Izang JC et al. · Jul 9, 2026
PCN-222(Co), a mesoporous Zr-based cobalt-porphyrin MOF, catalyses benzylic C-H amination under air, with added water, and with limiting C-H substrate.
Zhu Y et al. · Jul 7, 2026
We report the divergent reactivities of a trisilyl-substituted alane and its radical anionic species towards isocyanides and carbon monoxide. While the neutral Al(III) species forms coordination complexes, the Al(II) radical promotes cyanide formation. Notably, the radical anion mediates CO homologation to yield a C 3 fragment, which provides new insight into main-group CO homologation.
Kastner K et al. · Jul 7, 2026
3-Ketoglycals are versatile Michael acceptors widely used in chemical C -glycosylation. Here, we report the enzymatic equivalent of this transformation, catalysed by a 3-keto- C -glycoside lyase, enabling selective C -glycosylation of polyphenolic natural products. The reaction proceeds with remarkable chemo- and stereo-selectivity, affording aryl- C -β-glycosides.
Sevinc SK et al. · Jul 1, 2026
The most common cancer in women worldwide is still breast cancer. Among its subtypes, luminal A and triple-negative breast cancers present significant therapeutic challenges due to intrinsic drug resistance and absence of effective targeted treatments. The pharmacological potential of heterocyclic compounds has garnered more attention in recent years, and structures like pyrazolines, hydrazones, and triazoles are important in the development of new drugs. Compounds incorporating these scaffolds have been shown in numerous studies to have strong anticancer action. In this regard, pyrazoline derivatives have become a viable field of study for focused treatment approaches. This study focused on evaluating the cytotoxic potential of the 2-pyrazoline-5-one derivative compound against luminal-A (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines. The CCK-8 test was used to assess the impact on cell viability. Additionally, Annexin V/PI staining was used to identify the apoptotic effects, and fluorescence microscopy was used for analysis. The wound healing experiment was used to measure the capacity of cells to migrate, and migration process was monitored following scratch formation. The colony formation assay was used to assess the potential for cell proliferation, and clonal growth capacities were compared. Bax protein levels in compound-treated cancer cells were quantified by ELISA to investigate the apoptotic mechanism. IC50 values in MCF-7 and MDA-MB-231 cell lines were used to evaluate the cytotoxic effects of the 2-pyrazoline-5-one derivative. The compound exhibited strong cytotoxic activity and reduced cell viability in both cell lines in a concentration-dependent manner, with IC 50 values of 13 µM in MCF-7 cells and 16 µM in MDA-MB-231 cell. Furthermore, the compound effectively induced apoptosis and significantly suppressed colony formation and cell migration in both cell lines. Additionally, it showed a concentration-dependent rise in Bax protein levels, suggesting a pro-apoptotic action. These results confirm that the 2-pyrazoline-5-one derivative has strong antiproliferative and pro-apoptotic activity through Bax activation, providing a possible pathway for the creation of targeted treatments for breast cancer.
Karayavuz B et al. · Jul 1, 2026
Chirality is of great importance in drug development since both biological targets in the organism and the majority of pharmacologically active compounds created today are chiral. The synthesis and resolution of chiral compounds are critical steps while developing chiral drugs, as the chirality of a molecule can significantly affect its efficacy, safety (side effects and toxicity), and metabolism. While one enantiomer has therapeutic properties, the other enantiomer might be harmful, toxic, or ineffective. In recent years, the trends towards developing single enantiomer drugs have increased in the pharmaceutical industry. Various synthetic strategies and racemic resolution techniques are employed to obtain optically pure chiral drugs. Regulatory authorities also give more priority to assessing the biological efficacy of each chiral drug's enantiomer. This review summarizes the asymmetric synthesis and racemic resolution methods for producing pure enantiomeric pharmaceutical active ingredients and their synthetic intermediates, with examples from the pharmaceutical industry. By examining current approaches and challenges in the field, we aim to provide a comprehensive understanding of the processes that ensure the production of safe and effective chiral-specific drugs.
Zhang A et al. · Jul 1, 2026
In light of the centennial of the Schrödinger equation, this article addresses the popular idea that quantum mechanical effects play an important role in biological systems. We start by defining what is qualified as a quantum effect. We then clarify the idea that quantum mechanical tunneling is a crucial factor in enzyme catalysis. Here we show that quantum tunneling is in fact anticatalytic and that there is no consistent theoretical and experimental evidence that the tunneling effects are enhanced significantly by enzymes relative to the corresponding reference solution reactions. We next turn to electron transfer reactions, arguing that in most cases the efficiency of the reaction is controlled by classical effects. We also consider the low barrier hydrogen bond idea and clarify its anticatalytic nature. In addition, we present a specific case study of electron transfer in a protein system potentially responsible for bird navigation, providing a concrete example for evaluating the role of quantum and classical effects under biologically relevant conditions. We argue that for the electron transfer step in this system, the most important control is associated with the classical control of the relevant potential surfaces and the fluctuations of the key energy gaps.
Han P et al. · Jul 1, 2026
Collision-induced dissociation (CID) of small molecules, typically with a molecular mass below 1500 Da, is widely applied for the structural identification of drug metabolites, synthetic by-products and unknown compounds. Nonetheless, the interpretation of MS/MS spectra derived from protonated or sodiated molecules mainly relies on the comparison with literature data and proposed structures usually lack rigorous mechanistic justification and conclusive evidence. The commonly applied even-electron rule, as implemented in most literature and prediction software, does not support radical loss from protonated molecules. Similarly, fragmentation pathways of sodium adduct ions remain insufficiently explored and lack mechanistic rationalization. To improve the understanding of radical loss from even-electron nitro-containing compounds, a mechanistic study of fragmentation patterns of nifedipine, m-nifedipine, and related analogues was performed. Fragment ions generated from [M+H] + and [M+Na] + of nifedipine revealed distinct mechanisms compared with its positional isomers, while showing similarities with analogues like nisoldipine and aranidipine. The nitro group at the ortho position significantly influences fragment stability, leading to a unique fragmentation mechanism described as ortho effect. The mechanism was further investigated using isotope labelled analogs, ion mobility spectrometry (IMS), precursor ion scan (PIS), and density functional theory (DFT) calculations. Different approaches in combining IMS with MS/MS demonstrated strong capability for elucidation of fragmentation pathways.
Moreno-Pedraza A et al. · Jul 1, 2026
Mass spectrometry imaging (MSI) represents an exceptional tool for exploring complex biological systems spatially at the molecular level. However, its multidimensional nature and large data outputs make it challenging to extract meaningful biological insights. Advancements such as the METASPACE platform allow researchers to efficiently process, annotate, and interpret MSI datasets by leveraging machine learning and a cloud-based infrastructure. In this tutorial, we present a detailed and user-friendly R-pipeline designed to help METASPACE users navigate untargeted metabolomic annotations and translate them into practical biological insights, particularly in complex systems. This approach has broad potential applications, including diagnostics, drug discovery, environmental, and ecological research. We envision this pipeline will be particularly useful for newcomers to MSI and encourage experienced users to customize and extend it to meet more advanced analytical needs.
Sharma L et al. · Jul 1, 2026
Maintaining mitochondrial integrity and function is fundamental to cellular homeostasis. Cells rely on coordinated protein quality control (QC) systems-including intricate chaperone-protease networks, the ubiquitin-proteasome system, and cytosolic surveillance pathways-that together form a dynamic, cell-wide mitostasis network governing the import, folding, synthesis, and degradation of mitochondrial proteins. Disruption of mitochondrial homeostasis, for example, by impairing mitochondrial protein import, induces proteotoxic stress and contributes to human disease. Mass spectrometry (MS)-based proteomics has established itself as an indispensable method to dissect mitostasis at unprecedented depth by enabling systematic quantitative analysis of protein abundance, localization, interactions, stability, and dynamics. In this review, we highlight state-of-the-art MS technologies and multifaceted proteomics approaches used to study mitostasis on a proteome-wide level. These functional analysis approaches build on quantitative MS methods employing label-free, metabolic, and chemical labeling strategies, which allow precise tracking of proteome dynamics in response to different cellular conditions including stress. Spatial and interaction-based approaches, such as affinity purification-MS, proximity labeling, and complexome profiling, provide detailed insight into the organization and regulation of the complex mitochondrial organizing system, chaperone networks, and protein QC pathways. Furthermore, we discuss advanced methodologies such as nascent chain and dynamic proteomics strategies, which offer a proteome-wide comprehension of early stress responses and fast regulation. The skillful integration of temporal, spatial subcellular, interaction, nascent, and dynamic proteomics approaches now enables a systems-level assessment of mitostasis, paving the way for a holistic while nuanced understanding of this essential cellular process and the underlying molecular mechanisms.
Caporale M et al. · Jul 1, 2026
A practical approach to optically active erythro 3-amino-2-hydroxy acids has been developed and applied to the enantioselective synthesis of 3-phenylisoserine and naturally occurring 3-amino-2-hydroxy-6-methylheptanoic acid (AHMHA), a nonproteinogenic amino acid found in the marine cyclic oligopeptide perthamide C. The proposed synthetic methodology requires the enantioselective Sharpless syn-dihydroxylation of (E)-α,β-unsaturated esters followed by regioselective and stereoselective Mitsunobu azidation on the β-hydroxy group. Subsequent azide hydrogenation and ester hydrolysis provide the desired erythro 3-amino-2-hydroxy acids in high enantiopurity and overall yield. The proposed approach to AHMHA was more efficient and direct compared to the one previously reported in the literature. The absolute configuration of the diol precursor of AHMHA was assigned by ECD analysis of its biphenyl dioxolane, thereby also confirming the absolute configuration of the natural AHMHA.