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The calculations of vibrational circular dichroism (VCD) spectra are used for the analysis of conformers of various intermolecular systems, including (1:1) cysteine-water complexes. The VCD spectra are found to be highly sensitive to the water arrangement in such cysteine complexes.

The [2+2] cycloaddition reaction paths for allene-isocyanic acid (path A) and ketene-vinylimine (path B) additions are investigated by the MP2/aug-cc-pVDZ method. The atom in molecules (AIM) analysis of the electron density distribution in the transition-state (TS) structures helps in distinguishing the pericyclic from pseudopericyclic and from the nonplanar-pseudopericyclic types of reactions.

The structure and stability of nonlinear carbyne carbon clusters were estimated on the basis of ab initio quantum mechanical calculations. Spectroscopy of small carbon clusters had made possible the description of the structure of catenane, cyclic and knotted polycarbon chains containing 60 carbon atoms. The C60 topological isomers in mixtures can be identified by comparing the calculated 13C nuclear magnetic resonance spectra with that of C60 fullerene.

The reaction paths of [2+2] cycloaddition of the X=C=Y cumulenes were modeled at the MP2/aug-cc-pVDZ level. Cycloadditions of allene and CO2, CS2, or OCS lead in part to the same four-membered products as dimerization of either ketene or thioketene or addition of ketene and thioketene, respectively.

The aim of the study is to make a reliable assignment of the vibrational modes in the Fourier-transform infrared (FTIR) spectra of 5-halouracils trapped in low-temperature Ar matrixes. The infrared low-temperature Ar-matrix spectra of 5-halouracils and unsubstituted uracil are measured and interpreted in terms of the spectra calculated at the DFT/B3PW91/6-311G** level followed by a potential energy distribution (PED) analysis.

Structure and stability of 285 conformers of the vigabatrin molecule in the gas phase have been obtained by using two combined approaches of conformer search. The results showed rotational barriers for all the intramolecular rotations and that these motions are hindered and that for every rotation, the maxima and minima of potential energy dependence on the rotational angles occur at similar angles.

sEDA, pEDA, and cSAR descriptors of the substituent effect were determined for >30 monosubstituted benzenes in the first excited singlet S1 state at the LC-ωB97XD/aug-cc-pVTZ level. It was found that in the S1 state, the σ- and π-valence electrons are a bit less and a bit more affected, respectively, than in the S0 state, but basically, the effect in both states remains the same. In the S0 and S1 states, the d(C-X) distances to the substituent's first atom and the ring perimeter correlate with the sEDA and pEDA in the appropriate states, respectively. The energies and the gap of the frontier orbitals in the two states are linearly correlated and for the HOMO(S1), LUMO(S1), and HOMO(S1)-LUMO(S1) gap correlate also with the pEDA(S1) and cSAR(S1) descriptors. In all studied correlations, three similar groups of substituents can be distinguished, for which correlations (i) are very good, (ii) deviate slightly, and (iii) deviate significantly. Comparison of the shape of the HOMO(S0) and HOMO(S1) orbitals shows that for case (i) HOMO orbitals exhibit almost perfect antisymmetry against the benzene plane, for case (ii) the antisymmetry of HOMO in one of the states is either perturbed or changed, and for case (iii) one HOMO state has σ-character. [ABSTRACT FROM AUTHOR]

Two enantiomers of 2-methyl-N-(1-thien-2-ylethyl)propane-2-sulfonamide (TSA) were synthesized, and their VCD, ROA, IR, and Raman spectra were registered. The solved (S)-TSA X-ray structure shows a disorder connected to the presence of two TSA conformers differing by a slight rotation of the thiophene ring. Two molecules in the unit cell of the monoclinic P21 crystal form a net of NH···OS and C*H···OS hydrogen bonds. Out of a series of computational levels tested to interpret the spectra, the B3LYP functional combined with the def2TZVP basis set satisfactorily reproduces the experimental VCD and ROA spectra. To simulate the VCD spectra of TSA enantiomers in KBr pellets, dimers and tetramers, with two different positions of the thiophene ring, were considered. The VCD spectra measured in CDCl3 are completely different from those taken in KBr due to the conformational freedom of TSA in chloroform. Seven TSA conformers fall into two groups of opposite configurations at the pyramidal N atom forming the additional stereogenic center. However, the barriers between conformers in each group are lower than the energy of thermal motions at 300 K. Thus, all conformers, but the most stable in each group, are likely to be metastable states. The calculated IR, VCD, Raman, and ROA spectra of the conformers depend not only on the type of stereogenic N atom but also on the thiophene ring rotation. Yet, they are likely to coexist because of low barriers between them. Three approaches were tested to reproduce the chiroptical spectra in solution using PCM and hybrid solvation models. As a consequence, it was found that a model in which all conformers contribute to the spectra with equal population factors seems to best reproduce the experimental data. Such a result suggests that in a dissolved state in 300 K TSA occurs in a very shallow potential well and all of its conformers coexist. [ABSTRACT FROM AUTHOR]

In this paper we provide a computationalstudy of the l-methionine conformational landscape and VCDspectra in the gas phaseand a water environment simulated by implicit PCM and the hybrid model,i.e., a combination of explicit “microsolvation” andimplicit models. In the gas phase, two groups of conformers differingin H-bonding, i.e., OH···NH2and NH···OC,could be distinguished based solely on the IR ν(OH) and ν(NH)stretching vibrations range. On the other hand, VCD better reflectedchain differences. The most stable OH···NH2conformer was predicted to be easily detected, and the presenceof two out of four NH···OC conformers couldbe confirmed. Three zwitterionic methionine conformers were shownto dominate in water. Their VCD spectra, simulated within the hybridmodel at the B3LYP-IEF-PCM/aug-cc-pVDZ level of theory, indicatedthat they could be recognized in the mixture. Use of the hybrid modelis crucial for good reproduction of the hydrogen bonding pattern inthe VCD spectra of methionine in water solution. However, the 1300–800cm–1region of the skeleton vibrations of methionineappeared to be relatively insensitive to the model of the solvent. [ABSTRACT FROM AUTHOR]

The effect of heteroatom or heteroatomic group incorporation into unsaturated five- and six-membered cyclic systems was studied by means of DFT/B3LYP/aug-cc-pVDZ calculations. Two descriptors of the incorporation effect, sEDA(II) and pEDA(II), reflecting the influence of the incorporated atom or group on the population of the σ and π valence electrons, were constructed on the basis of natural bond orbital analysis. The sEDA(II) and pEDA(II) descriptors were shown to be linearly independent; the former correlated very well with electro-negativity scales, whereas the latter correlated with NICS(1)ZZ and HOMACC aromaticity indices. The two descriptors seem to be universal tools for analyzing different chemical and physicochemical effects occurring in unsaturated heterocyclic systems. [ABSTRACT FROM AUTHOR]

This paper presents a discussion of the interaction energies for selected conformers of chiral l-cysteine and their (1:1) complexes with water at the B3LYP/aug-cc-pVDZ level. From among more than forty calculated 1:1 complexes three groups of complexes were singled out and examined by the B3LYP/aug-cc-pVDZ calculated vibrational circular dichroism (VCD) spectra. On the basis of analysis of the () and () and (OH2) and (NH2) ranges, the VCD spectra were found to be sensitive to conformational changes and water arrangement in cysteine complexes, and to be especially useful for discriminating between different chiral forms of intermolecular hydrogen-bonding complexes. In particular, we show that the VCD modes of an achiral water molecule after complex formation acquire significant rotational strengths whose signs change in line with the geometry of the complex. Moreover, for some water arrangements the VCD spectra can be sensitive to water-wagging conformers and, in temperatures low enough, the intensive (Wfree) and (H2O) VCD bands may be sufficiently separated to be splitted into pair of oppositely directed bands. [ABSTRACT FROM AUTHOR]

The reaction paths of [2 + 2] cycloadditions of allene (H2C=C=CH2) to isocyanic acid (HN=C=O) and ketene (H2C=C=O) to vinylimine (H2C=C=NH), leading to all the possible 14 four-membered ring molecules, were investigated by the MP2/aug-cc-pVDZ method. In the two considered reactions, the 2-azetidinone (β-lactam) ring compounds were predicted to be the most stable thermodynamically in the absence of an environment. Although 4-methylene-2-azetidinone is the most stable product of the ketene−vinylimine cycloaddition, its activation barrier is higher than that for 4-methylene-2-iminooxetane by ca. 6 kcal/mol. Therefore, the latter product can be obtained owing to kinetic control. The activation barriers in the allene−isocyanic acid reactions are quite high, 50−70 kcal/mol, whereas in the course of the ketene−vinylimine cycloaddition they are equal to ca. 30−55 kcal/mol. All the reactions studied were found to be concerted and mostly asynchronous. Simulation of the solvent environment (toluene, tetrahydrofuran, acetonitrile, and water) by using Tomasi's polarized continuum model with the integral equation formalism (IEF-PCM) method showed the allene−isocyanic reactions remained concerted, yet the activation barriers were somewhat higher than those in the gas phase, whereas the ketene−vinylimine reactions became stepwise. The larger the solvent dielectric constant, the lower the activation barriers found. The lowest-energy pathways in the gas phase and in solvent were confirmed by intrinsic reaction coordinate (IRC) calculations. The atoms in molecules (AIM) analysis of the electron density distribution in the transition-state (TS) structures allowed us to distinguish pericyclic from pseudopericyclic from nonplanar−pseudopericyclic types of reactions. [ABSTRACT FROM AUTHOR]

A suite of internally functionalized Fe 4 L 6 cage complexes has been synthesized with lipophilic end groups to allow dissolution in varied solvent mixtures, and the scope of their molecular recognition of a series of neutral, nonpolar guests has been analyzed. The lipophilic end groups confer cage solubility in solvents with a wide range of polarities, from hexafluoroisopropanol (HFIP) to tetrahydrofuran, and the hosts show micromolar affinities for neutral guests, despite having no flat panels enclosing the cavity. These hosts allow interrogation of the effects of an internal functional group on guest binding properties, as well as solvent-based driving forces for recognition. Introducing polar effects to the interior of the cavity enhances guest binding affinity in nonpolar solvents; adding space-filling aliphatic groups reduces affinity in all cases. While high dielectric solvents such as acetonitrile strongly favor guest binding, "low dielectric, high polarity" solvents such as HFIP strongly occupy the cavity and prevent guest recognition. Analysis of the cage optical transitions shows that the guests interact with the central ligand cores and reside in close proximity to the internal functions. These results have implications for supramolecular catalysis: balancing directed host:guest interactions (e.g., H-bonds) with entropic effects from solvent displacement is essential for reactions in these (and related) biomimetic hosts.

Catalytic asymmetric transformation of donor-acceptor cyclopropanes (DACs) has been proven to be a highly valuable and robust strategy to construct diverse types of enantioenriched molecules. However, the use of 1,1,2,2-tetrasubstituted DACs to form products bearing quaternary stereocenters remains a long-term unsolved challenge. Here, we report the copper-catalyzed asymmetric aminative ring opening of tetrasubstituted alkynyl DACs that delivers a myriad of α-tertiary amines with high levels of enantioselectivities. The alkyne, amine, and ester moieties within the products enable diverse further applications, including the asymmetric synthesis of bioactive molecules. Mechanistic studies indicate that the zwitterionic intermediate bearing a copper-acetylide unit plays a key role in the process, which represents a new mode for achieving catalytic asymmetric transformation of DACs.

A series of nido -tricarbollides based on 10,11-X 2 -7-Me 3 N- nido -7,8,9-C 3 B 8 H 8 (X = H, Cl, Br, I) and their protonated, i.e. cationic, counterparts, which have an extra H-bridge over the B10-B11 vector in the nido open pentagonal belt, were prepared. Their structures have been verified by the joint ab initio (DFT)/GIAO(ZORA)/NMR approach, MS and HR-MS spectroscopy, and X-ray diffraction techniques. The iodination process is quite slow and could be monitored by 11 B NMR spectroscopy in conjunction with a computational search for the corresponding reaction pathway. These efforts have revealed the existence of monoiodo nido tricarbollide cationic motifs with an iodine atom in the positions that have features of an asymmetrical bridge over B10(H)-B11(H) in 10,11-H 2 -7-Me 3 N- nido -7,8,9-C 3 B 8 H 8 or B10(I)-B11(H) in 10,11-I,H-7-Me 3 N- nido -7,8,9-C 3 B 8 H 8 . Interestingly, 1,2-(COOH) 2 - closo -1,2-C 2 B 10 H 10 is one of the active acids, which confirms the earlier observation that a dicarboxylic acid based on o -carborane acts as a superacid.

Asymmetric catalysis involving a sulfoxide electrophile intermediate presents an efficient methodology for accessing stereogenic-at-sulfur compounds, such as sulfinate esters, sulfinamides, etc. , which have garnered increasing attention in modern pharmaceutical sciences. However, as the aza-analog of sulfoxide electrophiles, the asymmetric issues about electrophilic sulfinimidoyl species remain largely unexplored and represent a significant challenge in sulfur stereochemistry. Herein, we exhibit an anionic stereogenic-at-cobalt(III) complex-catalyzed asymmetric synthesis of chiral sulfinamides via chiral sulfinimidoyl iodide intermediates. Mechanistic investigations reveal that the catalytic cycle is initiated by asymmetric oxidative iodination, generating sulfinimidoyl iodides. These active intermediates subsequently undergo an enantiospecific nucleophilic substitution with water, affording a diverse array of enantioenriched sulfinamides. Notably, these sulfinamides exhibit promising antifungal activities against Sclerotinia sclerotiorum and serve as ideal platform molecules facilitating the stereospecific transformation into various stereogenic aza-sulfur compounds.

Organoids are multicellular structures formed in vitro from populations of individual cells allowing modeling of structural and functional aspects of organs and tissues in normal and diseased states. They offer unique opportunities to model and treat disease. Using a mouse embryonic stem cell line, we have cultured organoids that express markers of spinal cord motor neurons as well as motor neurons found within the peripheral nervous system. The morphology and select neurotransmitter content of the organoids and spinal cord explants were compared at different developmental time points. We found indications of maturation in the organoids over time, mirrored by similar trends in the spinal cord explants. Although the organoids contained the same neurotransmitters as the spinal cord explants, the developmental changes of these neurotransmitter levels were less marked in organoids. Given these differences, further work is required to optimize organoid growth conditions to better reproduce in vivo models when using organoids to study development.

Flavonoids are naturally occurring compounds found in fruits, vegetables, and other plant-based foods, and they are known for their health benefits, such as UV protection, antioxidant, anti-inflammatory, and antiproliferative properties. This study investigates whether flavonoids, such as quercetin and 2,3-dehydrosilybin, can act as photoactivatable carbon monoxide (CO)-releasing molecules under physiological conditions. CO has been recently recognized as an important signaling molecule. Here, we show that upon direct irradiation, CO was released from both flavonoids in PBS with chemical yields of up to 0.23 equiv, which increased to almost unity by sensitized photooxygenation involving singlet oxygen. Photoreleased CO reduced cellular toxicity caused by high flavonol concentrations, partially restored mitochondrial respiration, reduced superoxide production induced by rotenone and high flavonol levels, and influenced the G0/G1 and G2/M phases of the cell cycle, showing antiproliferative effects. The findings highlight the potential of quercetin and 2,3-dehydrosilybin as CO-photoreleasing molecules with chemopreventive and therapeutic implications in human pathology and suggest their possible roles in plant biology.

The formation of Lewy bodies (LB) is a pathological hallmark for synucleinopathies, which is an umbrella term for many diseases, including Parkinson's disease, Lewy body dementia, and multiple system atrophy. One of the main components of LB is the aggregates of phosphorylated modification of α-Synuclein at residue 129 (αS-129), a neuronal protein expressed in the dopaminergic neurons in the brain. There are equivocal results about the role of αS-129, suggesting its involvement in both potentiating pathology and a functional role to rescue pathology. Regardless, a potential therapeutic strategy for LB-based pathologies could be the identification of inhibitors of both αS and αS-129 aggregation. However, to the best of our knowledge, there are no reports of ligands that can potently inhibit the aggregation of αS-129. Our group has recently identified potent antagonists of αS aggregation based on the oligopyridylamide (synthetic protein mimetics) and oligoquinoline (foldamers) scaffolds. Both ligands were potent antagonists of αS aggregation-mediated disease phenotypes in various PD models. Here, we tested both ligands against αS-129 aggregation and the coaggregation of αS and αS-129 (αS/αS-129). Both ligands were potent antagonists of αS-129 aggregation and coaggregation of αS/αS-129 in biophysical and cellular models of PD. Both ligands rescued cell toxicity mediated by the coaggregation of αS/αS-129. To the best of our knowledge, these are the first ligands that potently inhibit the major component of LB. This finding will aid in the development of therapeutic insights into aggregation-related synucleinopathies.

The investigation of plasmonic chirality is a profound and intriguing topic, and the distinctive morphology of intrinsically chiral nanoparticles has prompted significant interest in the structure-activity relationship between particle morphology and chirality. In this work, the anisotropic etching of chiral helical gold nanorods (HGNRs) by a cetyltrimethylammonium bromide (CTAB)-HAuCl 4 complex was observed with an interesting bidirectional variation of intrinsic chirality that initially enhanced and subsequently weakened, which was related with the diversity in CTAB distribution. In addition, an ultrasensitive and convenient sensing platform for acetylcholinesterase was developed based on the circular dichroism signal recovery of HGNRs caused by the dual inhibition of HGNR etching. The distinctive etching process and mechanism of chiral nanoparticles offer new insights into understanding the structural features and biochemical applications of the plasmonic intrinsic chirality, which could be applied to the acquisition of chiral nanoparticles and sensitive detection platform based on chiral signal changes.

We report the intermolecular (4 + 3) cycloadditions of oxetanyl and azetidinyl enolsilanes with different dienes by silylium catalysis to generate bicyclic scaffolds. These enolsilanes were competent to react with furans, cyclopentadiene, and 1,3-cyclohexadiene to deliver cycloadducts in up to 96% yields.

Optical detection of the HSO 4 - ion in pure aqueous medium is rare, owing to the very high Gibbs free energy of hydration and ambiguity to distinguish with the isostructural H 2 PO 4 - ion. Herein, a pair of triphenylamine-based push-pull dyes with different numbers of terminal pyridine fragments, connected via an acetylenic linker, were synthesized by Sonogashira cross-coupling reaction. These two dyes displayed highly selective (LOD = 15.1/8.3 ppb), dual-mode color-changing responses toward the HSO 4 - ion in pure aqueous medium without any interference. Despite the halochromic behavior, both compounds exhibited very distinct optical responses with the HSO 4 - ion. The mechanistic investigation indicated that HSO 4 - was engaged in a bifurcated intermolecular hydrogen bonding interaction (leading to proton transfer) with pyridine nitrogen atoms that altered the extent of intramolecular charge transfer (ICT). The self-assembly of such protonated species was found to be prominent when sulfate was present as the counteranion. The extent of self-assembly was found to be more prominent for the trisubstituted, Y-shaped quadrupolar derivative than that observed for the linear, monosubstituted one. Furthermore, the present system was utilized for the detection of HSO 4 - ions in commercially available samples with satisfactory responses.

In this scientific work, a novel and green method for selective lipophilization of EVOO's bioactive phenolic alcohols (PAs), namely, tyrosol, hydroxytyrosol, and its metabolite homovanillyl alcohol as fatty acid esters, is elucidated. The PAs have been employed as hydrogen bond donors in the formation of natural deep eutectic solvents (NADES) with choline chloride (ChCl). The fast and cheap esterification method by in situ formation of choline chloride-based deep eutectic solvents promotes the derivatization of PAs with various fatty acids as acylating agents in the absence of organic solvents and catalysts. Furthermore, given the growing interest in the application of NADES formed by bioactive molecules in the pharmacological and cosmetic fields, we analyzed the activity of antioxidant enzymes, superoxide dismutase, and glutathione S-transferase of three chemical formulations obtained after the formation of PA-oleate in the H 2 O 2 -treated HaCat human keratinocytes cell line, assessing also their toxicity via the MTT assay.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder. This study investigated the mitigating effects of the Antrodia cinnamomea polysaccharide (ACP) on a letrozole-induced PCOS rat model. Results demonstrated that ACP reduced obesity and ameliorated dyslipidemia in PCOS rats. Moreover, ACP restored estrous cycle regularity, suppressed polycystic ovarian changes, and regulated serum levels of sex hormones, SOD, and MDA. Furthermore, ACP increased the α-diversity and modulated the abundance of phyla (Bacteroidetes, Firmicutes, and Verrucomicrobia) and genera ( Lactobacillus, Helicobacter, Akkermansia, Oscillospira, Coprococcus, Roseburia, Blautia, and Allobaculum ) in the gut microbiota. ACP also restored compromised intestinal barriers by upregulating the expression of ZO1, Occludin, Claudin1, and Claudin7 in the colon. ACP mitigated ovarian fibrosis by preventing activation of the NLRP3 inflammasome, decreasing the expression of fibrotic markers (TGF-β1, collagen-I, α-SMA, and CTGF), and regulating four ovarian fibrosis-associated metabolomics pathways. Generally, dietary ACP effectively ameliorated clinical symptoms and inhibited ovarian fibrosis in PCOS rats.

Highly selective extraction of uranium from seawater is currently extremely challenging. Although the amidoxime group (HAO) is the commonly used ligand in seawater uranium extraction, it also has strong binding capacity for vanadium ion. It has been shown that the introduction of phosphate groups into amidoxime-based adsorbents can improve the adsorption performance of materials through a synergistic effect between functional groups. In this work, we have systematically investigated the selective extraction behavior of the phosphate ligand (methylphosphonic acid, HL 1 ) for uranyl cation and the synergistic effect with amidoxime using density functional theory (DFT). The electron-donor-substituted derivatives of HL 1 (aminomethylphosphonic acid (HL 2 ) and methyl phosphate (HL 3 )) were also considered. Not unexpectedly, the results show that introduction of HL 1 into the amidoxime-based adsorbents improves the extraction and selectivity for uranyl cations. This is mainly due to the fact that HL 1 is more likely to deprotonate, which promotes the dissociation of [UO 2 (CO 3 ) 3 ] 4- , and the presence of the phosphate groups in the synergistic complexes alters the optimal coordination mode of VO 2 + . In addition, the HL 2 and HL 3 ligands further improve the uranium extraction performance, especially for HL 3 . This work provides guidelines for the rational design of sequestering ligands for uranium extraction from seawater.

The ethylene-forming enzyme (EFE) is a Fe(II)/2-oxoglutarate (2OG) and l-arginine (l-Arg)-dependent oxygenase that primarily decomposes 2OG into ethylene while also catalyzing l-Arg hydroxylation. While the hydroxylation mechanism in EFE is similar to other Fe(II)/2OG-dependent oxygenases, the formation of ethylene is unique. Various redesign strategies have aimed to increase ethylene production in EFE, but success has been limited, highlighting the need for alternate approaches. It is crucial to incorporate an accurate and comprehensive description of the integrative and multidimensional effects of the protein environment to enhance the redesign strategy in metalloenzymes, particularly in EFE. This involves understanding the role of the second coordination sphere (SCS) and long-range (LR) interacting residues, correlated motions, electronic structure, intrinsic electric field (IntEF), as well as the stabilization of transition states and reaction intermediates. In this study, we employ a molecular dynamics-based quantum mechanics/molecular mechanics approach to examine the integrative effects of the protein environment on reactions catalyzed by EFE variants from the first coordination sphere (FCS, D191E), SCS (A198V and R171A) and LR (E215A). The study uncovers how substitutions at different positions in EFE similarly impact the ethylene-forming reaction while posing distinct effects on the hydroxylation reaction. Results predict the effect of the variants in controlling the 2OG coordination mode in the Fe(II) center. Specifically, the study suggests that D191E uniquely prefers transitioning from an off-line to an in-line 2OG coordination mode before dioxygen binding. However, studies on the 2OG flip in the presence of off-line approaching dioxygen and dioxygen binding in the D191E variant indicate that the 2OG flip might not be feasible in the 5C Fe(II) state. Calculations show the possibility of a hydrogen atom transfer (HAT)-assisted oxygen flip in EFE and its variants (other than D191E). MD simulations elucidate the characteristic dynamic change in the α7 region in the D191E variant that might contribute to its increased hydroxylation reaction. Results indicate the possibility of forming an in-line ferryl from the IM2 (Fe(III)-partial bond intermediate) in the D191E variant. This alternative pathway from IM2 may also exist in WT EFE and other variants, which are yet to be explored. The study also delineates the impact of substitutions on the electronic structure and IntEF. Overall, the calculations support the idea that understanding the integrative and multidimensional effects of the protein environment on the reactions catalyzed by EFE variants provides the basics for improved enzyme redesign protocols of EFE to increase ethylene production. The results of this study will also contribute to the development of alternate redesign strategies for other metalloenzymes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A combined machine learning approach and first-principles calculations are employed to efficiently explore energetically favorable ternary compounds involving Pt and an immiscible Si-Sn pair of elements. We predict two stable Pt-Si-Sn ternary compounds (Pt 2 Si 2 Sn and Pt 8 SiSn 2 ) and reproduce the experimentally synthesized Pt 5 SiSn. The crystal structures of Pt 5 SiSn and Pt 8 SiSn 2 are composed of a SiPt 8 cube and SnPt 12 cuboctahedron. Based on these structural motifs, we design a series of Pt-Si-Sn ternary compounds that contain SiPt 8 and SnPt 12 units and discover some stable and metastable compounds. Partial flat bands near the Fermi level appear in these compounds, and the positions of partial flat bands move upward with increasing the Pt content. The partial flat bands are dominated by Pt atoms. These Pt-Si-Sn ternary compounds provide a platform to study flat band-related properties. Our results open a way to design new compounds in the ternary system.

The chemistry of molten salts has attracted great research interest owing to their wide applications in diverse fields. In the pyrochemical reprocessing of spent nuclear fuel or molten salt nuclear reactors, lanthanide elements as the principal fission products bring about changes in the composition and properties of molten salts. Herein, we report a comprehensive study on the coordination chemistry of the representative trivalent lanthanide ions (La 3+ /Nd 3+ ) in LiCl-KCl-CsCl using a multiscale strategy combining Raman spectroscopy, deep learning, and large-scale molecular dynamics (MD) simulations. The neural network potential (NNP)-based MD and Raman spectroscopy studies revealed that La 3+ /Nd 3+ ions prefer to form persistent octahedron complexes with the six-coordinated species as the dominant species at high temperatures. Compared to LaCl 6 3- , NdCl 6 3- shows higher stability with obviously longer lifetimes in LiCl-KCl-CsCl, as confirmed by the observed stronger interaction of Nd 3+ -Cl - pairs. The total and partial structure factors further indicated the formation of a more stable network structure in LiCl-KCl-CsCl containing NdCl 3 . Besides, the temperature exerts a larger influence on the local structures of the La 3+ species compared to the Nd 3+ analogues. According to the potential mean force calculations, the bond dissociation energies follow the order Ln-Cl > Li-Cl > K-Cl > Cs-Cl in LiCl-KCl-CsCl-LnCl 3 . The NNP-based large-scale MD simulations have been verified to be an efficient and powerful way in molten salt chemistry research.

Recent advancements in deep learning and generative models have significantly expanded the applications of virtual screening for drug-like compounds. Here, we introduce a multitarget transformer model, PCMol , that leverages the latent protein embeddings derived from AlphaFold2 as a means of conditioning a de novo generative model on different targets. Incorporating rich protein representations allows the model to capture their structural relationships, enabling the chemical space interpolation of active compounds and target-side generalization to new proteins based on embedding similarities. In this work, we benchmark against other existing target-conditioned transformer models to illustrate the validity of using AlphaFold protein representations over raw amino acid sequences. We show that low-dimensional projections of these protein embeddings cluster appropriately based on target families and that model performance declines when these representations are intentionally corrupted. We also show that the PCMol model generates diverse, potentially active molecules for a wide array of proteins, including those with sparse ligand bioactivity data. The generated compounds display higher similarity known active ligands of held-out targets and have comparable molecular docking scores while maintaining novelty. Additionally, we demonstrate the important role of data augmentation in bolstering the performance of generative models in low-data regimes. Software package and AlphaFold protein embeddings are freely available at https://github.com/CDDLeiden/PCMol.

The synthesis of actinide tetrarhenate complexes completes a series of iridate, osmate, and rhenate polyhydrides, allowing for structural and bonding comparisons to be made. Computational studies examine the bonding interactions, particularly between metals, in these complexes. Several factors─including metal oxidation state, coordination number, and dispersion effects─affect metal-metal distances and covalency in these actinide tetrametallates. Related osmium and rhenium octametallic U 2 M 6 clusters are synthesized and described, and subjected to similar structural and electronic analyses.

Geldanamycin remains a driver in the medicinal chemistry of heat shock protein 90 (Hsp90) inhibition, even half a century after its original isolation from nature. This Perspective focuses on the properties of the benzoquinone ring of the natural product that enable a range of functionalization reactions to take place. Therefore, inherent reactivity at C-17, where the methoxy group serves as a vinylogous ester, and at C-19 that demonstrates nucleophilic, enamide-type character toward electrophiles, and also as a conjugate acceptor to react with nucleophiles, has facilitated the synthesis of semisynthetic derivatives. Thus, a range of C-17-substituted amine derivatives has been investigated in oncology applications, with a number of compounds in this series reaching clinical trials. In contrast, the 19-position of geldanamycin has received less attention, although 19-substituted derivatives offer promise with markedly reduced toxicity compared to geldanamycin itself, while retaining Hsp90 inhibitory activity albeit with diminished potency in cellular studies.

Designing all-inorganic double perovskites through element mixing is a promising strategy to enhance their optoelectronic performance and structural stability. The complex interplay between multilevel structures and optoelectronic properties in element-mixed double perovskites necessitates further in-depth theoretical exploration. In this study, we employ screening strategies and multiscale simulations combining first-principles methods and device-scale continuum models to identify two novel element-mixed compounds, Rb 2 AgInCl 3 I 3 and Cs 2 AgInCl 3 I 3 , as promising candidates for photovoltaic applications. These compounds exhibit favorable structural factors and suitable direct band gaps. Theoretical investigations using first-principles methods with the HSE06 functional reveal direct band gaps of 0.98 and 1.26 eV for Rb 2 AgInCl 3 I 3 and Cs 2 AgInCl 3 I 3 , respectively, with corresponding optical absorption coefficients exceeding 10 5 cm -1 in the visible light range. Cs 2 AgInCl 3 I 3 features high charge mobilities of approximately 20 cm 2 ·V -1 ·s -1 and a notable single-junction spectroscopic limited maximum efficiency (SLME) of 25.54%. Further analysis using the device-scale continuum model simulated the nonradiative recombination effects on power conversion efficiency, integrating quantum-mechanically calculated optoelectronic properties. These theoretical investigations, which bridge composition engineering with multiscale simulations, provide valuable insights into screening novel, lead-free, halogen - mixed double metal perovskite optoelectronic devices, highlighting their potential for high-performance solar energy applications.

An intramolecular organocatalytic cascade dearomatizing spirocycloaddition reaction of indole-ynone compounds containing O -silyl-naphthol substituents has been developed with the use of a chiral bifunctional thiourea. This process was able to provide various structurally diverse polycyclic spiroindolines in high yields (up to 98%) with excellent stereoselectivities (>20:1 dr, up to 98% ee) involving the formation of carbonylvinylidene ortho -quinone methide intermediates.

Li-rich Mn-based cathode materials (LRMO) are promising for enhancing energy density of all-solid-state batteries (ASSBs). Nonetheless, the development of efficient Li + /e - pathways is hindered by the poor electrical conductivity of LRMO cathodes and their incompatible interfaces with solid electrolytes (SEs). Herein, we propose a strategy of in - situ bulk/interfacial structure design to construct fast and stable Li + /e - pathways by introducing Li 2 WO 4 , which reduces the energy barrier for Li + migration and enhances the stability of the surface oxygen structure. The reversibility of oxygen redox was improved, and the voltage decay of the LRMO cathode was addressed significantly. As a result, the bulk structure of the LRMO cathodes and the high-voltage solid-solid interfacial stability are improved. Therefore, the ASSBs achieve a high areal capacity (∼3.15 mAh/cm 2 ) and outstanding cycle stability of ≥1200 cycles with 84.1% capacity retention at 1 C at 25 °C. This study offers new insights into LRMO cathode design strategies for ASSBs, focusing on ultrastable high-voltage interfaces and high-loading composite electrodes.