Synergy Between Expert and Machine‐Learning Approaches Allows for Improved Retrosynthetic Planning

When computers plan multistep syntheses, they can rely either on expert knowledge or information machine‐extracted from large reaction repositories. Both approaches suffer from imperfect functions evaluating reaction choices: expert functions are heuristics based on chemical intuition, whereas machine learning (ML) relies on neural networks (NNs) that can make meaningful predictions only about popular reaction types. This paper shows that expert and ML approaches can be synergistic—specifically, when NNs are trained on literature data matched onto high‐quality, expert‐coded reaction rules, they achieve higher synthetic accuracy than either of the methods alone and, importantly, can also handle rare/specialized reaction types.     

Studies on hydrogen diffusivity in iron aluminides using the Devanathan–Stachurski method

An electrolytic method for cathodic hydrogen saturation developed by Devanathan and Stachurski was successfully used to study hydrogen diffusivity in iron aluminides. Both an appropriate electrolyte and a saturating current density are required for this method. A proper form of the saturation curve was only obtained with 35% NaCl electrolyte, which removed the oxide film blocking hydrogen penetration without further corrosive destruction of the iron aluminide. The optimum saturation current density for determining the most reliable diffusivity was 1.91 A/cm², yielding D_eff,H = 4.81 × 10⁻⁶ cm²/s for Fe–40 at.% Al.     

Low-T Asymptotic Expansion of the Solution to the Yang–Yang Equation

We prove that the unique solution to the Yang–Yang equation arising in the context of the thermodynamics of the so-called non-linear Schrödinger model admits a low-temperature expansion to all orders. Our approach provides a rigorous justification, for a certain class of non-linear integral equations, of the low-temperature asymptotic expansions that were argued previously in various works related to the low-temperature behaviour of integrable models.     

Collective uncertainty entanglement test

For a given pure state of a composite quantum system we analyze the product of its projections onto a set of locally orthogonal separable pure states. We derive a bound for this product analogous to the entropic uncertainty relations. For bipartite systems the bound is saturated for maximally entangled states and it allows us to construct a family of entanglement measures, we shall call collectibility. As these quantities are experimentally accessible, the approach advocated contributes to the task of experimental quantification of quantum entanglement, while for a three-qubit system it is capable to identify the genuine three-party entanglement.     

Synthetic studies on dicyclopenta[a,d]cyclooctane terpenoids: construction of the core structure of fusicoccins and ophiobolins on the route involving a Wagner-Meerwein rearrangement

The total diastereoselective synthesis of dicyclopenta[a,d]cyclooctane core skeleton of tricyclic terpenoids, fusicoccins, and ophiobolins is reported. The synthesis commences from 2-methylcyclopent-2-en-1-one and leads first to the easily accessible intermediary cyclopenta[8]annulene 18. The subsequent steps include two key transformations: shifting the angular methyl group from the angular to the neighboring position employing a carbocationic rearrangement (26 → 28) and construction of a quaternary stereogenic center via alkylation of α-methylcyclooctanone intermediate (38 → 48). In the context of the latter transformation, a series of model experiments on alkylation of 2-methylcyclooctan-1-one were conducted. The stereochemical assignments were verified by X-ray analyses of the key structures 39 and 50.     

Synthesis,Pharmacological Evaluation,and Computational Studies of Cyclic Opioid Peptidomimetics Containing β3-Lysine

Our formerly described pentapeptide opioid analog Tyr-c[D-Lys-Phe-Phe-Asp]NH₂ (designated RP-170), showing high affinity for the mu (MOR) and kappa (KOR) opioid receptors, was much more stable than endomorphine-2 (EM-2) in the rat brain homogenate and displayed remarkable antinociceptive activity after central (intracerebroventricular) and peripheral (intravenous ) administration. In this report, we describe the further modification of this analog, which includes the incorporation of a β³-amino acid, (R)- and (S)-β³-Lys, instead of D-Lys in position 2. The influence of such replacement on the biological properties of the obtained analogs, Tyr-c[(R)-β³-Lys-Phe-Phe-Asp]NH₂ (RP-171) and Tyr-c[(S)-β³-Lys-Phe-Phe-Asp]NH₂, (RP-172), was investigated in vitro. Receptor radiolabeled displacement and functional calcium mobilization assays were performed to measure binding affinity and receptor activation of the new analogs. The obtained data revealed that only one of the diastereoisomeric peptides, RP-171, was able to selectively bind and activate MOR. Molecular modeling (docking and molecular dynamics (MD) simulations) suggests that both compounds should be accommodated in the MOR binding site. However, in the case of the inactive isomer RP-172, fewer hydrogen bonds, as well as instability of the canonical ionic interaction to Asp¹⁴⁷, could explain its very low MOR affinity.     

Nitro-substituted Hoveyda-Grubbs ruthenium carbenes: enhancement of catalyst activity through electronic activation

The design, synthesis, stability, and catalytic activity of nitro-substituted Hoveyda-Grubbs metathesis catalysts are described. The highly active and stable meta- and para-substituted complexes are attractive from a practical point of view. These catalysts operate in very mild conditions and can be successfully applied in various types of metathesis [ring-closing metathesis, cross-metathesis (CM), and enyne metathesis]. Although the presence of a NO(2) group leads to catalysts that are dramatically more active than both the second-generation Grubbs's catalyst and the phosphine-free Hoveyda's carbene, enhancement of reactivity is somewhat lower than that observed for a sterically activated Hoveyda-Grubbs catalyst. Attempts to combine two modes of activation, steric and electronic, result in severely decreasing a catalyst's stability. The present findings illustrate that different Ru catalysts turned out to be optimal for different applications. Whereas phosphine-free carbenes are catalysts of choice for CM of various electron-deficient substrates, they exhibit lower reactivity in the formation of tetrasubstituted double bonds. This demonstrates that no single catalyst outperforms all others in all possible applications.     

Polarographic reduction of some derivatives of chalcone

The derivatives of chalcone listed in Table 1 were investigated by the method of classical polarography in mixtures of Britton-Robinson buffers and ethanol (1 : 1) of pH 2.68–12.4. Although the reduction of the compounds was much the same as described for chalcone some differences were found and are discussed. Essentially, two one-electron waves were obtained which correspond to the reduction of the ethylenic linkage to dihydro derivatives. Some compounds give an additional wave in alkaline medium the height of which depends on pH; the wave corresponds to the reduction of carbonyl group to a secondary alcohol. In alkaline medium the reduction was accompanied by hydration of the ethylenic linkage and then the hydration products of the electroactive species with the OH group in position 2′ cyclized at pH 12.4 to corresponding chromanone derivatives, which were reduced in one two-electron wave. Approximate hammett constants σ were calculated for EtOCOCH₂O and H₂NOCOCH₂O groups from polarographic data as ?0.22 and ?0.09, respectively.