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The Front Cover shows a round-bottomed flask containing a burgundy solution of diferrocenylphosphenium ion [Fc₂P][B(C₆F₅)₄], which was used in this work to activate various allenes. Dropwise addition to 2-(trimethylsilyl) penta-2,3-diene yields a bright red solution of a stable Wheland intermediate of ferrocene, whose solid-state structure is depicted as a ball-and-stick model. In front lies Saint Peter’s Key, a prominent feature of the City of Bremen’s coat of arms, representing the unlocked potential of highly reactive main group species. More information can be found in the Research Article by E. Hupf, J. Beckmann and co-workers (DOI: 10.1002/ceur.202500031).

The amyloid aggregation of α-synuclein is a central pathological hallmark of various synucleinopathies, including Parkinson disease. Consequently, developing strategies to eliminate α-synuclein amyloids represents a promising therapeutic approach. While amyloid-selective photooxygenation catalysts have shown potential in mitigating α-synuclein-related molecular pathologies, such as aggregation, seed activity, and amyloid-associated cytotoxicity, no effective methods have been established for targeting intracellular α-synuclein amyloids. Here, inspired by the structural features of an α-synuclein-selective positron emission tomography probe, we designed and synthesized catalyst 11, a novel compound optimized for intracellular applications. By balancing lipophilicity for membrane permeability, water solubility, and long-wavelength light absorption, catalyst 11 promotes the first photooxygenation of α-synuclein amyloids within living cells. Notably, catalyst 11 exhibits amyloid selectivity via a photodecay modulation mechanism upon amyloid binding. Our findings reveal significant photooxygenation of all four methionine residues in α-synuclein and crosslink formation suggestive of histidine oxygenation in cells. These results showcase catalyst 11 as a promising lead compound for advancing both chemical and biological investigations aimed at therapeutically targeting α-synuclein amyloidosis.

Peptide foldamers, each with a stereogenic C-terminal bis(squaramide) separated from an N-terminal amino acid “controller” by an α-aminoisobutyric acid (Aib) tetramer, have been shown to bind chloride. Chloride affinity is sensitive to the sense and strength of screw-sense induction by each N-terminal residue, a conformational preference that is relayed along the 1-nanometer-long helical foldamer. Chloride binding is weaker when the screw-sense preference of the chiral N-terminal residue matches that of the C-terminal binding site, whereas mismatches in screw-sense preferences give stronger chloride binding. X-ray crystallography and computational modeling provide a simple model for this relationship between chloride affinity and the screw-sense preferences of both terminal groups. Chloride binding allows these foldamers to act as ion carriers in the bulk phase, but in bilayers, the length of each foldamer is more important for activity. The use of a helical relay to remotely control the binding of an achiral anion may offer pathways toward the remote allosteric control of chloride binding by macromolecules.

The synthesis of sequence-defined oligomers with a high molecular weight has remained a challenge due to the lack of effective coupling methods, reduced reactivity and/or selectivity with increasing oligomer lengths, and poor solubility of suitable reactants and/or resulting macromolecules. Contributing to overcome these limitations, a room-temperature method for the construction of sequence-defined oligo-sulfonimidates via sulfur-phenolate exchange (SuPhenEx) reactions using an exponential growth strategy is reported. This method enables the efficient and rapid synthesis of sequence-defined oligo-sulfonimidates, up to a 16 mer (M_w = 6.5  kDa). Next, the versatility of this method is demonstrated by synthesizing a sequence-defined tetramer with four nonrepeating building blocks, and fusing it with the 16  mer by another SuPhenEx reaction, resulting in a sequence-defined 20 mer (66% isolated yield; M_w = 8.5 kDa). To the authors' best knowledge, this is the longest S(VI)–O-linked sequence-defined oligomer constructed to date. Given the flexibility of the route, constantly high yields of the SuPhenEx coupling, independent of the oligomer length, and the enantiospecific nature of SuPhenEx reactions on chiral species, this approach for the synthesis of sequence-defined oligo-sulfonimidates paves the way for further exploring the structure-property relationships of sequence-defined oligomers and other S(VI)-O-linked materials.

Within this work, the straightforward synthesis of alumanyl silyl-substituted coinage metal complexes (MCu (3a), Ag (3b), Au (3c)) from alumanyl silanide 1·Na·(DME)₂ and easily accessible N-heterocyclic carbene (NHC)-stabilized coinage metal chlorides NHC-M-Cl (NHC = IⁱPrMe; MCu(2a), Ag(2b), Au(2c)) is reported. Multinuclear nuclear magnetic resonance (NMR) spectroscopy and x-ray diffraction (XRD) analysis reveal an increase of the SiM bond strength in 3a-c descending the group. Consequently, regioselective insertion of CO₂ into the SiCu/SiAg bond of 3a and 3b is observed in addition to one molecule of CO₂ being inserted between the N-heterocyclic imine (NHI) ligand and the aluminum center yielding 4a and 4b. In case of 3c (Au), exclusive uptake of one CO₂ molecule by the NHI ligand is observed based on XRD analysis and multinuclear NMR analysis. The formation of 4a-c was studied in detail with labeled ¹³CO₂.

A novel class of well-defined rhodium and iridium complexes containing various chiral cyclic(alkyl)(amino)carbene (^ChiCAAC) ligands has been synthesized and fully characterized. While no enantioselectivity is observed with chiral Rh-CAAC, the Ir-CAAC counterparts demonstrate good performances in the asymmetric hydrogenation of various allylic alcohols and derivatives with up to 86% ee. Mechanistic studies, including deuteration experiments, reveal that the reduction proceeds via direct alkene hydrogenation rather than via isomerization.

Steady-state and time-resolved circularly polarized luminescence (CPL) are investigated for aqueous solutions of [Eu(pda)₂]⁻ (pda = 1,10-phenanthroline-2, 9-dicarboxylic acid) containing Δ/Λ-[Co(en)₃]³⁺ (en = ethylenediamine). CPL signals (|g_lum| ≈ 0.2 at maximum) are observed for the solutions at the f–f transition in [Eu(pda)₂]⁻, where the sign depends on the chirality of [Co(en)₃]³⁺. The emission intensity decreases with the increase of concentration of [Co(en)₃]³⁺ ([Co]). Time-resolved emission measurements show that the temporal profiles are well reproduced by three emission lifetime components τ₁ ≈ 10 μs, τ₂ ≈ 40-100 μs, and τ₃ ≈ 100-750 μs, where the lifetimes depend on [Co]. The shorter lifetimes of τ₁ and τ₂ are attributed to associated species of [Eu(pda)₂]⁻ and [Co(en)₃]³⁺, in which the energy transfer occurs. The time-resolved CPL reveals that the τ₁- and τ₂-components exhibit CPL, but the τ₃-component exhibits no CPL signal. Mole-ratio dependence of Δ/Λ-[Co(en)₃]³⁺ for the CPL signal shows that the CPL is exhibited from two associated species, such as [Eu(pda)₂]⁻·{[Co(en)₃]³⁺}₂, and the homo-associated species are favored over hetero-associated species. This indicates that a structural change induced by initial association of Δ/Λ-[Co(en)₃]³⁺ promotes further association of Δ/Λ-[Co(en)₃]³⁺. This is a chiral recognition by allosteric effect.

The epoxidation of ketones with α-monohalo borylsilylmethane reagents renders tetrasubstituted epoxides, opening a new reactive pathway by supression of Boron-Wittig or Peterson olefination pathways. This method enables the preparation of novel 1,1,2,2-tetrasubstituted borosilylepoxides with intrinsic control of the diastereoselectivity. A mechanism, based on density functional theory calculations, has been postulated analyzing the role of the α-iodo B, Si-ylide in the cyclization pathway. Complementarily, enolates generated from ketones can also interact with the α-monohalo diborylsilylmethane reagents to acceed the 1,1,2,2-tetrasubstituted borosilylepoxides. The versatility of these entities has been demonstrated through postfunctionalization reactions.

Bioconjugation has emerged as a powerful tool in modern chemical biology for creating new molecules with applications in both research and therapeutics. The modification of biomacromolecules—such as proteins, peptides, nucleic acids, carbohydrates, and related biomolecules—contributes to various fields, including biochemistry and materials science, with relevance to the development of biopharmaceuticals, such as antibody–drug conjugates. Over the past two decades, there has been a growing interest in developing simpler, milder, site-selective, and high-yielding synthetic protocols. Among these, photoinduced methods stand out, as light is a sustainable energy source that enables the formation of highly reactive intermediates under mild reaction conditions, typically well tolerated in bioconjugation. In recent years, photocatalyzed light-induced chemical processes have been extensively explored. However, reactions that proceed without external photocatalysts are especially appealing, particularly from economic and sustainability viewpoints. This Perspective article discusses the strategies developed over the past decade for photocatalyst-free photoinduced bioconjugation, with special focus on the formation of electron-donor/electron-acceptor complexes. Both biomolecule synthesis and late-stage functionalization will be addressed. Experimental limitations and the applicability of these protocols in biocompatible contexts will be evaluated. Beyond macromolecules, monomeric units, such as amino acids and nucleotides, are also considered.

The rational design of group III metallocene catalysts for styrene polymerization remains a complex challenge due to intertwined steric and electronic effects that govern monomer coordination and insertion. A generative and interpretable machine learning (ML) framework is presented, grounded in density functional theory (DFT) calculations, to predict and optimize the coordination energy (ΔH_coord) and activation barrier (ΔH_act) of the first styrene insertion step across 32 scandium and yttrium metallocenes. Key catalyst features—including Sterimol parameters, Tolman cone angle, metal-centroid distance, buried volume, and natural metal charge—are extracted and used as descriptors in various regression models. The best-performing ML models, notably support vector regressor-bagging and random forest regressors, achieve sub-2 kcal mol⁻¹ mean absolute error for ΔH_coord and 2.1 kcal mol⁻¹ for ΔH_act, exceeding the accuracy of DFT itself in some cases. SHapley Additive exPlanations analyses reveal steric parameters and metal acidity as primary drivers of catalyst performance. Using descriptor-space optimization and generative mapping to ligand architectures, candidate ligands predicted to achieve target insertion barriers are identified, with validated DFT agreement. This integrative strategy highlights a path toward data-driven, interpretable, and computationally efficient discovery of tailored polymerization catalysts. Through deliberate construction of both the descriptor space and the underlying chemical space, the approach remains effective in data-light regimes, establishing a generalizable strategy for inverse design across homogeneous catalytic reactions.