaxane cross‐linked polymers (RCPs). The RCPs demonstrated better swelling and stretching abilities compared with the corresponding covalent cross‐linked polymers.

Abstract

A dinuclear Pd^II complex possessing a cyclic ligand was developed as a novel doubly threaded [3]rotaxane scaffold and applied as a rotaxane cross‐linker reagent. The dinuclear complex (PdMC)₂ was prepared by one‐step macrocyclization followed by the double palladation reaction. ¹H NMR analysis and UV/Vis measurements revealed the formation of a doubly threaded pseudo[3]rotaxane by the complexation of (PdMC)₂ with 2 equivalents of 2,6‐disubstituted pyridine 3 through double metal coordination. The treatment of (PdMC)₂ with 2 equivalents of 4‐vinylpyridine (VP) afforded a doubly threaded [3]rotaxane cross‐linker (PdMC‐VP)₂ . Radical co‐polymerization of VP and t‐butylstyrene in the presence of (PdMC‐VP)₂ afforded a stable rotaxane cross‐linked polymer (RCP). An elastic RCP was also prepared by using n‐butyl acrylate as a monomer. The obtained RCPs exhibited higher swelling ability and higher mechanical toughness compared with the corresponding covalent cross‐linked polymers.

Information is encrypted into a secret code with imidazolium‐functionalized diacetylene secret inks that respond to heat as well as polarization. The secret code can be deciphered by wearing polaroid glasses and holding a burning torch.

Abstract

The development of smart inks that change color and transparency in response to external stimuli is very important for various fields, from modern art to safety and anticounterfeiting technology. A uniaxially oriented diacetylene thin film on a macroscopic area is obtained by coating, self‐assembling and topochemical photopolymerizing of imidazolium‐functionalized diacetylenes (M‐DA and T‐DA) and 4,6‐decadiyne ink (70 wt%:20 wt%:10 wt%) exhibiting a lyotropic smectic A liquid‐crystalline phase at room temperature. The color and transparency of letters and symbols written with the DA‐based secret inks change reversibly from blue to red as well as from colorless transparent to black opaque depending on the temperature and polarization axis. A secret code written with thermoresponsive and polarization‐dependent secret inks consisting of imidazolium‐functionalized diacetylenes is successfully deciphered by wearing polaroid glasses and holding a burning torch.

An exosome‐mimetic vesicle with reversible fusion and fission behaviors that can be controlled by a redox process was fabricated. This vesicle underwent a fusion process upon oxidation, while a fission process proceeded when reduced.

Abstract

The fusion and fission behaviors of exosomes are essential for the cell‐to‐cell communication. Developing exosome‐mimetic vesicles with such behaviors is of vital importance, but still remains a big challenge. Presented herein is an artificial supramolecular vesicle that exhibits redox‐modulated reversible fusion‐fission functions. These vesicles tend to fuse together and form large‐sized vesicles upon oxidation, undergo a fission process and then return to small‐sized vesicles through reduction. Noteworthy, the aggregation‐induced emission (AIE) characteristics of the supramolecular building blocks enable the molecular configuration during vesicular transformation to be monitored by fluorescence technology. Moreover, the presented vesicles are excellent nanocarrier candidates to transfer siRNA into cancer cells.

Nucleoside analogs are commonly used in the treatment of cancer and viral infections. Their syntheses benefit from decades of research but are often protracted, unamenable to diversification, and reliant on a limited pool of chiral carbohydrate starting materials. We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted acetaldehydes are fluorinated and then directly engaged in enantioselective aldol reactions in a one-pot reaction. A subsequent intramolecular fluoride displacement reaction provides a functionalized nucleoside analog. The versatility of this process is highlighted in multigram syntheses of d- or l-nucleoside analogs, locked nucleic acids, iminonucleosides, and C2'- and C4'-modified nucleoside analogs. This de novo synthesis creates opportunities for the preparation of diversity libraries and will support efforts in both drug discovery and development.

Nature Chemistry, Published online: 10 August 2020; doi:10.1038/s41557-020-0516-2

Patterns formed by artificial out-of-equilibrium chemical oscillating networks (such as the Belousov–Zhabotinsky reaction) are difficult to control with any precision. Now, it has been shown that low-intensity audible sound can be used to generate spatiotemporal patterns with a programmable distribution of redox- and pH-responsive chemical systems and supramolecular assemblies in solution.

Prolinyl phosphoramidates can release nucleotides in enzyme‐free reactions at pH 7.5 within hours. The hydrolytic pathway found may help in the design of new antiviral prodrugs.

Abstract

Phosphoramidates composed of an amino acid and a nucleotide analogue are critical metabolites of prodrugs, such as remdesivir. Hydrolysis of the phosphoramidate liberates the nucleotide, which can then be phosphorylated to become the pharmacologically active triphosphate. Enzymatic hydrolysis has been demonstrated, but a spontaneous chemical process may also occur. We measured the rate of enzyme‐free hydrolysis for 17 phosphoramidates of ribonucleotides with amino acids or related compounds at pH 7.5. Phosphoramidates of proline hydrolyzed fast, with a half‐life time as short as 2.4 h for Pro‐AMP in ethylimidazole‐containing buffer at 37 °C; 45‐fold faster than Ala‐AMP and 120‐fold faster than Phe‐AMP. Crystal structures of Gly‐AMP, Pro‐AMP, βPro‐AMP and Phe‐AMP bound to RNase A as crystallization chaperone showed how well the carboxylate is poised to attack the phosphoramidate, helping to explain this reactivity. Our results are significant for the design of new antiviral prodrugs.

The study of aggregation‐induced emission (AIE) creates many aggregate‐related research branches in which the structures and properties are quite different from those of their molecular components. By virtue of the emerging AIE research, the concept of “aggregate science” is proposed to fill the gap between molecules and aggregates, meanwhile providing a general platform for academic research at the mesoscale.

Abstract

Molecular science entails the study of structures and properties of materials at the level of single molecules or small interacting complexes of molecules. Moving beyond single molecules and well‐defined complexes, aggregates (i.e., irregular clusters of many molecules) serve as a particularly useful form of materials that often display modified or wholly new properties compared to their molecular components. Some unique structures and phenomena such as polymorphic aggregates, aggregation‐induced symmetry breaking, and cluster excitons are only identified in aggregates, as a few examples of their exotic features. Here, by virtue of the flourishing research on aggregation‐induced emission, the concept of “aggregate science” is put forward to fill the gaps between molecules and aggregates. Structures and properties on the aggregate scale are also systematically summarized. The structure–property relationships established for aggregates are expected to contribute to new materials and technological development. Ultimately, aggregate science may become an interdisciplinary research field and serves as a general platform for academic research.

Counting bricks in the wall: Chemically fueled assemblies are regulated by a chemical reaction cycle. A fast reaction cycle was recently introduced that shows exciting, dynamic self‐assembly behavior. However, analysis of its kinetic properties is challenging due to its speed. Thus, we introduce a simple, powerful method to quench all reactions in the reaction cycle. We show the accuracy and application for several reaction cycles and a range of molecular assemblies.

Abstract

In chemically fueled self‐assembly, the activation and deactivation of molecules for self‐assembly is coupled to a reaction cycle. In biological examples, these reactions are typically fast, such that the building blocks remain activated for mere seconds. In contrast, synthetic reaction cycles are slower for self‐assembly, i. e., with half‐lives on the order of minutes. In search of life‐like, dynamic behavior in synthetic systems, several groups explore faster reaction cycles that form transient labile building blocks with half‐lives of tens of seconds. These cycles show exciting properties, but brought about a new challenge, i. e., accurately analyzing the fast cycle is impossible with classical techniques. We thus introduce the notion of quenching chemical reaction cycles for self‐assembly. As a model, we use the fast carbodiimide‐fueled chemical reaction cycle and demonstrate a method that quenches all reactions immediately. We show its accuracy and demonstrate the application for several reaction cycles and a range of dissipative assemblies. Finally, we offer preliminary design rules to quench other chemically fueled reaction cycles.

Bind and deliver: Cationic oligoproline tightly complexes myo‐inositol hexakisphosphate (InsP₆) and delivers this eukaryotic messenger into the cell nucleus. The complexation is enabled by a conformational switch of the PPII‐helical oligoproline upon binding to InsP₆.

Abstract

Inositol hexakisphosphate (InsP₆) is a central member of the inositol phosphate messengers in eukaryotic cells. Tools to manipulate the level of InsP₆, particularly with compartment selectivity, are needed to enable functional cellular studies. We present cationic octa‐(4S)guanidiniumproline (Z8) for the delivery of InsP₆ into the cell nucleus. CD spectroscopy, binding affinity, dynamic light scattering, and computational studies revealed that Z8 binds tightly to InsP₆ and upon binding undergoes a conformational change from a PPII‐helical structure to a structure that forms aggregates. The unique conformational features of the cationic oligoproline enable complex formation and cellular delivery of InsP₆ with considerably greater efficacy than the flexible counterpart octaarginine.

Nature Nanotechnology, Published online: 20 July 2020; doi:10.1038/s41565-020-0734-1

A diffusion-reaction system in a gel matrix shows that concentration gradients can lead to an overall enhanced catalytic activity.

We describe an approach to taming air-sensitive chemical moieties important for solar energy conversation, electrochromic devices, photocatalysis, and biomimetic systems through supramolecular engineering of the solvent environment. Typically, transient radical species persist for over 6 months in air and have a lifetime in air more than 105 times that observed in aqueous environments. These findings will overcome many limitations for the use of these chemical species in a variety of energy applications.

Polymerization‐induced self‐assembly enables the at scale synthesis of nanoparticles with a high‐density display of peptide, tunable particle size, and tunable peptide loadings. The resulting peptide brush polymer nanoparticles exhibit enhanced stability, and cell uptake efficiency and efficacy in comparison with their peptide analogues, highlighting the potential of these peptide–polymer amphiphiles as peptide delivery systems.

Abstract

Herein, we report the photoinitiated polymerization‐induced self‐assembly (photo‐PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one‐pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL⁻¹) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide‐functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo‐PISA in the large‐scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.

Supramolecular eutectogels are an emerging class of materials that offer a new opportunity for generating functional gel materials in biocompatible anhydrous or low‐water media. Two guanosine‐based supramolecular G4 eutectogels with high ionic conductivity and solvent‐induced chiral inversion were developed that can be applied to fabricate a flexible electrochromic device.

Abstract

Supramolecular eutectogels, an emerging class of materials that have just developed very recently, offer a new opportunity for generating functional supramolecular gel materials in biocompatible anhydrous or low‐water media. As the first example of supramolecular G4 eutectogels, complexes of natural guanosine and H₃BO₃ exhibited excellent gelation capacity in choline chloride/alcohol deep eutectic solvents. The as‐prepared supramolecular eutectogels displayed unexpected solvent‐induced chiral inversion and significantly high ionic conductivity (up to 7.78 mS cm⁻¹), as well as outstanding thixotropic/injectable properties, high thermal stability and excellent electrochromic activity. These features make these versatile supramolecular G4 eutectogels promising candidates for developing next‐generation flexible electronics with low environmental impact.

Nature, Published online: 08 July 2020; doi:10.1038/s41586-020-2442-2

A mobile robot autonomously operates analytical instruments in a wet chemistry laboratory, performing a photocatalyst optimization task much faster than a human would be able to.

3′‐ and 5′‐amino oligonucleotides are chemically ligated through the formation of urea and squaramide artificial backbones. The squaramide linkage can be formed in mild reagent‐free buffered conditions, read‐through accurately by specific polymerases, and even cleaved and reformed on demand. To demonstrate its utility, the RNA‐to‐DNA reverse transcription step of RT‐qPCR is replaced with squaramide chemical ligation for direct RNA detection.

Abstract

Joining oligonucleotides together (ligation) is a powerful means of retrieving information from the nanoscale. To recover this information, the linkages created must be compatible with polymerases. However, enzymatic ligation is restrictive and current chemical ligation methods lack flexibility. Herein, a versatile ligation platform based on the formation of urea and squaramide artificial backbones from minimally modified 3′‐ and 5′‐amino oligonucleotides is described. One‐pot ligation gives a urea linkage with excellent read‐through speed, or a squaramide linkage that is read‐through under selective conditions. The squaramide linkage can be broken and reformed on demand, while stable pre‐activated precursor oligonucleotides expand the scope of the ligation reaction to reagent‐free, mild conditions. The utility of our system is demonstrated by replacing the enzymatically biased RNA‐to‐DNA reverse transcription step of RT‐qPCR with a rapid nucleic‐acid‐template‐dependent DNA chemical ligation system, that allows direct RNA detection.

Sensitive antennae : Light‐harvesting antennae were prepared by organizing fluorophores into DNA junctions. By using d ‐threoninol as a linker, donors could be accommodated in each arm at very high density. An acceptor was located at the center of each junction to evaluate antenna effects (see picture). Six‐ and eight‐way junctions showed the highest antenna effects. Distinct odd–even effects were also observed in yields of DNA junctions.

Abstract

Herein we report the construction of efficient light‐harvesting antennae by hybridization of DNA oligonucleotides containing high densities of fluorophores into DNA junctions through d ‐threoninol. Six pyrene donors could be incorporated into each arm without self‐quenching. A perylene acceptor was located at the center of the junction. Antenna effects of a duplex and three‐ to eight‐way junctions were systematically compared. Six‐ and eight‐way junctions had the highest antenna effects, and their effective absorption coefficients were 8.5 times higher than that of perylene. Interestingly, even‐numbered junctions had higher efficiencies than odd‐numbered junctions. Nondenaturing gel analyses and fluorescence lifetime measurements demonstrated that the strong odd–even effects were derived from differences in the stability of junctions. The results presented will guide the design of efficient artificial photosynthetic systems.