Catalytic enantioselective construction of vicinal quaternary carbon stereocenters

This review summarizes the advances in the catalytic enantioselective construction of vicinal quaternary carbon stereocenters, introduces major synthetic strategies and discusses their advantages and limitations, highlights the application of known protocols in the total synthesis of natural products, and outlines the synthetic opportunities.

This review summarizes the advances in catalytic enantioselective construction of vicinal quaternary carbon stereocenters, introduces major synthetic strategies and discusses their advantages and limitations, and outlines the synthetic opportunities.     

(Hetero)arene-fused boroles: a broad spectrum of applications

(Hetero)arene-fused boroles are a class of compounds containing a 5-membered boron diene-ring. Based on their molecular framework, the (hetero)arene-fused boroles can be considered as boron-doped polycyclic antiaromatic hydrocarbons and are thus of great interest. Due to the vacant p_z orbital on the 3-coordinate boron atom, the antiaromaticity and strain of the 5-membered borole ring, (hetero)arene-fused boroles possess strong electron accepting abilities and Lewis acidity. By functionalization, they can be tuned to optimize different properties for specific applications. Herein, we summarize synthetic methodologies, different strategies for their functionalization, and applications of (hetero)arene-fused boroles.

(Hetero)arene-fused boroles, ‘antiaromatic’ 2n-electron π-systems, more stable and more functionalizable than boroles, offer greater potential for a variety of applications.     

Machine-enabled inverse design of inorganic solid materials: promises and challenges

Developing high-performance advanced materials requires a deeper insight and search into the chemical space. Until recently, exploration of materials space using chemical intuitions built upon existing materials has been the general strategy, but this direct design approach is often time and resource consuming and poses a significant bottleneck to solve the materials challenges of future sustainability in a timely manner. To accelerate this conventional design process, inverse design, which outputs materials with pre-defined target properties, has emerged as a significant materials informatics platform in recent years by leveraging hidden knowledge obtained from materials data. Here, we summarize the latest progress in machine-enabled inverse materials design categorized into three strategies: high-throughput virtual screening, global optimization, and generative models. We analyze challenges for each approach and discuss gaps to be bridged for further accelerated and rational data-driven materials design.

The grand challenge of materials science, discovery of novel materials with target properties, can be greatly accelerated by machine-learned inverse design strategies.     

Controlling ultrasmall gold nanoparticles with atomic precision

Gold nanoparticles are probably the nanoparticles that have been best studied for the longest time due to their stability, physicochemical properties and applications. Controlling gold nanoparticles with atomic precision is of significance for subsequent research on their structures, properties and applications, which is a dream that has been pursued for many years since ruby gold was first obtained by Faraday in 1857. Fortunately, this dream has recently been partially realized for some ultrasmall gold nanoparticles (nanoclusters). However, rationally designing and synthesizing gold nanoparticles with atomic precision are still distant goals, and this challenge might rely primarily on rich atomically precise gold nanoparticle libraries and the in-depth understanding of metal nanoparticle chemistry. Herein, we review general synthesis strategies and some facile synthesis methods, with an emphasis on the controlling parameters determined from well-documented results, which might have important implications for future nanoparticle synthesis with atomic precision and facilitate related research and applications.

The synthesis strategy, methods and parameters for atomically precise gold nanoclusters were reviewed, and future outlook was also proposed.     

Debugging: putting the synthetic yeast chromosome to work

Synthetic genomics aims to de novo synthesize a functional genome redesigned from natural sequences with custom features. Designed genomes provide new toolkits for better understanding organisms, evolution and the construction of cellular factories. Currently maintaining the fitness of cells with synthetic genomes is particularly challenging as defective designs and unanticipated assembly errors frequently occur. Mapping and correcting bugs that arise during the synthetic process are imperative for the successful construction of a synthetic genome that can sustain a desired cellular function. Here, we review recently developed methods used to map and fix various bugs which arise during yeast genome synthesis with the hope of providing guidance for putting the synthetic yeast chromosome to work.

This review summarizes strategies used to map and repair various bugs in synthetic genomic sequences and provides guidance for the construction of synthetic yeast chromosomes that are capable of maintaining cell fitness.     

Tuning the stability of organic radicals: from covalent approaches to non-covalent approaches

Organic radicals are important species with single electrons. Because of their open-shell structure, they are widely used in functional materials, such as spin probes, magnetic materials and optoelectronic materials. Owing to the high reactivity of single electrons, they often serve as a key intermediate in organic synthesis. Therefore, tuning the stability of radicals is crucial for their functions. Herein, we summarize covalent and non-covalent approaches to tune the stability of organic radicals through steric effects and tuning the delocalization of spin density. Covalent approaches can tune the stability of radicals effectively and non-covalent approaches benefit from dynamicity and reversibility. It is anticipated that the further development of covalent and non-covalent approaches, as well as the interplay between them, may push the fields forward by enriching new radical materials and radical mediated reactions.

Covalent and non-covalent approaches to tune the stability of organic radicals through steric effects and the delocalization of spin density.     

Recent advances of AIE light-up probes for photodynamic therapy

As a new non-invasive treatment method, photodynamic therapy (PDT) has attracted great attention in biomedical applications. The advantages of possessing fluorescence for photosensitizers have made it possible to combine imaging and diagnosis together with PDT. The unique features of aggregation-induced emission (AIE) fluorogens provide new opportunities for facile design of light-up probes with high signal-to-noise ratios and improved theranostic accuracy and efficacy for image-guided PDT. In this review, we summarize the recent advances of AIE light-up probes for PDT. The strategies and principles to design AIE photosensitizers and light-up probes are firstly introduced. The application of AIE light-up probes in photodynamic antitumor and antibacterial applications is further elaborated in detail, from binding/targeting-mediated, reaction-mediated, and external stimuli-mediated light-up aspects. The challenges and future perspectives of AIE light-up probes in the PDT field are also presented with the hope to encourage more promising developments of AIE materials for phototheranostic applications and translational research.

AIE fluorogens provide new opportunities for the development of light-up probes for photodynamic therapy.     

Correlated motion and mechanical gearing in amphidynamic crystalline molecular machines

In this review we highlight the recent efforts towards the development of molecular gears with an emphasis on building molecular gears in the solid state and the role that molecular gearing and correlated motions may play in the function of crystalline molecular machines. We discuss current molecular and crystal engineering strategies, challenges associated with engineering correlated motion in crystals, and outline experimental and theoretical tools to explore gearing dynamics while highlighting key advances made to date.

Here we highlight recent efforts towards the development of molecular gears in the solid state and the role that molecular gearing and correlated motions may play in the function of crystalline molecular machines.     

Copper-catalyzed functionalization of enynes

The copper-catalyzed functionalization of enyne derivatives has recently emerged as a powerful approach in contemporary synthesis. Enynes are versatile and readily accessible substrates that can undergo a variety of reactions to yield densely functionalized, enantioenriched products. In this perspective, we review copper-catalyzed transformations of enynes, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations. Particular attention is given to the regiodivergent functionalization of 1,3-enynes, and the current mechanistic understanding of such processes.

The copper-catalyzed functionalization of enynes is a powerful approach to yield densely functionalized products. This review covers various transformations, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations.     

Recent advances in low oxidation state aluminium chemistry

The synthesis and isolation of novel low oxidation state aluminium (Al) compounds has seen relatively slow progress over the 30 years since such species were first isolated. This is largely due to the significant challenges in isolating these thermodynamically unstable compounds. Despite challenges with isolation, their reactivity has been widely explored and they have been utilized in a wide range of processes including the activation of strong chemicals bonds, as ligands to transition metals and in the formation of heterobimetallic M–M compounds. As such, attempts to isolate novel low oxidation state Al compounds have continued in earnest and in the last few years huge advances have been made. In this review we highlight the remarkable recent developments in the low oxidation state chemistry of aluminium and discuss the variety of new reactions these compounds have made possible.

Documenting the synthesis and isolation of novel low oxidation state aluminium (Al) compounds, which until recently has seen relatively slow progress over the 30 years since such species were first isolated.     

Confined space design by nanoparticle self-assembly

Nanoparticle (NP) self-assembly has led to the fabrication of an array of functional nanoscale systems, having diverse architectures and functionalities. In this perspective, we discuss the design and application of NP suprastructures (SPs) characterized by nanoconfined compartments in their self-assembled framework, providing an overview about SP synthetic strategies reported to date and the role of their confined nanocavities in applications in several high-end fields. We also set to give our contribution towards the formation of more advanced nanocompartmentalized SPs able to work in dynamic manners, discussing the opportunities of further advances in NP self-assembly and SP research.

This perspective gives an outlook on the design of interparticle confined nanocavities in self-assembled NP systems and their functional relevance.     

Directional asymmetry over multiple length scales in reticular porous materials

In nature and synthetic materials, asymmetry is a useful tool to create complex and functional systems constructed from a limited number of building blocks. Reticular chemistry has allowed the synthesis of a wide range of discrete and extended structures, from which modularity permits the controlled assembly of their constituents to generate asymmetric configurations of pores or architectures. In this perspective, we present the different strategies to impart directional asymmetry over nano/meso/macroscopic length scales in porous materials and the resulting novel properties and applications.

Design strategies for the controlled assembly of discrete and extended reticular materials with asymmetric configurations of pores or architectures.     

Cooperative catalytically active sites for methanol activation by single metal ion-doped H-ZSM-5

Catalytic conversion of methanol to aromatics and hydrocarbons is regarded as a key alternative technology to oil processing. Although the inclusion of foreign metal species in H-ZSM-5 containing Brønsted acid site (BAS) is commonly found to enhance product yields, the nature of catalytically active sites and the rationalization for catalytic performance still remain obscure. Herein, by acquiring comparable structural parameters by both X-ray and neutron powder diffractions over a number of metal-modified ZSM-5 zeolites, it is demonstrated for the first time that active pairs of metal site-BAS within molecular distance is created when single and isolated transition metal cation is ion-exchanged with the zeolites. According to our DFT model, this could lead to the initial heterolytic cleavage of small molecules such as water and methanol by the pair with subsequent reactions to form products at high selectivity as that observed experimentally. It may account for their active and selective catalytic routes of small molecule activations.

Diffraction studies and DFT calculations show the formation of frustrated Lewis pair (FLP) over M-ZSM-5 for heterolytic cleavage of CH₃OH.     

Switchable electrical conductivity in a three-dimensional metal–organic framework via reversible ligand n-doping

Redox-active metal–organic frameworks (MOFs) are promising materials for a number of next-generation technologies, and recent work has shown that redox manipulation can dramatically enhance electrical conductivity in MOFs. However, ligand-based strategies for controlling conductivity remain under-developed, particularly those that make use of reversible redox processes. Here we report the first use of ligand n-doping to engender electrical conductivity in a porous 3D MOF, leading to tunable conductivity values that span over six orders of magnitude. Moreover, this work represents the first example of redox switching leading to reversible conductivity changes in a 3D MOF.

Redox-active ligands are used to reversibly tune electrical conductivity in a porous 3D metal–organic framework (MOF).     

Coordination-based self-assembled capsules (SACs) for protein,CRISPR–Cas9, DNA and RNA delivery

Biologics, such as functional proteins and nucleic acids, have recently dominated the drug market and comprise seven out of the top 10 best-selling drugs. Biologics are usually polar, heat sensitive, membrane impermeable and subject to enzymatic degradation and thus require systemic routes of administration and delivery. Coordination-based delivery vehicles, which include nanosized extended metal–organic frameworks (nMOFs) and discrete coordination cages, have gained a lot of attention because of their remarkable biocompatibility, in vivo stability, on-demand biodegradability, high encapsulation efficiency, easy surface modification and moderate synthetic conditions. Consequently, these systems have been extensively utilized as carriers of biomacromolecules for biomedical applications. This review summarizes the recent applications of nMOFs and coordination cages for protein, CRISPR–Cas9, DNA and RNA delivery. We also highlight the progress and challenges of coordination-based platforms as a promising approach towards clinical biomacromolecule delivery and discuss integral future research directions and applications.

SACs can be efficiently used to load biologics such as proteins, CRISPR–Cas9, DNA and RNA and release them on-demand.     

Enantioselective transition metal catalysis directed by chiral cations

Enantioselective transition metal catalysis directed by chiral cations is the amalgamation of chiral cation catalysis and organometallic catalysis. Thus far, three strategies have been revealed: ligand scaffolds incorporated on chiral cations, chiral cations paired with transition metal ‘ate’-type complexes, and ligand scaffolds incorporated on achiral anions. Chiral cation ion-pair catalysis has been successfully applied to alkylation, cycloaddition, dihydroxylation, oxohydroxylation, sulfoxidation, epoxidation and C–H borylation. This development represents an effective approach to promote the cooperation between chiral cations and transition metals, increasing the versatility and capability of both these forms of catalysts. In this review, we present current examples of the three strategies and suggest possible inclusions for the future.

Enantioselective transition metal catalysis directed by chiral cations is the amalgamation of chiral cation catalysis and organometallic catalysis.     

A feasible approach for automatically differentiable unitary coupled-cluster on quantum computers

We develop computationally affordable and encoding independent gradient evaluation procedures for unitary coupled-cluster type operators, applicable on quantum computers. We show that, within our framework, the gradient of an expectation value with respect to a parameterized n-fold fermionic excitation can be evaluated by four expectation values of similar form and size, whereas most standard approaches, based on the direct application of the parameter-shift-rule, come with an associated cost of expectation values. For real wavefunctions, this cost can be further reduced to two expectation values. Our strategies are implemented within the open-source package Tequila and allow blackboard style construction of differentiable objective functions. We illustrate initial applications through extended adaptive approaches for electronic ground and excited states.

We develop computationally affordable and encoding independent gradient evaluation procedures for unitary coupled-cluster type operators, applicable on quantum computers.     

Design and enhanced gene silencing activity of spherical 2′-fluoroarabinose nucleic acids (FANA-SNAs)

Drug delivery vectors for nucleic acid therapeutics (NATs) face significant barriers for translation into the clinic. Spherical nucleic acids (SNAs) – nanoparticles with an exterior shell made up of DNA strands and a hydrophobic interior – have recently shown great potential as vehicles to improve the biodistribution and efficacy of NATs. To date, SNA design has not taken advantage of the powerful chemical modifications available to NATs. Here, we modify SNAs with 2′-deoxy-2′-fluoro-d-arabinonucleic acid (FANA-SNA), and show increased stability, enhanced gene silencing potency and unaided uptake (gymnosis) as compared to free FANA. By varying the spacer region between the nucleic acid strand and the attached hydrophobic polymer, we show that a cleavable DNA based spacer is essential for maximum activity. This design feature will be important when implementing functionalized nucleic acids into nanostructures for gene silencing. The modularity of the FANA-SNA was demonstrated by silencing two different targets. Transfection-free delivery was superior for the modified SNA compared to the free FANA oligonucleotide.

Optimizing FANA modified spherical nucleic acids (FANA-SNAs) for highly efficient delivery of nucleic acid therapeutics.     

Using steric hindrance to manipulate and stabilize metal halide perovskites for optoelectronics

The chemical instability of metal halide perovskite materials can be ascribed to their unique properties of softness, in which the chemical bonding between metal halide octahedral frameworks and cations is the weak ionic and hydrogen bonding as in most perovskite structures. Therefore, various strategies have been developed to stabilize the cations and metal halide frameworks, which include incorporating additives, developing two-dimensional perovskites and perovskite nanocrystals, etc. Recently, the important role of utilizing steric hindrance for stabilizing and passivating perovskites has been demonstrated. In this perspective, we summarize the applications of steric hindrance in manipulating and stabilizing perovskites. We will also discuss how steric hindrance influences the fundamental kinetics of perovskite crystallization and film formation processes. The similarities and differences of the steric hindrance between perovskite solar cells and perovskite light emission diodes are also discussed. In all, utilizing steric hindrance is a promising strategy to manipulate and stabilize metal halide perovskites for optoelectronics.

Manipulation on steric hindrance can influence the fundamental kinetics of perovskite crystallization and film formation, therefore stabilizing and passivating perovskite structures, and promoting the commercialization of stable perovskite devices.     

Salient features of the aza-Wacker cyclization reaction

The intramolecular aza-Wacker reaction has unparalleled potential for the site-selective amination of olefins, but it is perhaps underappreciated relative to other alkene oxidations. The first part of this review makes the distinction between classical and tethered aza-Wacker cyclization reactions and summarizes examples of the latter. The second portion focuses on developments in asymmetric aza-Wacker cyclization technology. The final part of the review summarizes applications of all classes of aza-Wacker cyclization reactions to natural product assembly.

The aza-Wacker cyclization reaction is a powerful strategy for alkene amination.