ChemistryEurope

Topping, Lydia; Mocanu, Elena M.; Fisher, S. Ronan; Hunter, Robert I.; Ben‐Ishay, Yasmin; Goldfarb, Daniella; Smith, Graham M.; Lovett, Janet E.; Butler, Stephen J.

doi: 10.1002/ceur.202500282pmid: N/A

Lanthanide(III) complexes are invaluable tools for probing protein structure and dynamics, enabling precise distance measurements and site‐specific labeling across electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and luminescence‐based techniques. Designing an optimal lanthanide tag requires high thermodynamic and kinetic stability, minimal linker flexibility, and rapid, quantitative reactivity under mild conditions. Herein, a short series of Ln(III) complexes developed as efficient protein tags is reported, each showing high chemoselectivity for cysteine and enabling labeling in aqueous solution under mild conditions (pH 8, 37 °C). Subtle modifications to the reactive arm of the parent Ln.L1 complex has a pronounced effect on tagging kinetics, with Tb.QuNO achieving >95% labeling of the free amino acid cysteine within 10 min. The more compact and readily synthesized Gd.PyNO also labels efficiently and exhibits a narrow EPR linewidth (3.1 mT average at Q‐band across three protein‐labeled samples), making it an optimal choice for many EPR applications. These findings highlight the critical role of linker design in lanthanide‐based probes for EPR spectroscopy and biological imaging.

Zhou, Weiping; Huynh, Gia Hao; Voituriez, Arnaud

doi: 10.1002/ceur.202500274pmid: N/A

The asymmetric total synthesis of myrmenaphthol A, a natural product isolated from a Hawaiian sponge of the genus myrmekioderma, has been achieved in 12 steps. The key transformation of this synthesis is a gold‐catalyzed [3,3]‐sigmatropic rearrangement of sulfonium, starting from a chiral sulfoxide substrate and propargyl silane. The development of the methodology includes the synthesis of benz[e]inden‐2‐one derivatives with quaternary centers (51–78% yield, 90%–99% ee).

Landrini, Martina; Guzmán, Jefferson; Hidalgo, Nereida; Gaona, Miguel Ángel; Moreno, Juan José; Campos, Jesús

doi: 10.1002/ceur.202500376pmid: N/A

Bulky terphenyl phosphine ligands allow the isolation of a masked low‐coordinate, highly polarized Au(I)/Pt(0) complex. At variance to the inertness of prior coordinatively saturated AuPt systems, this complex exhibits cooperative reactivity toward pyridines. CX activation is observed for 2‐halopyridines (X = I, Br, Cl), while selective ortho‐CH activation of pyridine‐N‐oxide yields an unexpected pyridylidene carbene structure. Computational studies support the synergistic effect of the two metals during bond activation and shed light on the electronic structure of some of these unique species.

Christodoulou, Stella; Dos Santos, Etienne; Poteau, Romuald; Maron, Laurent

doi: 10.1002/ceur.202500250pmid: N/A

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 (ΔHcoord) and activation barrier (ΔHact) 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 ΔHcoord and 2.1 kcal mol−1 for ΔHact, 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.

Korber, J. Nepomuk; Fürstner, Alois

doi: 10.1002/ceur.202500251pmid: N/A

(−)‐Isopulegol is a key intermediate in the industrial routes to (−)‐menthol. New aluminum catalysts are now presented for the diastereoselective transformation of citronellal to isopulegol, which carry tridentate tris(silanolate) ligands connected by a central arene ring. Such ligands are readily available on a multigram scale; the derived complexes can be regarded as soluble molecular proxies for Lewis‐acidic aluminum sites on a silica surface with the additional advantage of being tunable. Thus, proper choice of the substituents on the silicon linkers allows an appropriate binding site to be crafted in order to confer high chemo‐ and diastereoselectivity onto the carbonyl‐ene type cyclization reaction without compromising reactivity. Moreover, the chelate structure together with a certain rigidity of the ligand backbone imparts excellent stability onto the complexes even at 100 °C under reaction conditions; this makes the separation of product and catalyst by distillation possible as illustrated by a cycling experiment in which no loss of activity or selectivity was noticed over five runs. This thermal and chemical robustness, in combination with a stable performance, distinguishes the new complexes from the standard catalysts described in the literature carrying monodentate phenolate or silanolate ligands.

Hortigüela, Lidia; Morcillo, Sara P.

doi: 10.1002/ceur.70197pmid: N/A

Yuan, Zhenxuan; Bai, Yunxing; Huang, Weixin

doi: 10.1002/ceur.202500382pmid: N/A

Fundamental studies of diffusion processes on solid catalysts are challenging due to the lack of appropriate characterization techniques. Herein, using NH3 diffusion on various zeolites as an example, flow‐pulse adsorption microcalorimetry (FPAM) is demonstrated capable of characterizing diffusion processes on solid catalysts. Initial adsorption heats and differential adsorption heats of NH3 on zeolites are measured temperature‐dependent arising from the diffusion of adsorbed NH3 from the weakly adsorbed Lewis acidic sites (LAS) to the strongly adsorbed Brønsted acid sites (BAS). A model is then established to acquire the temperature‐dependent distributions of NH3 adsorbed at the LAS and BAS sites, from which the LAS‐to‐BAS diffusion barrier of adsorbed NH3 is derived between 3.1 and 7.4 kJ mol−1 mainly related to the binding energy of NH3 adsorbed at the LAS. The applicability of FPAM method is further demonstrated by determing the weak adsorption site‐to‐strong adsorption site diffusion barriers of adsorbed NH3 on silicalite‐1 and adsorbed C3H6 on MOR‐10 as 7.3 and 17.9 kJ mol−1, respectively. The established FPAM method is a general method and will greatly enable the studies of diffusion processes on solid catalysts, a key elementary step capable of regulating their catalytic performances.

Evans, Rhodri Ll.; Martínez‐Crespo, Luis; Doerner, Benedicte; Gomila, Rosa M.; Whitehead, George F. S.; Frontera, Antonio; Webb, Simon J.

doi: 10.1002/ceur.202500195pmid: N/A

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.

Fritz, Marco D.; Kelly, John A.; Balázs, Gábor; Wolf, Robert

doi: 10.1002/ceur.202500257pmid: N/A

The utilization of two electronically distinct elements for the cooperative activation of white phosphorus (P4) is a promising route to novel and reactive polyphosphido complexes. Herein, the preparation of cyclooctadiene Co–Zn complexes and their application in the activation of white phosphorus (P4) to synthesize new phosphorus‐rich sandwich complexes are reported. The complexes [Zn{Co(tBu2C2P2)(COD)}2] (1, COD = cycloocta‐1,5‐diene), [(acac)Zn{Co(tBu2C2P2)(COD)}] (2, acac = acetylacetonate), [(Dippnacnac)Zn{Co(tBu2C2P2)(COD)}] (3, Dippnacnac = CH({2,6‐iPr2‐C6H3}NCMe)2), and [(Ar)Zn{Co(tBu2C2P2)(COD)}] (4, Ar = C6H3‐2,6{C6H3‐2,6‐iPr2}2) are prepared by transmetalation of [(Depnacnac)Mg{Co(tBu2C2P2)(COD)}] (F, Depnacnac= CH({2,6‐Et2‐C6H3}NCMe)2) with zinc(II) salts. Complex 1 reacts with cyclohexyl isonitrile (CyNC) to afford isonitrile complexes [ZnCo2(tBu2C2P2)2(COD)(CyNC)2] (5) and [Zn{Co(tBu2C2P2)(CyNC)2}2] (6). Single‐crystal X‐ray diffraction data and quantum chemical studies employing Atoms In Molecules and Natural Bond Orbital methods reveal weak covalent Co–Zn interactions in complexes 1—6. Compound 1 reacts with P4 to produce [Zn2Co4(μ‐P2)2(tBu2C2P2)4(COD)2] (7) and subsequently [Zn2Co4(μ‐P2)4(tBu2C2P2)4] (8), featuring bridging diphosphorus ligands. A stepwise mechanism for the formation of 8 is elucidated through 31P nuclear magnetic resonance  spectroscopic monitoring studies. Chemical oxidation of 8 generates the triple‐decker sandwich complex [{Co(tBu2C2P2)}2(μ‐P4)] (9) with a cyclo‐P4 middle deck.