Chemical Science

doi: 10.1039/d5sc90059jpmid: N/A

doi: 10.1039/d5sc90060cpmid: N/A

Zhang, Hongjie

doi: 10.1039/d5sc90034dpmid: 39975765

Copper has emerged as a promising target for cancer therapy, with extensive studies on copper accumulation-induced cuproptosis. However, the potential of copper depletion-induced cuproptosis remains largely unexplored. Recently, Zhou et al. (M. Zhou, F. Muhammad, Y. Zhang, T. Li, J. Feng, J. Zhao and H. Wei, Chem. Sci., 2025, https://doi.org/10.1039/D4SC04712E) reported an innovative strategy for copper depletion-based cuproptosis. Notably, this approach leverages the solubility product principle, a mechanism not previously addressed in studies, to achieve effective tumor therapy through the disruption of copper homeostasis.

Bian, Zhengyi; Gomez, Eric; Gruebele, Martin; Levine, Benjamin G.; Link, Stephan; Mehmood, Arshad; Nie, Shuming

doi: 10.1039/d4sc05843gpmid: 39958645

The physico-chemical properties of ‘bottom-up’ carbon dots synthesized from small molecules feature both generalities, such as sp2-networked carbon and core-surface energy transfer, and heterogeneities, due to the unpredictable location of heteroatoms and often non-crystalline structure. Here we focus our review on three aspects of these systems: (1) coupling characterization with bottom-up synthesis to identify and remove confounding byproducts such as small molecules or hydrogen-rich polymers; (2) single-particle characterization to obtain unambiguous information on carbon dots and highlight the distribution of properties around the ensemble average; (3) electronic structure of carbon dots and how it can help elucidate the origin of important properties such as optical absorption and fluorescence from a heterogeneous ensemble of carbon dots.

Tsuruta, Mitsuki; Shil, Sumit; Taniguchi, Shinya; Kawauchi, Keiko; Miyoshi, Daisuke

doi: 10.1039/d4sc06959epmid: 39935503

Aberrant expansion of GGGGCC DNA repeats that form G-quadruplexes (G4) is the main cause of amyotrophic lateral sclerosis (ALS). Expanded GGGGCC repeats induce liquid–liquid phase separation (LLPS) through their interaction with cellular proteins. Furthermore, GGGGCC expansion induces cytosine methylation (mC). Previous studies have shown that even slight chemical modifications of RNAs and proteins can drastically affect their LLPS ability, yet the relationship between LLPS and epigenetic DNA modifications like mC remains unexplored. As a model system, we investigated the effects of mC on LLPS induced by GGGGCC repeat DNAs and show for the first time that mC suppresses LLPS by altering the topology of G4 from being parallel to antiparallel.

Pang, Qi; Zhang, Mengke; Song, Yang; Liu, Yueying; Tang, Manqi; Su, Sunqi; Qiu, Lang; Xiao, Yao; Guo, Xiaodong

doi: 10.1039/d4sc07037bpmid: 39911339

Lithium-rich cathode materials are some of the most promising choices for lithium-ion batteries due to their excellent energy density (>900 W h kg−1). However, severe voltage/capacity degradation during cycling has seriously hindered the further commercialization of lithium-rich cathode materials. Current research efforts are focused on enhancing their voltage and capacity retention. Here, the coating of FeF3 on specific crystal planes is utilized to achieve a degradation trend that is very different from that of the as-received material. Using this as an entry point, the relationship between voltage and capacity degradation was studied in depth. The oriented coated material undergoes a more drastic phase transition during cycling, yet its voltage decay remains basically the same as that of the original sample (769.6 mV after 200 cycles, compared to 723.5 mV for the original sample). Notably, the capacity retention rate is significantly improved (97% after 200 cycles vs. 75% for the pristine material). These findings suggest that the capacity degradation and the voltage decay do not interact with each other and that the phase transition during cycling does not seem to negatively affect the voltage. This conclusion can also be extrapolated to other oxygen-reducing oxide systems to help understand the relationship between capacity and voltage decay. The modification is generalized and applicable to other cathode materials.

Kelly, Nicole L.; Borthwick, Emma A. L.; Lawrence, Gaynor B.; Wheatley, Paul S.; Hughes, Colan E.; Harris, Kenneth D. M.; Morris, Russell E.; Ashbrook, Sharon E.

doi: 10.1039/d4sc07931kpmid: 39926704

Zeolite-formation mechanisms have long been the subject of intensive study, with most work concentrating on hydrothermal mechanisms. However, non-traditional zeolite syntheses that do not rely on hydrothermal crystallisation have provided a number of new routes to interesting and unexpected new materials, but their formation mechanisms remain poorly understood. Here, we show how simultaneous in situ liquid- and solid-state 29Si NMR spectroscopy can reveal the mechanism of the formation of a zeolite from a layered silicate precursor. The study provides evidence for the species that are intercalated into the layered material and establishes those that are involved in building the inter-layer, zeolitic connections as a function of time during the zeolite formation process.

Deutscher, Robin C. E.; Meyners, Christian; Repity, Maximilian L.; Sugiarto, Wisely Oki; Kolos, Jürgen M.; Maciel, Edvaldo V. S.; Heymann, Tim; Geiger, Thomas M.; Knapp, Stefan; Lermyte, Frederik; Hausch, Felix

doi: 10.1039/d4sc06917jpmid: 39916884

Molecular glues are a new drug modality with the potential to engage otherwise undruggable targets. However, the rational discovery of molecular glues for desired targets is a major challenge and most known molecular glues have been discovered by serendipity. Here we present the first fully synthetic FKBP12-mTOR molecular glues, which were discovered from a FKBP-focused, target-unbiased ligand library. Our biochemical screening of >1000 in-house FKBP ligands yielded one hit that induced dimerization of FKBP12 and the FRB domain of mTOR. The crystal structure of the ternary complex revealed that the hit targeted a similar surface on the FRB domain compared to natural product rapamycin but with a radically different interaction pattern. Structure-guided optimization improved potency 500-fold, and led to compounds which initiate FKBP12-FRB complex formation in cells. Our results show that molecular glues targeting flat surfaces can be discovered by focused screening and support the use of FKBP12 as a versatile presenter protein for molecular glues.

Carpenter, Barry K.

doi: 10.1039/d4sc08748hpmid: 39981038

The division of electrocyclic reactions into “allowed” and “forbidden” classes carries the implication that reactions of the latter class are so energetically penalised that they will occur only if their “allowed” alternatives are rendered effectively impossible. The present work tests that assumption, using NEVPT2 and DFT calculations on a variety of cyclobutene ring openings and (Z)-1,3,5-hexatriene ring closures, and their benzannelated congeners. The results show the assumption to be incorrect. The potential energy differences between “forbidden” and “allowed” transition states are found to cover a wide range of values, with the smallest being less than half the classical barrier to internal rotation of ethane. It follows that planning a total synthesis on the presumption that electrocyclic reactions will always follow the “allowed” stereochemical course is an unreliable strategy because other commonly occurring factors, such as routine steric and electronic substituent effects, can easily outweigh the electronic penalty for following the nominally forbidden mechansim. A particular case involving a proposed synthetic route to a class of anticancer compounds is highlighted as an example.

Hosokawa, Naoki; Ozawa, Kyohei; Koike, Kazuhide; Tamaki, Yusuke; Ishitani, Osamu

doi: 10.1039/d4sc08268kpmid: 39926711

While the quantum yields of photosensitiser-derived one-electron-reduced species (OERSs) significantly impact the overall efficiencies of various redox-photosensitised photocatalytic reactions, the primary factors that influence them remain unclear. In this study, we systematically compared the photochemical formation quantum yields for OERSs associated with Ru(ii) and Os(ii) tris-diimine, cis, trans-[ReI(diimine)(CO)2(PR3)2]+, and cyclometalated Ir(iii) complexes in the presence of the same 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole (BIH) reductant. The reduction potentials of the excited metal complexes, the heavy-atom effects of the central metal ions, and the oxidation potentials and charges of their OERSs were examined, which reveals that the driving force for photoinduced electron-transfer is the most important factor that determines the quantum yields associated with photochemical OERS formation. For complexes with higher oxidation power in their excited states, the formation quantum yield of OERSs divided by the quenching efficiency of the excited state by BIH is greater. This finding suggests that a higher photoinduced electron-transfer exergonicity promotes electron transfer over larger excited-complex/BIH distances, which in turn enables more-efficient separation of the resulting OERSs and one-electron-oxidised BIH species.