Why are information-theoretic descriptors powerful predictors of atomic and molecular polarizabilities.

CONTEXT: We rationalize the excellent performance of information-theoretic descriptors for predicting atomic and molecular polarizabilities. It seems that descriptors which capture information about the change in valence-shell structure, especially the relative Fisher information measures, are particularly useful. Using this, we can rationalize why the G3 form of the relative Fisher information, which measures the deviation of effective nuclear charge between an atom-in-a-molecule and the reference pro-atom, is especially effective as a predictor of molecular polarizability. METHODS: There are no methods used in this paper, which relies on mathematical derivation and analysis.

Information-theoretic quantities as effective descriptors of electrophilicity and nucleophilicity in density functional theory.

CONTEXT: Electrophilicity and nucleophilicity are two vastly important chemical concepts gauging the capability of atoms in molecules to accept and donate the maximal number of electrons. In our earlier studies, we proposed to simultaneously quantify them using the Kullback-Leibler divergence from the information-theoretic approach in density functional theory. However, several issues with this scheme remain to be clarified such as its general validity, predictability, and relationship with other information-theoretic quantities. In this work, we revisit the matter with bigger datasets and deeper theoretical insights. Five information-theoretic quantities including Kullback-Leibler divergence, Hirshfeld charge, Ghost-Berkowitz-Parr entropy, and second and third orders of relative Onicescu information energy are found to be reliable and robust descriptors of electrophilicity and nucleophilicity propensities. Employing these five descriptors, we design a list of new compounds and predict their electrophilicity and nucleophilicity scales. This work should markedly improve our confidence and capability in applying information-theoretic quantities to evaluate electrophilicity and nucleophilicity propensities and henceforth pave the route for more applications of these quantities from information-theoretic approach in density functional theory in the future. METHODS: All structures were fully optimized at the M06-2X/6-311 + G(d) level of DFT functional using the Gaussian 16 package (version C01) with integration grids and tight self-consistent-field convergence. The solvent effect was taken into account by using the implicit solvent model (CPCM) in the CH2Cl2 solvent, and all 3D contour surfaces of Fukui function, local temperature, and ITA (information-theoretic approach) quantities were generated by GaussView. The Multiwfn 3.8 program was used to calculate the ITA indexes and atomic charges.

Density-based quantification of steric effects: validation by Taft steric parameters from acid-catalyzed hydrolysis of esters.

The steric effect is one of the most widely used concepts for chemical understanding in publications and textbooks, yet a well-accepted formulation of this effect is still elusive. Experimentally, this concept was quantified by the acid-catalyzed hydrolysis of esters, yielding the so-called Taft steric parameter. Theoretically, we recently proposed a density-based scheme to quantify the effect from density functional theory. In this work, we directly compare these two schemes, one from theory and the other from experiment. To this end, we first establish the ester hydrolysis mechanism with multiple water molecules explicitly considered and then apply the energetic span model to represent the hydrolysis barrier height between the two schemes. Our results show that the barrier height of the reaction series is strongly correlated with both Taft steric parameters from experiment and steric quantification from theory. We also obtained strong correlations with steric potential, steric force, and steric charge from our theoretical scheme. Strong correlations with a few information-theoretic quantities are additionally unveiled. To the best of our knowledge, this is the first time in the literature that such a direct comparison between theoretical and experimental results is made. These results also suggest that our proposed two-water three-step mechanism for ester hydrolysis is effective, and our theoretical quantification of the steric effect is valid, robust, and experimentally comparable. In our view, this work should have satisfactorily addressed the issue of how the steric effect can be formulated and quantified, and thus it lays the groundwork for future applications.

Pichia pastoris composition expressed aerolysin mutant of Aeromonas veronii as an oral vaccine evaluated in zebrafish (Danio rerio).

Vaccines are one of the most practical means to stop the spreading of Aeromonas veronii in aquaculture. In this study, virulence factor aerolysin mutant NTaer which has lost its hemolytic activity was used as a target antigen. Pichia pastoris constitutive secretory expression NTaer (GS115-NTaer) was used as a potential safe oral vaccine to evaluate its effectiveness on zebrafish immunity. The result shows that vaccination of GS115- NTaer for four weeks did not affect the growth performance of the host, while eliciting an effective immune protective response. Compared with the control group, the GS115-NTaer could significantly up-regulate the relative expression level of the intestinal tight junction protein 1α (TJP1α) gene, and significantly increased the contents of lysozyme (LYZ), complement C3 and C4 in the gut, indicating that the innate immune response of the fish was activated. The relative gene expression levels of macrophage-expressed gene 1 (MPEG1) and T cell receptor (TCR-α) in the gut, and MPEG1, CD4, CD8, TCR-α, GATA3, and T-bet in the spleen were all increased significantly, indicating that the cellular immune response of the fish was activated. Furthermore, the contents of serum IgM and intestinal mucosa IgZ antibodies were significantly increased, which showed that humoral immunity was also activated. Moreover, inoculation with GS115-NTaer significantly changed the structure of gut microbiota. In particular, the relative ratio of (Firmicutes + Fusobacteriota + Bacteroidota)/Proteobacteria was significantly higher than that of the control and GS115 groups. Lastly, the vaccinated fish were challenged with A. veronii, and the relative percent survival of GS115 and the GS115-NTear groups was 14.28% and 33.43%. This improvement of immunity was not only due to the specific immune response but also attributed to the improvement of innate immunity and the gut microbiota which was demonstrated by the germ-free zebrafish model. Collectively, this study provides information on the effectiveness of GS115-NTear as an oral vaccine for the green prevention and control of A. veronii infection in fish aquaculture.

A general and mild synthetic method for fused-ring electronic acceptors.

Fused-ring electronic acceptors (FREAs) have transformed the field of organic solar cells. However, the prevailing syntheses of FREAs suffer from low yield, difficulty in separation, and high cost. Here, we report new and streamlined syntheses with three distinctive key steps. First, a universal approach to fuse neighboring aromatic units via a single carbon atom is demonstrated with ytterbium triflate and boron trifluoride as the catalysts. This approach allows the incorporation of diverse side-chain combinations. Second, nitrogen atom fusing neighboring aromatics is realized by using oxo-molybdenum catalyst, featuring lower reaction temperatures and enhanced yields. Third, an organic catalyst, proline, is identified to catalyze the aldol condensation with high yield to afford the most typical FREAs having acceptor-donor-acceptor (ADA) configurations. Our new chemistries enable easy syntheses of a wide range of FREAs, substantially expanding the scope and availability of these coveted materials at reduced synthetic cost, particularly for organic electronics.

Synthesis of Lactams via a Chiral Phosphoric Acid-Catalyzed Aniline Cyclization.

The enantioenriched lactams disclosed in this work are synthesized concisely in four steps. In the penultimate reaction, a benzylamine species complexes with a chiral phosphoric acid to produce benzo-fused δ-lactams equipped with an all-carbon quaternary stereocenter. Partial and full reductions were carried out on the ester and amide moieties, and a Suzuki-Miyaura cross-coupling expanded the molecule from the aromatic ring. Finally, our method was successful at a >1 g scale, indicating that the method has important practical use.

Energetic Information from Information-Theoretic Approach in Density Functional Theory as Quantitative Measures of Physicochemical Properties.

The Hohenberg-Kohn theorem of density functional theory (DFT) stipulates that energy is a universal functional of electron density in the ground state, so energy can be thought of having encoded essential information for the density. Based on this, we recently proposed to quantify energetic information within the framework of information-theoretic approach (ITA) of DFT (J. Chem. Phys. 2022, 157, 101103). In this study, we systematically apply energetic information to a variety of chemical phenomena to validate the use of energetic information as quantitative measures of physicochemical properties. To that end, we employed six ITA quantities such as Shannon entropy and Fisher information for five energetic densities, yielding twenty-six viable energetic information quantities. Then, they are applied to correlate with physicochemical properties of molecular systems, including chemical bonding, conformational stability, intermolecular interactions, acidity, aromaticity, cooperativity, electrophilicity, nucleophilicity, and reactivity. Our results show that different quantities of energetic information often behave differently for different properties but a few of them, such as Shannon entropy of the total kinetic energy density and information gain of the Pauli energy density, stand out and strongly correlate with several properties across different categories of molecular systems. These results suggest that they can be employed as quantitative measures of physicochemical properties. This work not only enriches the body of our knowledge about the relationship between energy and information, but also provides scores of newly introduced explicit density functionals to quantify physicochemical properties, which can serve as robust features for building machine learning models in future studies.

Steric Effect and Intrinsic Electrophilicity and Nucleophilicity from Conceptual Density Functional Theory and Information-Theoretic Approach as Quantitative Probes of Chemical Reactions.

Appreciating reactivity in terms of physicochemical effects for chemical processes is one of the most important undertakings in chemistry. While transition state (TS) theory provides the framework enabling the reliable calculation of the barrier height for a given elementary step, analytical tools are necessary to gain insight into key factors governing the different processes during chemical reactions. In this contribution, we partition the potential energy surface of an elementary step along the intrinsic coordinate into three segments, the so-called Pre-TS, TS, and Post-TS regions, and then determine the most important factors dictating each segment. This analysis is based on the use of both reactivity descriptors from conceptual density functional theory and concepts from the information-theoretic approach in density functional theory. We found that in both Pre-TS and Post-TS regions, steric effects are the dominant factors, whereas in the TS region, it is the intrinsic electrophilic and nucleophilic propensity of the transition state structure that governs the reactivity. The wide applicability of our approach is shown by a validation for a total of 37 organic and inorganic reactions. Different partition approaches from density functional theory, energy decomposition analysis and wavefunction-based resonance theory are employed to support our main conclusions.

Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects.

Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3-GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2-GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3-GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.

Dietary Bacillus velezensis T23 fermented products supplementation improves growth, hepatopancreas and intestine health of Litopenaeus vannamei.

This study aimed to elucidate the effects of dietary fermented products of Bacillus velezensis T23 on the growth, immune response and gut microbiota in Pacific white shrimp (Litopenaeus vannamei). Shrimp were fed with diets containing fermentation products of B. velezensis T23 at levels of (0, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 g/kg) for 4 weeks, to assess the influence on shrimp growth. The results showed that 0.3 and 0.4 g/kg T23 supplementation improved shrimp growth and feed utilization. Based on these results we selected these three diets (Control, 0.3T23 and 0.4T23) to assess the effect on immune response and gut microbiota of shrimp. Compared with the control, the 0.3T23 and 0.4T23 groups enhanced lipase and α-amylase activities in the gut significantly. Moreover, the 0.4T23 group decreased TAG and MDA levels in hepatopancreas, ALT and AST levels of serum significantly (P < 0.05). In hepatopancreas, CAT and SOD activities were improved observably and the MDA content was reduced markedly in both T23 groups. The expressions of antimicrobial related genes, Cru and peroxinectin in the 0.3T23 group, and proPO and peroxinectin in the 0.4T23 group were up-regulated remarkably (P < 0.05). Moreover, hepatopancreas of shrimp fed with a diet amended with T23 showed a significant down-regulated expression of nf-kb and tnf-α genes, while expressions of tgf-ß was considerably up-regulated. Furthermore, serum LPS and LBP contents were reduced markedly in T23 groups. Intestinal SOD and CAT were noteworthy higher in T23 groups (P < 0.05). In the intestine of shrimp fed on the diet enriched with T23 the expression of nf-κb and tnf-α exhibited markedly down-regulated, whereas hif1α was up-regulated (P < 0.05). Besides, in the intestine of shrimp grouped under T23, Cru and peroxinectin genes were markedly up-regulated (P < 0.05). Dietary 0.3 g/kg T23 also upregulated the ratio of Rhodobacteraceae to Vibrionaceae in the gut of the shrimp. Taken together, the inclusion of B. velezensis T23 in the diet of shrimp enhanced the growth and feed utilization, enhanced hepatopancreas and intestine health.

Microstructure and Hardness Characteristics of Swing-Arc SAW Hardfacing Layers.

Hot-rolled backup rolls are widely used in steel rolling and usually need to be repaired by arc hardfacing after becoming worn. However, a corrugated-groove defect commonly occurs on the roll surface due to the uneven hardness distribution in the hardfacing layers, affecting the proper usage of the roll. Accordingly, a new swing-arc submerged arc welding (SA-SAW) process is proposed to attempt to solve this drawback. The microstructure and hardness are then investigated experimentally for both SAW and SA-SAW hardfacing layers. It is revealed that a self-tempering effect occurs in the welding pass bottom and the welding pass side neighboring the former pass for both processes, refining the grain in the two areas. In all the zones, including the self-tempering zone (STZ), heat-affected zone (HAZ), and not-heat-affected zone in the welding pass, both SAW and SA-SAW passes crystallize in a type of columnar grain, where the grains are the finest in STZ and the coarsest in HAZ. In addition, the arc swing improves the microstructure homogeneity of the hardfacing layers by obviously lowering the tempering degree in HAZ while promoting the even distribution of the arc heat. Accordingly, the hardness of the SA-SAW bead overall increases and distributes more uniformly with a maximum difference of < 80 HV0.5 along the horizontal direction of the bead. This hardness difference in SA-SAW is accordingly decreased by ~38.5% compared to that of the SAW bead, further indicating the practicability of the new process.

Chiral Jahn-Teller Distortion in Quasi-Planar Boron Clusters.

In this work, we have observed that some chiral boron clusters (B16-, B20-, B24-, and B28-) can simultaneously have helical molecular orbitals and helical spin densities; these seem to be the first compounds discovered to have this intriguing property. We show that chiral Jahn-Teller distortion of quasi-planar boron clusters drives the formation of the helical molecular spin densities in these clusters and show that elongation/enhancement in helical molecular orbitals can be achieved by simply adding more building blocks via a linker. Aromaticity of these boron clusters is discussed. Chiral boron clusters may find potential applications in spintronics, such as molecular magnets.

Harvesting Chemical Understanding with Machine Learning and Quantum Computers.

It is tenable to argue that nobody can predict the future with certainty, yet one can learn from the past and make informed projections for the years ahead. In this Perspective, we overview the status of how theory and computation can be exploited to obtain chemical understanding from wave function theory and density functional theory, and then outlook the likely impact of machine learning (ML) and quantum computers (QC) to appreciate traditional chemical concepts in decades to come. It is maintained that the development and maturation of ML and QC methods in theoretical and computational chemistry represent two paradigm shifts about how the Schrödinger equation can be solved. New chemical understanding can be harnessed in these two new paradigms by making respective use of ML features and QC qubits. Before that happens, however, we still have hurdles to face and obstacles to overcome in both ML and QC arenas. Possible pathways to tackle these challenges are proposed. We anticipate that hierarchical modeling, in contrast to multiscale modeling, will emerge and thrive, becoming the workhorse of in silico simulations in the next few decades.

Relative cooperativity in neutral and charged molecular clusters using QM/MM calculations.

QM/MM methods have been used to study electronic structure properties and chemical reactivity in complex molecular systems where direct electronic structure calculations are not feasible. In our previous work, we showed that non-polarizable force fields, by design, describe intermolecular interactions through pairwise interactions, overlooking many-body interactions involving three or more particles. In contrast, polarizable force fields account partially for many-body effects through polarization, but still handle van der Waals and permanent electrostatic interactions pairwise. We showed that despite those limitations, polarizable and non-polarizable force fields can reproduce relative cooperativity achieved using density functional theory due to error compensation mechanisms. In this contribution, we assess the performance of QM/MM methods in reproducing these phenomena. Our study highlights the significance of the QM region size and force field choice in QM/MM calculations, emphasizing the importance of parameter validation to obtain accurate interaction energy predictions.

C(sp3)-H (N-Phenyltetrazole)thiolation as an Enabling Tool for Molecular Diversification.

Methods enabling the broad diversification of C(sp3)-H bonds from a common intermediate are especially valuable in chemical synthesis. Herein, we report a site-selective (N-phenyltetrazole)thiolation of aliphatic and (hetero)benzylic C(sp3)-H bonds using a commercially available disulfide to access N-phenyltetrazole thioethers. The thioether products are readily elaborated in diverse fragment couplings for C-C, C-O, or C-N construction. The C-H functionalization proceeds via a radical-chain pathway involving hydrogen atom transfer by the electron-poor N-phenyltetrazolethiyl radical. Hexafluoroisopropanol was found to be essential to reactions involving aliphatic C(sp3)-H thiolation, with computational analysis consistent with dual hydrogen bonding of the N-phenyltetrazolethiyl radical imparting increased radical electrophilicity to facilitate the hydrogen atom transfer. Substrate is limiting reagent in all cases, and the reaction displays an exceptional functional group tolerance well suited to applications in late-stage diversification.

Fragment-Based Deep Learning for Simultaneous Prediction of Polarizabilities and NMR Shieldings of Macromolecules and Their Aggregates.

Simultaneous prediction of the molecular response properties, such as polarizability and the NMR shielding constant, at a low computational cost is an unresolved issue. We propose to combine a linear-scaling generalized energy-based fragmentation (GEBF) method and deep learning (DL) with both molecular and atomic information-theoretic approach (ITA) quantities as effective descriptors. In GEBF, the total molecular polarizability can be assembled as a linear combination of the corresponding quantities calculated from a set of small embedded subsystems in GEBF. In the new GEBF-DL(ITA) protocol, one can predict subsystem polarizabilities based on the corresponding molecular wave function (thus electron density and ITA quantities) and DL model rather than calculate them from the computationally intensive coupled-perturbed Hartree-Fock or Kohn-Sham equations and finally obtain the total molecular polarizability via a linear combination equation. As a proof-of-concept application, we predict the molecular polarizabilities of large proteins and protein aggregates. GEBF-DL(ITA) is shown to be as accurate enough as GEBF, with mean absolute percentage error <1%. For the largest protein aggregate (>4000 atoms), GEBF-DL(ITA) gains a speedup ratio of 3 compared with GEBF. It is anticipated that when more advanced electronic structure methods are used, this advantage will be more appealing. Moreover, one can also predict the NMR chemical shieldings of proteins with reasonably good accuracy. Overall, the cost-efficient GEBF-DL(ITA) protocol should be a robust theoretical tool for simultaneously predicting polarizabilities and NMR shieldings of large systems.

Optimized Incorporation of Furan into Diketopyrrolopyrrole-Based Conjugated Polymers for Organic Field-Effect Transistors.

Flexible electronics have received considerable attention in the past decades due to their promising application in rollable display screens, wearable devices, implantable devices, and other electronic applications. In particular, conjugated polymers are favored for flexible electronics due to their mechanical flexibility and potential for solution-processed fabrication techniques, such as blade-coating, roll-to-roll printing, and high-throughput printing allowing for high-performance transistor devices. Thiophene is the prevailing conjugated unit to construct these conjugated polymers due to its favorable electronic properties. On the other hand, furans are among the few conjugated moieties that are easily derived from bio renewable resources. To promote sustainability, we selectively introduced furan into the conjugated backbone of a high-mobility polymer scaffold and systematically studied the effect on the microstructure and charge transport. We show that partially and selectively replacing thiophene units with furan can yield nearly comparable performance compared to the all-thiophene polymer. This strategy offers an improvement in the sustainability of the polymer by incorporating bio-sourced furan without sacrificing the high-performance characteristics. Meanwhile, polymers with incorrect or complete furan incorporation show reduced mobilities. This work serves to develop coherent structure-morphology-performance relationships; such knowledge will establish guidelines for the future development of sustainable, furan-based conjugated materials.

Some Recent Advances in Density-Based Reactivity Theory.

Establishing a chemical reactivity theory in density functional theory (DFT) language has been our intense research interest in the past two decades, exemplified by the determination of steric effect and stereoselectivity, evaluation of electrophilicity and nucleophilicity, identification of strong and weak interactions, and formulation of cooperativity, frustration, and principle of chirality hierarchy. In this Featured Article, we first overview the four density-based frameworks in DFT to appreciate chemical understanding, including conceptual DFT, use of density associated quantities, information-theoretic approach, and orbital-free DFT, and then present a few recent advances of these frameworks as well as new applications from our studies. To that end, we will introduce the relationship among these frameworks, determining the entire spectrum of interactions with Pauli energy derivatives, performing topological analyses with information-theoretic quantities, and extending the density-based frameworks to excited states. Applications to examine physiochemical properties in external electric fields and to evaluate polarizability for proteins and crystals are discussed. A few possible directions for future development are followed, with the special emphasis on its merger with machine learning.

The interaction between lipid and vitamin D3 impacts lipid metabolism and innate immunity in Chinese mitten crabs Eriocheir sinensis.

As a fat-soluble vitamin, vitamin D3 relies on fat to perform its biological function, affecting lipid metabolism and innate immunity. This study used different percentages of lipid and vitamin D3 diets to evaluate the synergistic effects on the growth, lipid metabolism and immunity of juvenile Eriocheir sinensis (5.83 ± 0.01 g) for 56 days, including low lipid (LL, 1.5%) and normal lipid (NL, 7.5%) and three levels of vitamin D3: low (LVD, 0 IU/kg), medium (MVD, 9000 IU/kg) and high (HVD, 27,000, IU/kg). The synergistic effect of lipid and vitamin D3 was not significant on growth but significant on ash content, total protein, hepatopancreas lipid content, hemolymph 1α,25-hydroxy vitamin D3 [1α,25(OH)2D3] content, hepatopancreas lipolysis and synthesis genes. Crabs fed normal lipid (7.5%) and medium vitamin D3 (9000 IU/kg) had the highest hepatopancreas index, hemolymph 1α,25(OH)2D3 content, antibacterial ability, immune-related genes and hepatopancreatic lipid synthesis genes expression, but down-regulated the lipolysis genes expression. In contrast, crabs fed diets with low lipid percentage (1.5%) had low growth performance, hemolymph 1α,25(OH)2D3, mRNA levels of lipid synthesis genes, antibacterial ability and immune-related gene expression. At the 1.5% lipid level, excessive or insufficient vitamin D3 supplementation led to the obstruction of ash and protein deposition, reduced growth and molting, aggravated the reduction in antioxidant capacity, hindered antimicrobial peptide gene expression and reduced innate immunity, and resulted in abnormal lipid accumulation and the risk of oxidative stress. This study suggests that diets' lipid and vitamin D3 percentage can enhance antioxidant capacity, lipid metabolism and innate immunity in E. sinensis. A low lipid diet can cause growth retardation, reduce antioxidant capacity and innate immunity, and enhance lipid metabolism disorder.