Abstract In this study, we developed a hybrid methodology for machine learning-driven optimization of continuous-flow reaction with a polymer-supported Pd catalyst, aiming to boost both productivity and elucidate influencing factors in the reaction conditions. A porous polymer bearing phosphine ligand was prepared by polymerization-induced phase separation, and Pd was coordinated to the support to construct the flow reactor. Suzuki–Miyaura cross-coupling reactions were performed in the continuous-flow system. Combining Bayesian optimization and linear regression realized optimization of continuous-flow conditions and analysis of key influencing factors, demonstrating the utility of the present machine learning method. Indeed, the continuous-flow system with the monolith reactor was also applicable to a range of chloroarenes, which emphasized the importance of our catalytic system for fine chemical production.

Abstract Coordination polymers that precisely incorporate two closely related ligands differing only in their substituents are often difficult to construct because such ligands tend to be randomly distributed within the framework. In this study, we demonstrate a quasiracemic strategy that enables well-defined incorporation of differently substituted ligands into a single coordination polymer. Given that racemates crystallize more readily than single enantiomers owing to the complementary of mirror-imaged structures, a quasiracemic pairs of methyl- and ethyl-substituted bis(4-pyridyl) ligands assembles with Cu(I) iodide to form a double-bridged polymer containing acetonitrile molecules within its channel structure. Intriguingly, this polymer constructed from the quasiracemic ligands exhibits unique adsorption behavior toward benzonitrile compared with the analogue polymers constructed from the corresponding racemic methyl- or ethyl-substituted ligands. This study provides a new design principle for controlling guest inclusion capability of metal–organic structures.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) is a cysteine protease that is essential for viral replication. A virtual alanine scan for all residues of SARS-CoV-2 Mpro was performed in this study, which resulted in a total of 289 artificial mutants. Threshold values for root mean square deviation (RMSD)–based classification to extract drug resistance candidates were investigated. Known resistance and nonresistance mutations were defined using a publicly available database, and statistical metrics were utilized to evaluate the validity of the thresholds. We further examined whether changing the thresholds would help us correctly identify mutants that are already known to cause drug resistance. By using the best criterion determined by the F1 score, 33 mutants were identified as potential drug resistance candidates. Under the most refined prediction conditions, 23 mutants—which include five that have been experimentally reported to confer drug resistance—were identified as potential resistance-related mutations. Molecular dynamics simulations revealed that certain distant mutations, like P252A and T304A, can alter ligand configurations. Virtual alanine scan combined with optimized RMSD-based criteria can provide a practical framework for predicting resistance-related mutations, even for residues located far from the catalytic dyad.

Abstract Au clusters supported on reducible metal oxides exhibit high catalytic activity for CO oxidation even at temperatures below 273 K. In a previous study, the activation barrier for CO oxidation over Au/ZnO exhibited a significant variation at approximately 253 K when the catalyst was prepared under conditions including H2 reduction, whereas no such change was observed when it was prepared under air-oxidation conditions. Herein, this variation was elucidated by examining the reaction mechanisms of CO oxidation over Au/ZnO catalysts with stoichiometric and reduced surfaces using density functional theory calculations. The results show that catalytic reactions were promoted on the reduced surface compared with those on the stoichiometric surface because of the strong activation of adsorbed O2. Furthermore, the variation in the activation barriers for CO oxidation over Au/ZnO with H2 reduction pretreatment above 253 K may be attributed to the change from a reduced surface to a stoichiometric surface.

Abstract To investigate the effects of pore size on the water structure in polysaccharide hydrogels, differential scanning calorimetric measurements were performed on a freeze cross-linked hydrogel of carboxymethyl cellulose nanofiber (CMCF) and conventional agarose hydrogel. The melting points and relative amounts of 4 types of water were analyzed as functions of water content. In addition to the 3 well-known types of water (i.e. bound, intermediate, and free water) in hydrogels, intermediate water was classified into 2 types: 1st and 2nd intermediate water (IW), depending on the structure around amphiphilic polymers. The melting point of 1st IW, which forms hydrogen bonds with bound water, decreases as the water content decreases for both hydrogels. Similar trends observed for both hydrogels suggest that the effects of pore size on 1st IW are negligible. In contrast, significant differences between the CMCF and agarose hydrogels were observed in the relative amount of 2nd IW, which exists at the interface between free water and the hydrophobic regions of polymers. The results indicate that the relative amount of 2nd IW, which depends on the specific surface area of the pore walls determined by pore size, is a key factor in the physicochemical properties of hydrogel materials.

Abstract Countercation dynamics play a crucial yet largely unexplored role in governing the electronic properties of molecular conductors. Herein, we demonstrate that the fluctuations of flexible supramolecular cations in [Ni(dmit)2]-based molecular conductors (dmit2− = 2-thioxo-1,3-dithiol-4,5-dithiolate) can directly modulate their correlated electronic states. Two salts with nearly spherical supramolecular cations featuring Na+ and Cs+ ions encapsulated by unsubstituted [24]crown-8, Na([24]crown-8)[Ni(dmit)2]3 and Cs2([24]crown-8)2[Ni(dmit)2]7, are synthesized and systematically compared. Detailed crystallographic, magnetic, and transport studies reveal a striking contrast between the two systems. In Na([24]crown-8)[Ni(dmit)2]3, the structural distortion of the Na+-encapsulating [24]crown-8 enables thermally activated large-amplitude out-of-plane fluctuations, thus selectively enhancing the vibrational motion of terminal S atoms in [Ni(dmit)2] layers and leading to the temperature-dependent modulation of transfer integrals, anomalous magnetic behavior requiring a temperature-dependent exchange interaction, and one-dimensional variable-range hopping transport. In contrast, Cs2([24]crown-8)2[Ni(dmit)2]7 features a planar-confined Cs+-based supramolecular cation and suppressed fluctuation transfer to anion layers, thus exhibiting conventional Heisenberg-chain magnetism and Arrhenius-type semiconducting behavior. These results establish supramolecular-cation dynamics as a powerful design parameter for controlling electronic correlation and transport in molecular conductors.

Abstract A lead(II) complex coordinated by a sterically demanding o-phenylenediamido ligand is synthesized. The ligand is redox-active to reach the diiminobenzosemiquinone radical anion state. This state is generated by an electrochemical method or a chemical oxidation using AgOTf, but the oxidation number of the central metal is not changed. In the presence of toly-sulfonyl lazides (Tol-N3), the chemical oxidation of the lead(II) complex at −80 °C gives the nitrene-radical-bound lead(II) complex, which also contains the diiminobenzosemiquinone ligand. Kinetic studies on the generation of the nitrene-radical-bound complexes reveal that the rate-determining step involves a binding step of the tolyl-sulfonyl azide to the lead(II) center or a N2 elimination step from the azide-bound complex. The rate-determining step is controlled by changing the substituent of the tolyl-sulfonyl azide.

Abstract Conventional acid catalysis for the Markovnikov-selective hydroamination of alkenes using anilines has limitations regarding substrate scope and low regioselectivity attributed to the buffering effect of anilines and competing Friedel–Crafts alkylation, respectively. Herein, we demonstrate the Markovnikov hydroamination of aliphatic alkenes using anilines through light-driven triple catalysis consisting of cobalt, photoredox, and weak Brønsted acid catalysts under blue light-emitting diode (LED) irradiation. Our protocol enables the generation of an alkyl cobalt(IV) species from aliphatic alkenes under weak acidic conditions, expanding the accessible N-alkylanilines and N,N-dialkylanilines. As the alkyl cobalt(IV) species reacts with anilines in an SN2 manner, unlike free carbocation, Friedel–Crafts alkylation is completely suppressed. When a Brønsted acid catalyst is replaced with Lewis base/acid pair catalysts, the quadruple catalytic system is amenable to the N-alkylation of azoles.

Abstract Engineered hemoproteins incorporating synthetic metal porphyrinoids with non-natural tetrapyrrole frameworks are known to exhibit unique catalytic properties which are not observed in native hemoproteins. We previously reported the reconstitution of myoglobin with an iron corrole complex (Mb-FeCor) leading to unique catalytic activity in H2O2-dependent peroxidation. To optimize the amino acid sequence of the active site of myoglobin for this noncanonical corrole complex, we performed genetic engineering of Mb-FeCor based on the directed evolution methodology. After 3 rounds of directed evolution, a triple mutant Mb(L89F/H97F/I107F)-FeCor was obtained as a best-performing catalyst, exhibiting a 24-fold higher initial rate for ABTS peroxidation relative to the original Mb-FeCor. Furthermore, the kcat/KM value of this engineered variant was calculated to be 16 μM–1s−1, exceeding that of horseradish peroxidase (HRP, 0.12 μM–1s−1). These results demonstrate that combining synthetic porphyrinoid incorporation with directed evolution of a protein scaffold provides an efficient strategy for improving the catalytic activity of hemoprotein-based artificial metalloenzymes.

Abstract The development of new molecular building blocks for the construction of elaborate molecular assemblies extends the chemical space for materials exploration. Representative organic components for the design of homochiral metal-organic frameworks (MOFs) usually exhibit C1- or C2-symmetry. Herein, we synthesized a chiral D2-symmetric ligand via functionalization of a figure-eight macrocycle, cyclobisbiphenylenecarbonyl (CBBC). This ligand adopts a distinctive concave-type tetradentate coordination geometry, and the resulting MOF, CBBCMOF, features a quasi-honeycomb framework enveloped by double-helical ligand assembly. The pore size of the chiral nanochannel exceeds 10 Å, which enables CBBCMOF to encapsulate various guest molecules, including aromatic hydrocarbons, alcohols, and dyes. Furthermore, CBBCMOF achieves the enantioselective encapsulation of racemic 1,1′-bi-2-naphthol with a high enantiomeric excess (up to 68% ee). Thus, CBBCMOF functions as a stationary phase to separate the enantiomers of medium-sized chiral molecules. These results demonstrate that highly symmetric chiral molecules such as CBBC function as an effective building block for the design of advanced porous materials.