Ligand-Directed Shape Reconfiguration in Inorganic Materials.

Polymer elastomers with reversible shape-changing capability have led to significant development of artificial muscles, functional devices, and soft robots. By contrast, reversible shape transformation of inorganic nanoparticles is notoriously challenging due to their relatively rigid lattice structure. Here, the authors demonstrate the synthesis of shape-changing nanoparticles via an asymmetrical surface functionalization process. Various ligands are investigated, revealing the essential role of steric hindrance from the functional groups. By controlling the unbalanced structural hindrance on the surface, the as-prepared clay nanoparticles can transform their shape in a fast, facile, and reversible manner. In addition, such flexible morphology-controlled mechanism provides a platform for developing self-propelled shape-shifting nanocollectors. Owing to the ion-exchanging capability of clay, these self-propelled nanoswimmers (NS) are able to autonomously adsorb rare earth elements with ultralow concentration, indicating the feasibility of using naturally occurring materials for self-powered nanomachine.

The Stereochemical Course of DmdC, an Enzyme Involved in the Degradation of Dimethylsulfoniopropionate.

The acyl-CoA dehydrogenase DmdC is involved in the degradation of the marine sulfur metabolite dimethylsulfonio propionate (DMSP) through the demethylation pathway. The stereochemical course of this reaction was investigated through the synthesis of four stereoselectively deuterated substrate surrogates carrying stereoselective deuterations at the α- or the ß-carbon. Analysis of the products revealed a specific abstraction of the 2-pro-R proton and of the 3-pro-S hydride, establishing an anti elimination for the DmdC reaction.

The Biological Activities of Polyether Ionophore Antibiotic Routiennocin is Independent of Absolute Stereochemistry.

Carboxylic polyether ionophores (CPIs) are among the most prevalent agricultural antibiotics (notably in the US) and these compounds have been in use for decades. The potential to reposition CPIs beyond veterinary use, e. g. through chemical modifications to enhance their selectivity window, is an exciting challenge and opportunity, considering their general resilience towards resistance development. Given the very large societal impact of these somewhat controversial compounds, it is surprising that many aspects of their mechanisms and activities in cells remain unclear. Here, we report comparative biological activities of the CPI routiennocin and two stereoisomers, including its enantiomer. We used an efficient convergent synthesis strategy to access the compounds and conducted a broad survey of antibacterial activities against planktonic cells and biofilms as well as the compounds' effects on mammalian cells, the latter assessed both via standard cell viability assays and broad morphological profiling. Interestingly, similar bioactivity of the enantiomeric pair was observed across all assays, strongly suggesting that chiral interactions do not play a decisive role in the mode of action. Overall, our findings are consistent with a mechanistic model involving highly dynamic behaviour of CPIs in biological membranes.

Evaluation of the stereochemical quality of predicted RNA 3D models in the RNA-Puzzles submissions.

In silico prediction is a well-established approach to derive a general shape of an RNA molecule based on its sequence or secondary structure. This paper reports an analysis of the stereochemical quality of the RNA three-dimensional models predicted using dedicated computer programs. The stereochemistry of 1052 RNA 3D structures, including 1030 models predicted by fully automated and human-guided approaches within 22 RNA-Puzzles challenges and reference structures, is analyzed. The evaluation is based on standards of RNA stereochemistry that the Protein Data Bank requires from deposited experimental structures. Deviations from standard bond lengths and angles, planarity, or chirality are quantified. A reduction in the number of such deviations should help in the improvement of RNA 3D structure modeling approaches.

Breaking Cycles: Saponification-Enhanced NMR Fingerprint Matching for the Identification and Stereochemical Evaluation of Cyclic Lipodepsipeptides from Natural Sources.

We previously described NMR based fingerprint matching with peptide backbone resonances as a fast and reliable structural dereplication approach for Pseudomonas cyclic lipodepsipeptides (CLiPs). In combination with total synthesis of a small library of configurational CLiP congeners this also allows unambiguous determination of stereochemistry, facilitating structure-activity relationship studies and enabling three-dimensional structure determination. However, the on-resin macrocycle formation in the synthetic workflow brings considerable burden and limits universal applicability. This drawback is here removed altogether by also transforming the native CLiP into a linearized analogue by controlled saponification of the ester bond. This eliminates the need for macrocycle formation, limiting the synthesis effort to linear peptide analogues. NMR fingerprints of such linear peptide analogues display a sufficiently distinctive chemical shift fingerprint to act as effective discriminators. The approach is developed using viscosin group CLiPs and subsequently demonstrated on putisolvin, leading to a structural revision, and tanniamide from Pseudomonas ekonensis COR58, a newly isolated lipododecapeptide that defines a new group characterized by a ten-residue large macrocycle, the largest to date in the Pseudomonas CLiP portfolio. These examples demonstrate the effectiveness of the saponification- enhanced approach that broadens applicability of NMR fingerprint matching for the determination of the stereochemistry of CLiPs.

Asymmetric Synthesis with Organoselenium Compounds - The Past Twelve Years.

The discovery and synthetic applications of novel organoselenium compounds and their reactions proceeded rapidly during the past fifty years and such processes are now carried out routinely in many laboratories. At the same time, the growing demand for new enantioselective processes provided new challenges. The convergence of selenium chemistry and asymmetric synthesis led to key developments in the 1970s, although the majority of early work was based on stoichiometric processes. More recently, greater emphasis has been placed on greener catalytic variations, along with the discovery of novel reactions and a deeper understanding of their mechanisms. The present review covers the literature in this field from 2010 to early 2023 and encompasses asymmetric reactions mediated by chiral selenium-based reagents, auxiliaries, and especially, catalysts. Protocols based on achiral selenium compounds in conjunction with other species of chiral catalysts, as well as reactions that are controlled by chiral substrates, are also included.

Nucleophilic Substitution at Phosphorus Centres - Old and Recent Studies and a Final Solution of Mechanistic and Related Stereochemical Problems.

Among many problems of a fundamental value in the heteroatom chemistry the mechanism and stereochemistry of the nucleophilic substitution reaction at the phosphorus and other heteroatom centres have attracted great attention of phosphorus chemists already in the middle of the last century. This review, which does not have a comprehensive character, summarizes the selected original contributions aimed at solution of the mechanism of SN2-P reaction and its relationship with stereochemistry. The breakthrough in these studies was the Westheimer's concept and his rules which is presented at the beginning of this article. Next, a series of papers is presented where the stereochemistry of the substitution at phosphorus was investigated in cyclic five-, four- and six-membered ring phosphorus compound. The majority of these reactions have been found to occur with retention of the P-configuration. In the third part of this account, the selected examples of substitution reactions at phosphorus in acyclic compounds are discussed. As the results of all the investigations discussed did not allow to undoubtedly ascribe the mechanism (SN2 or A-E) to the investigated reactions, in the last part the SN-P reactions are presented, the mechanism of which has been established by combination of the stereochemical and DFT-studies.

Counting the truxillines-11 or more, the question is now.

Truxillines are a group of tropane alkaloids present in coca leaves that are formed by photochemical dimerization of cinnamoylcocaine(s). Proportion of different truxilline forms present in cocaine serves as its geographical, manufacture, and storage "fingerprint"; thus, the quantitative determination of truxilline content represents one of the powerful methods of analysis and characterization of cocaine samples. Contrary to the statements repeatedly presented in the literature, namely, that there exist exactly 11 truxillines and that every single truxilline is diastereomer of any other, here we show that, in fact, a total of 15 truxillines exist, which can be divided in two structurally isomeric groups-five mutually diastereomeric truxillates and 10 mutually diastereomeric truxinates.

Chirality-matched catalyst-controlled macrocyclization reactions.

Macrocycles, formally defined as compounds that contain a ring with 12 or more atoms, continue to attract great interest due to their important applications in physical, pharmacological, and environmental sciences. In syntheses of macrocyclic compounds, promoting intramolecular over intermolecular reactions in the ring-closing step is often a key challenge. Furthermore, syntheses of macrocycles with stereogenic elements confer an additional challenge, while access to such macrocycles are of great interest. Herein, we report the remarkable effect peptide-based catalysts can have in promoting efficient macrocyclization reactions. We show that the chirality of the catalyst is essential for promoting favorable, matched transition-state relationships that favor macrocyclization of substrates with preexisting stereogenic elements; curiously, the chirality of the catalyst is essential for successful reactions, even though no new static (i.e., not "dynamic") stereogenic elements are created. Control experiments involving either achiral variants of the catalyst or the enantiomeric form of the catalyst fail to deliver the macrocycles in significant quantity in head-to-head comparisons. The generality of the phenomenon, demonstrated here with a number of substrates, stimulates analogies to enzymatic catalysts that produce naturally occurring macrocycles, presumably through related, catalyst-defined peripheral interactions with their acyclic substrates.

Reanalysis of a µ opioid receptor crystal structure reveals a covalent adduct with BU72.

BACKGROUND: The first crystal structure of the active µ opioid receptor (µOR) exhibited several unexplained features. The ligand BU72 exhibited many extreme deviations from ideal geometry, along with unexplained electron density. I previously showed that inverting the benzylic configuration resolved these problems, establishing revised stereochemistry of BU72 and its analog BU74. However, another problem remains unresolved: additional unexplained electron density contacts both BU72 and a histidine residue in the N-terminus, revealing the presence of an as-yet unidentified atom. RESULTS: These short contacts and uninterrupted density are inconsistent with non-covalent interactions. Therefore, BU72 and µOR form a covalent adduct, rather than representing two separate entities as in the original model. A subsequently proposed magnesium complex is inconsistent with multiple lines of evidence. However, oxygen fits the unexplained density well. While the structure I propose is tentative, similar adducts have been reported previously in the presence of reactive oxygen species. Moreover, known sources of reactive oxygen species were present: HEPES buffer, nickel ions, and a sequence motif that forms redox-active nickel complexes. This motif contacts the unexplained density. The adduct exhibits severe strain, and the tethered N-terminus forms contacts with adjacent residues. These forces, along with the nanobody used as a G protein substitute, would be expected to influence the receptor conformation. Consistent with this, the intracellular end of the structure differs markedly from subsequent structures of active µOR bound to Gi protein. CONCLUSIONS: Later Gi-bound structures are likely to be more accurate templates for ligand docking and modelling of active G protein-bound µOR. The possibility of reactions like this should be considered in the choice of protein truncation sites and purification conditions, and in the interpretation of excess or unexplained density.

Deciphering the Absolute Configuration of Murgantiol Isomers in the Pheromone Blend of the Rice Stink Bug, Mormidea v-luteum (Hemiptera, Pentatomidae).

The males-produced pheromone blend of the Mormidea v-luteum (Hemiptera, Pentatomidae) consists in two isomers of zingiberenol (1) and three of murgantiol (2). While the absolute configuration of the zingiberenol isomers has been described, the configurations of the murgantiol isomers remained unexplored. So, our objective was to identify the absolute configuration of the murgantiol isomers (2 a-c) in the pheromone blend. To achieve this, we initially performed dehydration of the natural extract followed by enantiomeric resolution and, as a result, the three isomers was identified as (4R,1'S)-murgantiol. By leveraging the fixed cis and trans relationships among all pheromone components, we established the configuration at C-1 for isomers 2 a and 2 b is S, while that of 2 c is R. Finally, employing microchemical Sharples asymmetric dihydroxylation and epoxide ring closure, we determined the absolute configuration of the epoxide ring. Consequently, the natural isomers 2 a, 2 b, and 2 c were identified as (1S,4R,1'S,4'R)-, (1S,4R,1'S,4'S)-, and (1R,4R,1'S,4'S)-murgantiol, respectively.

Discovery of internal rotation and conformers of 1,2-dichloroethane: the dawn of the concept of conformation.

In 1932, Mizushima and Higasi reported the dependence of the dipole moments of 1,2-dichloroethane on both temperature and solvent in the Proceedings of the Imperial Academy, Japan. This report was followed by their first proposal of the existence of conformers that exchanged by internal rotation about a C-C single bond based on experimental data. Their monumental work marked the beginning of the essential concept of conformation in modern stereochemistry. Their proposal was later confirmed by the direct observation of the anti and gauche conformers of 1,2-dichloroethane by Raman spectroscopy, and further supported by other experimental and theoretical methods. The relative stabilities of the anti and gauche conformers of 1,2-dichloroethane and other 1,2-disubstituted ethanes were discussed in terms of steric, electrostatic, and stereoelectronic effects based on analysis of calculated data. Those studies influenced the development of subsequent research in organic chemistry, such as the conformational analysis of cyclohexane derivatives and the isolation of chiral gauche conformers.

A new flavonolignan from milk thistle (Silybum marianum).

A new flavonolignan, sonyamandin (1), along with other known compounds was isolated from the aerial parts and seeds extracts of Silybum marianum (milk thistle) collected from Jordan. The known ones are ursolic acid (2), oleanolic acid (3), maslinic acid (4), oleic acid (5), ß-sitosterol (6), ß-, sitosteryl glucoside (7), apigenin (8), kaempferol-3-O-rhamnoside (9), apigenin-7-O-ß-D-glycoside (10), isosylibin A (11), isosylibin B (12), and silybin B (13). The absolute stereochemistry of 1 was confirmed by 2D NMR and CD analysis.

Stereoselective Ring-opening Polymerization of S-Carboxyanhydrides Using Salen Aluminum Catalysts: A Route to High-Isotactic Functionalized Polythioesters.

Polythioesters are important sustainable polymers with broad applications. The ring-opening polymerization (ROP) of S-Carboxyanhydrides (SCAs) can afford polythioesters with functional groups that are typically difficult to prepare by ROP of thiolactones. Typical methods involving organocatalysts, like dimethylaminopyridine (DMAP) and triethylamine (Et3 N), have been plagued by uncontrolled polymerization, including epimerization for most SCAs resulting in the loss of isotacticity. Here, we report the use of salen aluminum catalysts for the selective ROP of various SCAs without epimerization, affording functionalized polythioester with high molecular weight up to 37.6 kDa and the highest Pm value up to 0.99. Notably, the ROP of TlaSCA (SCA prepared from thiolactic acid) generates the first example of a isotactic crystalline poly(thiolactic acid), which exhibited a distinct Tm value of 152.6 °C. Effective ligand tailoring governs the binding affinity between the sulfide chain-end and the metal center, thereby maintaining the activity of organometallic catalysts and reducing the occurrence of epimerization reactions.

Changing Liquid Crystal Helical Pitch with a Reversible Rotaxane Switch.

The transmission of chiral information between the molecular, meso and microscopic scales is a facet of biology that remains challenging to understand mechanistically and to mimic with artificial systems. Here we demonstrate that the dynamic change in the expression of the chirality of a rotaxane can be transduced into a change in pitch of a soft matter system. Shuttling the position of the macrocycle from far-away-from to close-to a point-chiral center on the rotaxane axle changes the expression of the chiral information that is transmitted across length scales; from nanometer scale constitutional chirality that affects the conformation of the macrocycle, to the centimeter scale chirality of the liquid crystal phase, significantly changing the pitch length of the chiral nematic structure.

One Collision-Two Substituents: Gas-Phase Preparation of Xylenes under Single-Collision Conditions.

The fundamental reaction pathways to the simplest dialkylsubstituted aromatics-xylenes (C6 H4 (CH3 )2 )-in high-temperature combustion flames and in low-temperature extraterrestrial environments are still unknown, but critical to understand the chemistry and molecular mass growth processes in these extreme environments. Exploiting crossed molecular beam experiments augmented by state-of-the-art electronic structure and statistical calculations, this study uncovers a previously elusive, facile gas-phase synthesis of xylenes through an isomer-selective reaction of 1-propynyl (methylethynyl, CH3 CC) with 2-methyl-1,3-butadiene (isoprene, C5 H8 ). The reaction dynamics are driven by a barrierless addition of the radical to the diene moiety of 2-methyl-1,3-butadiene followed by extensive isomerization (hydrogen shifts, cyclization) prior to unimolecular decomposition accompanied by aromatization via atomic hydrogen loss. This overall exoergic reaction affords a preparation of xylenes not only in high-temperature environments such as in combustion flames and around circumstellar envelopes of carbon-rich Asymptotic Giant Branch (AGB) stars, but also in low-temperature cold molecular clouds (10 K) and in hydrocarbon-rich atmospheres of planets and their moons such as Triton and Titan. Our study established a hitherto unknown gas-phase route to xylenes and potentially more complex, disubstituted benzenes via a single collision event highlighting the significance of an alkyl-substituted ethynyl-mediated preparation of aromatic molecules in our Universe.

Regioselective Oxidative Phenol Coupling by a Mushroom Unspecific Peroxygenase.

Bioactive dimeric (pre-)anthraquinones are ubiquitous in nature. Their biosynthesis via an oxidative phenol coupling (OPC) step is catalyzed by either cytochrome P450 enzymes, peroxidases, or laccases. While the biocatalysis of OPC in molds (Ascomycota) is well-known, the respective enzymes of mushroom-forming fungi (Basidiomycota) are still unknown. Here, we report on the biosynthesis of the atropisomers phlegmacin A1 and B1, unsymmetrical 7,10'-homo-coupled dihydroanthracenones of the mushroom Cortinarius odorifer. The biosynthesis was heterologously reconstituted in the mold Aspergillus niger. We show that methylation of the dimeric (pre-)anthraquinone building block atrochrysone to its 6-O-methyl ether torosachrysone by the O-methyltransferase (CoOMT1) precedes the regioselective homo-coupling to phlegmacin, catalyzed by an unspecific peroxygenase (CoUPO1). Our results revealed an unprecedented UPO-mediated unsymmetric OPC reaction, thereby expanding the biocatalytic portfolio of OPC-type reactions beyond the commonly reported enzymes. The findings highlight the pivotal role of OPC in natural processes, demonstrating that Basidiomycota employed peroxygenases to develop the ability to selectively couple aryls, distinct and convergent to any other group of organisms.

Kinetic Resolution Polymerization Enabled Chemical Synthesis of Perfectly Isotactic Polythioesters.

Isotactic polythioesters (PTEs) that are thioester analogs to natural polyhydroxyalkanoates (PHAs) have attracted growing attention due to their distinct properties. However, the development of chemically synthetic methods for preparing isotactic PTEs has long been an intricate endeavour. Herein, we report the successful synthesis of perfectly isotactic PTEs via stereocontrolled ring-opening polymerization. This binaphthalene-salen aluminium (SalBinam-Al) catalyst promoted a robust polymerization of rac-α-substituted-ß-propiothiolactones (rac-BTL and rac-PTL) with highly kinetic resolution, affording perfectly isotactic P(BTL) and P(PTL) with Mn up to 276 kDa. Impressively, the isotactic P(BTL) formed a supramolecular stereocomplex with improved thermal property (Tm=204 °C). Ultimately, this kinetic resolution polymerization enabled the facile isolation of enantiopure (S)-BTL, which could efficiently convert to an important pharmaceutical building block (S)-2-benzyl-3-mercapto-propanoic acid. Isotactic P(PTL) served as a tough and ductile material comparable to the commercialized polyolefins. This synthetic system allowed to access of isotactic PTEs, establishing a powerful platform for the discovery of sustainable plastics.

Stereoinvertive SN1 Through Neighboring Group Participation.

Neighboring group participation, the assistance of non-conjugated electrons to a reaction center, is a fundamental phenomenon in chemistry. In the framework of nucleophilic substitution reactions, neighboring group participation is known to cause rate acceleration, first order kinetics (SN1), and retention of configuration. The latter phenomenon is a result of double inversion: the first one when the neighboring group displaces the leaving group, and the second when a nucleophile substitutes the neighboring group. This powerful control of stereoretention has been widely used in organic synthesis for more than a century. However, neighboring group participation may also lead to inversion of configuration, a phenomenon which is often overlooked. Herein, we review this unique mode of stereoinversion, dividing the relevant reactions into three classes with the aim to introduce a fresh perspective on the different modes of stereoinversion via neighboring group participation as well as the factors that control this stereochemical outcome.

Synthesis, Structures and Properties of Trioxa[9]circulene and Diepoxycyclononatrinaphthalene.

This article presents trioxa[9]circulene (3) as a novel member of hetero[n]circulenes. Its synthesis began with the synthesis of dimethoxydioxa[8]helicene (5) and used dimethoxydiepoxycyclononatrinaphthalene (4) as a key intermediate, despite the condensation reaction predominantly yielding a 1,4-addition byproduct. The structures and properties of 3-5 were extensively investigated using experimental and computational methods. Analysis of the crystal structures reveal elongation of the internal C-C bonds in the nine-membered ring of 3 compared to 4 and 5. Computational studies demonstrate the remarkable flexibility of trioxa[9]circulene's saddle-shaped polycyclic framework, while the other two compounds are rigid with large racemization barriers. Optically pure forms of 4 and 5 exhibit absorption and luminescence dissymmetry factors on the order of 10-2, with smaller values observed for compound 4. In the crystal structures, molecules of 3 stack to form columns with remarkable π-π overlap, and the π-π interactions of 4 exhibit short intermolecular C-to-C contacts. Consequently, the solution-processed film of 4 functioned as a p-type organic semiconductor in field effect transistors.