N-vinyl azoles are prevalent moieties in pharmaceuticals, and fluorovinyl groups are widely recognized as carbonyl bi-oisosteres in drug design. Thus, N-fluorovinylated heteroarenes represent highly desirable functional groups in medicinal chemistry. To streamline the development of novel N-fluorovinylation and N-pentafluoropropenylation reactions, herein we safely handle fluorinated gases, such as vinylidene fluoride (VDF) and hexafluoropropene (HFP), as solid reagents using a metal–organic framework (MOF), Mg2(dobdc) (dobdc4− = 2,5-dioxidobenzene-1,4-dicarboxylate). Free (NH)-heteroarenes react directly with VDF via a defluorinative pathway under mild conditions, yielding terminal N-fluorovinylated products. Various complex, biologically active molecules smoothly undergo N-fluorovinylation under these conditions in much higher yields than with the gas alone. Mechanistic investigations, including deuterium incorpo-ration experiments and density functional theory calculations, suggest that this transformation represents a rare example of a concerted nucleophilic vinylic substitution (SNV) process. This protocol can be performed on gram scale, and the resulting N-fluorovinyl moieties can be further diversified to yield valuable motifs, such as N-fluorocyclopropyl groups. Finally, this defluorinative coupling can be generalized to other fluorinated alkene gases, such as HFP. Overall, this robust defluorinative coupling offers a straightforward strategy for synthesizing diverse fluorinated heteroarenes from readily available starting materials, providing broad access to these valuable motifs for the first time.
Abstract Electromicrobial production technologies (EMP) aim to combine renewable electricity and microbial metabolism. We have constructed molecular to reactor scale models of EMP systems using H 2 -oxidation and extracellular electron transfer (EET). We predict the electrical-to-biofuel conversion efficiency could rise to ≥ 52% with in vivo CO 2 -fixation. H 2 and EET-mediated EMP both need reactors with high surface areas. H 2 -diffusion at ambient pressure requires areas 20 to 2,000 times that of the solar photovoltaic (PV) supplying the system. Agitation can reduce this to less than the PV area, and the power needed becomes negligible when storing ≥ 1.1 megawatts. EET-mediated systems can be built that are ≤ 10 times the PV area and have minimal resistive energy losses if a conductive extracellular matrix (ECM) with a resistivity and height seen in natural conductive biofilms is used. The system area can be reduced to less than the PV area if the ECM conductivity and height are increased to those of conductive artificial polymers. Schemes that use electrochemical CO 2 -fixation could achieve electrical-to-fuel efficiencies of almost 50% with no complications of O 2 -sensitivity.
Fluorine is an increasingly common substituent in pharmaceuticals and agrochemicals because it improves the bioavailability and metabolic stability of organic molecules. Fluorinated gases represent intuitive building blocks for the late-stage installation of fluorinated groups, but they are generally overlooked because they require the use of specialized equipment. We report a general strategy for handling fluorinated gases as benchtop-stable solid reagents using metal-organic frameworks (MOFs). Gas-MOF reagents are prepared on gram-scale and used to facilitate fluorovinylation and fluoroalkylation reactions. Encapsulation of gas-MOF reagents within wax enables stable storage on the benchtop and controlled release into solution upon sonication, which represents a safer alternative to handling the gas directly. Furthermore, our approach enables high-throughput reaction development with these gases.
Carbon capture and utilization or sequestration (CCUS) from industrial point sources and direct air capture (DAC) are both necessary to curb the rising atmospheric levels of CO2. Amine scrubbers, the current leading carbon capture technology, suf-fer from poor oxidative and thermal stability, limiting their long-term cycling stability under oxygen-rich streams such as air and the emissions from natural gas combined cycle (NGCC) power plants. Herein, we demonstrate that the hydroxide-based cyclodextrin metal-organic framework (CD-MOF) Rb2CO3 CD-MOF ST possesses high CO2 capacities from dry dilute streams at low temperatures and humid streams at elevated temperatures. Additionally, it displays good thermal, oxidative, and cycling stabilities and selective CO2 capture under mixed gas conditions in dynamic breakthrough experiments. Unex-pectedly, under dry, hot conditions, a shift in the CO2 adsorption mechanism—from reversibly formed bicarbonate to irre-versibly formed carbonate—is observed, as supported by gas sorption and spectroscopic studies. This mechanistic switch, akin to urea formation in amine-functionalized sorbents, has not been previously reported in a hydroxide-based material and sheds new light on the interplay between bicarbonate and carbonate species during CO2 capture. Our findings provide valuable insight for the design of next-generation materials containing oxygen-based nucleophiles for carbon capture appli-cations.
Hydrogen sulfide (H2S) is an endogenous gasotransmitter with potential therapeutic value for treating a range of disorders, such as ischemia-reperfusion injury resulting from a myocardial infarction or stroke. However, the medicinal delivery of H2S is hindered by its corrosive and toxic nature. In addition, small molecule H2S donors often generate other reactive and sulfur-containing species upon H2S release, leading to unwanted side effects. Here, we demonstrate that H2S release from biocompatible porous solids, namely metal-organic frameworks (MOFs), is a promising alternative strategy for H2S delivery under physiologically relevant conditions. In particular, through gas adsorption measurements and density functional theory calculations we establish that H2S binds strongly and reversibly within the tetrahedral pockets of the fumaric acid-derived framework MOF-801 and the mesaconic acid-derived framework Zr-mes, as well as the new itaconic acid-derived framework CORN-MOF-2. These features make all three frameworks among the best materials identified to date for the capture, storage, and delivery of H2S. In addition, these frameworks are non-toxic to HeLa cells and capable of releasing H2S under aqueous conditions, as confirmed by fluorescence assays. Last, a cellular ischemia-reperfusion injury model using H9c2 rat cardiomyoblast cells corroborates that H2S-loaded MOF-801 is capable of mitigating hypoxia-reoxygenation injury, likely due to the release of H2S. Overall, our findings suggest that H2S-loaded MOFs represent a new family of easily-handled solid sources of H2S that merit further investigation as therapeutic agents. In addition, our findings add Zr-mes and CORN-MOF-2 to the growing lexicon of biocompatible MOFs suitable for drug delivery.
Perfluorocompound (PFC) gases play vital roles in microelectronics processing. Requirements for ulta-high purities traditionally necessitate use of virgin sources and thereby hinder the capture, purification, and reuse of these costly gases. Most importantly, gaseous PFCs are incredibly potent greenhouse gases with atmospheric lifetimes on the order of 103-104 years, and thus any environmental emissions have an outsized and prolonged impact on our climate. The development of sorbents that can capture PFC gases from industrial waste streams has lagged substantially behind the progress made over the last decade in capturing CO2 from both point emission sources and directly from air. Herein, we show that the metal–organic framework Zn(fba) (fba2– = 4,4’-(hexafluoroisopropylidene)bis-benzoate) displays an equilibrium selectivity for CF4 adsorption over N2 that surpasses those of all water-stable sorbents that have been reported for this separation. This selectivity is enabled by adsorption within narrow corrugated channels lined with ligand-based aryl rings, a site within this material that has not previously been realized as being accessible to guests. Analyses of adsorption kinetics and X-ray diffraction data are used to characterize sorption and diffusion of small adsorbates within these channels and strongly implicate rotation of the linker aryl rings as a gate that modulates transport of CF4 through a crystallite. Multi-component breakthrough measurements demonstrate that Zn(fba) is able to resolve CF4 and N2 under flowing mixed-gas conditions. Taken together, this work illuminates a more complete picture of the dynamic structure of Zn(fba), and also points toward general design principles that can enable large CF4 selectivities in sorbents with more favorable kinetic profiles.
Fluorine is ubiquitous in the pharmaceutical and agrochemical industries because it improves the bioavailability and metabolic stability of molecules. However, most modern fluoroalkylation and fluorovinylation protocols rely on reagents that are expensive, explosive, or otherwise challenging to use. Fluorinated gaseous reagents are promising alternatives that are overlooked for late-stage functionalization because they require specialized equipment. Herein, we report a general strategy for safely handling inexpensive fluorinated gaseous building blocks as benchtop-stable solid reagents using porous metal–organic frameworks (MOFs). Gas–MOF reagents are employed to facilitate novel fluorovinylation and fluoroalkylation reactions, which represent safe, efficient, and atom-economical alternatives to current methods. Our approach enables high-throughput reaction development with any gaseous reagent, opening the door for the development of myriad new synthetic transformations.
Covalent organic frameworks linked by carbon-carbon double bonds (C=C COFs) are an emerging class of crystalline, porous, and conjugated polymeric materials with potential applications in organic electronics, photocatalysis, and energy storage. Despite the rapidly growing interest in sp
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