Abstract:

Nitrogen-containing molecules are foundational to modern synthesis, spanning a wide range of pharmaceuticals, agrochemicals, life science and functional materials. Recent advances in photochemical and electrochemical methods have begun to redefine how C–N bonds can be constructed, expanding beyond traditional thermally driven metal-catalysed cross-couplings to encompass radical, hybrid, and fully metal-free pathways. These strategies can offer precise control over redox events, access to otherwise inaccessible intermediates and greater modularity in reaction design, thereby enabling transformations that are operationally simple, scalable and increasingly sustainable. In this Review, we systematically summarize photochemical, electrochemical and electrophotochemical C–N cross-coupling reactions, spanning mechanistic principles, catalytic paradigms, reaction classes and synthetic applications. We highlight convergent trends across these fields, analyse their distinct advantages and provide a forward-looking perspective on their potential and future development.

Heterologous saRNA prime – multivalent protein boost strategy induces broad and durable immunity against SARS-CoV-2 and MERS-CoV

Dominik Renn, Justine S. McPartlan, Srinivas Banala, Fabian Kiessling, Poulami Talukder, Christian W. Mandl, Jörg Eppinger, Jasdave S. Chahal, Magnus Rueping

Sci Rep, 2026, 16, 14565

DOI: 10.1038/s41598-026-44645-8

Abstract:

The continuing emergence of SARS- and MERS-related coronaviruses underscores the urgent need for pan-SARBECo vaccines capable of eliciting broad and durable protective immune responses across divergent lineages (Cankat et al. in Cell. Mol. Immunol. 21(2):103–118, 2024). We present a heterologous prime-boost vaccination strategy combining a modified dendrimer nanoparticle (DNP)-encapsulated self-amplifying (saRNA) prime with an alum-adjuvanted multivalent protein booster containing receptor-binding domains (RBDs) from SARS-CoV-2 (Wuhan-Hu-1 and B.1.351) and MERS-CoV. This approach leverages the potent immunogenicity of RNA priming together with the breadth and safety of protein subunit boosting (Bruno et al. in Npj Vaccines 10(1):108, 2025; Kim et al. in Vaccines 13(8):797, 2025) to expand coronavirus coverage. In preclinical mouse and hamster models, the heterologous RNA-protein regimen elicited robust antibody responses with markedly enhanced magnitude, durability, and cross-variant breadth compared with homologous RNA or protein vaccination alone. Inclusion of the MERS-CoV RBD in the booster broadened the response without compromising SARS-CoV-2 immunity. These findings establish a versatile and scalable vaccination strategy with potential to inform the development of next-generation, broadly protective vaccines against emerging coronaviruses.

Abstract:

Dearomative functionalization of arenes represents a powerful synthetic strategy for the rapid assembly of complex chemical architectures. A significant challenge in this process is overcoming the inherent aromaticity of arenes. Here, leveraging the potential of organic electrolysis, we show the development of a dearomative syn-1,4-hydroalkylation reaction targeting electron-deficient arenes and heteroarenes. This electrochemical approach, conducted under mild, operationally straightforward and scalable conditions, facilitates the synthesis of alkylated syn-1,4-cyclohexadienes with high chemoselectivity, regioselectivity and stereoselectivity. In addition, this alkylation protocol is controllable and switchable. By employing a niobium plate as the anode and nBu4NBr as the supporting electrolyte, our method enables the para-selective C(sp2)–H alkylation of (hetero)arenes via electrolysis. Both reactions exhibit broad substrate scope and demonstrate excellent compatibility with various electron-deficient arenes and alkyl bromides. Furthermore, preliminary mechanistic studies and density functional theory calculations have been performed to elucidate the reaction mechanism and to rationalize the observed chemoselectivity, regioselectivity and stereoselectivity.

Abstract:

Photocatalysis is a powerful tool for the synthesis of organic molecules, yet its widespread application is hindered by the dependence on high-energy light sources and expensive metal-based catalysts, which can limit scalability and environmental sustainability. In this study, we present a modular design strategy for organic dyes engineered for efficient red-light absorption, enabling photocatalytic reactions under low-energy irradiation. Our findings establish a clear relationship between the oxidation potential of the photocatalyst and the nature of its donor moiety, as well as between the reduction potential and the electronic characteristics of its core structure. Moreover, we demonstrate that the E0-0 energy of a photocatalyst can be predicted via multivariate linear regression using the donor's oxidation potential and the core's reduction potential as descriptors. Utilizing this strategy, we synthesized red-light-absorbing photocatalysts that efficiently promote C─heteroatom cross-coupling reactions under mild conditions. This approach overcomes the limitations of blue-light photocatalysis by offering broad substrate compatibility, including π-conjugated aryl bromides and photolabile functional groups, while minimizing undesirable hydrodehalogenation. By reducing reliance on precious metals and improving energy efficiency, our approach provides a scalable alternative to traditional photocatalysis and advances the development of metal-free photocatalysts for sustainable chemistry.

Abstract:

The direct functionalization of alcohols via C–O bond cleavage is a synthetically valuable but challenging transformation. In this work, we report a reductive C(sp3)–C(sp2) cross-coupling reaction between benzyl alcohols and a broad range of aryl chlorides. The success of this transformation is attributed to the development of low-coordinate cobalt/bipyridine complexes, which enable the selective conversion of benzyl alcohols into the corresponding diarylmethanes, while minimizing undesired homocoupling of either the benzyl alcohol or aryl chlorides.

Abstract:

Activating catalytically inert planar sites and achieving high-rate CO2 to formic acid conversion remain key challenges for industrial implementation of bismuth nanoflower-based electrocatalyst. Here, we integrate in-situ reconstruction of Bi nanoclusters with heterointerfacial electric fields at a Bi/Cu junction. The dual (geometric + electronic) activation creates secondary cluster sites, enhances interfacial charge transformation, and improves the selectivity to the key product formic acid. The resulting catalyst achieves > 87 % Faradaic efficiency across a wide current density range (100–600 mA cm−2) and enables mole-scale production of pure formic acid (≈ 0.16 mol) over 100 h of continuous operation in a solid electrolyte reactor. In-situ studies and DFT calculations reveal a synergistic mechanism of planar surface activation by cluster engineering and electric field-enhanced intermediate binding. This work establishes a scalable and integrative catalyst-interface-reactor framework for practical CO2 electrolysis toward a liquid hydrogen carrier.

Abstract:

Solid-phase peptide synthesis (SPPS) is the backbone of modern peptide production. However, it relies heavily on relatively toxic solvents and generates significant waste, limiting its sustainability and scalability. To address these limitations, we report the first fully solvent-less peptide coupling protocol for SPPS enabled by Resonant Acoustic Mixing (RAM), representing a step toward greener peptide manufacturing. This method eliminates bulk solvent use, reagent pre-dissolution, and pre-activation during coupling by using mechanical agitation to drive efficient amide bond formation. Optimized conditions (95g acceleration, 5 min, 1.5 equiv. Fmoc-amino acids) afford rapid and clear reactions with high conversion and purity. Notably, no external solvent is added during coupling; instead, residual solvent retained from resin pre-swelling creates a localized microenvironment sufficient for in situ activation. Compared to conventional SPPS, this protocol significantly reduces solvent and reagent use, reaction time, and waste. Process Mass Intensity (PMI) calculations show clear improvements, highlighting the method's environmental and economic benefits. This approach was validated by synthesizing two bioactive peptides (IKVAV and Angiotensin 1–7) in high yield and purity, and further demonstrated excellent scalability in a tenfold scale-up.