Angewandte Chemie International Edition

Liu, Juan; Qing, Yujia; Zhou, Linna; Chen, Shaomeng; Li, Xuefei; Zhang, Yujia; Bayley, Hagan

doi: 10.1002/anie.202408665pmid: 38976418

Enzyme‐enabled biobatteries are promising green options to power the next‐generation of bioelectronics and implantable medical devices. However, existing power sources based on enzymatic biofuel chemistry exhibit limited scale‐down feasibility due to the solid and bulky battery structures. Therefore, miniature and soft alternatives are needed for integration with implants and tissues. Here, a biobattery built from nanolitre droplets, fuelled by the enzyme‐enabled oxidation of reduced nicotinamide adenine dinucleotide, generates electrical outputs and powers ion fluxes in droplet networks. Optimization of the droplet biobattery components ensures a stable output current of ~13,000 pA for over 24 h, representing a more than 600‐fold increase in output over previous approaches, including light‐driven processes. The enzyme‐enabled droplet biobattery opens new avenues in bioelectronics and bioiontronics, exemplified by tasks such as the ability to drive chemical signal transmission in integrated synthetic tissues.

Wu, Jicheng; Lu, Hailin; Xu, Ximing; Rao, Lang; Ge, Yun

doi: 10.1002/anie.202404889pmid: 38977426

Immune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti‐CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high‐mannose glycans into the nanobody against CD47 (HM‐nCD47) and subsequently displayed HM‐nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM‐nCD47‐CVs, the nCD47 enabled the blockade of the CD47/SIRPα axis, and the HM enhanced recognition of mannose‐binding lectin, all synergistically activating the macrophage‐mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM‐nCD47‐CVs possessed significantly extended half‐lives and increased accumulation at the tumor site, resulting in a remarkable macrophage‐dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM‐nCD47‐CVs represent a new immunotherapeutic platform for cancer and other diseases.

Otroshchenko, Tatiana; Sharapa, Dmitry I.; Fedorova, Elizaveta A.; Zhao, Dan; Kondratenko, Evgenii V.

doi: 10.1002/anie.202410646pmid: 38972838

Ethylene dimerization is an industrial process that is currently carried out using homogeneous catalysts. Here we present a highly active heterogeneous catalyst containing minute amounts of atomically dispersed Pd. It requires no co‐catalyst(s) or activator(s) and significantly outperforms previously reported catalysts tested under similar reaction conditions. The selectivity to C4‐ and C6‐hydrocarbons was about 80 % and 10 % at 42 % ethylene conversion at 200 °C using an industrially relevant feed containing 50 vol % ethylene, respectively. Our kinetic and catalyst characterization experiments complemented by density functional theory calculations provide molecular insights into the local environment of isolated Pd(II)Ox species and their role in achieving high activity in the target reaction. When the developed catalyst was rationally integrated with a Mo‐containing olefin metathesis catalyst in the same reactor, the formed butenes reacted with ethylene to propylene with a selectivity of 98 % at about 24 % ethylene conversion.

Saha, Abhishek; Bishara, Laila A.; Saed, Yakop; Vamisetti, Ganga B.; Mandal, Shaswati; Suga, Hiroaki; Ayoub, Nabieh; Brik, Ashraf

doi: 10.1002/anie.202409012pmid: 39115450

Despite the great advances in discovering cyclic peptides against protein targets, their reduced aqueous solubility, cell permeability, and activity of the cyclic peptide restrict its utilization in advanced biological research and therapeutic applications. Here we report on a novel approach of structural alternation of the exocyclic and linker parts that led to a new derivative with significantly improved cell activity allowing us to dissect its mode of action in detail. We have identified an effective cyclic peptide (CP7) that induces approximately a 9‐fold increase in DNA damage accumulation and a remarkable increase in apoptotic cancer cell death compared to the reported molecule. Notably, treating cells with CP7 leads to a dramatic decrease in the efficiency of non‐homologous end joining (NHEJ) repair of DNA double‐strand breaks (DSBs), which is accompanied by an increase in homologous recombination (HR) repair. Interestingly, treating BRCA1‐deficient cells with CP7 restores HR integrity, which is accompanied by increased resistance to CP7. Additionally, CP7 treatment increases the sensitivity of cancer cells to ionizing radiation. Collectively, our findings demonstrate that CP7 is a selective inhibitor of NHEJ, offering a potential strategy to enhance the effectiveness of radiation therapy.

doi: 10.1002/anie.202484491pmid: N/A

Wang, Jiangjiang; Dong, Xiao; Feng, Guanghui; Lu, Xiaocheng; Wu, Gangfeng; Li, Guihua; Li, Shoujie; Mao, Jianing; Chen, Aohui; Song, Yanfang; Zeng, Jianrong; Wei, Wei; Chen, Wei

doi:

Fudickar, Werner; Linker, Torsten

doi: 10.1002/anie.202411079pmid: 39022983

We present the design of an anthracenyl–naphthyl (ANT‐NAPH) dyad and its application as a luminescent 4‐stage photo switch. Both segments can individually react with singlet oxygen to switch off an optical response. In their initial form the larger ANT component reacts significantly faster and thus an ANTO2‐NAPH stage is turned on, observed by optical response of the remaining NAPH. To reduce its reactivity, ANT is substituted with two pyridine rings. This concept is first investigated and quantified on ANT and NAPH as separated molecules. Upon protonation the reaction of ANT becomes significantly slower. For the three possible pyridyl isomers this effect increases along the order meta<para<ortho. With the pyridyl nitrogen in ortho position the reaction completely toggles from ANT to NAPH. Application of this concept on the dyad allows to turn on the ANT‐NAPHO2 stage with optical response of the remaining ANT. The sequence of protonation‐oxygenation‐neutralization is thereby the only possible way to isolate the unfavored form ANT‐NAPHO2. In the dyad ANT and NAPH are directly attached and their coupling constitutes a non‐oxygenated third stage, where the NAPH luminescence is quenched and ANT luminescence is enhanced. Reaction of both NAPH and ANT to ANTO2‐NAPHO2 constitutes the fourth dark stage.

Hawkins, Bill C.; Chalker, Justin M.; Coote, Michelle L.; Bissember, Alex C.

doi: 10.1002/anie.202407207pmid: 39075778

This Minireview examines a selection of case studies that showcase distinctive and enabling electrochemical approaches that have allowed for the generation and reaction of carbocation intermediates under mild conditions. Particular emphasis is placed on the progress that has been made in this area of organic synthesis and polymer chemistry over the past decade.