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The asymmetric total syntheses of four pleurotin natural products, namely, (-)-pleurotin, (+)-leucopleurotin, (+)-leucopleurotinic acid, and (+)-dihydropleurotinic acid, were described in a concise manner. Key transformations feature a Johnson-Claisen rearrangement, a diastereo-controlled sequential hydroboration-oxidation, a SOMO/photoredox activated aldehyde α-alkylation, and oxidative cyclizations.

The Möbius rule predicts that a planar four-membered metallacycle can be aromatic with four mobile electrons, but such a simple ring has escaped recognition because it usually favors Hückel anti-aromaticity. Here, we report that a quasi-square four-membered actinide compound (Pa 2 B 2 ) is doubly Möbius aromatic. Chemical bonding analyses reveal that this diboron protactinium molecule has four delocalized π electrons in addition to four delocalized σ electrons, satisfying the 4n Möbius rule for both σ and π components. Energetically, the block-localized wavefunction method, which is the simplest variant of ab initio valence bond theory, shows that the delocalization energy for the π and σ electrons reaches up to 65.0 and 72.3 kcal/mol, respectively, while the extra cyclic resonance energy (ECRE) amounts to 45 kcal/mol. The large positive ECRE values strongly confirm the unprecedented double Möbius aromaticity in Pa 2 B 2 . We anticipate that this new type of aromatic molecule can enrich the concept of Möbius aromaticity and open a new avenue for actinide compounds.

The revival of ternary halides Li-M-X (M = Y, In, Zr, etc.; X = F, Cl, Br) as solid-state electrolytes (SSEs) shows promise in realizing practical solid-state batteries due to their direct compatibility toward high-voltage cathodes and favorable room-temperature ionic conductivities. Most of the reported superionic halide SSEs have a structural pattern of [MCl 6 ] x - octahedra and generate a tetrahedron-assisted Li + ion diffusion pathway. Here, we report a new class of zeolite-like halide frameworks, SmCl 3 , for example, in which 1-dimensional channels are enclosed by [SmCl 9 ] 6- tricapped trigonal prisms to provide a short jumping distance of 2.08 Å between two octahedra for Li + ion hopping. The fast Li + diffusion along the channels is verified through ab initio molecular dynamics simulations. Similar to zeolites, the SmCl 3 framework can be grafted with halide species to obtain mobile ions without altering the base structure, achieving an ionic conductivity over 10 -4 S cm -1 at 30 °C with LiCl as the adsorbent. Moreover, the universality of the interface-bonding behavior and ionic diffusion in a class of framework materials is demonstrated. It is suggested that the ionic conductivity of the MCl 3 /halide composite (M = La-Gd) is likely in correlation with the ionic conductivity of the grafted halide species, interfacial bonding, and framework composition/dimensions. This work reveals a potential class of halide structures for superionic conductors and opens up a new frontier for constructing zeolite-like frameworks in halide-based materials, which will promote the innovation of superionic conductor design and contribute to a broader selection of halide SSEs.

The molecular structures synthesizable by organic chemists dictate the molecular functions they can create. The invention and development of chemical reactions are thus critical for chemists to access new and desirable functional molecules in all disciplines of organic chemistry. This work seeks to expedite the exploration of emerging areas of organic chemistry by devising a machine-learning-guided workflow for reaction discovery. Specifically, this study uses machine learning to predict competent electrochemical reactions. To this end, we first develop a molecular representation that enables the production of general models with limited training data. Next, we employ automated experimentation to test a large number of electrochemical reactions. These reactions are categorized as competent or incompetent mixtures, and a classification model was trained to predict reaction competency. This model is used to screen 38,865 potential reactions in silico, and the predictions are used to identify a number of reactions of synthetic or mechanistic interest, 80% of which are found to be competent. Additionally, we provide the predictions for the 38,865-member set in the hope of accelerating the development of this field. We envision that adopting a workflow such as this could enable the rapid development of many fields of chemistry.

The enabling of high energy density of all-solid-state lithium batteries (ASSLBs) requires the development of highly Li + -conductive solid-state electrolytes (SSEs) with good chemical and electrochemical stability. Recently, halide SSEs based on different material design principles have opened new opportunities for ASSLBs. Here, we discovered a series of Li x ScCl 3+ x SSEs ( x = 2.5, 3, 3.5, and 4) based on the cubic close-packed anion sublattice with room-temperature ionic conductivities up to 3 × 10 -3 S cm -1 . Owing to the low eutectic temperature between LiCl and ScCl 3 , Li x ScCl 3+ x SSEs can be synthesized by a simple co-melting strategy. Preferred orientation is observed for all the samples. The influence of the value of x in Li x ScCl 3+ x on the structure and Li + diffusivity were systematically explored. With increasing x value, higher Li + , lower vacancy concentration, and less blocking effects from Sc ions are achieved, enabling the ability to tune the Li + migration. The electrochemical performance shows that Li 3 ScCl 6 possesses a wide electrochemical window of 0.9-4.3 V vs Li + /Li, stable electrochemical plating/stripping of Li for over 2500 h, as well as good compatibility with LiCoO 2 . LiCoO 2 /Li 3 ScCl 6 /In ASSLB exhibits a reversible capacity of 104.5 mAh g -1 with good cycle life retention for 160 cycles. The observed changes in the ionic conductivity and tuning of the site occupations provide an additional approach toward the design of better SSEs.

Multinuclear complexes as metallo-agents for clinical use have caught extensive attention. In this paper, using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as both a functioning unit and a constructing junction, we build a series of DOTA-branched organic frameworks with multiple chelating holes by organizing DOTA layer by layer. These giant chelators are well characterized, which reveals their nanosized and soft structures. Further experiments demonstrate that they could efficiently hold abundant metal ions with much higher kinetic stabilities than the conventional small DOTA chelator. Their corresponding polynuclear complexes containing Gd 3+ , Tb 3+ , or both show superior imaging properties, excellent feasibility for peripheral modification, and unusual kinetic stability. This work can be easily extended to the fabrication of diverse homomultinuclear complexes and core/shell heteromultinuclear complexes with multifunctional properties. We expect that this new type of giant molecules and the ligand-branching strategy would open up a new avenue for the design and construction of next-generation polymetallic agents with high performance and stabilities for biomedical applications.

The Sierpiński triangle (ST) is a well-known fractal structure. Synthesis of stable molecular STs with robust covalent linkages is attractive but challenging. Here, we demonstrate the formation of a series of high-quality covalent STs via the on-surface dehydration reaction of 1,3-benzenediboronic acid with the presence of water as an equilibrium regulator at ambient atmosphere. Extended molecular fractals up to third generation are obtained, as disclosed by scanning tunnel microscope. The covalent STs show intriguing bright and dark contrasts irrespective of the fractal generations, which is related with epitaxial relationship of fractal structure to the underlying graphite lattice, as supported by theoretical simulations.

Conventionally, phase diagrams serve as road maps for the design and synthesis of materials. However, bulk phase diagrams are often not as predictive for the synthesis of nanometric materials, mainly due to the increased significance of surface energy. The change of surface energy can drastically alter the total energy of the nanocrystals and thus yields a polymorph or metastable phase different from the stable phase in bulk, providing a means for controlling the synthesis of metastable phases. To achieve a theoretical and systematical understanding on the polymorphism of nanomaterials, metallic cobalt was chosen as a model system, where the two polymorphs, fcc and hcp phases, can be tuned with 100% selectivity in a solvothermal reaction. Advanced in situ synchrotron X-ray diffraction (XRD) technique and density functional theory (DFT) calculations were complementarily employed to reveal the size- and surface-dependent polymorphism at nanometer scale. The nanometric phase diagram provides a general predictive approach to guide the synthesis of metastable materials.

We report the first example of C-I···π halogen bonding driven supramolecular helix in highly dilute solution of micromolar concentration, using alanine based bilateral I-substituted N-amidothioureas that contain helical fragments, the β-turn structures. The halogen bonding interactions afford head-to-tail linkages that help to propagate the helicity of the helical fragments. In support of this action of the halogen bonding, chiral amplification was observed in the supramolecular helix formed in acetonitrile solution. The present finding provides alternative tools in the design of self-assembling macromolecules.

All-solid-state Li-batteries using solid-state electrolytes (SSEs) offer enhanced safety over conventional Li-ion batteries with organic liquid electrolytes due to the nonflammable nature of SSEs. The superior mechanical strength of SSEs can also protect against Li dendrite penetration, which enables the use of the highest specific capacity (3861 mAh/g) and lowest redox potential (-3.04 V vs standard hydrogen electrode) anode: Li metal. However, contact between the Li metal and SSEs presents a major challenge, where a large polarization occurs at the Li metal/SSE interface. Here, the chemical properties of a promising oxide-based SSE (garnet) changed from "super-lithiophobicity" to "super-lithiophilicity" through an ultrathin coating of amorphous Si deposited by plasma-enhanced chemical vapor deposition (PECVD). The wettability transition is due to the reaction between Li and Si and the in situ formation of lithiated Si. As a result, symmetric cells composed of a Si-coated garnet-structured SSE and Li metal electrodes exhibited much smaller impedance and excellent stability upon plating/stripping cycles compared to cells using bare garnet SSE. Specifically, the interfacial resistance between Li and garnet dramatically decreased from 925 to 127 Ω cm(2) when lithiated Si was formed on the garnet. Our discovery of switchable lithiophobic-lithiophilic surfaces to improve the Li metal/SSE interface opens opportunities for improving many other SSEs.

The anomeric effect plays a central role in carbohydrate chemistry, but its origin is controversial, and both the hyperconjugation model and the electrostatic model have been proposed to explain this phenomenon. Recently, Cocinero et al. designed a peptide sensor, which can bind to a sugar molecule methyl D-galactose, and claimed that the anomeric effect can be sensed by the spectral changes from the β- to the α-complex, which are ultimately attributed to the lone pair electron density change on the endocyclic oxygen atom [Nature 2011, 469, 76; J. Am. Chem. Soc. 2011, 133, 4548]. Here, we provide strong computational evidence showing that the observed spectral changes simply come from the conformational differences between the α- and β-anomers, as the replacement of the endocyclic oxygen atom with a methylene group, which disables both the endo- and the exo-anomeric effects in methyl D-galactose, leads to similar spectral shifts. In other words, the "sensor" cannot probe the anomeric effect as claimed. We further conducted detailed energetic and structural analyses to support our arguments.

Phosphoglucose isomerase (PGI), which catalyzes the reversible interconversion of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), is represented by two evolutionarily distinct protein families. One is a conventional type in eubacteria, eukaryotes, and a few archaea, where the active sites contain no metal ions and reactions proceed via the cis-enediol intermediate mechanism. The second type, found recently in euryarchaeota species, belongs to metalloenzymes, and controversies exist over whether the catalyzed isomerization occurs via the cis-enediol intermediate mechanism or a hydride shift mechanism. We studied the reversible interconversion of the open-chain form G6P and F6P catalyzed by the metal-containing Pyrococcus furiosus PGI by performing QM(B3LYP)/MM single-point optimizations and QM(PM3)/MM molecular dynamics simulations. A zwitterion intermediate-based mechanism, which involves both proton and hydride transfers, has been put forward. The presence of the key zwitterionic intermediate in this mechanism can effectively reconcile the controversial mechanisms and rationalize the enzymatic reaction. Computations show that the overall isomerization process is quite facile, both dynamically and thermodynamically. The crucial roles of conserved residues have been elucidated on the basis of computations on their alanine mutants. In particular, Tyr152 pushes the H1 transfer through a hydride-shift mechanism and dominates the stereochemistry selectivity of the hydrogen transfer. The rest of the conserved residues basically maintain the substrate in the near-attack reactive conformation and mediate the proton transfer. Although Zn(2+) is not directly involved in the reaction, the metal ion as a structural anchor constructs a hydrogen bond wire to connect the substrate to the outer region, providing a potential channel for hydrogen exchange between the substrate and solvent.

Molecular dynamics (MD) simulations have been performed at the atomic level to study the ammonium/ammonia transport across the Escherichia coli AmtB membrane protein. Although ammonia primarily exists in the form of NH(4)(+) in aqueous solution, the recent X-ray structure determination of AmtB reveals that the ammonium/ammonia transporter proteins are ammonia-conducting channels rather than ammonium ion transporters [Khademi, S.; et al. Science 2004, 305, 1587; Zheng, L.; et al. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 17090]. Our simulations showed that the entrance of NH(4)(+) into the periplasmic recruitment vestibule requires only 3.1 kcal/mol of energy. This is consistent with the X-ray crystal structure, where one NH(4)(+) is captured in the binding vestibule. In this vestibule, NH(4)(+) loses one water of hydration, but the loss is compensated by a hydrogen bond, first with the backbone carbonyl oxygen of Phe161 then with the hydroxyl group of Ser219, as well as the stabilizing pi-cation interactions with the aromatic rings of Trp148 and Phe107 in the AmtB protein. In the end of this recruitment vestibule, the phenyl ring of Phe107 dynamically switches to an open state. This is correlated with a slight rotation and shifting of the indole ring of Trp148, which eventually creates a slot for the initially buried carboxylate group of Asp160 to become exposed to the bulk solvent. A hydrogen bond wire between NH(4)(+) and the carboxylate group of Asp160 via two water molecules was observed. Thus, Asp160 is most likely the proton acceptor from NH(4)(+). This explains the high conservation of Asp160 in Amt proteins and why the D160A mutant would completely quench the activity of AmtB [Javelle, A.; et al. J. Biol. Chem. 2004, 279, 8530; Marini, A. M.; et al. Curr. Genet. 2006, 49, 364]. Once NH(4)(+) deprotonates, the phenyl ring of Phe215 rotates to open, and the subsequent passage of NH(3) through the channel is straightforward.

As a simple yet strongly binding electron donor-acceptor (EDA) complex, BH(3)NH(3) serves as a good example to study the electron pair donor-acceptor complexes. We employed both the ab initio valence bond (VB) and block-localized wave function (BLW) methods to explore the electron transfer from NH(3) to BH(3). Conventionally, EDA complexes have been described by two diabatic states: one neutral state and one ionic charge-transferred state. Ab initio VB self-consistent field (VBSCF) computations generate the energy profiles of the two diabatic states together with the adiabatic (ground) state. Our calculations evidently demonstrated that the electron transfer between NH(3) and BH(3) falls in the abnormal regime where the reorganization energy is less than the exoergicity of the reaction. The nature of the NH(3)-BH(3) interaction is probed by an energy decomposition scheme based on the BLW method. We found that the variation of the charge-transfer energy with the donor-acceptor distance is insensitive to the computation levels and basis sets, but the estimation of the amount of electron transferred heavily depends on the population analysis procedures. The recent resurgence of interest in the nature of the rotation barrier in ethane prompted us to analyze the conformational change of BH(3)NH(3), which is an isoelectronic system with ethane. We found that the preference of the staggered structure over the eclipsed structure of BH(3)NH(3) is dominated by the Pauli exchange repulsion.

The nature and strength of the cation-pi interaction in protein-ligand binding are modeled by considering a series of nonbonded complexes involving N-substituted piperidines and substituted monocylic aromatics that mimic the delta-opioid receptor-ligand binding. High-level ab initio quantum mechanical calculations confirm the importance of such cation-pi interactions, whose intermolecular interaction energy ranges from -6 to -12 kcal/mol. A better understanding of the electrostatics, polarization, and other intermolecular interactions is obtained by appropriately decomposing the total interaction energy into their individual components. The energy decomposition analysis is also useful for parametrizing existing molecular mechanics force fields that could then account for energetic contributions arising out of cation-pi interactions in biomolecules. The present results further provide a framework for interpreting experimental results from point mutation reported for the delta-opioid receptor.

Ab initio molecular orbital and combined QM/MM Monte Carlo simulations have been carried out to investigate the origin of the unusually high acidity of Meldrum's acid. Traditionally, the high acidity of Meldrum's acid relative to that of methyl malonate has been attributed to an additive effect due to the presence of two E esters in the dilactone system. However, the present study reveals that there is significant nonadditive effect that also makes major contributions. This results from preferential stabilization of the enolate anion over that of Meldrum's acid due to anomeric stereoelectronic interactions. To investigate solvent effects on the acidity in aqueous solution, the relative acidities of Z and E conformers of methyl acetate have been determined in combined ab initio QM/MM simulations. There is significant solvent effect on the conformational equilibria for both the neutral ester and its enolate anion in water, leading to stabilization of the E stereoisomer. However, the computed solvent effect of 4.4 kcal/mol in favor of the E isomer of methyl acetate is largely offset by the favorable solvation of 3.4 kcal/mol for the E conformer of the enolate anion. This leads to an enhanced acidity of 3.4 kcal/mol for the (E)-methyl acetate in water over the Z conformer. In Meldrum's acid, it is the preferential stabilization of the enolate anion due to anomeric effects coupled with the intrinsically higher acidity of the E conformation of ester that is responsible for its high acidity.