High-rate CO electroreduction in acid is severely restricted by the intrinsic trade-off between gas and ion transport. In conventional catalyst layers, these conflicting transport requirements are spatially entangled wit...High-rate CO electroreduction in acid is severely restricted by the intrinsic trade-off between gas and ion transport. In conventional catalyst layers, these conflicting transport requirements are spatially entangled within the same disordered pore network, leading to severe mass transport limitations and salt precipitation at industrial current densities. Here, we report a dual-channel covalent organic framework (COF) binder designed to structurally decouple gas and ion fluxes. The Kagome-topology framework features hydrophobic CF-lined triangular channels for unimpeded CO diffusion and separate hexagonal channels functionalized with ionic groups for electrolyte transport. We find that the cationic derivative (C-iCOF) effectively exports locally generated OH, thereby buffering the interfacial pH and mitigating carbonate formation. At 300 mA cm in acidic media (pH = 1), the Cu/C-iCOF catalyst achieves a 49.1% ethylene Faradaic efficiency (FE) and a 42.7% single-pass carbon efficiency (SPCE) for C products. Mechanistic studies reveal that the cationic channels stabilize an ordered interfacial water network and *CO intermediates, favoring C-C coupling through an Eley-Rideal (ER) pathway while suppressing hydrogen evolution. These findings demonstrate that the topological separation of transport pathways is effective for managing the microenvironment in gas-involving multiphase electrocatalysis.
Radical-driven photocatalytic alkane upgrading is attractive yet suffers from poor selectivity due to unselective reactive oxygen species, making the precise steering toward milder, longer-lived superoxide (·O) over hydr...Radical-driven photocatalytic alkane upgrading is attractive yet suffers from poor selectivity due to unselective reactive oxygen species, making the precise steering toward milder, longer-lived superoxide (·O) over hydroxyl radicals a formidable challenge. Here, using WO as a model semiconductor incapable of one-electron O reduction to ·O, we show that coupling with plasmonic Au nanoparticles can re-excite photoelectrons to access the thermodynamically favorable superoxide route. This shift elevates reduction potential, sustains charge separation, and directs the formation of ·O and CHOOH intermediates, while weakened O adsorption on Au allows ·O migration and selective redox C-O coupling. Consequently, Au-WO achieves benchmark visible-light (λ > 420 nm) ethane oxidation with >80% selectivity and up to 100 mmol·L CHCOOH. By steering oxygen activation away from unselective HO/·OH chemistry, this work demonstrates that plasmonic re-excitation enables controlled superoxide generation for selective oxygenate synthesis and establishes a general paradigm for overcoming the redox limitations of visible-light oxidation chemistry.
Doyle MGJ, Jespersen ME, Noureen S
… +10 more, Chen Z, Jefferson TL, Baptista CA, Houot M, Struijs JJC, Goult CA, Bakulin AA, Paton RS, Avestro AJ, Gouverneur V
Recent advances in C-F bond activation of per- and polyfluoroalkyl substances (PFAS) have enabled complete degradation of fluorochemical waste, yet achieving precise, site-selective monodefluorination continues to presen...Recent advances in C-F bond activation of per- and polyfluoroalkyl substances (PFAS) have enabled complete degradation of fluorochemical waste, yet achieving precise, site-selective monodefluorination continues to present a significant synthetic challenge. Here, we demonstrate that -arylphenothiazine photocatalysts enable controlled halodefluorination of perfluoroalkyl compounds using simple halide salts. Mechanistic studies support a consecutive photoinduced electron transfer (conPET) manifold, where the photocatalyst operates as a potent excited-state reductant and oxidant in succession under single- or multiwavelength irradiation. Single-electron halide oxidation is mediated by a transient radical cation superoxidant *[PC], which facilitates net halogen metathesis with high fidelity. This study further exemplifies the redox versatility of -arylphenothiazine photosensitizers and contributes to the development of mechanistically diverse methods for functionalization of strong C-F bonds in polyfluorinated molecules.
Oxidative addition at transition metals underpins modern cross-coupling reactions but remains largely unrealized at main-group centers for aryl halides. Here, we show that photoinduced disproportionation can serve as an...Oxidative addition at transition metals underpins modern cross-coupling reactions but remains largely unrealized at main-group centers for aryl halides. Here, we show that photoinduced disproportionation can serve as an enabling strategy for such transformations. Visible light promotes the oxidative addition of aryl iodides to a Ga(I) metallylene, providing, to our knowledge, the first example of aryl C-I activation at a group 13 center. Mechanistic studies suggest that this transformation is not consistent with direct excited-state reactivity with the Ga(I) complex. Instead, photoexcitation generates a triplet state of gallylene that undergoes intermolecular electron transfer with ground-state gallylene, triggering disproportionation to a reactive radical ion pair. This radical ion-pair manifold, which is enabled by ligand-centered redox ambivalence, provides a viable pathway to bond activation. These findings suggest that photoinduced disproportionation could represent a distinct activation mode for achieving transition-metal-like oxidative addition at main-group elements.
Winegar PH, Hudson GA, Benedict RP
… +10 more, Sy CZ, Han TY, FitzGerald DM, Mahajan RS, Gravel PJ, Roberts JB, Lanclos N, Huang M, Iavarone AT, Keasling JD
Saponins are natural products that consist of triterpene or sterol cores decorated with oxidations, glycosylations, and sometimes other modifications. Many saponins are utilized as nutraceutics (e.g., glycyrrhizin) or th...Saponins are natural products that consist of triterpene or sterol cores decorated with oxidations, glycosylations, and sometimes other modifications. Many saponins are utilized as nutraceutics (e.g., glycyrrhizin) or therapeutics (e.g., QS-21 and digitoxin/digoxin). The structure-activity relationships that govern saponin bioactivity can be identified by studying structurally related saponins; however, the production of varied sets of saponins remains challenging via either chemical (semi)synthesis or native/heterologous biosynthesis. This report describes the discovery that the GT1 family enzyme GuUGT73F15 () can be used to biosynthesize many different saponins via triterpene/sterol C3 β--glycosylation. GuUGT73F15 utilized 22 sugar acceptors (C3 hydroxyl-containing triterpenes/sterols) and 12 sugar donors (uridine diphosphate [UDP]-sugars) as substrates to produce 130 unique monoglycosylated saponins, of which more than 100 have not been reported as natural products to the best of our knowledge. GuUGT73F15 also accepted 13 cyclohexanol- and phenol-type molecules as minimized sugar acceptors. Based on Boltz-2x predictions, the broad substrate scope of GuUGT73F15 is hypothesized to arise from its varied sugar acceptor binding poses and consistent sugar donor binding poses. Applications of broad C3 β--glycosylation activity were exemplified via the production of antibody-saponin conjugates as well as the microbial biosynthesis and the biosynthesis of advanced QS-21 intermediates. Together, GuUGT73F15 is a versatile biocatalytic tool that can be utilized to produce libraries of high-value saponin natural products and new-to-nature saponins.
Metal chalcohalides are a fascinating new class of crystalline solids with a unique chemical bonding hierarchy which combines the notable stability of metal chalcogenides along with the enhanced electronic tunability of...Metal chalcohalides are a fascinating new class of crystalline solids with a unique chemical bonding hierarchy which combines the notable stability of metal chalcogenides along with the enhanced electronic tunability of metal halides. Metal chalcohalides with their complex structures are promising candidates for thermoelectrics if they can exhibit halide-like low thermal conductivity alongside chalcogenide-like enhanced electrical conductivity. However, most metal chalcohalides mimic a wide band gap electronic structure similar to metal halides, limiting overall electrical transport and thus reducing their applicability in thermoelectrics. Here, we present a metal chalcohalide, TlTeI, with a narrow band gap and degenerate semiconductor-like significant electrical conductivity. We explore the structural and chemical bonding attributes of TlTeI and demonstrate it to be suitable for low thermal conductivity arising from its complex crystal structure with significant bonding hierarchy. TlTeI, in its octahedral Tl sublattice, exhibits a multicentric bonded structural framework. This bonding feature allows delocalization of electrons, which permits symmetry-allowed three-center antibonding and interactions of I-Tl-I and Te-Tl-Te, respectively. These antibonding interactions at the top of the valence band near the Fermi level make interatomic force constants extremely soft and reduce the lattice thermal conductivity to the glass limit. With the combined effects of these features, TlTeI exhibits an extraordinarily high -type thermoelectric figure of merit of ∼1.2 at ∼650 K in its pristine form. Our investigations highlight the role of multicentric antibonding features to realize record-high thermoelectric performance in mixed anionic chalcohalides.
Metal-organic frameworks (MOFs) with intrinsic dual proton-electron conductivity are highly desirable for energy conversion devices and chemical separation, yet merging these properties within a single crystalline phase...Metal-organic frameworks (MOFs) with intrinsic dual proton-electron conductivity are highly desirable for energy conversion devices and chemical separation, yet merging these properties within a single crystalline phase remains a challenge. Here, we report two novel Mn(II)-based conjugated MOFs that share similar building blocks, but diverge into distinct topologies: a kagome lattice () and an unprecedented pseudo topology (Mn-HHTP-). These frameworks exhibit sharply contrasting conduction profile: Mn-HHTP demonstrates excellent electronic conductivity (8.4 × 10 S cm at room temperature), but limited proton transport (3.6 × 10 S cm) at 98% relative humidity (RH), whereas the pseudo topology exhibits more balanced electronic conductivity (2.4 × 10 S cm) and proton conductivity (4.5 × 10 S cm at 98% RH). Crystallographic and computational studies indicate that the efficient π-π stacking in topology promotes charge delocalization and through-space charge transport for electrical conduction, while the pseudo topology leverages framework-incorporated water molecules and acetate moieties to establish efficient hydrogen-bonding networks for proton transport. This work highlights the critical role of topological control in modulating mixed-conduction properties and offers valuable insights for designing multifunctional MOFs for ambipolar devices, bioelectronics, and energy systems.
Polymer gels with biphasic architectures enable diverse functions, such as enhanced mechanical robustness and programmable drug release. Conventional fabrication of biphasic gels typically relies on the copolymerization...Polymer gels with biphasic architectures enable diverse functions, such as enhanced mechanical robustness and programmable drug release. Conventional fabrication of biphasic gels typically relies on the copolymerization of monomers with differing solvent affinities, which constrains structural diversity and tunability. In this study, we introduce "polymerization-induced solvent phase separation" (PI-SPS) as a novel and facile solvent-driven strategy for constructing biphasic gels. Polymerization of a homogeneous precursor solution containing two mutually immiscible solvents and a monomer triggers solvent demixing, yielding a hierarchical structure in which a polymer-rich continuous phase composed of the good solvent encapsulates dispersed droplets of the less favorable solvent-rich phase. We demonstrate the generality of PI-SPS across systems comprising water, organic solvents, and ionic liquids. The resulting biphasic architectures confer emergent properties, including self-healing ability, shape-memory behavior, and enhanced crack resistance, with a fracture energy of 4600 J m derived from the spatial organization of solvent domains and polymer networks. Overall, the PI-SPS strategy provides a versatile platform for engineering multiphase soft materials through controlled tuning of solvent affinities.
Chimeric Antigen Receptor T-cell (CAR-T) therapies represent a powerful modality for treating a variety of hematological cancers. However, limited efficacy in broader disease contexts, particularly solid tumors, undersco...Chimeric Antigen Receptor T-cell (CAR-T) therapies represent a powerful modality for treating a variety of hematological cancers. However, limited efficacy in broader disease contexts, particularly solid tumors, underscores the need for improved CAR design to enhance potency, persistence, and safety. Key design features of CARs have been profoundly informed by extensive knowledge of the T-cell receptor (TCR) and its interactome. To advance CAR-T therapies, new functionally relevant proteins are needed to support engineering efforts. Until now, the actual molecular microenvironment surrounding CARs has remained poorly defined, chiefly due to the lack of a characterization method with the required precision and sensitivity. Herein, we introduce μMap-CAR, a high-resolution photocatalytic proximity labeling platform featuring key methodological optimizations that enable direct elucidation of the CAR interactome on live T-cell surfaces. The platform performs robustly in a model CAR-T cell system under both resting and simulated activation conditions. The high sensitivity of μMap-CAR allows interrogation of interactome differences upon CAR endodomain alterations, linking perturbed signaling networks directly to CAR components. We further deliver the first high-resolution intrinsic CAR interactome in primary T-cells, defined by shared interactors across donors, and validate candidates via super-resolution microscopy and CAR-T activation perturbation. This platform constitutes a powerful, broadly applicable tool for CAR interactome profiling while also providing actionable targets for proximity-guided CAR engineering applications.
Biomolecular condensates undergo dynamic maturation, transitioning from liquid-like droplets to gel-like or solid-like assemblies, exhibiting structural heterogeneity in response to biochemical cues. Synthetic coacervate...Biomolecular condensates undergo dynamic maturation, transitioning from liquid-like droplets to gel-like or solid-like assemblies, exhibiting structural heterogeneity in response to biochemical cues. Synthetic coacervate droplets formed via liquid-liquid phase separation (LLPS) have emerged as simplified models of these condensates and of protocells. Yet, the understanding of complex phase behaviors of liquid-like droplets in both biological and chemical contexts remains less explored, limiting our understanding of biological function and the design of droplet-based soft materials and protocells. Here, we introduce a chemically programmable strategy to dynamically modulate droplet phase transitions through controlled polymer-network cross-linking. Reactive cross-linkers selectively engage polymers within liquid-like droplets, progressively increasing internal microviscosity and inducing a liquid-to-solid transition. Beyond uniform phase regulation, network cross-linking drives spatially heterogeneous phase separation via polymer demixing and Ostwald ripening, with reaction-diffusion dynamics critically shaping both thermodynamically stable and metastable droplets. Using orthogonal cleavable cross-linkers, we further demonstrate chemical control over droplet liquefaction and the generation of multiphasic structures with pathway-dependent configurations. Integration of photoresponsive cross-linkers with digital-micromirror device (DMD) technology enables precise spatial photopatterning of droplet networks. This work establishes a versatile framework for elucidating the structural principles of microphase separation within coacervates and provides a blueprint for designing dynamic soft materials and synthetic protocells.
At the Ångström scale, water confined between two-dimensional layers behaves fundamentally differently from bulk water; this behavior governs ion transport in natural and engineered nanofluidic systems, yet the mechanism...At the Ångström scale, water confined between two-dimensional layers behaves fundamentally differently from bulk water; this behavior governs ion transport in natural and engineered nanofluidic systems, yet the mechanisms by which confined water mediates selective ion transport remain poorly understood. As classical descriptions of aqueous ion transport break down under extreme confinement, experimental studies often face challenges in controlling both nanoconfined structure and surface chemistry, limiting our ability to explain and predict water and ion behavior in subnanometer channels and membranes. Here, we show that 2D TiCT MXene nanosheets with precisely controlled interlayer spacing (0.9-5.0 Å), surface terminations, and electrode potentials provide a platform to systematically tune ion transport. Combined experimental measurements, including ion permeation, spatial secondary-ion mass spectrometry, and Fourier transform infrared spectroscopy, together with molecular dynamics simulations, reveal that ultranarrow confinement reorganizes confined water, imposes ion-specific energetic penalties for dehydration, and modulates ion-MXene interactions. Li permeation in horizontally aligned TiCT channels is 2 orders of magnitude faster than in conventional vertically aligned MXene membranes, while electrochemical surface charge modulation further regulates ion selectivity. These coupled effects of confinement, surface chemistry, and water-mediated energetics define a transport regime beyond classical diffusion, offering design principles for artificial ion channels and high-performance membranes for ion separation, water desalination, and sustainable water treatment technologies.
Si-rhodamine (SiR) and its derivatives have advanced bioimaging research because of their high photostability and bright near-infrared (NIR) emissions. However, the rational design of SiR derivatives with high fluorogeni...Si-rhodamine (SiR) and its derivatives have advanced bioimaging research because of their high photostability and bright near-infrared (NIR) emissions. However, the rational design of SiR derivatives with high fluorogenicity remains challenging. Herein, we report a general strategy for developing high-performance fluorogenic SiR derivatives, termed SFs, by incorporating a molecular rotor at the meso position of the SiR scaffold. This design enables a twisted intramolecular charge transfer (TICT)-based mechanism for fluorescence on/off switching, which results in the achievement of a maximum fluorescence on/off ratio of more than 3000-fold. Chloroalkane (CA)-conjugated SFs exhibit high cellular brightness and outstanding photostability, enabling robust and high-contrast fluorescent labeling of HaloTag in live cells and in vivo. Their suitability for use in stimulated emission depletion microscopy enables advanced fluorescence imaging with subdiffraction resolution in live cells. We demonstrate the ability of SFs to construct chemigenetic Ca indicators with large dynamic ranges, enabling sensitive detection of intracellular and in vivo Ca dynamics using both fluorescence intensity and lifetime. This work establishes a general design strategy for NIR fluorogenic dyes, thus opening new avenues for advanced bioimaging and biosensing.
The microscopic hydration structure of excess protons (H) at the air/water interface remains elusive despite extensive surface-specific studies. In bulk water, hydrated protons exhibit a broad vibrational "proton continu...The microscopic hydration structure of excess protons (H) at the air/water interface remains elusive despite extensive surface-specific studies. In bulk water, hydrated protons exhibit a broad vibrational "proton continuum" arising from dynamically delocalized hydration structures. However, proton hydration at aqueous interfaces has not been resolved. Here, we combine interface-selective heterodyne-detected vibrational sum frequency generation (HD-VSFG) spectroscopy with molecular dynamics (AIMD) simulations to investigate aqueous HCl surfaces over a wide concentration range (0-9 M). HD-VSFG spectroscopy reveals pronounced changes in the interfacial vibrational spectra with increasing HCl concentration: (1) the amplitude of the free OH band decreases monotonically, reflecting depletion of normal interfacial water molecules; (2) the amplitude of the hydrogen-bonded OH band markedly increases upon addition of 1 M HCl, which is attributable to the enhanced orientation of water molecules in the electric double layer formed by the excess protons and Cl; and (3) the amplitude of a low-frequency feature gradually increases while extending its spectrum to develop into the proton continuum at high HCl concentrations (>5 M). AIMD simulations indicate a significant asymmetry of the location of the excess proton localized at the interface at low HCl concentration, whereas this asymmetry is substantially reduced at high concentrations. This suggests that interfacial protons preferentially adopt localized, Eigen-like hydration structure under weakly acidic conditions, while more delocalized Eigen-Zundel-Eigen-like hydration structure becomes accessible at highly acidic conditions. This study indicates that the preferred hydration structure of excess protons at the water surface depends on the HCl concentration, providing crucial insights into proton transfer at aqueous interfaces.
Chiral cyclophanes are structurally intriguing macrocycles found in natural products and pharmaceuticals with promising biological activities. The development of efficient asymmetric macrocyclization strategies is theref...Chiral cyclophanes are structurally intriguing macrocycles found in natural products and pharmaceuticals with promising biological activities. The development of efficient asymmetric macrocyclization strategies is therefore of great importance, yet remains a formidable challenge due to the entropic penalty and stereochemical complexities inherent to macrocyclization. Here, we report a palladium-catalyzed atroposelective C-H macrocyclization using l--leucine as a chiral transient directing group. This method enables the efficient construction of a broad range of chiral cyclophanes with varied ring sizes in good yields (up to 88%) and excellent enantioselectivities (up to 99% ee) and further allows the dynamic kinetic resolution of prochiral macrocycles via intermolecular C-H olefination. The synthetic utility of this strategy is demonstrated by the asymmetric total synthesis of isoplagiochin D, which was completed in 10 linear steps with 16.8% overall yield and 97% ee.
Radical carbonylation has emerged as a crucial and alternative method for introducing carbonyl groups with enhanced selectivity and broader substrate compatibility. However, currently, the substrates suitable for these p...Radical carbonylation has emerged as a crucial and alternative method for introducing carbonyl groups with enhanced selectivity and broader substrate compatibility. However, currently, the substrates suitable for these processes are primarily limited to those that can undergo radical induction to form the corresponding monoradicals as key intermediates. Herein, we report a photocatalytic energy transfer-enabled diradical carbonylative cyclization of bicyclo[1.1.0]butanes with CO and commercially abundant alkenes/alkynes to assemble a variety of 4-oxo bicyclo[3.1.1]-heptanes and heptenes. The subsequent diversification of the incorporated carbonyl group further allows rapid exploration of structurally varied derivatives. Density functional theory computations reveal that the success of the reaction is determined by the competition between the desired three-component [2σ + 2 + 2π] cyclization pathway and the [2σ + 2π] cycloaddition and alkene dimerization pathways.
Cold sensation is mediated by TRPM8, a polymodal ion channel activated by temperature, pH, voltage, and cooling compounds such as menthol. Despite its central role in thermosensation and pharmacology, the molecular basis...Cold sensation is mediated by TRPM8, a polymodal ion channel activated by temperature, pH, voltage, and cooling compounds such as menthol. Despite its central role in thermosensation and pharmacology, the molecular basis of menthol-mediated activation remains unclear, particularly how temperature influences ligand binding and channel activation. Polymodal ion channels further challenge site-centric views of ligand binding, as function emerges from coupled conformational equilibria and environment-dependent membrane partitioning. Here, we investigate temperature-dependent menthol distribution in TRPM8 using flooding molecular dynamics simulations of open and closed channel conformations across a physiological temperature range. This approach reveals distributed, low-affinity interactions that are not captured by discrete binding-site models. Below the TRPM8 activation threshold (<300 K), menthol preferentially accumulates in intracellular and interfacial regions, whereas above this threshold it redistributes toward transmembrane regions, indicating that temperature-dependent activation regimes reshape ligand partitioning at the protein-membrane interface. Across all conditions, menthol behaves as a low-affinity multisite ligand sampling a continuum of metastable interaction regions, consistent with experimentally identified interaction regions spanning the N-terminal domain, pore domain, voltage sensor-like domain (VSLD), and C-terminal region. A two-state allosteric model indicates that these temperature-dependent occupancy patterns shift the open-closed equilibrium of TRPM8. Together, these results suggest that temperature regulates function not only through channel energetics but also by modulating ligand interactions at the protein-membrane interface. This work identifies temperature-dependent ligand partitioning as a key physicochemical determinant of ligand efficacy in polymodal ion channels and provides molecular-level insight into menthol modulation of TRPM8.
We present the next generation of AMP, a neural network potential (NNP) with anisotropic message passing designed to study large biomolecular systems at DFT accuracy in the condensed phase using a multiscale approach sim...We present the next generation of AMP, a neural network potential (NNP) with anisotropic message passing designed to study large biomolecular systems at DFT accuracy in the condensed phase using a multiscale approach similar to quantum-mechanics/molecular-mechanics (QM/MM) with electrostatic embedding. We trained AMPv3 on our recently published biomolecular multiscale simulation (BMS25) data set and demonstrated the model's high efficiency, which enabled us to simulate proteins involving thousands of atoms at DFT accuracy in addition to explicit MM solvent for up to 100 ns, which presents a major leap for contemporary NNPs. We observe excellent scaling to large systems on a single GPU. AMPv3-BMS25 (or AMP-BMS for short) shows promising performance on benchmarks, and we demonstrate that the model can be used to accurately estimate experimental properties, including solvation free energies of small molecules and structural features of proteins. Finally, AMP-BMS/MM was employed to predict the free-energy profiles of reactions catalyzed by the enzymes chorismate mutase and fluoroacetate dehalogenase. In total, AMP-BMS/MM was used to simulate proteins in the condensed phase for a cumulative 23 μs simulation time or 48 billion integration steps. This work establishes AMP-BMS as a highly efficient and accurate model for multiscale simulations of biomolecules.
A dual-catalytic approach for the regioselective synthesis of iodinated semisaturated fused heterobicycles is reported. The one-pot sequential use of copper and palladium under blue-light irradiation enables the efficien...A dual-catalytic approach for the regioselective synthesis of iodinated semisaturated fused heterobicycles is reported. The one-pot sequential use of copper and palladium under blue-light irradiation enables the efficient synthesis of 1,2,3-triazole-fused piperidines in high yields from acyclic precursors, avoiding the need for highly reactive small-ring alkynes. Medicinally relevant compounds and functionally diverse product derivatives are described. The cooperativity between two independent bond-forming cycles is explored, and mechanistic studies of the photochemical palladium-catalyzed carboiodination suggest that cyclization is light-dependent.
While the reactivity of excited radical anions and cations has received considerable attention in modern photoredox catalysis, the photochemistry of charge-neutral organic radicals remains underexplored. Here, we present...While the reactivity of excited radical anions and cations has received considerable attention in modern photoredox catalysis, the photochemistry of charge-neutral organic radicals remains underexplored. Here, we present direct laser spectroscopic evidence showing that a neutral boryl radical remains unreactive in the lowest electronically excited state formed after red light excitation. However, it can initiate photoreduction from an upper excited state reached using blue light. This represents an important deviation from typical photochemical behavior, in which only the lowest excited state of a given spin multiplicity is expected to be reactive. Transient absorption spectroscopy provides further insight into the reactivity between charge-neutral radical species and substrates, particularly regarding their propensity to undergo in-cage charge recombination events that influence the quantum yield of overall photoreactions, an aspect that differs conceptually from previously investigated radical cations and anions, where light typically induces charge shift rather than charge separation processes. These insights are complemented by a detailed mechanistic picture describing how boryl radicals regenerate from boronium cations, enabling catalytic turnover in synthetically relevant borylation reactions. The gained mechanistic insights are broadly relevant to photoredox catalysis and carry important implications for synthetic photochemistry, artificial photosynthesis, and the photodegradation of environmentally harmful substances.