Fluorescent dyes are an indispensable part of the scientific enterprise. Xanthene-based fluorophores, like fluorescein and rhodamine, have been in continual use across numerous fields since their invention in the late 19 century. Modern methods to synthesize and expand the scope of xanthene dye chemistry have enabled new colors, enhanced stability, and improved brightness. Modifications to the 3-position of xanthene dyes have been, until recently, less well-explored. Here, we discuss how small changes to the identity of the substituent at the 3-position of fluoresceins and rhodamines can profoundly alter the properties of xanthene dyes, with the potential to unlock new applications at the interface of chemistry and biology.

Graspetides are a class of RiPPs (ribosomally synthesized and post-translationally modified peptides) defined by the presence of ester or amide side chain-side chain linkages resulting in peptide macrocycles. The graspetide name comes from the ATP-grasp enzymes that install the side chain-side chain linkages. This review covers the early, activity-based isolation of the first graspetides, marinostatins and microviridins, as well as the key genomics-driven experiments that established graspetide as RiPPs. The mechanism and structure of graspetide-associated ATP-grasp enzymes is discussed. Genome mining methods to discover new graspetides as well as the analytical techniques used to determine the linkages in graspetides are described. Extant knowledge on the bioactivity of graspetides as protease inhibitors is reviewed. Further chemical modifications to graspetides as well graspetide engineering studies are also described. We conclude with several suggestions about future directions of graspetide research.

In this paper, we propose ways to address diversity, equity, and inclusion (DEI) challenges and outline steps and methodologies for creating allies and empowering leaders to support DEI efforts in science, technology, engineering, mathematics, and medicine (STEMM) for underrepresented minorities (URMs).

Organic peroxides are becoming popular intermediates for novel chemical transformations. The weak O-O bond is readily reduced by transition metals, including iron and copper, to initiate a radical cascade process that breaks C-C bonds. Great potential exists for the rapid generation of complexity, originating from the ability to couple the resulting free radicals with a wide range of partners. First, this review article discusses the history and synthesis of organic peroxides, providing the context necessary to understand this methodology. Then, it highlights 91 examples of recent applications of the radical functionalization of C-C bonds accessed through the transition metal-mediated reduction of organic peroxides. Finally, we provide some comments about safety when working with organic peroxides.

Nagib and Rajanbabu share a clever approach to remote desaturation triggered by metal-catalysed hydrogen atom transfer (mHAT) to an alkene, followed by intramolecular 1,6-HAT, and terminated via mHAT. This method both realizes a valuable synthetic transformation and provides multiple lessons for the design of HAT-mediated reactions.

Inspired by the role of -heterocyclic carbenes (NHCs) in natural enzymatic processes, chemists have harnessed the umpolung (polarity reversal) reactivity of these reactive, Lewis basic species over the past few decades to construct key chemical bonds. While NHCs continue to play a role in two-electron transformations, their unique redox properties enable a variety of useful, stabilized radical species to be accessed via single-electron oxidation or reduction. As a result, their utility in synthesis has grown rapidly concurrent with the revival of radical chemistry, highlighted by their extensive use as reactive single-electron species in recent years.

Realizing cooperativity between ligands and metal centers in the transfer of proton and electron equivalents has the potential to facilitate faster, selective, and novel transformations. Recent advances in the synthesis and application of ligands with these design features illustrate the value of this biomimetic strategy in synthetic chemistry.

Cation-coupled chloride cotransporters (CCCs) modulate the transport of sodium and/or potassium cations coupled with chloride anions across the cell membrane. CCCs thus help regulate intracellular ionic concentration and consequent cell volume homeostasis. This has been largely exploited in the past to develop diuretic drugs that act on CCCs expressed in the kidney. However, a growing wealth of evidence has demonstrated that CCCs are also critically involved in a great variety of other pathologies, motivating most recent drug discovery programs targeting CCCs. Here, we examine the structure-function relationship of CCCs. By linking recent high-resolution cryogenic electron microscopy (cryo-EM) data with older biochemical/functional studies on CCCs, we discuss the mechanistic insights and opportunities to design selective CCC modulators to treat diverse pathologies.

Metal complexes have been widely used for applications in the chemical and physical sciences due to their unique electronic and stereochemical properties. For decades the use of metal complexes for medicinal applications has been postulated and demonstrated. The distinct characteristics of metal complexes, including their molecular geometries (that are not readily accessed by organic molecules), as well as their ligand exchange, redox, catalytic, and photophysical reactions, give these compounds the potential to interact and react with biomolecules in unique ways and by distinct mechanisms of action. Herein, the potential of metal complexes to act as components bioactive therapeutic compounds is discussed.

Recently, DNA-encoded library (DEL) technology has emerged as an innovative screening modality for the rapid discovery of therapeutic candidates in pharmaceutical settings. This platform enables a cost-effective, time-efficient, and large-scale assembly and interrogation of billions of small organic ligands against a biological target in a single experiment. An outstanding challenge in DEL synthesis is the necessity for water-compatible transformations under ambient conditions. To access uncharted chemical space, the adoption of photoredox catalysis in DELs, including Ni-catalyzed manifolds and radical/polar crossover reactions, has enabled the construction of novel structural scaffolds through regulated odd-electron intermediates. Herein, a critical discussion of the validation of photoredox-mediated alkylation in DEL environments is presented. Current synthetic gaps are highlighted and opportunities for further development are speculated upon.

Phototherapy, including photodynamic therapy and photothermal therapy, exploits light to activate photo-reactions that kill cancer cells. Recent studies show that phototherapy can not only kill irradiated tumor cells, but also elicit a tumor specific immune response. This phenomenon breaks the limitations of conventional phototherapy, and has reinvigorated phototherapy-related research in the era of cancer immunotherapy. Nanoparticles play essential roles in this new campaign for allowing simultaneous delivery of photo-reactive agents and immune modulators. Some nanoparticles are potent adjuvants on their own and can augment anticancer immunity to fight off tumor relapse and metastasis. In this review, we summarize recent advances on exploiting nanoparticle-based photodynamic therapy and photothermal therapy for cancer immunotherapy, with an emphasis on nanoplatform design and functions.

Harnessing the chemistry of onium ylide intermediates generated from transition metal catalysis is a powerful strategy to convert simple precursors into complex scaffolds. While the chemistry of onium ylides has been studied for over three decades, transformations of aziridinium ylides have just recently emerged as a versatile way to exploit the strain of these reactive intermediates to furnish densely functionalized -heterocycles in a highly stereocontrolled manner. Herein, we provide a short overview of the key concepts and recent developments in this area, with a focus on how mechanistic studies to delineate the factors controlling the reactivity of aziridinium ylides can stimulate fruitful future investigations.

Gold redox chemistry holds the promise of unique reactivities and selectivities that are different to other transition metals. Recent studies have utilized strain release, ligand design, and photochemistry to promote the otherwise sluggish oxidative addition to Au(I) complexes. More details on the reductive elimination from Au(III) complexes have also been revealed. These discoveries have facilitated the development of gold redox catalysis and will continue to offer mechanistic insight and inspiration for other transition metals. This review highlights how research in organometallic chemistry has led to gold redox catalysis, as well as applications in materials science, bioconjugation, and radiochemical synthesis.

Bioelectric devices can probe fundamental biological dynamics and improve the lives of human beings. However, direct application of traditional rigid electronics onto soft tissues can cause signal transduction and biocompatibility issues. One common mitigation strategy is the use of soft-hard composites to form more biocompatible interfaces with target cells or tissues. Here, we identify several soft-hard composite designs in naturally occurring systems. We use these designs to categorize the existing bioelectric interfaces and to suggest future opportunities. We discuss the utility of soft-hard composites for a variety of interfaces, such as and electronic or optoelectronic sensing and genetic and non-genetic modulation. We end the review by proposing new soft-hard composites for future bioelectric studies.