Aromaticity and antiaromaticity are pivotal concepts in chemistry, with significant implications for molecular properties and reactivity. In particular, thanks to their increased conductivity and small HOMO–LUMO energy gaps, antiaromatic molecules are promising for use in organic electronics. The inherent instability of such molecules is often addressed by carbocyclic fusion, which also reduces the antiaromaticity of the core structure. Herein, we have employed a computational approach to explore the effects of heterocyclic fusion on the s-indacene core, focusing on three main aspects: the impact of the heteroatom, the heterocycle, and extended conjugation. We found that the heteroatoms themselves can substantially modulate antiaromaticity, and that the site of substitution plays a large role in the extent of stabilization afforded. Heterocycle fusion further modulates antiaromaticity, though to a lesser extent than the heteroatom effect. This effect diminishes upon benzannelation, highlighting the complexity of aromatic and antiaromatic interplay. Our findings offer a nuanced understanding of the factors affecting antiaromaticity in s-indacene-based polycyclic systems, providing a conceptual framework for predicting and tuning these properties for applications in organic electronics. This work underscores the importance of both substitution position and heterocyclic fusion in designing stable antiaromatic compounds.

PATAI’s Chemistry of Functional Groups publishes comprehensive reviews on all aspects of specific functional groups. Each volume contains outstanding surveys on theoretical and computational aspects, NMR, MS, other spectroscopic methods and analytical chemistry, structural aspects, thermochemistry, photochemistry, synthetic approaches and strategies, synthetic uses and applications in chemical and pharmaceutical industries, biological, biochemical, and environmental aspects. To date, over 150 volumes have been published in the series.

Many biological molecular motors and machines are driven by chemical reactions that occur in specific catalytic sites. We study whether the arrival of molecules to such an active site can be accelerated by the presence of a nearby inactive site. Our approach is based on comparing the steady-state current in simple models to reference models without an inactive site. We identify two parameter regimes in which the reaction is accelerated. We then find the transition rates that maximize this acceleration and use them to determine the underlying mechanisms in each region. In the first regime, the inactive site stores a molecule to release it following a reaction, when the neighboring catalytic site is empty. In the second regime, the inactive site releases a molecule when the catalytic site is full, to impede the molecules from leaving the active site before they react. For the storage mechanism, which is more likely to be biologically relevant, the acceleration can reach up to 15%, depending on parameters.

Aggressive and therapy-resistant cancers present a significant challenge to treatment and are associated with poor patients survival. Identifying molecular pathways and compounds that target these pathways is critical for improving patient outcomes. RNF4, an E3-ubiquitin ligase, is pivotal in oncoprotein stabilization and DNA repair, enhancing cancer cell survival driving tumorigenesis. Elevated RNF4 levels are associated with poor prognosis in cancer patients. Here, we describe the development of R4VPs, proteolysis-targeted chimeras-like (PROTACs-like). R4VPs promote RNF4 degradation and reduce the levels of its stabilized oncoproteins. Notably, R4VPs induce ferroptotic cell death selectively in cancer cells, sparing non-tumorigenic and primary cells. Surprisingly, R4VPs-induced ferroptosis is independent of RNF4 but preferentially targets tumor-driving mutations, particularly those in the EGFR pathway, while not affecting PI3K-transformed cells. R4VPs effectively induce cell death in therapy-resistant melanoma and sarcomas including patient-derived sarcoma tumor cells. Our findings highlight the potential of ferroptosis inducers such as R4VPs as a therapeutic strategy for therapy resistance, aggressive, and hard-to-treat cancers.

High-harmonic generation (HHG) is a nonlinear process in which a material sample is irradiated by intense laser pulses, causing the emission of high harmonics of incident light. HHG has historically been explained by theories employing a classical electromagnetic field, successfully capturing its spectral and temporal characteristics. However, recent research indicates that quantum-optical effects naturally exist or can be artificially induced in HHG, such as entanglement between emitted harmonics. Even though the fundamental equations of motion for quantum electrodynamics (QED) are well-known, a unifying framework for solving them to explore HHG is missing. So far, numerical solutions have employed a wide range of basis-sets, methods, and untested approximations. Based on methods originally developed for cavity polaritonics, here we formulate a numerically accurate QED model consisting of a single active electron and a single quantized photon mode. Our framework can, in principle, be extended to higher electronic dimensions and multiple photon modes to be employed in ab initio codes for realistic physical systems. We employ it as a model of an atom interacting with a photon mode and predict a characteristic minimum structure in the HHG yield vs phase-squeezing. We find that this phenomenon, which can be used for novel ultrafast quantum spectroscopies, is partially captured by a multitrajectory Ehrenfest dynamics approach, with the exact minima position sensitive to the level of theory. On the one hand, this motivates using multitrajectory approaches as an alternative for costly exact calculations. On the other hand, it suggests an inherent limitation of the multitrajectory formalism, indicating the presence of entanglement and true quantum effects (especially prominent for atomic and molecular resonances). Our work creates a roadmap for a universal formalism of QED-HHG that can be employed for benchmarking approximate theories, predicting novel phenomena for advancing quantum applications, and for the measurements of entanglement and entropy.

The Small Ubiquitin-like Modifier (SUMO) is a crucial post-translational modifier of proteins, playing a key role in various cellular functions. All SUMOs are synthesized as precursor proteins that must be proteolytically processed. However, the maturation process of cleaving the extending C-terminal tail, preceding SUMOylation of substrates, remains poorly understood, especially within cellular environments. Chemical protein synthesis coupled with cell delivery offers great opportunities to prepare SUMO analogues to investigate this process in vitro and in live cells. Applying this unique combination we show that SUMO2 analogues containing the native tail undergo rapid cleavage and nuclear localisation, while a Gly93Ala mutation impairs cleavage and alters localisation. Tail mutations (Val94Glu, Tyr95Ala) affected cleavage rates, highlighting roles in SUMO–SENP protease interactions. In cells, SUMO2 analogues containing tail mutations underwent cleavage and subsequently incorporated into promyelocytic leukemia nuclear bodies (PML-NBs). These findings advance our understanding of SUMO2 maturation and provide a foundation for future studies of this process for different SUMO paralogues in various cell lines and tissues.

The quest to enhance the sensitivity of electron spin resonance (ESR) is an ongoing challenge. One potential strategy involves increasing the frequency, for instance, moving from Q-band (approximately 35 GHz) to W-band (approximately 94 GHz). However, this shift typically results in higher transmission and switching losses, as well as increased noise in signal amplifiers. In this work, we address these shortcomings by employing a W-band probehead integrated with a cryogenic low-noise amplifier (LNA) and a microresonator. This configuration allows us to position the LNA close to the resonator, thereby amplifying the acquired ESR signal with minimal losses. Furthermore, when operated at cryogenic temperatures, the LNA exhibits unparalleled noise levels that are significantly lower than those of conventional room temperature LNAs. We detail the novel probehead design and provide some experimental results at room temperature as well as cryogenic temperatures for representative paramagnetic samples. We find, for example, that spin sensitivity of ~ 3 × 10⁵ spins/√Hz is achieved for a sample of phosphorus doped ²⁸Si, even for sub-optimal sample geometry with potential improvement to < 10³ spins/√Hz in more optimal scenarios.

Nickel hydroxide is a leading alternative to platinum group metals for electrocatalysis of the ammonia oxidation reaction (AOR), an important process for energy conversion and environmental remediation. Nevertheless, the dependence of AOR electrocatalysis on the different crystalline phases at the electrode surface (α-Ni(OH)₂/γ-NiOOH vs. β-Ni(OH)₂/β-NiOOH) has never been investigated. Herein, the crystalline β-Ni(OH)₂ and the disordered α-Ni(OH)₂ were synthesized and characterized by XRD, HRSEM, and Raman and FTIR spectroscopies. The respective electrocatalytic activity of the two phases was analysed at a broad range of ammonia concentrations (0.01–2 M) and pH values (11–13). Both phases electrocatalyze the oxidation of NH₃ to N₂, as proven by online mass spectrometry, but the α-Ni(OH)₂/γ-NiOOH couple is more active. At high ammonia concentrations (>1 M), surface poisoning by adsorbed NH₃ prevents access to OH⁻, leading to less NiOOH formation, lower AOR currents, and suppression of the OER side reaction. The poisoning is strong and irreversible on α-Ni(OH)₂, as confirmed by soaking experiments. The difference in ammonia adsorption and electrocatalytic activity between the α-Ni(OH)₂ and β-Ni(OH)₂ emphasizes the importance of understanding the phase space of nickel hydroxide electrodes when designing low-cost electrocatalysts for the nitrogen cycle.

Over the last hundred years, significant progress has been made in the chemistry of organo-f complexes, enhancing our understanding of their reactivity in both stoichiometric and catalytic processes. In the last three decades, there has been a significant rise in interest surrounding the electrophilic d0/fn chemistry of organo-f element complexes, attributable to their distinctive structure-reactivity relationships and remarkable efficacy in homogeneous catalysis. The influence of ligand design, encompassing electronic and steric considerations, on the catalytic efficacy of organo-f-complexes in diverse organic reactions is now broadly acknowledged. Notable progress in actinide chemistry has underscored their unique efficacy compared to lanthanides and transition metals. The stability of low-valent actinide complexes and the function of 5f orbitals in bonding and reactivity are, nevertheless, issues that continue to be extensively debated. Although actinides may share certain characteristics with transition metals in their chemical behaviors, they frequently reveal complementary or even enhanced reactivity. The increasing number of records in the Cambridge database highlights their escalating significance, facilitating more advanced chemical designs. The conventional view of actinide complexes as highly oxophilic has been limited by catalytic poisoning, which has restricted their use in oxygen-related processes. As a result, applications for these compounds have mostly found usage in cyclic ester polymerization, small-molecule activation, and hydroelementation. This review presents a comprehensive update on the synthesis, characteristics, and applications of important organoactinide complexes in organic processes. In conclusion, we present our Quo Vadis perspective, posing critical inquiries and articulating our insights regarding the future trends and advancements in this domain.

Polybenzenoid hydrocarbons (PBHs) have garnered significant attention in the field of organic electronics due to their unique electronic properties. To facilitate the design and discovery of new functional organic materials based on these compounds, it is necessary to assess their diradical character. However, this usually requires expensive multireference calculations. In this study, we demonstrate rapid identification and quantification of open-shell character in PBHs using the fractional occupation number weighted electron density metric (N_FOD) calculated with the semiempirical GFN2-xTB (xTB) method. We apply this approach to the entire chemical space of PBHs containing up to 10 rings, a total of over 19k molecules, and find that approximately 7% of the molecules are identified as having diradical character. Our findings reveal a strong correlation between xTB-calculated N_FOD and the more computationally expensive Yamaguchi y and DFT-calculated N_FOD, validating the use of this efficient method for large-scale screening. Additionally, we identify a linear relationship between size and N_FOD value and implement a size-dependent threshold for open-shell character, which significantly improves the accuracy of diradical identification across the chemical space of PBHs. This size-aware approach reduces false positive identifications from 6.97% to 0.38% compared to using a single threshold value. Overall, this work demonstrates that xTB-calculated N_FOD provides a rapid and cost-effective alternative for large-scale screening of open-shell character in PBHs.