Chemical manipulation of naturally occurring peptides offers a convenient route for generating analogs to screen against different therapeutic targets. However, the limited success of the conventional chemical libraries has urged chemical biologists to adopt alternative methods such as phage and mRNA displays and create libraries of a large number of variants for the screening and selection of novel peptides. Messenger RNA (mRNA) display provides great advantages in terms of the library size and the straightforward recovery of the selected polypeptide sequences. Importantly, the integration of the flexible in vitro translation (FIT) system with the mRNA display provides the basis of the random nonstandard peptides integrated discovery (RaPID) approach for the introduction of diverse nonstandard motifs, such as unnatural side chains and backbone modifications. This platform allows the discovery of functionalized peptides with tight binding against virtually any protein of interest (POI) and therefore shows great potential in the pharmaceutical industry. However, this method has been limited to targets generated by recombinant expression, excluding its applications to uniquely modified proteins, particularly those with post-translational modifications.

Bimetallic catalysts hold promise in tailoring the catalytic activity and selectivity of transition metals for important chemical processes due to the synergistic coupling between the constituent elements that can connect catalytical active sites. However, it remains a challenge to construct an ideal bimetallic catalyst to study the respective or cooperative effects of the two transition metals within the bimetallic catalyst on the overall catalytic performance because multiple factors are always convoluted, such as the size dispersity of particles, the inhomogeneous structure, and the unknown exact location of the two metal elements in any particle. Therefore, almost all of the current studies give rise to the statistics of the overall catalytic performance from all of the particles in a bimetallic catalyst or at least the observed performance reflects an ensemble average of all metal atoms in a particle. Atomically precise metal nanoclusters have attracted catalysis scientists since their total structures (core plus surface) were solved by single-crystal X-ray crystallography, thereby providing unparalleled opportunities to build a precise correlation of catalyst structures with catalytic properties at an atomic level. Within this field, we are interested in identifying catalytically active sites and further constructing the active sites by an atom-by-atom manipulation, which are typically challenging for conventional particle-based heterogeneous catalysts and organometallics-based complex catalysts.

Chirality is ubiquitous in the universe and in living creatures over detectable length scales from the subatomic to the galactic, as exemplified in the two extremes by subatomic particles (neutrinos) and spiral galaxies. Between them are living creatures that display multiple levels of chirality emerging from hierarchically assembled asymmetric building blocks. Not too far from the bottom of this pyramid are the foundational building blocks with chiral atomic centers on sp3 carbon atoms exemplified by l-amino acids and d-sugars that are self-assembled into higher-order structures with increasing dimensions forming highly complex, amazingly functional, and energy-efficient living systems. The organization and materials employed in their construction inspired scientists to replicate complex living systems via the self-assembly of chiral components. Multiple studies pointed to unexpected and unique electromagnetic properties of chiral structures with nanoscale and microscale dimensions, including giant circular dichroism and collective circularly polarized scattering that their constituent units did not possess.

The requested change is to the Acknowledgments, where Alexander Bunnell was inadvertently not acknowledged in the original article. This work was supported by the NIH NIGMS (R35GM1361332). We gratefully acknowledge Alexander Bunnell for conducting the reactions shown in Scheme 5. This article has not yet been cited by other publications.

With unparalleled programmability, DNA has evolved as a powerful scaffold for engineering intricate and dynamic systems that can perform diverse tasks. By allowing serial detection of molecular targets in complex cellular milieus, increasingly sophisticated DNA sensors have not only promoted significant advances in unveiling the fundamental mechanisms of various pathophysiological processes but also provided a useful toolkit for disease diagnostics based on molecular signatures. Despite much progress, an inherent limitation of DNA-based sensors is that they often lack spatial control and cell-type selectivity for the sensing activity because of their “always active” design mechanism. Since most molecular targets of interests are not exclusive to disease cells, they are also shared by normal cells, the application of such biosensors for disease-specific imaging is limited by inadequate signal-to-background ratios due to indistinguishable signal response in both disease and normal cells. Therefore, imparting biosensors with spatial controllability remains a key issue to achieve molecular imaging with high sensitivity and cell specificity.

Developing next-generation colloidal semiconductor nanocrystals with high-quality optoelectronic properties and precise processability relies on achieving complete mastery over the surface characteristics of nanocrystals (NCs). This requires precise engineering of the ligand–NC surface interactions, which poses a challenge due to the complex reactivity of the multiple binding sites across the entire surface. Accordingly, recent progress has been made by strategically combining well-defined surface models with quantitative surface reactions to advance our understanding and manipulation of NC surface chemistry. Our lab has contributed to this progress by developing a size-dependent shape model of IV–VI NCs, gaining insights into their unique facet-specific chemistry, and developing a systematic ligand modification strategy for target applications. Furthermore, we have created well-defined facets in III–V NCs via a co-passivation strategy, addressing the previously lacking specific shapes.

Properties of colloidal semiconductor nanocrystals with a single-crystalline structure are largely dominated by their surface structure at an atomic-molecular level, which is not well understood and controlled, due to a lack of experimental tools. However, if viewing the nanocrystal surface as three relatively independent spatial zones (i.e., crystal facets, inorganic−ligands interface, and ligands monolayer), we may approach an atomic-molecular level by coupling advanced experimental techniques and theoretical calculations.

Development of multifunctional nanoparticles (NPs) with desired properties is a significant topic in the field of nanotechnology and has been anticipated to revolutionize cancer diagnosis and treatment modalities. The surface character is one of the most important parameters of NPs that can directly affect their in vivo fate, bioavailability, and final theranostic outcomes and thus should be carefully tuned to maximize the diagnosis and treatment effects while minimizing unwanted side effects. Surface engineered NPs have utilized various surface functionality types and approaches to meet the requirements of cancer therapy and imaging. Despite the various strategies, these surface modifications generally serve similar purposes, namely, introducing therapeutic/imaging modules, improving stability and circulation, enhancing targeting ability, and achieving controlled functions. These surface engineered NPs hence could be applied in various cancer diagnosis and treatment scenarios and continuously contribute to the clinical translation of the next-generation NP-based platforms toward cancer theranostics.

Nanostructured copper-based materials have emerged as a new generation of robust architectures for realizing high-performing and reliable interconnection in modern electronic packaging. As opposed to traditional interconnects, nanostructured materials offer better compliance during the packaging assembly process. Due to the high surface area-to-volume ratio of nanomaterials, they also enable joint formation by sintering through thermal compression at much lower temperatures compared to bulk counterparts. Nanoporous Cu (np-Cu) films have been employed in electronic packaging as materials that facilitate a chip-to-substrate interconnection, realized by a Cu-on-Cu bonding after sintering.

In the pursuit of maximizing the energy supply and sustainable energy development, high-energy-density energy storage systems beyond lithium-ion batteries are surging. The metal-catalysis battery, composed of a metal anode, electrolyte, and redox-coupled electrocatalyst cathode with gas, liquid, or solid as active reactants, is regarded as a promising energy storage and conversion system due to its dual functions of energy storage and chemical production. In this system, with the assistance of a redox-coupled catalyst, during discharging, the reduction potential energy of the metal anode is converted into chemicals along with electrical energy generation, while the external electrical energy is translated to the reduction potential energy of the metal anode and the oxidation potential energy of the reactants during charging. In this loop, the electrical energy and sometimes chemicals can be generated simultaneously. Although intensive effort has been devoted to the exploration of redox-coupled catalysts, the essence of the metal-catalysis battery, which is the prerequisite for further development and application, has been overlooked.

In nature, the coenzyme NAD(P)H is utilized for the transfer of hydrogen and electrons in biocatalytic reduction, which involves the process of recycling, coenzyme usage, and reduction. Inspired by the biological system, a series of nonregenerable achiral and chiral NAD(P)H models were synthesized and employed. However, this approach faced intractable limitations, such as the need for an equivalent amount of mimics, accompanied by the production of byproducts, which resulted in poor atom economy and difficult separation of products. Therefore, the development of new and efficient methodologies for synthesis, regeneration, and application of the NAD(P)H models in organic synthesis is greatly desired.

Electrochemistry has a central role in addressing the societal issues of our time, including the United Nations’ Sustainable Development Goals (SDGs) and beyond. At a more basic level, however, elucidating the nature of electrode–electrolyte interfaces is an ongoing challenge due to many reasons, but one obvious reason is the fact that the electrode–electrolyte interface is buried by a thick liquid electrolyte layer. This fact would seem to preclude, by default, the use of many traditional characterization techniques in ultrahigh vacuum surface science due to their incompatibility with liquids. However, combined UHV-EC (ultrahigh vacuum-electrochemistry) approaches are an active area of research and provide a means of bridging the liquid environment of electrochemistry to UHV-based techniques. In short, UHV-EC approaches are able to remove the bulk electrolyte layer by performing electrochemistry in the liquid environment of electrochemistry followed by sample removal (referred to as emersion), evacuation, and then transfer into vacuum for analysis.

Umpolung, a term describing the reversal of innate polarity, has become an indispensable tool to unlock new chemical space by overcoming the limitations of natural polarity. Introduced by Dieter Seebach in 1979, this principle has had a tremendous impact on synthetic organic chemistry, offering previously inaccessible retrosynthetic disconnections. In contrast to the great progress made over the past decades for the generation of effective acyl anion synthons, the umpolung at the α-position of carbonyls (converting enolates into enolonium ions) has long proved challenging and only recently regained traction. Aiming to develop synthetic approaches to α-functionalization capable of complementing enolate chemistry, our group initiated, nearly 6 years ago, a program devoted to the α-umpolung of carbonyl derivatives. In this Account, following an overview of established methods, we will summarize our findings in this rapidly developing field. We focus on two distinct, yet related, topics of two carbonyl classes: (1) amides, where umpolung is enabled by electrophilic activation, and (2) ketones, where umpolung is enabled using hypervalent iodine reagents. Our group has developed several protocols to allow amide umpolung and subsequent α-functionalization, relying on electrophilic activation. Over the course of our investigations, transformations that are particularly challenging using enolate-based approaches, such as the direct α-oxygenation, α-fluorination, and α-amination of amides as well as the synthesis of 1,4-dicarbonyls from amide substrates, have been unlocked. Based on some of our most recent studies, this method has been shown to be so general that almost any nucleophile can be added to the α-position of the amide. In this Account, special emphasis will be placed on the discussion of mechanistic aspects. It is important to note that recent progress in this area has involved a shift in focus, moving even further away from the amide carbonyl, a development that shall also be detailed in a final subsection that highlights our latest investigations of umpolung-based remote functionalization of the β- and γ-positions of amides. The second section of this Account covers our more recent work dedicated to the exploration of the enolonium chemistry of ketones, unlocked through the use of hypervalent iodine reagents. By placing our work in the context of previous pioneering achievements, which mainly focused on the α-functionalization of carbonyls, we discuss new skeletal reorganizations of enolonium ions enabled by the unique properties of incipient positive charges α to electron-deficient moieties. Transformations such as intramolecular cyclopropanations and aryl migrations are covered and supplemented by detailed insight into the unusual nature of the intermediate species, including nonclassical carbocations.

Characterized by the reverse intersystem crossing (RISC) process from the triplet state (T1) to the singlet state (S1), thermally activated delayed fluorescence (TADF) emitters, which produce light by harvesting both triplet and singlet excitons without noble metals, are considered to be third-generation organic electroluminescent materials. Rapid advances in molecular design criteria, understanding the photophysics underlying TADF, and applications of TADF materials as emitters in organic light-emitting diodes (OLEDs) have been achieved. Theoretically, enhanced spin–orbit coupling (SOC) between singlet and triplet states can result in a fast RISC process and thus a high light-emitting efficiency according to Fermi’s golden rule. Therefore, regulating the nature of triplet excited states by elaborate molecular design to improve SOC is an effective approach to high-efficiency TADF-based OLEDs. Generally, on one hand, the increased local excited (LE) populations of the excited triplet state can significantly improve the nature flips between S1 and T1. On other hand, the reduced energy gap between S1 and the lowest triplet with a charge transfer (CT) characteristic can also enhance their vibronic coupling. Consequently, it is vital to determine how to regulate the nature of triplet excited states by molecular design to guide the material synthesis, especially for polymeric emitters.

Closed-loop cycling of green hydrogen is a promising alternative to the current hydrocarbon economy for mitigating the energy crisis and environmental pollution. It stores energy from renewable energy sources like solar, wind, and hydropower into the chemical bond of dihydrogen (H2) via (photo)electrochemical water splitting, and then the stored energy can be released on demand through the reverse reactions in H2–O2 fuel cells. The sluggish kinetics of the involved half-reactions like hydrogen evolution reaction (HER), oxygen evolution reaction (OER), hydrogen oxidation reaction (HOR), and oxygen reduction reaction (ORR) limit its realization. Moreover, considering the local gas–liquid–solid triphase microenvironments during H2 generation and utilization, rapid mass transport and gas diffusion are critical as well. Accordingly, developing cost-effective and active electrocatalysts featuring three-dimensional hierarchically porous structures are highly desirable to promote the energy conversion efficiency. Traditionally, the synthetic approaches of porous materials include soft/hard templating, sol–gel, 3D printing, dealloying, and freeze-drying, which often need tedious procedures, high temperature, expensive equipment, and/or harsh physiochemical conditions. In contrast, dynamic electrodeposition on bubbles using the in situ formed bubbles as templates can be conducted at ambient conditions with an electrochemical workstation. Moreover, the whole preparation process can be finished within minutes/hours, and the resulting porous materials can be employed as catalytic electrodes directly, avoiding the use of polymeric binders like Nafion and the consequent issues like limited catalyst loading, reduced conductivity, and inhibited mass transport.

Peptides are essential components of living systems and contribute to critical biological processes, such as cell proliferation, immune defense, tumor formation, and differentiation. Therefore, peptides have attracted considerable attention as targets for the development of therapeutic products. The incorporation of unnatural amino acid residues into peptides can considerably impact peptide immunogenicity, toxicity, side effects, water solubility, action duration, and distribution and enhance the peptides’ druggability. Typically, the direct modification of natural amino acids is a practical and effective approach for promptly obtaining unnatural amino acids. However, selective functionalization of multiple C(sp3)–H bonds with comparable chemical reactivities in the peptide side chains remains a formidable challenge. Furthermore, chemical modifications aimed at highly reactive (nucleophilic and aromatic) groups on peptide side chains can interfere with the biological activity of peptides.

Catalytic intermolecular hydroamination of alkenes is an atom- and step-economical method for the synthesis of amines, which have important applications as pharmaceuticals, agrochemicals, catalysts, and materials. However, hydroaminations of alkenes in high yield with high selectivity are challenging to achieve because these reactions often lack a thermodynamic driving force and often are accompanied by side reactions, such as alkene isomerization, telomerization, and oxidative amination. Consequently, early examples of hydroamination were generally limited to the additions of N–H bonds to conjugated alkenes or strained alkenes, and the catalytic hydroamination of unactivated alkenes with late transition metals has only been disclosed recently. Many classes of catalysts, including early transition metals, late transition metals, rare-earth metals, acids, and photocatalysts, have been reported for catalytic hydroamination. Among them, late transition-metal complexes possess several advantages, including their relative ease of handling and their high compatibility of substrates containing polar or sensitive functional groups.

Hair is a natural polymeric composite primarily composed of tight macrobundles of keratin proteins, which are highly responsive to external stimuli, similarly to the hydrogels and other natural fibrous gel systems like collagen and fibrin.

The enhanced catalytic properties of alloy nanostructures have made them a focus of extensive research in the field of catalysis. Alloy nanostructures can be classified into two types: disordered alloys (also known as solid solutions) and ordered intermetallics. The latter are of particular interest as they possess long-range atomic scale ordering, which leads to well-defined active sites that can be used to accurately assess structure–property relationships and their impact on (electro)catalytic performance.

The controlled doping of organic semiconductors (OSCs) is crucial not only for improving the performance of electronic and optoelectronic devices but also for enabling efficient thermoelectric conversion and spintronic applications. The mechanism of doping for OSCs is fundamentally different from that of their inorganic counterparts. In particular, the interplay between dopants and host materials is complicated considering the low dielectric constant, strong lattice-charge interaction, and flexible nature of materials. Recent experimental breakthroughs in the molecular design of dopants and the precise doping with high spatial resolution call for more profound understandings as to how the dopant interacts with the charge introduced to OSCs and how the admixture of dopants alters the electronic properties of host materials before one can exploit controllable doping to realize desired functionalities.