Maxime A. Siegler

Herein, we report the synthesis, characterization, and reactivity of Cu-acetate and Ni-acetate complexes bound by tridentate redox-active ligands capable of reaching three molecular oxidation states. The reduced complexes ([XMOAc]2–) were characterized by single-crystal X-ray diffraction analysis, depicting metal-acetate cores stabilized by intramolecular H-bonding interactions. Cyclic voltammetry measurements indicate that [XMOAc]2– can be reversibly oxidized to [XMOAc]– and [XMOAc], and that the reduction potentials varied depending on the ligand substitution. The oxidation of [XMOAc]2– to [XMOAc]– and [XMOAc] was accomplished using 1 and 2 equiv of ferrocenium, respectively. The proton-coupled electron transfer reactivity of the oxidized complexes was analyzed in detail. Thermochemical analysis determined that the [XMOAc] species had higher affinities toward H atom equivalents than [XMOAc]–, and that the systems with electron-withdrawing groups were more prone to undergo reductive protonation. The kinetics for the reactions of [XMOAc]– and [XMOAc] with TEMPOH (1-hydroxy-2,2,6,6-tetramethylpiperidine) showed that the [XNiOAc]– complexes depict enhanced reaction rates. These findings contradict our thermochemical analysis (i.e., complexes with higher thermodynamic tendency to accept H atoms usually react faster) and are explained by tunneling effects. Further analysis of the PCET reactions provided further evidence that nonthermodynamic factors govern the PCET reactivity of the Ni-semiquinone oxidants.

Aptamer-based molecular monitors enable continuous, real-time tracking of analytes in complex environments, including in vivo, but their practical deployment is limited by short operational lifetimes of only hours. This instability arises in part from the electrochemical interrogation of the aptamer-bound redox reporter methylene blue, whose standard potential overlaps with oxygen reduction on gold electrodes, leading to peroxide generation and, concomitantly, accelerated sensor degradation. We previously demonstrated that peroxide accumulates to tens-to-hundreds of micromolar on the sensor surface under typical operating conditions. Here, we address this limitation by rationally designing redox reporters with more positive standard potentials, beyond the range of oxygen electroreduction. Using electron-withdrawing substituents and extended conjugation strategies, we developed a new reporter, Netz Lab Blue, exhibiting a standard potential 160 mV more positive than methylene blue. Aptamer-based monitors incorporating Netz Lab Blue withstand ≥10,000 interrogation cycles in buffered saline without measurable signal loss, whereas methylene blue-based sensors lose >20% signal under identical conditions. In oxygen-saturated solutions, Netz Lab Blue-based sensors retain full stability over the same duty cycle while methylene blue-based devices fail completely. Additionally, Netz Lab Blue delivers 40% higher signal gain for the same aptamer sequence and under identical packing density relative to methylene blue. These improvements translate directly to biological environments, where Netz Lab Blue‑based sensors exhibit stable performance in rat blood and support continuous, real‑time in vivo drug monitoring in the brain of rodents using two distinct aptamer sensors. By eliminating peroxide generation during electrochemical interrogation, this new redox reporter markedly extends sensor lifetime and performance, potentially enabling continuous molecular monitoring over days to weeks in biomedical applications that seek to interrogate human physiology.

Catalysis underpins modern chemical innovation, yet halogen-bond catalysts remain underdeveloped. Herein, we introduce a charged hydrogen bond-enhanced halogen bond (HBeXB) platform that intensifies σ-hole electrophilicity to unlock reactivity. Mechanistic, spectroscopic, and computational studies reveal a cooperative network of hydrogen bonding, halogen bonding, and nonclassical C–H interactions, delivering exceptional catalytic rates. The modular design of these scaffolds establishes a broadly applicable strategy for next generation organocatalysis.

Bis-amido-bis-sulfonamido, [Fe{4-NO2C6H3-1,2-(NCOCMe2NSO2)2CR1R2}(OH2)]− [2; R1/R2 = H/H (2a), H/CH3 (2b), CH3/CH3 (2c)], are NewTAML (NT) iron(III) oxidation catalysts. Herein we identify and mechanistically characterize a ligand-centered, catalyst-lifetime-controlling site (CR1R2), termed a KillSwitch (KS), that enables balancing technical performance with potential safety constraints in NT/Oxidant process design. Under catalytic conditions, CR1R2 sites containing two or one hydrogen(s), (2a, 2b, respectively), undergo deprotonation to form electron-rich ylides that accelerate NT oxidative degradation. The 2a–c series defines a KS susceptibility gradient arising from differential C–H bond acidities controlling the ylide-forming deprotonation─2a, 2b, and 2c represent high-susceptibility-, intermediate-susceptibility-, and null-susceptibility KS states, respectively, thereby providing substantial catalyst functional lifetime control with 2a < 2b ≪ 2c. Kinetic analysis gives similar 2a–c rate constants for H2O2 activation (kI) and substrate oxidation (kII), while catalyst inactivation rate constants (ki) increase markedly and differentially with increasing pH for 2a and 2b, but remain pH-independent for 2c, which degrades more slowly through a separate pathway. Access to null-KS 2c─essential for testing the KS hypothesis─required a decade-long synthetic effort culminating in the quantitative methylation of deprotonated 2b. The KS is expected to be transferable to other NTs with oxidative reactivities distinct from 2a–c, enabling a new dimension in catalyst design that broadly decouples catalytic oxidative aggression from catalyst lifetime. The KS thus provides a practical, safe, and sustainable by design strategy for balancing technical performances against catalyst lifetimes, should shorter-lived NTs become desirable in response to discoveries of postrelease NT adverse environmental effects.

The first conjugated polymers with functional Si–Si crosslinks are reported. In addition to complete structural characterization using solid-state NMR techniques, the electronic structure of the polymers are supported by electrochemical studies.

The synthesis and characterization of a series of nonheme Fe(II), Mn(II), and Co(II) complexes, MII(BNPAPh2O)(Cl) (M = Fe, Mn, Co), are reported. These complexes were characterized using single-crystal X-ray crystallography, 1H NMR spectroscopy, and ATR-FTIR spectroscopy to establish their structural and electronic properties. Their reactivity with dioxygen revealed distinct metal-dependent pathways. The Mn(II) complex undergoes ligand-based C–N bond cleavage, forming a pentanuclear cluster, whereas the Fe(II) complex reacts with O2 to generate a well-defined FeIII(BNPAPh2O)(OH)(Cl) species, relevant to the rebound intermediate in nonheme iron halogenases. In contrast, the Co(II) complex exhibits no detectable reactivity toward O2. These differences illuminate the intrinsic metal-dependent factors that govern O2 activation and underscore the central role of metal identity in tuning reactivity and selectivity in bioinorganic oxidation chemistry.

The two‐electron water oxidation reaction (2e ⁻ ‐WOR) and oxygen reduction reaction (2e ⁻ ‐ORR) represent sustainable and promising processes for the electrochemical synthesis of hydrogen peroxide (H ₂ O ₂ ). The main factor hampering the realization of a paired electrochemical cell for H ₂ O ₂ production is finding appropriate catalysts for both 2e ⁻ ‐ORR and 2e ⁻ ‐WOR, able to work under the same experimental conditions. Herein we show that Cu(tmpa)) and Sn‐TMPyP are compatible and efficient catalysts for 2e ⁻ ‐ORR and 2e ⁻ ‐WOR, respectively. They have been used to assemble a paired electrochemical cell for H ₂ O ₂ production. The latter exhibits a total overpotential of 570 mV, distributed between the two electrodes. During a 3 h bulk electrolysis experiment, the cathodic Faradaic efficiency ranged from 15% to 19% with a H ₂ O ₂ production rate of 1.6 µmol h ^{− 1} cm ^{− 2} . Meanwhile, at the anode, the Faradaic efficiency stabilized between 40% and 50%, yielding a H ₂ O ₂ production rate of 3.5 µmol h ^{− 1} cm ^{− 2} . The remarkable activity of Sn‐TMPyP as a catalyst for the 2e ⁻ ‐WOR, ranking among the highest reported for molecular catalysts, is ascribed to the selection of a carbonate buffer as the electrolyte, which enhanced catalytic performance by facilitating dissociation of H ₂ O ₂ from the Sn catalyst. This work establishes a new benchmark for homogeneous dual‐electrode H ₂ O ₂ electrosynthesis.

The two‐electron water oxidation reaction (2e ⁻ ‐WOR) and oxygen reduction reaction (2e ⁻ ‐ORR) represent sustainable and promising processes for the electrochemical synthesis of hydrogen peroxide (H ₂ O ₂ ). The main factor hampering the realization of a paired electrochemical cell for H ₂ O ₂ production is finding appropriate catalysts for both 2e ⁻ ‐ORR and 2e ⁻ ‐WOR, able to work under the same experimental conditions. Herein we show that Cu(tmpa)) and Sn‐TMPyP are compatible and efficient catalysts for 2e ⁻ ‐ORR and 2e ⁻ ‐WOR, respectively. They have been used to assemble a paired electrochemical cell for H ₂ O ₂ production. The latter exhibits a total overpotential of 570 mV, distributed between the two electrodes. During a 3 h bulk electrolysis experiment, the cathodic Faradaic efficiency ranged from 15% to 19% with a H ₂ O ₂ production rate of 1.6 µmol h ^{− 1} cm ^{− 2} . Meanwhile, at the anode, the Faradaic efficiency stabilized between 40% and 50%, yielding a H ₂ O ₂ production rate of 3.5 µmol h ^{− 1} cm ^{− 2} . The remarkable activity of Sn‐TMPyP as a catalyst for the 2e ⁻ ‐WOR, ranking among the highest reported for molecular catalysts, is ascribed to the selection of a carbonate buffer as the electrolyte, which enhanced catalytic performance by facilitating dissociation of H ₂ O ₂ from the Sn catalyst. This work establishes a new benchmark for homogeneous dual‐electrode H ₂ O ₂ electrosynthesis.

Persulfides (RSSH) have been proposed as key players in biochemical transformations that often involve iron, including iron–sulfur cluster assembly, H₂S regulation, post translational modifications, and mitochondrial sulfur oxidation. An example of the latter is found in the O₂-mediated oxidation of glutathione persulfide to sulfite dianion (SO₃^2–) catalyzed by ETHE1, a nonheme iron persulfide dioxygenase (PDO). The iron-mediated mechanism of persulfide oxidation by PDOs remains poorly understood, and there are no synthetic analogues to date. Herein, we report the synthesis, characterization, and O₂ reactivity of a rare iron(II)-alkylpersulfide complex. The adamantyl persulfide anion (AdSS-) was isolated and characterized by X-ray diffraction as a complex with potassium 18-crown-6 [K(18-crown-6)][AdSS], and employed in the synthesis of a new dinuclear iron(II) complex, [(Fe^II(Me₃TACN))₂(μ₂-SSAd)₃][OTf] (1). Complex 1 was characterized by single crystal X-ray diffraction (XRD), UV–vis, ¹H/¹⁹F NMR, and ⁵⁷Fe Mössbauer spectroscopy. Reaction of 1 with O₂ in CH₃CN affords a diiron(III) oxo-bridged complex [(Fe^III(Me₃TACN))₂(μ-O)(μ₂-SO₄)(μ₂-SO₃Ad)][OTf] (2) identified by XRD, and SO₃^2– (∼0.5 equiv per Fe₂). Isotopic labeling studies using ¹⁸O₂ and H₂¹⁸O, supported by control experiments and ESI-MS analysis, indicate that SO₃^2– production proceeds via an iron-centered S-oxygenation mechanism similar to that proposed for persulfide dioxygenases.