Light Alters the NH3 vs N2H4 Product Profile in Iron-catalyzed Nitrogen Reduction via Dual Reactivity from an Iron Hydrazido (Fe=NNH2) Intermediate

Whereas synthetically catalyzed nitrogen reduction (N₂R) to produce ammonia is widely studied, catalysis to instead produce hydrazine (N₂H₄) has received less attention despite its considerable mechanistic interest. Herein, we disclose that irradiation of a tris(phosphine)borane (P₃^B) Fe catalyst, P₃^BFe⁺, significantly alters its product profile to increase N₂H₄ versus NH₃; P₃^BFe⁺ is otherwise known to be highly selective for NH₃. We posit a key terminal hydrazido intermediate, P₃^BFe=NNH₂, as selectivity-determining. Whereas its singlet ground state undergoes protonation to liberate NH₃, a low-lying triplet excited state leads to reactivity at N_α and formation of N₂H₄. Associated electrochemical and spectroscopic studies establish that N₂H₄ lies along a unique product pathway; NH₃ is not produced from N₂H₄. Our findings are distinct from the canonical mechanism for hydrazine formation, which proceeds via a diazene (HN=NH) intermediate and showcase light as a tool to tailor selectivity.     

A De Novo-Designed Type 3 Copper Protein Tunes Catechol Substrate Recognition and Reactivity

De novo metalloprotein design is a remarkable approach to shape protein scaffolds toward specific functions. Here, we report the design and characterization of Due Rame 1 (DR1), a de novo designed protein housing a di-copper site and mimicking the Type 3 (T3) copper-containing polyphenol oxidases (PPOs). To achieve this goal, we hierarchically designed the first and the second di-metal coordination spheres to engineer the di-copper site into a simple four-helix bundle scaffold. Spectroscopic, thermodynamic, and functional characterization revealed that DR1 recapitulates the T3 copper site, supporting different copper redox states, and being active in the O₂-dependent oxidation of catechols to o-quinones. Careful design of the residues lining the substrate access site endows DR1 with substrate recognition, as revealed by Hammet analysis and computational studies on substituted catechols. This study represents a premier example in the construction of a functional T3 copper site into a designed four-helix bundle protein.     

Late-Stage Functionalisation of Pyridine-Containing Bioactive Molecules: Recent Strategies and Perspectives

Late-Stage Functionalisation (LSF) is an innovative technique that has been successfully applied to the C−H diversification of pharmaceuticals. However, LSF of the pyridine ring in drug-like molecules is often unselective. As a result, a mixture of structurally related products is obtained, thus making the purification tedious and time-consuming. This review shines a light on recent strategies addressing the selectivity issue in the LSF of complex natural products or drugs containing the pyridine moiety. Specifically, we have reviewed the efforts reported both in academia and industries with the hope of providing a guide for the LSF of elaborated pyridines.     

Target-Specific Bioorthogonal Reactions for Precise Biomedical Applications

Bioorthogonal chemistry is a promising toolbox for dissecting biological processes in the native environment. Recently, bioorthogonal reactions have attracted considerable attention in the medical field for treating diseases, since this approach may lead to improved drug efficacy and reduced side effects via in situ drug synthesis. For precise biomedical applications, it is a prerequisite that the reactions should occur in the right locations and on the appropriate therapeutic targets. In this minireview, we highlight the design and development of targeted bioorthogonal reactions for precise medical treatment. First, we compile recent strategies for achieving target-specific bioorthogonal reactions. Further, we emphasize their application for the precise treatment of different therapeutic targets. Finally, a perspective is provided on the challenges and future directions of this emerging field for safe, efficient, and translatable disease treatment.     

Metal-Organic Frameworks for Breakthrough Separation of 2-Butene Isomers with High Dynamic Selectivity and Capacity

Developing porous sorbents represents a potential energy-efficient way for industrial gas separation. However, a bottleneck for reducing the energy penalty is the trade-off between dynamic adsorption capacity and selectivity. Herein, we showed this problem can be overcome by modulating the kinetic and thermodynamic separation behaviours in metal–organic frameworks for sieving 2-butene geometric isomers, which are desired for upgrading the raffinates to higher value-added end products. We found that the iron-triazolate framework can realize the selective shape screening of 2-butene isomers assisted by electrostatic interactions at the pore apertures. Further introducing uncoordinated N binding sites by ligand substitution lowered the gas diffusion barrier and greatly boosted the dynamic separation performance. In breakthrough tests under ambient conditions, trans-2-C₄H₈ can be efficiently separated from cis-2-C₄H₈ with a record capacity of 2.10 mmol g⁻¹ with high dynamic selectivity of 2.39.