The recent emergence of signaling roles for transition metals presages a broader contribution of these elements beyond their traditional functions as metabolic cofactors. New chemical approaches to ...identify the sources, targets and physiologies of transition-metal signaling can help expand understanding of the periodic table in a biological context.
Direct solar-powered production of value-added chemicals from CO2 and H2O, a process that mimics natural photosynthesis, is of fundamental and practical interest. In natural photosynthesis, CO2 is ...first reduced to common biochemical building blocks using solar energy, which are subsequently used for the synthesis of the complex mixture of molecular products that form biomass. Here we report an artificial photosynthetic scheme that functions via a similar two-step process by developing a biocompatible light-capturing nanowire array that enables a direct interface with microbial systems. As a proof of principle, we demonstrate that a hybrid semiconductor nanowire–bacteria system can reduce CO2 at neutral pH to a wide array of chemical targets, such as fuels, polymers, and complex pharmaceutical precursors, using only solar energy input. The high-surface-area silicon nanowire array harvests light energy to provide reducing equivalents to the anaerobic bacterium, Sporomusa ovata, for the photoelectrochemical production of acetic acid under aerobic conditions (21% O2) with low overpotential (η < 200 mV), high Faradaic efficiency (up to 90%), and long-term stability (up to 200 h). The resulting acetate (∼6 g/L) can be activated to acetyl coenzyme A (acetyl-CoA) by genetically engineered Escherichia coli and used as a building block for a variety of value-added chemicals, such as n-butanol, polyhydroxybutyrate (PHB) polymer, and three different isoprenoid natural products. As such, interfacing biocompatible solid-state nanodevices with living systems provides a starting point for developing a programmable system of chemical synthesis entirely powered by sunlight.
A key challenge in the field of electrochemical carbon dioxide reduction is the design of catalytic materials featuring high product selectivity, stability, and a composition of earth-abundant ...elements. In this work, we introduce thin films of nanosized metal–organic frameworks (MOFs) as atomically defined and nanoscopic materials that function as catalysts for the efficient and selective reduction of carbon dioxide to carbon monoxide in aqueous electrolytes. Detailed examination of a cobalt–porphyrin MOF, Al2(OH)2TCPP-Co (TCPP-H2 = 4,4′,4″,4‴-(porphyrin-5,10,15,20-tetrayl)tetrabenzoate) revealed a selectivity for CO production in excess of 76% and stability over 7 h with a per-site turnover number (TON) of 1400. In situ spectroelectrochemical measurements provided insights into the cobalt oxidation state during the course of reaction and showed that the majority of catalytic centers in this MOF are redox-accessible where Co(II) is reduced to Co(I) during catalysis.
Reactive oxygen species (ROS) are a family of molecules that are continuously generated, transformed and consumed in all living organisms as a consequence of aerobic life. The traditional view of ...these reactive oxygen metabolites is one of oxidative stress and damage that leads to decline of tissue and organ systems in aging and disease. However, emerging data show that ROS produced in certain situations can also contribute to physiology and increased fitness. This Perspective provides a focused discussion on what factors lead ROS molecules to become signal and/or stress agents, highlighting how increasing knowledge of the underlying chemistry of ROS can lead to advances in understanding their disparate contributions to biology. An important facet of this emerging area at the chemistry-biology interface is the development of new tools to study these small molecules and their reactivity in complex biological systems.
Formaldehyde (FA) is a reactive carbonyl species (RCS) produced in living systems that has been implicated in epigenetics as well as in the pathologies of various cancers, diabetes, and heart, liver, ...and neurodegenerative diseases. Traditional methods for biological FA detection rely on sample destruction and/or extensive processing, resulting in a loss of spatiotemporal information. To help address this technological gap, we present the design, synthesis, and biological evaluation of a fluorescent probe for live-cell FA imaging that relies on a FA-induced aza-Cope rearrangement. Formaldehyde probe-1 (FAP-1) is capable of detecting physiologically relevant concentrations of FA in aqueous buffer and in live cells with high selectivity over potentially competing biological analytes. Moreover, FAP-1 can visualize endogenous FA produced by lysine-specific demethylase 1 in a breast cancer cell model, presaging the potential utility of this chemical approach to probe RCS biology.
Site-selective bioconjugation to native protein residues is a powerful tool for protein functionalization, with cysteine and lysine side chains being the most common points for attachment owing to ...their high nucleophilicity. We now report a strategy for histidine modification using thiophosphorodichloridate reagents that mimic post-translational histidine phosphorylation, enabling fast and selective labeling of protein histidines under mild conditions where various payloads can be introduced via copper-assisted alkyne–azide cycloaddition (CuAAC) chemistry. We establish that these reagents are particularly effective at covalent modification of His-tags, which are common motifs to facilitate protein purification, as illustrated by selective attachment of polyarginine cargoes to enhance the uptake of proteins into living cells. This work provides a starting point for probing and enhancing protein function using histidine-directed chemistry.
Emerging from the origins of supramolecular chemistry and the development of selective chemical receptors that rely on lock‐and‐key binding, activity‐based sensing (ABS)—which utilizes molecular ...reactivity rather than molecular recognition for analyte detection—has rapidly grown into a distinct field to investigate the production and regulation of chemical species that mediate biological signaling and stress pathways, particularly metal ions and small molecules. Chemical reactions exploit the diverse chemical reactivity of biological species to enable the development of selective and sensitive synthetic methods to decipher their contributions within complex living environments. The broad utility of this reaction‐driven approach facilitates application to imaging platforms ranging from fluorescence, luminescence, photoacoustic, magnetic resonance, and positron emission tomography modalities. ABS methods are also being expanded to other fields, such as drug and materials discovery.
ABSolute selectivity: Stemming from supramolecular chemical receptors that rely on lock‐and‐key binding, activity‐based sensing (ABS) methods utilizing a variety of chemical reaction approaches offer the highly selective detection of small molecules and metals in biological systems. This Review discusses key design principles, reaction development, and sensing methods, and gives an outlook on this emerging field.
Hydrogen sulfide (H
2
S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions ...to human health and disease. H
2
S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H
2
S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H
2
S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H
2
S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H
2
S pools in living systems. Three main strategies used in molecular probe development for H
2
S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploits the strong nucleophilicity and reducing potency of H
2
S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H
2
S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.
This review highlights progress in the development of molecular probes for live cell imaging of hydrogen sulfide and other reactive sulfur species, including sulfite, bisulfite, sulfane sulfur species, and S-nitrosothiols.
Hydrogen sulfide (H2S) is emerging as an important mediator of human physiology and pathology but remains difficult to study, in large part because of the lack of methods for selective monitoring of ...this small signaling molecule in live biological specimens. We now report a pair of new reaction-based fluorescent probes for selective imaging of H2S in living cells that exploit the H2S-mediated reduction of azides to fluorescent amines. Sulfidefluor-1 (SF1) and Sulfidefluor-2 (SF2) respond to H2S by a turn-on fluorescence signal enhancement and display high selectivity for H2S over other biologically relevant reactive sulfur, oxygen, and nitrogen species. In addition, SF1 and SF2 can be used to detect H2S in both water and live cells, providing a potentially powerful approach for probing H2S chemistry in biological systems.
Natural photosynthesis harnesses solar energy to convert CO₂ and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion ...in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatible inorganic catalysts. The hydrogen is then used by living cells as a source of reducing equivalents for conversion of CO₂ to the value-added chemical product methane. Using platinum or an earth-abundant substitute, α-NiS, as biocompatible hydrogen evolution reaction (HER) electrocatalysts andMethanosarcina barkerias a biocatalyst for CO₂ fixation, we demonstrate robust and efficient electrochemical CO₂ to CH₄ conversion at up to 86% overall Faradaic efficiency for ≥7 d. Introduction of indium phosphide photocathodes and titanium dioxide photoanodes affords a fully solar-driven system for methane generation from water and CO₂, establishing that compatible inorganic and biological components can synergistically couple light-harvesting and catalytic functions for solar-to-chemical conversion.
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