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1. Stereodivergent atom-transfer radical cyclization by engineered cytochromes P450

   https://doi.org/10.1126/science.abk1603  

   Zhou, Qi; Chin, Michael; Fu, Yue; Liu, Peng; Yang, Yang (December 2021, Science)

   Naturally occurring enzymes can be a source of unnatural reactivity that can be molded by directed evolution to generate efficient biocatalysts with valuable activities. Owing to the lack of exploitable stereocontrol elements in synthetic systems, steering the absolute and relative stereochemistry of free-radical processes is notoriously difficult in asymmetric catalysis. Inspired by the innate redox properties of first-row transition-metal cofactors, we repurposed cytochromes P450 to catalyze stereoselective atom-transfer radical cyclization. A set of metalloenzymes was engineered to impose substantial stereocontrol over the radical addition step and the halogen rebound step in these unnatural processes, allowing enantio- and diastereodivergent radical catalysis. This evolvable metalloenzyme platform represents a promising solution to tame fleeting radical intermediates for asymmetric catalysis. 

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2. From Molecules to Molecular Surfaces. Exploiting the Interplay Between Organic Synthesis and Electrochemistry

   https://doi.org/10.1021/acs.accounts.9b00578  

   Jing, Q.; Moeller, K. D. (January 2020, Accounts of chemical research)

   For many years, we looked at electrochemistry as a tool for exploring, developing, and implementing new synthetic methods for the construction of organic molecules. Those efforts examined electrochemical methods and mechanisms and then exploited them for synthetic gain. Chief among the tools utilized was the fact that in a constant current electrolysis the working potential at the electrodes automatically adjusted to the oxidation (anode) or reduction (cathode) potential of the substrates in solution. This allowed for a systematic examination of the radical cation intermediates that are involved in a host of oxidative cyclization reactions. The result has been a series of structure-activity studies that have led to far greater insight into the behavior of radical cation intermediates and in turn an expansion in our capabilities of using those intermediates to trigger interesting synthetic reactions. With that said, the relationship between synthetic organic chemistry and electrochemistry is not a "one-way" interaction. For example, we have been using modern synthetic methodology to construct complex addressable molecular surfaces on electroanalytical devices that in turn can be used to probe biological interactions between small molecules and biological receptors in "real-time" as the interactions happen. Synthetic chemistry can then be used to recover the molecules that give rise to positive signals so that they can be characterized. The result is an analytical method that both gives accurate data on the interactions and provides a unique level of quality control with respect to the molecules giving rise to that data. Synthetic organic chemistry is essential to this task because it is our ability to synthesize the surfaces that defines the nature of the biological problems that can be studied. But the relationship between the fields does not end there. Recently, we have begun to show that work to expand the scope of microelectrode arrays as bioanalytical devices is teaching us important lessons for preparative synthetic chemistry. These lessons come in two forms. First, the arrays have taught us about the on-site generation of chemical reagents, a lesson that is being used to expand the use of paired electrochemical strategies for synthesis. Second, the arrays have taught us that reagents can be generated and then confined to the surface of the electrode used for that generation. This has led to a new approach to taking advantage of molecular recognition events that occur on the surface of an electrode for controlling the selectivity of a preparative reaction. In short, the confinement strategy developed for the arrays is used to insure that the chemistry in a preparative electrolysis happens at the electrode surface and not in the bulk solution. This account details the interplay between synthetic chemistry and electrochemistry in our group through the years and highlights the opportunities that interplay has provided and will continue to provide in the future. 

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3. Photoinduced 1,2-dicarbofunctionalization of alkenes with organotrifluoroborate nucleophiles via radical/polar crossover

   https://doi.org/10.1039/d1sc02547c  

   Cabrera-Afonso, María Jesús; Sookezian, Anasheh; Badir, Shorouk O.; El Khatib, Mirna; Molander, Gary A. (July 2021, Chemical Science)

   null (Ed.)

   Alkene 1,2-dicarbofunctionalizations are highly sought-after transformations as they enable a rapid increase of molecular complexity in one synthetic step. Traditionally, these conjunctive couplings proceed through the intermediacy of alkylmetal species susceptible to deleterious pathways including β-hydride elimination and protodemetalation. Herein, an intermolecular 1,2-dicarbofunctionalization using alkyl N -(acyloxy)phthalimide redox-active esters as radical progenitors and organotrifluoroborates as carbon-centered nucleophiles is reported. This redox-neutral, multicomponent reaction is postulated to proceed through photochemical radical/polar crossover to afford a key carbocation species that undergoes subsequent trapping with organoboron nucleophiles to accomplish the carboallylation, carboalkenylation, carboalkynylation, and carboarylation of alkenes with regio- and chemoselective control. The mechanistic intricacies of this difunctionalization were elucidated through Stern–Volmer quenching studies, photochemical quantum yield measurements, and trapping experiments of radical and ionic intermediates. 

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4. Bio‐inspired Nonheme Iron Oxidation Catalysis: Involvement of Oxoiron(V) Oxidants in Cleaving Strong C−H Bonds

   https://doi.org/10.1002/anie.201906551  

   Kal, Subhasree; Xu, Shuangning; Que, Jr., Lawrence (March 2020, Angewandte Chemie International Edition)

   Abstract Nonheme iron enzymes generate powerful and versatile oxidants that perform a wide range of oxidation reactions, including the functionalization of inert C−H bonds, which is a major challenge for chemists. The oxidative abilities of these enzymes have inspired bioinorganic chemists to design synthetic models to mimic their ability to perform some of the most difficult oxidation reactions and study the mechanisms of such transformations. Iron‐oxygen intermediates like iron(III)‐hydroperoxo and high‐valent iron‐oxo species have been trapped and identified in investigations of these bio‐inspired catalytic systems, with the latter proposed to be the active oxidant for most of these systems. In this Review, we highlight the recent spectroscopic and mechanistic advances that have shed light on the various pathways that can be accessed by bio‐inspired nonheme iron systems to form the high‐valent iron‐oxo intermediates. 

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5. Electronic Chemical Sensors Based on Conductive Framework Materials

   https://doi.org/10.1021/acs.analchem.4c02522  

   Ambrogi, Emma K; Mirica, Katherine A (March 2025, Analytical Chemistry)

   The development of portable electronic chemical sensors is key to solving a number of challenges, including monitoring environmental and industrial hazards, as well as understanding and improving human health. Framework materials possess several desirable characteristics that make them well-suited for electroanalytical applications, including high surface area, atomically precise distribution of active sites, and tunable properties that can be leveraged through modular reticular chemistry. This review highlights the emergence of conductive framework materials as active components in electrically transduced chemical sensors, including the development of new materials for the detection of a wide variety of analytes in both gas and liquid phase. The efforts to gain fundamental understanding of the molecular interactions and sensing mechanisms between framework materials and analytes are described, along with applications of these materials on portable and flexible substrates. The review suggests areas for further study, including the study of material−analyte interactions at the molecular level and the continued development of scalable methods for the integration of framework materials into low-power, portable sensing devices. 

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