Sharath Kandambeth, Rajesh Kancherla, Kuntal Pal, Taslim Melliti, Mostafa Zeama, Vinayak S. Kale, Issatay Nadinov, Abdulaziz M. Alali, Osama Shekhah, Omar F. Mohammed, Magnus Rueping, Mohamed Eddaoudi
Angew. Chem. Int. Ed. 2025, e202503328
DOI: 10.1002/anie.202503328
Abstract:
In this work we have successfully synthesized a series of novel semiconducting 2D catecholate metal-organic frameworks (MOFs) based on naphthazarin ligands by utilizing unraveled metal-acetyl acetonate linkage chemistry. The synthesized Ce-Naph MOF exhibited excellent light absorption properties and chemical stability across various solvents. Its insoluble and stable framework, combined with an optimal band gap, enabled its use as a photocatalyst for organic transformations. For the first time, Ce-Naph MOF is explored as a heterogeneous catalyst for photocatalytic applications specifically for the selective C–H amination of alkanes, achieving yields of up to 89% under ambient conditions. We propose that the initial metal-to-ligand charge transfer in Ce-Naph MOF, promoted by light, is essential for forming an active alkoxy-Ce(IV)-species. This species subsequently undergoes ligand-to-metal charge transfer to generate the alkoxy radical, which acts as a hydrogen atom transfer reagent to activate alkanes. Furthermore, Ce-Naph MOF demonstrated long-term cyclic stability, maintaining its catalytic activity and structural integrity over five cycles, highlighting its durability as a heterogeneous catalyst. We are confident that this straightforward and practical methodology opens new avenues for industrial applications, significantly advancing the fields of metal catalysis, photocatalysis, and sustainable chemistry.
18. Selective Alkylarylation Difunctionalization of 1,3-Butadienes via Nickel/Photoredox Dual Catalysis
Aidana Gimnkhan, Rajesh Kancherla, Krishnamoorthy Muralirajan, Magnus Rueping
Org. Lett. 2025,
DOI: 10.1021/acs.orglett.5c01518
Abstract:
Photocatalytic multicomponent reactions are at the forefront of organic synthesis. In recent years, the dicarbofunctionalization of olefins has received significant attention, with nickel serving as a key transition metal catalyst under photochemical conditions. However, achieving regioselective 1,4-alkylarylation of dienes with alkyl and aryl bromides remains challenging. In this work, we present a Ni/photoredox dual catalysis approach for the regioselective alkylarylation of dienes, offering a mild reaction that eliminates the need for stochiometric metal reductants. Broad substrate scope and mechanistic investigations are presented that support the proposed reaction mechanism.
17. Palladium-Catalyzed Alkyl Amination of Olefins via Radical-Polar Crossover at Room Temperature
Anurag Singh, Kuntal Pal, Sayan Dutta, Arnab Dey, Rajesh Kancherla, Bholanath Maity, Luigi Cavallo, Magnus Rueping
Angew. Chem. Int. Ed. 2025, e202503446
DOI: 10.1002/anie.202503446
Abstract:
In contrast to traditional ground-state palladium catalyzed alkyl Heck reactions, which are thermodynamically unfavourable and endothermic, excited-state palladium catalysis facilitates single-electron mechanisms, with light primarily driving the formation of alkyl radicals from triplet-state Pd(0). Here, we report a novel and mechanistically distinct Pd-catalyzed reaction, where the key hybrid alkyl Pd(I)-radical intermediate is generated from the triplet-state Pd(II) at room temperature. This hybrid species engages in the addition to dienes and conjugated enynes, producing a transposed open-shell allyl Pd(I)-radical, which undergoes radical-polar crossover (RPC) to yield the desired alkyl amination products. Density functional theory (DFT) studies offer insights into the reaction mechanism, confirming the involvement of hybrid alkyl/allyl Pd(I) radical species as key intermediates.
16. A formal vinylogous Schmidt reaction: nitrogen insertion of para-quinone methides
Bo Wang, Chen Zhu, Yanhao Dong, Chen Kong, Hanxiao Zhu, Tiandi Ding, Guoyue Wei, Yatong Yang, Xin Zhao, Magnus Rueping, Qingqiang Yao, Kun Zhao, Yan Li, Ying Zhi
Org. Chem. Front., 2025
DOI: 10.1039/D5QO00476D
Abstract:
Compared with recent nitrogen addition reactions, which mainly focus on the styrene motif, feasible modification of a conjugated C(sp2)–C(sp2) single bond is rare due to its robustness. Herein, we report a facile nitrogen introduction to the conjugated C(sp2)–C(sp2) bond of p-QMs through a vinylogous Schmidt process, using N-OTs carbamate as a bench-stable ambiphilic nitrogen source. Depending on the electron-donating ability of the ortho-substituent on the benzene ring, the reaction underwent the formal vinylogous Schmidt process through an aziridine intermediate or a 1,6-addition/cyclization step delivering benzoxazolidine or dihydroindazole scaffolds, respectively. This study not only expands the application boundary of the Schmidt reaction but also provides a new strategy for nitrogen addition to a C(sp2)–C(sp2) bond.
15. Nanobody-Based Lateral Flow Assay for Rapid Zika Virus Detection
Yuli Peng, Atheer Alqatari, Fabian Kiessling, Dominik Renn, Raik Grünberg, Stefan T. Arold, Magnus Rueping
ACS Synth. Biol. 2025, 14, 3, 890–900
DOI: 10.1021/acssynbio.4c00819
Abstract:
Zika virus infections remain severely underdiagnosed due to their initial mild clinical symptoms. However, recent outbreaks have revealed neurological complications in adults and severe deformities in newborns, emphasizing the critical need for accurate diagnosis. Lateral flow assays (LFAs) provide a rapid, cost-effective, and user-friendly method for antigen testing at point-of-care, bedside, or in home settings. LFAs utilizing nanobodies have multiple benefits over traditional antibody-based techniques, as nanobodies are much smaller, more stable, and simpler to manufacture. We introduce a nanobody-based LFA for the rapid identification of Zika virus antigens. Starting from two previously reported nanobodies recognizing the Zika nonstructural protein 1 (NS1), we evaluate periplasmic and cytosolic nanobody expression and test different purification tags and immobilization strategies. We quantify nanobody binding kinetics and validate their mutually noncompetitive binding. Avidity effects boost the capture of the tetrameric target protein by 3 orders of magnitude and point to a general strategy for higher sensitivity LFA sensing. The nanobody LFA detects Zika NS1 with a limit of detection ranging from 25 ng/mL in buffer to 1 ng/mL in urine. This nanobody-LFA has the potential to facilitate on-site and self-diagnosis, improve our understanding of Zika infection prevalence, and support public health initiatives in regions affected by Zika virus outbreaks.
14. Electrochemical C-H functionalization reaction of N-heterocycles with alkyl iodides
Yaseen Hussain, Ganga Sankar, Magnus Rueping Rene M. Koenigs
Chem. Commun., 2025, Accepted Manuscript
DOI: 10.1039/D5CC01836F
Abstract:
Herein we report an electro catalyzed alkylation of heterocycles with alkyl halide through a XAT strategy. A wide range of alkyl halides (Br, I) were tolerated to deliver the alkylated heterocycles. Further, azauracil bearing various functionalities and bioactive molecules viz. isozepac, borneol, menthol etc. also delivered the corresponding alkylated products in acceptable yield. We consider that the reaction proceeds by initial oxidation of triethylamine under electrochemical conditions, followed by deprotonation to α-amino radical intermediate. Then the radical intermediate abstracts the halogen atom from the alkyl halide to generate the alkyl radical and α-halo amine. Finally, the intermediate adds onto the imine carbon followed by deprotonation and subsequent oxidation to provide the esired product.
Deshen Kong, Liang Yi, Alice Nanni, Magnus Rueping
Nat Commun, 2025, 16, 3983
DOI: 10.1038/s41467-025-59358-1
Abstract:
Photocatalysis has greatly advanced in organic synthesis but still confronts challenges, including light attenuation in reaction media and excessive solvent utilization. These issues lead to inefficiencies, particularly in heterogeneous cloudy mixtures and in scaling-up applications. Integrating photocatalysis with mechanochemistry offers a nascent but promising solution to these challenges. Herein, we present a scalable photo-mechanochemical platform that combines visible-light photocatalysis with Resonant Acoustic Mixing (RAM), enabling efficient cross-coupling reactions under solvent-minimised conditions. This approach demonstrates broad substrate tolerance, accommodating a variety of aryl (hetero) halides and N-, O-, P-, S-nucleophiles. The protocol supports scaling up to 300 mmol, representing a 1500-fold increase, while maintaining exceptionally low catalyst loading and achieving up to 9800 turnover numbers (TON). The generality of this platform is further validated by its applicability to other synthetic transformations.
Gentoku Takasao, Bholanath Maity, Sayan Dutta, Rajesh Kancherla, Magnus Rueping, Luigi Cavallo
ACS Catal. 2025, 15, 5915−5927
DOI: 10.1021/acscatal.4c06474
Abstract:
We present an in silico workflow to streamline the identification of promising N-heterocyclic carbenes (NHCs) as ligands in metal catalysis or as catalysts in organocatalysis. Central to this workflow is the NHC-cracker database, which contains over 200 descriptors for 1781 nonredundant NHCs, each documented as an NHC-metal complex in the Cambridge Structural Database. To demonstrate its utility, we applied it to two catalytic problems using literature data. First, we analyzed 21 Ru–NHC complexes active in the ethenolysis of cyclic olefins. An MLR (multivariate linear regression) model trained on 11 Ru complexes based on NHCs in NHC-cracker successfully rationalized the behavior of the remaining 10 complexes. Second, we examined an Ir–Ni dual-catalyzed Csp2–Csp3 cross-coupling reaction involving five experimentally tested NHC skeletons. Using a multiscale workflow, we created DFT-based data sets to train two MLR models: one for productive substrate activation and another for detrimental NHC dimerization. Consistent with experiments, the models identified oxazoles as reactive, while benzimidazoles, triazoles, thiazoles, and untested cyclic (alkyl)(amino)carbenes were predicted as nonreactive. Experimental validation confirmed the latter’s lack of productive substrate activation, supporting the proposed mechanistic scenario.
Prashant S. Shinde, Valmik S. Shinde, Magnus Rueping
Chem. Sci., 2025, 16, 6273-6281
DOI: 10.1039/D5SC00297D
Abstract:
We report a Ni-catalyzed cascade reaction leading to the arylation of an alkyne-induced acyl migration and the formation of all-carbon tetra-substituted alkenes in good yields with exclusive Z-selectivity. This transformation involves the generation of a nucleophilic vinyl-Ni species through regioselective syn-aryl nickelation of the alkynes, followed by an intramolecular acyl migration. The steric and electronic properties of the phosphine ligands are crucial for achieving high regio- and stereocontrol in this migratory carbo-acylation process. The synthetic utility of the resulting Z-tetra-substituted alkenes is also demonstrated.
10. Ru-OV Site-Mediated Product Selectivity Switch for Overall Photocatalytic CO2 Reduction
C. Feng, M. Hu, S. Zuo, J. Luo, P. Castaño, Y. Ren, M. Rueping, H. Zhang
Adv. Mater. 2025, 37, 2411813
DOI:10.1002/adma.202411813
Abstract:
The photocatalytic reduction of carbon dioxide (CO2) to methane (CH4) represents a sustainable route for directly converting greenhouse gases into chemicals but poses a significant challenge in achieving high selectivity due to thermodynamic and kinetic limitations during the reaction process. This work establishes Ru-OV active sites on the surface of TiO2 by anchoring coordination unsaturated Ru single-atoms, which stabilize crucial reaction intermediates and facilitate local mass transfer to achieve dual optimization of the thermodynamics and kinetics of the overall photocatalytic CO2 reduction. Combining operando spectroscopy with density functional theory (DFT) calculations indicates that oxygen vacancies (OV) inhibits the desorption of *CO, whereas Ru facilitates proton extraction. This configuration not only lowers the overall activation energy barrier but has also been engineered to serve as a selectivity switch, changing the reaction route to produce CH4 instead of CO. Consequently, the Ru-OV/TiO2 exhibits a 195.4-fold improvement in the CH4 yield compared to TiO2, accompanied by an increase in selectivity to 81%.
Haifeng Chen, Magnus Rueping
Chem. Sci., 2025, 16, 6317-6324
DOI: 10.1039/D4SC07923J
Abstract:
Electrochemically driven carbon–carbon formation is receiving considerable interest in organic synthesis. In this study, we present an electrochemically driven method for the formation of C(sp3)–C(sp3) bonds using readily available allylic carbonates, as well as primary, secondary, and tertiary alkyl bromides as electrophiles. This approach offers a highly selective route for synthesizing a broad range of allylic products with excellent functional group tolerance, all without the need for transition metal catalysts. Remarkably, this method also enables the smooth late-stage functionalization of various natural product- and drug-derived substrates, yielding the corresponding complex allylalkanes.
Wenting Feng, Bin Chang, Yuanfu Ren, Debin Kong, Hua Bing Tao, Linjie Zhi, Mohd Adnan Khan, Rashed Aleisa, Magnus Rueping, Huabin Zhang
Adv. Mater. 2025, 2416012
DOI: 10.1002/adma.202416012
Abstract:
Proton exchange membrane water electrolysis (PEMWE) represents a promising technology for renewable hydrogen production. However, the large-scale commercialization of PEMWE faces challenges due to the need for acid oxygen evolution reaction (OER) catalysts with long-term stability and corrosion-resistant membrane electrode assemblies (MEA). This review thoroughly examines the deactivation mechanisms of acidic OER and crucial factors affecting assembly instability in complex reaction environments, including catalyst degradation, dynamic behavior at the MEA triple-phase boundary, and equipment failures. Targeted solutions are proposed, including catalyst improvements, optimized MEA designs, and operational strategies. Finally, the review highlights perspectives on strict activity/stability evaluation standards, in situ/operando characteristics, and practical electrolyzer optimization. These insights emphasize the interrelationship between catalysts, MEAs, activity, and stability, offering new guidance for accelerating the commercialization of PEMWE catalysts and systems.
Yuli Peng, Yaning Huang, Fabian Kiessling, Dominik Renn, Magnus Rueping
ACS Synth. Biol. 2025, 14, 420-430
DOI: 10.1021/acssynbio.4c00592
Abstract:
The COVID-19 pandemic has highlighted the critical need for pathogen detection methods that offer both low detection limits and rapid results. Despite advancements in simplifying and enhancing nucleic acid amplification techniques, immunochemical methods remain the preferred choice for mass testing. These methods eliminate the need for specialized laboratories and highly skilled personnel, making home testing feasible. The here developed low-cost, easily producible and nanobody-based LFAs for the rapid detection of SARS-CoV-2 and MERS-CoV adhere to the essential criteria of the World Health Organization’s recommended ASSURED guidelines. The overall design enables rapid adaptation to emerging and evolving virus variants, with the flexibility to incorporate either specifically binding nanobodies or broadly binding nanobodies as needed. Moreover, the results are noticeable to the naked eye, which is important for point-of-care diagnostic. Additionally, this is the first reported nanobody-based MERS-CoV LFA and the first nanobody-based sandwich LFA that can be observed with the naked eye. We established a reliable protocol for conjugating gold nanoparticles with carboxyl groups to nanobodies produced in E. coli. We demonstrate nanobody-based Lateral Flow Assays (LFAs) for the rapid detection of SARS-CoV-2 and MERS-CoV in single and dual formats as point-of-care diagnostic tools. The developed LFAs are highly sensitive and successfully detected analytes at clinically relevant diagnostic cut-off values. Additionally, our results confirmed that the LFAs have a long shelf life and can be produced cost-effectively and with ease.
6. Ultrafast Charge Transfer on Ru-Cu Atomic Units for Enhanced Photocatalytic H2O2 Production
C. Feng, J. Alharbi, M. Hu, S. Zuo, J. Luo, H. S. Al Qahtani, M. Rueping, K.-W. Huang, H. Zhang
Adv. Mater. 2025, 38, 2411813
DOI: 10.1002/adma.202406748
Abstract:
Photosensitizer-assisted photocatalytic systems offer a solution to overcome the limitations of inherent light harvesting capabilities in catalysts. However, achieving efficient charge transfer between the dissociative photosensitizer and catalyst poses a significant challenge. Incorporating photosensitive components into reactive centers to establish well-defined charge transfer channels is expected to effectively address this issue. Herein, the electrostatic-driven self-assembly method is utilized to integrate photosensitizers into metal–organic frameworks, constructing atomically Ru-Cu bi-functional units to promote efficient local electron migration. Within this newly constructed system, the [Ru(bpy)2]2+ component and Cu site serve as photosensitive and catalytic active centers for photocarrier generation and H2O2 production, respectively, and their integration significantly reduces the barriers to charge transfer. Ultrafast spectroscopy and in situ characterization unveil accelerated directional charge transfer over Ru-Cu units, presenting orders of magnitude improvement over dissociative photosensitizer systems. As a result, a 37.2-fold enhancement of the H2O2 generation rate (570.9 µmol g−1 h−1) over that of dissociative photosensitizer system (15.3 µmol g−1 h−1) is achieved. This work presents a promising strategy for integrating atomic-scale photosensitive and catalytic active centers to achieve ultrafast photocarrier transfer and enhanced photocatalytic performance.
5. Allylgermane synthesis via facile and general nickela-electrocatalyzed electrophile coupling
Haifeng Chen, Cai Zhai, Chen Zhu, Magnus Rueping
Chem Catalysis, 2025, 101257
DOI: 10.1016/j.checat.2024.101257
Abstract:
Organogermanes have played a significant role in organic chemistry, and effective strategies for accessing various organogermanes are crucial for advancing their applications. However, the formation of allylgermanes under electrophile coupling is still unexplored. Herein, we describe a germylative allylation applying readily accessible allylic carbonates and chlorogermanes. The newly developed method demonstrates good selectivity and high functional group compatibility under mild conditions and provides a variety of allylgermanes, as well as allyl tin, in good yields. Mechanistic and density functional theory (DFT) studies revealed the synergistic catalytic process in detail.
4. Fine-Tuning NIR-Absorbing BODIPYs for Photoacoustic Detectionof Hypochlorous Ion (OCl⁻)
Prosenjit Isar, Tarushyam Mukherjee, Tengfei Ji, Alexander Nellessen, Jean-Michel Merkes, Fabian Kiessling, Magnus Rueping, Srinivas Banala
Chem. Asian J. 2025, e202401869
DOI: 10.1002/asia.202401869
Abstract:
Highly reactive oxygen and nitrogen species (ROS/RNS) play crucial roles in various pathological conditions. Among them, hypochlorous ion (OCl⁻), a potent ROS, is associated in numerous oxidative stress-related disorders. Elevated levels of OCl⁻ are thus recognized as a biomarker for diagnosing inflammatory conditions. To enable selective detection of OCl⁻ via photoacoustic (PA) imaging, we present development of a near infrared(NIR)-absorbing BODIPY-based acoustogenic probe. Four regioisomers of methoxyphenols-conjugated BODIPYs were synthesized to investigate the positional influence on OCl− selectivity over other ROS/RNS. Our study reveals that only one isomer, 4-methoxy phenol conjugation, exhibited exceptional selectivity for OCl− without any competitive reactions, making it suitable for PA imaging. This study highlights the importance of regioisomers characterization in achieving intricate selectivity among competing reactive species. The fine-tuning and development of a suitable dye now enable the optimization of physicochemical properties for in vivo OCl− detection using PA imaging.
3. Tracking Water Splitting Activity by Cocatalyst Identity in SrTiO3
Nursaya Zhumabay, Jeremy A. Bau, Rafia Ahmad, Laurentiu Braic, Huabin Zhang, Luigi Cavallo, Magnus Rueping
Small Struct. 2025, 6, 2400283
DOI: 10.1002/sstr.202400283
Abstract:
Photocatalytic water splitting is the most idealistic route to green hydrogen production, but the extensive material requirements for this reaction make it difficult to realize good photocatalysts. Noble metal cocatalysts are often added to photocatalysts to aid in charge separation and improve surface kinetics for H2 evolution. In this study, the high activity of the promising photocatalyst Al-doped SrTiO3 is demonstrated to be ultimately dependent on the cocatalyst used as much as the presence of Al dopant. By tracking the band energetics of photocatalyst electrodes using operando electrochemical ATR-SEIRAS, cocatalysts (especially Rh) are found to shift the quasi-Fermi levels and metal-semiconductor flat-band potentials of photocatalysts in an anodic direction. Furthermore, the size of the shift directly correlates with overall water splitting activity, demonstrating that SrTiO3 becomes more active as photo-generated electrons are stabilized further from the conduction band. Rh on Al-doped SrTiO3 provides the most advantageous band tailoring as confirmed by DFT, and is experimentally found to provide this effect by eliminating Ti3+-related surface traps in the presence of Al dopants. Therefore, the effect of cocatalysts on water splitting activity is more complicated than previously thought.
2. Scalable Depolymerizing Transesterification and Amidation of (Poly)lactic Acid (PLA) enabled by Resonant Acoustic Mixing - Recycling and Upcyling of PLA
Anton S. Makarov, Magnus Rueping
Green Chem. 2025, 26, 716-721
DOI: 10.1039/d4gc04623d
Abstract:
This study presents a scalable mechanochemical method for the upcycling of (poly)lactic acid (PLA) into industrially valuable alkyl lactate esters via organocatalytic depolymerizing transesterification enabled by resonant acoustic mixing (RAM). The process is characterized by its simplicity, requiring neither grinding media nor a co-solvent and utilizing nearly stoichiometric amounts of an alcohol reaction partner in the presence of an inexpensive, easily accessible catalyst. Additionally, the mechanochemistry is successfully extended to the upcycling of post-consumer PLA for the synthesis of various substituted esters and lactamides.
1. Ba/Ti MOF: A Versatile Heterogeneous Photoredox Catalyst for Visible-Light Metallaphotocatalysis
I. S. Khan, L. Garzon-Tovar, R. Kancherla, N. Kolobov, A. Dikhtiarenko, M. Almalki, A. Shkurenko, V. Guillerm, K. N. Le, G. Shterk, C. H. Hendon, M. Eddaoudi, J. Gascon, M. Rueping
Adv. Mater. 2025, 37, 2405646
DOI: 10.1002/adma.202405646
Abstract:
The field of sustainable catalysis is evolving rapidly, with a strong emphasis on developing catalysts that enhance efficiency. Heterogeneous photocatalysis has emerged as a promising and mild approach to address the persistent challenges. Among various heterogeneous photocatalysts, Metal-Organic Frameworks (MOFs) have gained significant attention for their exceptional performance and recyclability in photocatalytic reactions. In this context, contrary to the conventional homogeneous Ir or Ru-based photocatalysts, which face significant challenges in terms of availability, cost, scalability, and recyclability, we have developed a new Ba/Ti MOF (ACM-4) as a heterogeneous catalyst that could mimic/outperform the conventional photocatalysts, offering a more sustainable solution for efficient chemical processes. Its redox potential and triplet energy are comparable to or higher than the conventional catalysts, organic dyes, and metal semiconductors, enabling its use in both electron transfer and energy transfer applications. It facilitates a broad range of coupling reactions involving pharmaceuticals, agrochemicals, and natural products, and is compatible with various transition metals such as Ni, Cu, Co, and Pd as co-catalysts. Notably, ACM-4 can be easily recovered and reused multiple times with minimal loss in efficiency. The effectiveness of the ACM-4 as a photocatalyst is supported by comprehensive material studies and photophysical experiments. These significant findings underscore the potential of ACM-4 as a highly versatile and cost-effective photoredox catalyst, providing a sustainable, one-material solution for efficient chemical processes.