Jing Sun

Nature Biomedical Engineering, Published online: 22 January 2024; doi:10.1038/s41551-024-01176-9

A handy go-between may soon assist authors and editors.

Nature, Published online: 06 July 2022; doi:10.1038/s41586-022-05033-0

Intrinsically unidirectional chemically fuelled rotary molecular motors

The temporal and spatial control of natural systems has aroused great interest for the creation of synthetic mimics. Herein, a dynamic boronic ester based non-equilibrium self-assembly strategy has enabled the creation of programmable and transient supramolecular chiral G-quadruplex hydrogels with tunable lifetimes from minutes, to hours, to days, as well as high transparency and conductivity, excellent injectability, and self-healing properties.

Abstract

The temporal and spatial control of natural systems has aroused great interest for the creation of synthetic mimics. By using boronic ester based dynamic covalent chemistry and coupling it with an internal pH feedback system, we have developed a new chemically fueled reaction network for non-equilibrium supramolecular chiral G-quadruplex hydrogels with programmable lifetimes from minutes, to hours, to days, as well as high transparency and conductivity, excellent injectability, and rapid self-healing properties. The system can be controlled by the kinetically controlled in situ formation and dissociation of dynamic boronic ester bonds between the cis-diol of guanosine (G) and 5-fluorobenzoxaborole (B) in the presence of chemical fuels (KOH and 1,3-propanesultone), thereby leading to a precipitate-solution-gel-precipitate cycle under non-equilibrium conditions. A combined experimental-computational approach showed the underlying mechanism of the non-equilibrium self-assembly involves aggregation and disaggregation of right-handed helical G-quadruplex superstructures. The proposed dynamic boronic ester-based non-equilibrium self-assembly strategy offers a new option to design next-generation adaptive and interactive smart materials.

Chiral bile salt biosurfactant with low molecular weight can self-assemble into supramolecular helices by interaction with oppositely charged polymers. A controlled condensation of the supramolecular helices into DNA-like hexagonally packed bundles and toroids can be achieved when using block copolymers of opposite charge and increasing the bile salt content.

Abstract

Condensation of DNA helices into hexagonally packed bundles and toroids represents an intriguing example of functional organization of biological macromolecules at the nanoscale. The condensation models are based on the unique polyelectrolyte features of DNA, however here we could reproduce a DNA-like condensation with supramolecular helices of small chiral molecules, thereby demonstrating that it is a more general phenomenon. We show that the bile salt sodium deoxycholate can form supramolecular helices upon interaction with oppositely charged polyelectrolytes of homopolymer or block copolymers. At higher order, a controlled hexagonal packing of the helices into DNA-like bundles and toroids could be accomplished. The results disclose unknown similarities between covalent and supramolecular non-covalent helical polyelectrolytes, which inspire visionary ideas of constructing supramolecular versions of biological macromolecules. As drug nanocarriers the polymer–bile salt superstructures would get advantage of a complex chirality at molecular and supramolecular levels, whose effect on the nanocarrier assisted drug efficiency is a still unexplored fascinating issue.

The DAP mediated prebiotic phosphorylation of nucleosides/nucleotides/oligonucleotides produces a spectrum of the corresponding mono-, di-, and tri(amido)phosphorylated derivatives which are substrates for both prebiotic-oligomerization and biotic-polymerization/ligation. The compatibility of the phosphorylation and activation chemistry across a broad spectrum of (oligo)nucleos(t)ide structures suggests a smoother transition from chemistry to biology.

Abstract

Polymerization of nucleic acids in biology utilizes 5′-nucleoside triphosphates (NTPs) as substrates. The prebiotic availability of NTPs has been unresolved and other derivatives of nucleoside-monophosphates (NMPs) have been studied. However, this latter approach necessitates a change in chemistries when transitioning to biology. Herein we show that diamidophosphate (DAP), in a one-pot amidophosphorylation-hydrolysis setting converts NMPs into the corresponding NTPs via 5′-nucleoside amidophosphates (NaPs). The resulting crude mixture of NTPs are accepted by proteinaceous- and ribozyme-polymerases as substrates for nucleic acid polymerization. This phosphorylation also operates at the level of oligonucleotides enabling ribozyme-mediated ligation. This one-pot protocol for simultaneous generation of NaPs and NTPs suggests that the transition from prebiotic-phosphorylation and oligomerization to an enzymatic processive-polymerization can be more continuous than previously anticipated.

A family of ¹⁸O₂-phosphoramidites facilitates synthetic access on gram-scale to various isotopically pure ¹⁸O-labelled phosphate products, like nucleotides, inositol phosphates, polyphosphates, and DNA. The utility of these ¹⁸O-natural products is underlined in the assignment of various metabolites from biological matrices using capillary electrophoresis electrospray ionisation triple quadrupole mass spectrometry.

Abstract

Stable isotope labelling is state-of-the-art in quantitative mass spectrometry, yet often accessing the required standards is cumbersome and very expensive. Here, a unifying synthetic concept for ¹⁸O-labelled phosphates is presented, based on a family of modified ¹⁸O₂-phosphoramidite reagents. This toolbox offers access to major classes of biologically highly relevant phosphorylated metabolites as their isotopologues including nucleotides, inositol phosphates, -pyrophosphates, and inorganic polyphosphates. ¹⁸O-enrichment ratios >95 % and good yields are obtained consistently in gram-scale reactions, while enabling late-stage labelling. We demonstrate the utility of the ¹⁸O-labelled inositol phosphates and pyrophosphates by assignment of these metabolites from different biological matrices. We demonstrate that phosphate neutral loss is negligible in an analytical setup employing capillary electrophoresis electrospray ionisation triple quadrupole mass spectrometry.

Nature Materials, Published online: 14 October 2021; doi:10.1038/s41563-021-01122-z

The solvent-free conversion of phthalonitrile derivatives into phthalocyanines in the bulk is described, involving a reductive cyclotetramerization step and the formation of one-dimensional single-crystalline fibres. This solvent-free autocatalytic supramolecular polymerization may enable for a sustainable fabrication of multi-block supramolecular copolymers.

Nature Chemistry, Published online: 11 October 2021; doi:10.1038/s41557-021-00791-2

In biological systems, controlled molecular motion along a particular path is realized by protein motors that travel along microtubule filaments. Now, control of motion with light has been achieved in a synthetic supramolecular system, in which anionic porphyrin molecules move along the fibres of a bis-imidazolium gel upon irradiation.

Introducing anisotropy into supramolecular polymers requires a highly controlled assembly mechanism, and few examples have been demonstrated. Using a multistep method in an aqueous solution, DNA polymers were assembled into supramolecular fibers that displayed different DNA sequences in discrete segments along their lengths. A unique ion- and heat-driven “thermosetting” mechanism enabled this assembly. The microscopic structure was also shown to be sensitive to the stereochemical sequence of the DNA-polymer building blocks, which translated into morphological differences in the supramolecular fibers.

In solution, a prebiotically plausible ribozyme formed from short oligonucleotides reversibly cleaves an RNA substrate. However, in the presence of poly-L-lysine, phase separation occurs owing to charge interactions between the oppositely charged RNA and peptide. The resulting compartments greatly enhance ribozyme activity, driving the reaction equilibrium towards the ligation of long and complex RNA in mild conditions.

Abstract

The ability of RNA to catalyze RNA ligation is critical to its central role in many prebiotic model scenarios, in particular the copying of information during self-replication. Prebiotically plausible ribozymes formed from short oligonucleotides can catalyze reversible RNA cleavage and ligation reactions, but harsh conditions or unusual scenarios are often required to promote folding and drive the reaction equilibrium towards ligation. Here, we demonstrate that ribozyme activity is greatly enhanced by charge-mediated phase separation with poly-L-lysine, which shifts the reaction equilibrium from cleavage in solution to ligation in peptide-RNA coaggregates and coacervates. This compartmentalization enables robust isothermal RNA assembly over a broad range of conditions, which can be leveraged to assemble long and complex RNAs from short fragments under mild conditions in the absence of exogenous activation chemistry, bridging the gap between pools of short oligomers and functional RNAs.

A prebiotic pathway is developed to solve the mystery of the natural selection of ribose as the exclusive sugar for RNA. It is unveiled that metal-doped-clays exhibit the unique capability to selectively retain and stabilize ribose from the complex Formose mixture, as well as to promote subsequent syntheses toward RNA.

Nature Communications, Published online: 10 September 2021; doi:10.1038/s41467-021-25668-3

The “anti-branching rule”, introduced in 1950, excludes branched polyphosphates from biological relevance due to their supposedly rapid hydrolysis. Here, the authors synthesize monodisperse branched polyphosphates and demonstrate their unexpected stability in water, as well as provide evidence for their competence in phosphorylation.

Nature Communications, Published online: 17 August 2021; doi:10.1038/s41467-021-25299-8

Dissipative self-assembly, which requires a continuous supply of fuel to maintain the assembled states far from equilibrium, is the foundation of biological systems but it remains a challenge to introduce light as fuel into artificial dissipative self-assemblies. Here, the authors report an artificial dissipative self-assembly system that is constructed from light-induced amphiphiles.

A fuel-driven and enzyme-regulated supramolecular hydrogel has the inherent ability to tune its behavior from a redox-responsive to a self-regulating system. Feedback arises due to in situ formation of oxidation fuel in the chemical reaction network.

Abstract

Chemical reaction networks (CRN) embedded in hydrogels can transform responsive materials into complex self-regulating materials that generate feedback to counter the effect of external stimuli. This study presents hydrogels containing the β-cyclodextrin (CD) and ferrocene (Fc) host–guest pair as supramolecular crosslinks where redox-responsive behavior is driven by the enzyme–fuel couples horse radish peroxidase (HRP)–H₂O₂ and glucose oxidase (GOx)–d-glucose. The hydrogel can be tuned from a responsive to a self-regulating supramolecular system by varying the concentration of added reduction fuel d-glucose. The onset of self-regulating behavior is due to formation of oxidation fuel in the hydrogel by a cofactor intermediate GOx[FADH₂]. UV/Vis spectroscopy, rheology, and kinetic modeling were employed to understand the emergence of out-of-equilibrium behavior and reveal the programmable negative feedback response of the hydrogel, including the adaptation of its elastic modulus and its potential as a glucose sensor.

Nature Chemistry, Published online: 09 August 2021; doi:10.1038/s41557-021-00751-w

Nature uses out-of-equilibrium systems to control hierarchical assembly. Now, a dissipative chemical system has been shown to slowly release monomer DNA strands from a high-energy reservoir, regulating self-assembly by switching the mechanism of supramolecular polymerization at the single-molecule level. This process heals fibre defects, converting branched, heterogeneous networks into nanocable superstructures.