Jing Sun

The spontaneous emergence of long RNA molecules on the early Earth, a phenomenon central to the RNA World hypothesis, continues to remain an enigma in the field of origins of life. Few studies have looked at the nonenzymatic oligomerization of cyclic mononucleotides under neutral to alkaline conditions, albeit in fully dehydrated state. In this study, we systematically investigated the oligomerization of cyclic nucleotides under prebiotically relevant conditions, wherein starting reactants were subjected to repeated dehydration–rehydration (DH–RH) regimes. DH–RH conditions, a recurring geological theme that was prevalent on prebiotic Earth, are driven by naturally occurring processes including diurnal cycles and tidal pool activity. These conditions have been shown to facilitate uphill oligomerization reactions. The polymerization of 2'–3' and 3'–5' cyclic nucleotides of a purine (adenosine) and a pyrimidine (cytidine) was investigated. Additionally, the effect of amphiphiles was also evaluated. Furthermore, to discern the effect of "realistic" conditions on this process, the reactions were also performed using a hot spring water sample from a candidate early Earth environment. Our study showed that the oligomerization of cyclic nucleotides under DH–RH conditions resulted in intact informational oligomers. Amphiphiles increased the stability of both the starting monomers and the resultant oligomers in selected reactions. In the hot spring reactions, both the oligomerization of nucleotides and the back hydrolysis of the resultant oligomers were pronounced. Altogether, this study demonstrates how nonenzymatic oligomerization of cyclic nucleotides, under both laboratory-simulated prebiotic conditions and in a candidate early Earth environment, could have resulted in RNA oligomers of a putative RNA World.

It′s in your DNA: Inherited features from an individual′s genome are used as an encryption key to protect digital data stored in synthetic DNA. Although the encryption key and cyphertext originate from very different sources, the chemical nature of the information is identical and can consequently be analyzed with the same reading technology.

Abstract

Today, we can read human genomes and store digital data robustly in synthetic DNA. Herein, we report a strategy to intertwine these two technologies to enable the secure storage of valuable information in synthetic DNA, protected with personalized keys. We show that genetic short tandem repeats (STRs) contain sufficient entropy to generate strong encryption keys, and that only one technology, DNA sequencing, is required to simultaneously read the key and the data. Using this approach, we experimentally generated 80 bit strong keys from human DNA, and used such a key to encrypt 17 kB of digital information stored in synthetic DNA. Finally, the decrypted information was recovered perfectly from a single massively parallel sequencing run.

A spiropolymer (P1a2b, see picture) demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating non‐toxicity in non‐cancerous cells.

Abstract

Heteroatom‐containing spiropolymers were constructed in a facile manner by a catalyst‐free multicomponent spiropolymerization route. P1a2b as the most potent of these spiropolymers, demonstrates cluster‐triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti‐apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating a good biocompatibility and non‐toxicity in non‐cancerous cells. The combined results from solution and cell‐based cluster‐triggered emission studies, docking, protein expression experiments and cytotoxicity data strongly support the MDM2‐binding hypothesis and indicate a potential application as a fluorescent cancer marker as well as therapeutic for this spiropolymer.

Close O−O contacts make me redder: The tetrafurylethene AIE luminogen has a strong red morphochromism going from the aggregate to the crystalline phase (27 nm). This is due to unusually short O−O contacts that are facilitated by circularly delocalized π electron density between the furan rings.

Abstract

We have studied the photophysics of tetrafurylethene, an aggregation‐induced emission luminogen with exceptionally short intramolecular O−O distances of 2.80 Å and a significant red‐shifted morphochromism (27 nm) when going from the aggregate to the crystal. The short O−O distances, which are substantially smaller than the sum of the van der Waals radii (3.04 Å), are due to the fact that the oxygen atoms act as an electronic bridge connecting the furan rings on opposite ends of the central double bond, giving rise to a circular delocalization of the π‐electron density across the rings. In the excited state the O−O distance is further reduced to 2.70 Å; the increased O−O interaction causes a narrowing of the HOMO–LUMO gap, resulting in the red morphochromism of the emission. Our results show the structural origin of the red‐shifted emission lies in close O−O contacts, paving the way for understanding the clusteroluminescence of oxygen‐rich non‐conjugated systems that emit visible light.

Directly quantifying a spatially varying stress in soft materials is currently a great challenge. We propose a method to do that by detecting a change in visible light absorption. We incorporate a spiropyran (SP) force–activated mechanophore cross-linker in multiple-network elastomers. The random nature of the network structure of the polymer causes a progressive activation of the SP force probe with load, detectable by the change in color of the material. We first calibrate precisely the chromatic change in uniaxial tension. We then demonstrate that the nominal stress around a loaded crack can be detected for each pixel and that the measured values match quantitatively finite element simulations. This direct method to quantify stresses in soft materials with an internal force probe is an innovative tool that holds great potential to compare quantitatively stresses in different materials with simple optical observations.

The importance of the whole picture : Aggregation‐induced emission (AIE) research demonstrates that many properties and functions that are absent in molecular species can be found in molecular aggregates. AIE research thus emphasizes the significance of aggregate science in addition to molecular science for materials development.

Abstract

Aggregation‐induced emission (AIE) describes a photophysical phenomenon in which molecular aggregates exhibit stronger emission than the single molecules. Over the course of the last 20 years, AIE research has made great strides in material development, mechanistic study and high‐tech applications. The achievements of AIE research demonstrate that molecular aggregates show many properties and functions that are absent in molecular species. In this review, we summarize the advances in the field of AIE and its related areas. We specifically focus on the new properties of materials attained by molecular aggregates beyond the microscopic molecular level. We hope this review will inspire more research into molecular ensembles at and beyond the meso level and lead to the significant progress in material and biological science.

Sequence‐dependent interactions between DNA and upconversion nanoparticles (UCNPs) are systematically investigated. Poly‐cytosine (poly‐C) has a high affinity for the UCNP surface. Based on this finding, a general strategy to synthesize monodispersed DNA‐UCNP conjugates is developed using poly‐C‐containing diblock DNA strands, which can be used for DNA‐guided UCNP assembly.

Abstract

DNA‐modified lanthanide‐doped upconversion nanoparticles (DNA‐UCNPs) that combine the functions of DNA and the optical features of UCNPs have shown great promise in a wide range of fields. However, challenges remain in precisely tethering and orienting the DNA strands on the UCNP surface. Herein, we systematically investigate the sequence dependence of DNAs in their interactions with UCNPs, and reveal that poly‐cytosine (poly‐C) has high affinity for the UCNP surface. A general approach to synthesize monodispersed DNA‐UCNP conjugates is developed using poly‐C‐containing diblock DNA strands. The poly‐C segment of the DNA strand binds to the surfaces of UCNPs and the second segment is oriented perpendicularly on the UCNP surface, making the DNA‐UCNPs highly stable and monodispersed in aqueous solution. The dense layer of DNA on the UCNP surface enables the programmable assembly of UCNPs with other DNA‐functionalized nanoparticles or DNA origamis through hybridization, resulting in the formation of well‐organized complex structures.

Switch and tune ! The trans –cis conformational switching of 2,2’‐bipyridine in response to acid was exploited to tune supramolecular polymerization processes. For this purpose, the aqueous self‐assembly of a bipyridine‐based linear bolaamphiphile that self‐assembles under standard conditions into cooperative supramolecular polymers was investigated. Interestingly, acid‐triggered protonation of the bipyridine unit induces a molecular conformational change from linear (trans ) to cis (V‐shaped) that leads to an attenuated supramolecular growth into shorter fibers.

Abstract

Besides their widespread use in coordination chemistry, 2,2’‐bipyridines are known for their ability to undergo cis–trans conformational changes in response to metal ions and acids, which has been primarily investigated at the molecular level. However, the exploitation of such conformational switching in self‐assembly has remained unexplored. In this work, the use of 2,2’‐bipyridines as acid‐responsive conformational switches to tune supramolecular polymerization processes has been demonstrated. To achieve this goal, we have designed a bipyridine‐based linear bolaamphiphile, 1 , that forms ordered supramolecular polymers in aqueous media through cooperative aromatic and hydrophobic interactions. Interestingly, addition of acid (TFA) induces the monoprotonation of the 2,2’‐bipyridine moiety, leading to a switch in the molecular conformation from a linear (trans ) to a V‐shaped (cis ) state. This increase in molecular distortion along with electrostatic repulsions of the positively charged bipyridine‐H⁺ units attenuate the aggregation tendency and induce a transformation from long fibers to shorter thinner fibers. Our findings may contribute to opening up new directions in molecular switches and stimuli‐responsive supramolecular materials.

Out‐of‐equilibrium assembly : Diacid precursors assemble into unstable aqueous anhydride macrocycles on treatment with carbodiimide chemical fuels, even though initial anhydride generation is unselective for cyclization versus polymerization. The efficiency of assembly results from both fuel‐independent (anhydride exchange) and fuel‐dependent (selective hydrolysis) mechanisms.

Abstract

Dissipative assembly has great potential for the creation of new adaptive chemical systems. However, while molecular assembly at equilibrium is routinely used to prepare complex architectures from polyfunctional monomers, species formed out of equilibrium have, to this point, been structurally very simple. In most examples the fuel simply effects the formation of a single short‐lived covalent bond. Herein, we show that chemical fuels can assemble bifunctional components into macrocycles containing multiple transient bonds. Specifically, dicarboxylic acids give aqueous dianhydride macrocycles on treatment with a carbodiimide. The macrocycles are assembled efficiently as a consequence of both fuel‐dependent and fuel‐independent mechanisms; they undergo slower decomposition, building up as the fuel recycles the components, and are a favored product of the dynamic exchange of the anhydride bonds. These results create new possibilities for generating structurally sophisticated out‐of‐equilibrium species.

Solid‐state fluorescence : A strategy for designing solid‐state fluorescent materials based on the tuning of their molecular packing mode by regioisomerization is proposed. Changing the molecular packing from a long‐range cofacial mode to a discrete cross packing, an ACQ‐to‐AIE transformation can be realized, achieving highly bright solid‐state materials.

Abstract

The traditional design strategies for highly bright solid‐state luminescent materials rely on weakening the intermolecular π–π interactions, which may limit diversity when developing new materials. Herein, we propose a strategy of tuning the molecular packing mode by regioisomerization to regulate the solid‐state fluorescence. TBP‐e ‐TPA with a molecular rotor in the end position of a planar core adopts a long‐range cofacial packing mode, which in the solid state is almost non‐emissive. By shifting molecular rotors to the bay position, the resultant TBP‐b ‐TPA possesses a discrete cross packing mode, giving a quantum yield of 15.6±0.2 %. These results demonstrate the relationship between the solid‐state fluorescence efficiency and the molecule's packing mode. Thanks to the good photophysical properties, TBP‐b ‐TPA nanoparticles were used for two‐photon deep brain imaging. This molecular design philosophy provides a new way of designing highly bright solid‐state fluorophores.

Fluorogens with aggregation‐induced emission (AIEgens) have stimulated the development of AIE molecular probes and AIE nanoparticle probes for various biomedical applications. This Review reveals how the AIE probes have evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications.

Abstract

The concept of aggregation‐induced emission (AIE) has opened new opportunities in many research fields. Motivated by the unique feature of AIE fluorogens (AIEgens), during the past decade, many AIE molecular probes and AIE nanoparticle (NP) probes have been developed for sensing, imaging and theranostic applications with excellent performance outperforming conventional fluorescent probes. This Review summarizes the latest advancement of AIE molecular probes and AIE NP probes and their emerging biomedical applications. Special focus is to reveal how the AIE probes are evolved with the development of new multifunctional AIEgens, and how new strategies have been developed to overcome the limitations of traditional AIE probes for more translational applications via fluorescence imaging, photoacoustic imaging and image‐guided photodynamic/photothermal therapy. The outlook discusses the challenges and future opportunities for AIEgens to advance the biomedical field.

The development of novel photosensitizing agents with aggregation‐induced emission (AIE) properties have fueled significant advances in the field of photodynamic therapy (PDT). Herein, electroporation method was used to prepare tumor‐exocytosed exosome/AIEgen hybrid nano‐vesicles (termed DES) that could facilitate efficient tumor penetration. Dexamethasone was then used to normalize vascular function within the TME to reduce local hypoxia, thereby significantly enhancing the PDT efficacy of DES nano‐vesicles, allowing them to effectively inhibit tumor growth. We achieved the hybridization of AIEgen and biological tumor‐exocytosed exosomes for the first time, and combine PDT approaches with normalizing the intratumoral vasculature as a means of reducing local tissue hypoxia. Together, this work highlights a new valuable approach to design AIEgen based PDT systems and underscores the potential clinical value of AIEgens.

Ground control : Self‐assembly of achiral AIEgens (AIE=aggregation induced emission) and chiral donors with metal ions into metal—organic frameworks (MOFs) enabled solid‐state emission and through‐space chirality transfer. The fluorescence/circularly polarized luminescence (CPL) MOFs have a reversible, dual‐mode mechano‐response through grinding and ultrasound.

Abstract

Circularly polarized luminescence (CPL) is attractive in understanding the excited‐state chirality and developing advanced materials. Herein, we propose a chiral reticular self‐assembly strategy to unite achiral AIEgens, chirality donors, and metal ions to fabricate optically pure AIEgen metal–organic frameworks (MOFs) as efficient CPL materials. We have found that CPL activity of the single‐crystal AIEgen MOF was generated by the framework‐enabled strong emission from AIEgens and through‐space chirality transfer from chirality donors to achiral AIEgens via metal‐ion bridges. For the first time, a dual mechano‐switched blue and red‐shifted CPL activity was achieved via ultrasonication and grinding, which enabled the rotation or stacking change of AIEgen rotors with the intact homochiral framework. This work provided not only an insightful view of the aggregation induced emission (AIE) mechanism, but also an efficient and versatile strategy for the preparation of stimuli‐responsive CPL materials.

Chemists helping local communities : The SARS‐CoV‐2 outbreak causing the respiratory disease COVID‐19 has had a major impact on society. Where can chemists help in this hour of need? From preparing hand sanitizers, to working on antiviral drug candidates, and providing fact‐based outreach in collaboration with their chemical societies are options discussed in this contribution.

Abstract

The SARS‐CoV‐2 outbreak causing the respiratory disease COVID‐19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three‐pronged approach is proposed.

The DNA Code : A novel steganography and cryptography molecular information coding (MIC) strategy in a reconfigurable DNA origami domino array (DODA) is demonstrated. This strategy opens new opportunities for high‐density information storage and information security against decoding, duplication, and forgery, overcoming the key difficulties in MIC technologies.

Abstract

DNA nanostructures with programmable nanoscale patterns has been achieved in the past decades, and molecular information coding (MIC) on those designed nanostructures has gained increasing attention for information security. However, achieving steganography and cryptography synchronously on DNA nanostructures remains a challenge. Herein, we demonstrated MIC in a reconfigurable DNA origami domino array (DODA), which can reconfigure intrinsic patterns but keep the DODA outline the same for steganography. When a set of keys (DNA strands) are added, the cryptographic data can be translated into visible patterns within DODA. More complex cryptography with the ASCII code within a programmable 6×6 lattice is demonstrated to demosntrate the versatility of MIC in the DODA. Furthermore, an anti‐counterfeiting approach based on conformational transformation‐mediated toehold strand displacement reaction is designed to protect MIC from decoding and falsification.

Transition metal–catalyzed coupling reactions have become one of the most important tools in modern synthesis. However, an inherent limitation to these reactions is the need to balance operations, because the factors that favor bond cleavage via oxidative addition ultimately inhibit bond formation via reductive elimination. Here, we describe an alternative strategy that exploits simple visible-light excitation of palladium to drive both oxidative addition and reductive elimination with low barriers. Palladium-catalyzed carbonylations can thereby proceed under ambient conditions, with challenging aryl or alkyl halides and difficult nucleophiles, and generate valuable carbonyl derivatives such as acid chlorides, esters, amides, or ketones in a now-versatile fashion. Mechanistic studies suggest that concurrent excitation of palladium(0) and palladium(II) intermediates is responsible for this activity.

Greater than the sum of the parts : The combination of a covalent polymer (CP) and a supramolecular polymer (SP) has led to networks (CSPs) in which the properties of the component polymers are not only retained, but improved upon. The CSPs show improved mechanical performance (stiffness, strength, stretchability, toughness, and elastic recovery) as well as improved dynamic properties (self‐healing, stimuli‐responsiveness, and reprocessing).

Abstract

Nature has engineered delicate synergistic covalent and supramolecular polymers (CSPs) to achieve advanced life functions, such as the thin filaments that assist in muscle contraction. Constructing artificial synergistic CSP materials with bioinspired mechanically adaptive features, however, represents a challenging goal. Here, we report an artificial CSP system to illustrate the integration of a covalent polymer (CP) and a supramolecular polymer (SP) in a synergistic fashion, along with the emergence of notable mechanical and dynamic properties which are unattainable when the two polymers are formed individually. The synergistic effect relies on the peculiar network structures of the SP and CPs, which endow the resultant CSPs with overall improved mechanical performance in terms of the stiffness, strength, stretchability, toughness, and elastic recovery. Moreover, the dynamic properties of the SP, including self‐healing, stimuli‐responsiveness, and reprocessing, are also retained in the CSPs, thus leading to their application as programmable and tunable materials.

Bacterial resistance threatens to destroy the achievements of antibiotic therapy. As P. Uhl and co‐workers report in their Communication on https://doi.org/10.1002/anie.202002727page 8823, a 1000‐fold increase in the activity of the reserve antibiotic vancomycin was achieved by using peptide conjugates. This approach reveals the potential of chemically modifying proven natural products as an alternative to the costly de novo development of active substances.

Nature Chemistry, Published online: 13 April 2020; doi:10.1038/s41557-020-0452-1