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The Bürgenstock Conference is a prestigious symposium in organic chemistry that has been running since 1965. The conference is known for its exclusive and luxurious venue, limited number of participants, and undisclosed program. Due to the Covid pandemic, the conference was postponed for two years, but it finally took place in 2023. The conference featured 13 plenary speakers who shared their latest research and knowledge in various areas of chemistry. The conference also honored Prof. Andreas Pfaltz as a Guest of Honor for his contributions to asymmetric catalysis. The special issue of Helvetica Chimica Acta commemorates the 56th Bürgenstock conference. [Extracted from the article]

This document is an introduction to a special collection of papers in honor of Robert Deschenaux, a chemist who made significant contributions to the field of soft materials. Deschenaux was born in Switzerland in 1957 and obtained his PhD in chemistry in 1983. Throughout his career, he conducted research on various topics including metal complexes, liquid-crystalline materials, and dendrimers. Deschenaux also played a role in teaching and promoting chemistry. The special collection of papers was organized to celebrate his retirement and his outstanding contributions to the field. [Extracted from the article]

Lukas Hintermann Guest Editor Technische Universität München Footnotes 1 "Tagesgespräche: Antonio Togni zum Uno-Jahr der Chemie", Schweizer Radio und Fernsehen (SRF), 15.2.2011; SRF Tagesschau 3.3.2019: "Interview-Sequenzen über 150 Jahre Periodensystem". On January 14, 2021, I Antonio Togni i , full professor of organometallic chemistry at ETH Zurich ( I Figure i 1), reached an important and inevitable milestone of his career, namely his 65th birthday, and, as a consequence, retirement. [Extracted from the article]

In this short essay, I re‐emphasize the inter‐relationship between mentoring doctoral students or postdocs and the never ending problem of assessing the quality of scientific outputs. It includes the plea to mentees and mentors not to employ an overblown language in papers, posters and lectures, which constitute a gross exaggeration of the true state of affairs. Doubt is also cast on the present use of Hirsch‐factors and other bibliometric data as well as certain social media claiming to be effective in assessing scientific quality. [ABSTRACT FROM AUTHOR]

Amines, crucial components in various industries, play a pivotal role in the synthesis of pharmaceuticals, agrochemicals, and specialty chemicals. Recognizing the environmental impact of conventional methods for their preparation, our study centers on the utilization of abundantly available natural molecules, specifically amino acids, as precursors for short chain amine synthesis. This paper focuses on the biocatalyst, L‐valine decarboxylase from Streptomyces viridifaciens (VlmD), delving into the substrate scope, catalytic activity, and cost‐effective scalability of an enzymatic process for amine synthesis. Additionally, we investigate the feasibility of immobilizing VlmD, aiming to pave the way for its effective use in industrial applications. Our study exploits the SpinChem system and provides a comprehensive understanding of the potential and limitations of this biocatalyst. Notably, our yields for key amines (8.42 g ⋅ d−1 for isobutylamine, 5.23 g ⋅ d−1 for isoamylamine, 5.16 g ⋅ d−1 for (S)‐2‐methylbutylamine, 3.78 g ⋅ d−1 for 3‐(methylthio)propylamine, and 10.52 g ⋅ d−1 for (R)‐1‐amino‐2‐propanol) demonstrate the process efficiency and potential for industrial scalability. [ABSTRACT FROM AUTHOR]

Achieving the lowest phase transition temperature with minimal chemical modification in highly crystalline π‐conjugated molecules is a universal problem in related research fields. This paper reports room‐temperature liquefication of diphenylpyrene isomers by introducing bulky yet flexible branched alkyl chains through molecular desymmetrization. Six isomers with different symmetries depending on the positions of the phenyl groups and alkyl groups were synthesized, and three of the isomers were found to be liquids at 25 °C, a state in which they have remained for more than five years. Although it is generally believed that the lower the symmetry of a molecule, the less likely it is to crystallize, one molecule with a relatively high molecular symmetry unexpectedly did not crystallize, which was evidenced by the kinetic inhomogeneity of this amorphous material (practically stable liquid) assessed by rheological analysis. [ABSTRACT FROM AUTHOR]

Recently, the application of magnetic fields to chiral chemical systems has been rewarding. In a forward‐looking 1986 paper, 'Chiral Metals?', Wallis, Karrer, and Jack D. Dunitz forecast 'that the limitation to proper symmetry elements in a chiral conductor could be associated with the emergence of new properties, those connected with interactions between applied electric and magnetic fields and their internal counterparts.' This was a prescient remark, but it has become manifest in ways that would not have been foreseen in its details by the authors. Here are reviewed the development of chiral conductors broadly imagined by Dunitz and coworkers, based on enantiopure tetrathiafulvalene derivatives that restrict space groups to those that have only symmetry operations of the first kind, as well as the new emergent properties associated with the transport of electrons when magnetic fields are applied to chiral crystals among other systems. These include electrical magnetochiral anisotropy (eMChA), inverse electrical magnetochiral anisotropy (ieMChA), helimagnetism and chirality induced spin selectivity (CISS). The conclusion discussing the circumstances under which achiral TTF crystals becomes chiral, only seems to introduce an oxymoron. [ABSTRACT FROM AUTHOR]

The development of water‐soluble hosts for the selective recognition of aromatic amino acids is highly desirable and may serve as a tool to facilitate drug discovery and enable fabrication of sensors for point‐of‐care monitoring in the context of phenylketonuria disease. This paper presents the synthesis and characterization of a water‐soluble molecular cleft which is demonstrated to selectively bind aromatic amino acid guests over other amino acids in aqueous medium, favoring ʟ‐Trp over ʟ‐Phe and ʟ‐Tyr by a factor of approximately five. Host/guest‐interaction forces were studied by 1H‐NMR titrations complemented by fluorescence titrations and isothermal titration calorimetry. The here presented results provide a starting point for future optimizations in our efforts to selectively identify and quantify individual aromatic amino acids in aqueous medium. [ABSTRACT FROM AUTHOR]

Software from the MiCMoS Molecular Simulation platform (sites.unimi.it/xtal_chem_group/) and from the CryGen set of programs (www.angelogavezzotti.it) is used to prepare a molecular structure from a line formula for a non‐existent molecule, dubbed 'fakein'. Possible crystal structures are generated in chiral space groups P21 and P212121, and for racemate in space groups P1− and P21/c. Lattice energies and crystal densities are in line with experimental values for organic molecules. Chiral crystals are less stable, and may not easily form hydrogen bonds, while bulk crystal stabilization is provided mostly by polarization‐dispersion. Hydrogen bonding and crystal packing are discussed in terms of molecular pairing modes. Links to possible experiments and to absolute crystal structure prediction are outlined, but the main aim here is to demonstrate that relevant solid‐state information can be derived if that goal is not achieved, actually even if the real substance is not available. [ABSTRACT FROM AUTHOR]

The secret of being a successful scientist is to work hard and to always believe in yourself and your ideas. My four top papers 1 G. Schäfer, T. Fleischer, M. Ahmetovic, S. Abele, 'Development of a Scalable Route for a Key Thiadiazole Building Block via Sequential Sandmeyer Bromination and Room-Temperature Suzuki-Miyaura Coupling', Org. 2 G. Schäfer, M. Ahmetovic, S. Abele, 'Scalable Synthesis of Trifluoromethylated Imidazo-Fused N-Heterocycles Using TFAA and Trifluoroacetamide as CF 3 -Reagents', Org. [Extracted from the article]

In depth headspace analysis of the slow degradation of β‐alkylthioalkanones in ambient air led to the discovery of a novel δ‐cleavage pathway, by which β‐mercaptoketones are released. Since β‐mercaptoketones are potent natural aroma compounds occurring in many fruits, herbs and flowers, the discovery of an enzyme‐independent molecular precursor for this class of high‐impact molecules is of practical importance. Moreover, the formation of β‐diketones and aldehydes by concomitant oxidation at the α‐sulfur‐position enhances the versatility of this class of aroma precursors. A mechanistic model is proposed which suggests that the oxidative degradation occurs through a novel Pummerer‐type rearrangement of initially formed persulfoxides. [ABSTRACT FROM AUTHOR]

Poly(ADP‐ribose)polymerase‐1 (PARP‐1) is a promising target for antitumor agents. This study presents the first evidence of hydroxamic acids as efficient PARP inhibitors. Molecular docking and molecular dynamics simulations revealed that N−O substituted phenanthridinones form a complex interplay with PARP‐1. A series of cyclic aryl hydroxamic acids, N‐(benzyloxy)‐ and N‐(hydroxy)phenanthridinones, were prepared through a ligand‐free methodology from N‐(benzyloxy)benzamides using dual C−H/N−H bond activation. Three of the computed hit compounds exhibited significant activity in cell‐based and enzymatic assays, inhibiting PARP‐1 in the low‐nanomolar range. The antiproliferative activity of all prepared compounds and the reference compounds PJ34 and Olaparib was evaluated in cancer cells (HepG2, BxPC3, MDA‐MD‐231, and HeLa) and in noncancer cell lines (NIH 3T3 and HEK 293). An N‐(benzyloxy)‐ and an N‐(hydroxy)phenanthridinone showed the most promising properties as leads for developing therapeutics with a submicromolar activity window. The study highlights the potential utility of this scaffold for PARP inhibitors and the importance of target‐specific design to minimize toxicity and side effects. [ABSTRACT FROM AUTHOR]

2‐(3‐Bromophenyl)‐2H‐1,2,3‐triazole is a low molecular‐weight building block that is not readily accessible in pure form by standard synthetic approaches due to competing formation of the triazol‐1‐yl regioisomer. After investigation of a wide range of synthetic routes, a process based on construction of the triazole heterocycle by cyclization of an activated dihydrazone was developed. A suitable isolation method had to be identified before embarking on a demonstration run on >100 g scale without the need for chromatography. The new process delivered the desired building block in 48 % overall yield over four telescoped steps with excellent purity (99 % a/a). [ABSTRACT FROM AUTHOR]

The research efforts to attain a suitable process for the timely delivery of Gemlapodect for initial toxicological and phase 1/2 clinical studies are described. The original discovery chemistry route was hampered by considerable safety issues and low overall yield. The safety issues were solved by the introduction of a copper‐catalyzed oxidative cyclization while a novel process for the synthesis of the pyrazole building block as well as the implementation of a palladium‐catalyzed coupling between the pyrazole amide and the bromo‐triazolopyridine scaffolds contributed to improve the route efficiency. Overall, a safe and sustainable process was attained that allowed the production of up to 19.2 kg of drug substance with a reduced number of steps and an increased overall yield. [ABSTRACT FROM AUTHOR]

The immobilization of Rose Bengal onto Merrifield resin and its application in the light‐driven metal‐free thiocyanation of azaheterocycles in continuo were investigated. The supported photocatalyst was used in batch reactions under heterogeneous conditions, with different azaheterocycles, and proved to efficiently promote the reaction. Its recovery and recycle were also demonstrated for up to four times. The resin‐supported Rose Bengal was then employed under continuous flow conditions, affording thiocyanate functionalized azaheterocycles with higher space‐time‐yields than the in‐batch transformations, and in a shorter reaction time. The easily modification of the SCN groups was also demonstrated by synthetizing trifluoromethyl thioethers and sulfenyl tetrazoles derivates in high yields. [ABSTRACT FROM AUTHOR]

Strigolactones are one of the phytohormones, which have multiple activities on plant growth and development. Since these strigolactone activities are highly associated with crop yield, use of strigolactone could be a promising technology in modern sustainable agriculture. The major strigolactones in corn root exudates have been identified as zealactone 1a/b and zeapyranolactone. We recently disclosed the first total synthesis of zealactone 1a/b together with its biological activity in corn. Herein, we describe the design and synthesis of simplified analogues of both corn‐derived strigolactones with their bioavailability in soil and their biological activities. These compounds would be potential leads for the development of synthetic strigolactones for the agronomical use in a more sustainable crop production. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are an important family of molecules in science and technology. Amino‐substituted PAHs are promising building blocks to create attractive molecules for materials science. However, the synthetic limitations have hampered to produce diverse structures of amino‐substituted PAHs. Here we describe a novel efficient synthetic method to access amino‐substituted PAHs through the electrocyclization of highly reactive keteniminium species. We demonstrated the synthesis of various amino‐substituted PAHs and disclosed some of their photophysical properties. Furthermore, combination with theoretical calculation revealed that the multiple electrocyclization reactions of keteniminium species is a stepwise process and the fusion of additional aromatic ring to the substrate accelerates the electrocyclization. [ABSTRACT FROM AUTHOR]

This work examines theoretically the problem of the migration of borane groups between the nitrogen atoms of pyrazolyl rings. We have studied as a model the BH2 pyrazol‐1‐yl derivatives to determine the effects of substituents on the pyrazole ring; also 1‐(9‐borabicyclo[3.3.1]nonan‐9‐yl)‐1H‐pyrazoles to compare the calculated barriers with the experimental ones as well as to determine steric effects, i. e., how the buttressing effect increases the rate. The interacting quantum atoms methodology has been used for partitioning the energy of the systems in their stationary points into the contribution of pyrazole and BH2 group and their mutual interaction. [ABSTRACT FROM AUTHOR]

The investigation of the biphenylene (BP)‐tetracyanoethylene (TCNE) π‐molecular complex is reported. The first study on this complex appeared in 1961 and was considered as a charge transfer complex with a symmetric, co‐planar arrangement of the components. Moreover, it was assumed that this arrangement is not only dictated by the formation of a Mulliken‐type donor‐acceptor complex, but also by the electronic stabilization of the 'cyclobutadieneoid' central ring of biphenylene through complex formation. Yet, crystal structure and associated computational analysis have not verified these predictions so far. We found that factors other than charge‐transfer interactions are most influential in the crystal formation. The low association constant in solution, and the weak interaction between the components in the 1 : 1 crystal structure point towards the low contribution of charge transfer interactions to their binding. Nevertheless, the presence of these interaction is hinted by the color of its solution and verified by theoretical calculations. Furthermore, Nucleus Independent Chemical Shift (NICS) calculations were carried out to characterize potential changes in the (anti)aromatic character of BP upon complex formation. The NICS(0) values of the rings of BP exhibit tiny changes both in the BP‐TCNE dimer and in the crystal, which also suggests weak electronic interactions between them. [ABSTRACT FROM AUTHOR]

The synthesis by transmetallation and in‐depth characterisation by IR spectroscopy of five half‐sandwich ruthenium and osmium dithiocarbamato isonipecotamide glycoconjugate complexes are presented herein. The evaluation of their in vitro cytotoxicity and of the zinc precursors' in vitro cytotoxicity towards ovarian cancer (A2780 and A2780cisR) and normal prostate (PNT2) cells is reported. While the cytotoxicity of the compounds is rather limited, some selectivity is observed. [ABSTRACT FROM AUTHOR]

In the past few years, there has been significant interest within the forensic community regarding the deployment of portable solutions that provide real‐time results. This article introduces an innovative technology or technology architecture that enables the integration of a handheld device, specifically, Viavi MicroNIR, with a cloud‐based system. This cloud system encompasses a server responsible for data processing and a mobile application acting as a user interface. To demonstrate the transformative impact of this technology on field operators, the analysis of cannabis specimens has been utilized. System's capacity to distinguish between CBD‐type and THC‐type cannabis has been particularly highlighted, along with the remarkable congruence observed between the near‐infrared (NIR) spectra and the reference analytical method involving ultra‐high‐performance liquid chromatography (UHPLC) The article will present the advantages of this application primarily focusing on its potential to alleviate the burden on laboratories by expediting routine illicit drug analysis. Viavi MicroNIR technology provides laboratory personnel with additional time to handle more complex cases, thereby enhancing overall efficiency. [ABSTRACT FROM AUTHOR]

With the aim of achieving bioorthogonal intracellular catalysis, a library of platinum(II) complexes was synthesized. Their non‐toxicity to living cells was demonstrated and their catalytic activity was evaluated on a cyclization reaction leading to a highly fluorescent coumarin. None of the platinum complexes showed any catalytic activity for coumarin synthesis. Still, we demonstrated that the silver salt AgSbF6 commonly used to 'activate' metal catalysts by removing a chloride is a very efficient catalyst for the studied intramolecular cyclization reaction. [ABSTRACT FROM AUTHOR]

Liquid Crystals are thought of as being complex fluids, underpinned by self‐assembly and self‐organisation within partially ordered fluids, and which sit between solid and liquid states of matter. The realm of the field stretches from low molar mass to polymeric materials, from organic to inorganic substances, and from being functional materials to biological organelles. In this article, we explore the cusp of the change over from nano‐ to macro‐sciences through the formation of 'supermolecular' systems, and we debate if such materials are in fact oligomers or materials having giant molecules possessing discrete chemical constitutions? We performed this investigation by synthesising mesogenic materials based upon difluoroterphenyls, terminally substituted with a chiral motif based on (S)‐2‐octanol, and which could be appended onto a variety of siloxane scaffolds. We studied the structures and properties of six mesomorphic materials in which we systematically increased the number of mesogenic units attached to the scaffold. [ABSTRACT FROM AUTHOR]

Lilybelle and Biomuguet are currently the only renewable and biodegradable non‐spermotoxic Lilial replacers. Being non‐aromatic, these lack however some of the green, aquatic aspects of Lilial that are present in the captive odorant Nympheal, 3‐(4‐isobutyl‐2‐methylphenyl)propanal, which is not available from renewable resources. Therefore, the influence of the aromatic nucleus on the odor of four new hydrogenated Nympheal derivatives was investigated, which were all accessible from the isobutyl Hagemann's ester that was synthesized in 75 % yield from isovaleraldehyde with two equivalents of ethyl acetoacetate. The respective Hagemann's ester was alkylated with 3‐bromopropanal dimethyl acetal and subjected to decarboxylative saponification, followed by hydride reduction and dehydration through the corresponding mesylate to furnish, after deprotection with formic acid, the corresponding exo‐ and endo‐dihydro‐Nympheal derivative. Full or partial hydrogenation of the central acetal‐protected intermediate provided after deprotection the analogous fully saturated analogue or the cyclohexene derivative. The olfactory properties of these four novel Nympheal derivatives are discussed and rationalized by computational olfactophore models. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials have attracted the attention of the scientific community for more than 30 years now; first with fullerene, then with nanotubes and now with graphene and graphene related materials. Graphene quantum dots (GQDs) are nanoparticles of graphene that can be synthesized following two approaches, namely top‐down and bottom‐up methods. The top‐down synthesis used harsh chemical and/or physical treatments of macroscopic graphitic materials to obtain nanoparticles, while the second is based on organic chemistry through the synthesis of polycyclic aromatic hydrocarbons exhibiting various sizes and shapes that are perfectly controlled. The main drawback of this approach is related to the low solubility of carbon materials that prevents the synthesis of nanoparticles containing more than few hundreds of sp2 carbon atoms. Here we report on the synthesis of a family of rectangular‐shaped graphene quantum dots containing up to 162 sp2 carbon atoms. These graphene quantum dots are not functionalized on their periphery in order to keep the maximum similarity with nanoparticles of pure graphene. We chose water with sodium deoxycholate surfactant to study their dispersion and their optical properties (absorption, photoluminescence and photoluminescence excitation). The electronic structure of the particles and of their aggregates are studied using Tight‐Binding (TB). We observe that the larger particles (GQD 3 and GQD 4) present a slightly better dispensability than the smaller ones, probably because the larger GQDs can accommodate more surfactant molecules on each side, which helps to stabilize their dispersion in water. [ABSTRACT FROM AUTHOR]

Here we redesigned the branches of polyamidoamine (PAMAM) dendrimers by moving the amide carbonyl group on the other side of the amide nitrogen atom, transforming the β‐alaninyl‐amidoethylamine branch, which easily undergoes retro‐Michael reactions and renders PAMAMs intrinsically unstable, into a more stable glycyl‐amidopropylamine branch. The resulting inverse PAMAM (i‐PAMAM) dendrimers have the same carbon framework as PAMAMs and only differ by the position of the carbonyl group. In contrast to PAMAMs which are prepared in solution and are difficult to purify, we synthesize i‐PAMAMs using high‐temperature solid‐phase peptide synthesis by iterative coupling and deprotection of the commercially available N,N‐bis(N′‐Fmoc‐3‐aminopropyl)glycine and purify them preparative reverse phase HPLC. Our i‐PAMAM dendrimers show no detectable degradation over time. We demonstrate this new class of dendrimers with the synthesis of antimicrobial dendrimers with potent yet non‐membrane disruptive activities against both Gram‐negative and Gram‐positive bacteria. [ABSTRACT FROM AUTHOR]

Agostic interactions involving titanium are textbook examples for C−H bond activation. Therefore, it is surprising that there is no study in the literature in which the hydrogen atom in the C−H⋅⋅⋅Ti interaction has been determined reliably, although nearly all the criteria for assessing the strength and character of the agostic interaction depend on the hydrogen atom and its position. Here, we demonstrate with quantum crystallographic techniques how hydrogen atoms in a series of three titanium amides can indeed be localized accurately and precisely based on routine single‐crystal X‐ray diffraction data. Once the hydrogen positions have been established, theoretical and experimentally fitted bonding analyses reveal that the C−H⋅⋅⋅Ti interaction becomes stronger with increasing inter‐ligand London dispersion stabilization of bulky alkyl groups. [ABSTRACT FROM AUTHOR]

While the halogen bond has been recognised and studied for over a hundred years, it is only in more recent times that chemists have begun to apply it and see its possibilities as another supramolecular interaction that can be deployed in the preparation of materials. This review takes one of those areas, liquid crystals, and considers examples of motifs that have been deployed successfully to generate new mesogens. In particular, rather than attempting to be comprehensive, the article reviews critically data from well‐characterised systems and seeks to first make some comparisons with analogous hydrogen‐bonded materials, before considering how the lability and flexibility of the halogen bond expresses itself in liquid crystal behaviour. [ABSTRACT FROM AUTHOR]

The history of discovery by Rosetta Reusch of oligo‐ and poly‐β‐hydroxybutyrates (OHBs and PHBs) consisting of less than ca. 150 HB units is described. These 'short‐chain' biopolymers can be detected in all living organisms and have numerous physiological activities of fundamental importance for the chemistry of life. The largest are components of ion channels such as Ca2+‐polyphosphate‐PHB (Ca‐PPi‐PHB) in genetically competent E. coli and in mammalian mitochondria. Sequences with chain lengths < ca. 30 occur covalently attached to proteins (post‐translational PHBylation), and methyl esters of the dimer and trimer are used by certain bacteria as highly efficient antioxidants. With synthetic monodisperse OHBs (up to 128mer) our group has contributed structural investigations, and we have shown that OHBs≥16 alone make phospholipid bilayer vesicles permeable to Ca ions. An extensive biochemical analysis of the TRPM8 protein channel, responsible for the sense of heat in our skin, proved to be fully active only when PHBylated. Reasons for the difficulty of detecting OHBs and PHBs are discussed: the polyester chain is highly flexible, and there is ester cleavage by base, acid, nucleophiles, Lewis acids, and heat – in stark contrast to peptides. PHBs may be called a ubiquitous but fleeting species in the chemistry of life – worth being appreciated and studied much more intensively in the future! A speculation about PHB's possible role in prebiotic compartmentalization is presented, and recent uses of compartmentalization in organic synthesis are briefly mentioned. Portions of the figures used herein were presented in a lecture at the International Symposium on Biopolymers on September 13, 2022, in Sion (Switzerland). [ABSTRACT FROM AUTHOR]

The binding of the terdentate precursor 2,2′‐(4‐methyl‐3,5‐divinylpyridine‐2,6‐diyl)bis(1‐allyl‐5‐bromo‐1H‐benzo[d]imidazole) (1) to the lanthanide container [Ln(hfac)3] (Ln=La, Eu, Gd, Y, Er; H‐hfac=1,1,1,5,5,5‐hexafluoropentane‐2,4‐dione) ensures the cis‐cis orientation of the two adjacent α,α′‐diimine units that is required for the successful intramolecular Grubb ring‐closing metathesis generating the target rigid 6‐methyl‐9,11‐dihydro‐1H,3H‐2λ2,10λ2‐pyrido[2,3‐c:6,5‐c′]bis(azepine) scaffold decorated with two terminal 5‐bromo‐1H‐benzo[d]imidazole in ligand L7. The bond valence analysis of the crystal structures of the associated nine‐coordinate adducts [L7Ln(hfac)3] (Ln=La, Eu, Gd, Er, Y) reveals a satisfying match between the rigid terdentate cavity and the size of the bound lanthanide metal, with a pronounced preference for the largest lanthanum cation. Thermodynamic studies in dichloromethane confirm the formation of [L7Ln(hfac)3] adducts with unprecedented stabilities due to the removal of the energy penalty associated with trans‐trans to cis‐cis reorganization. The introduction of saturated methylene groups within the polyaromatic ligand backbone breaks extended aromatic delocalization and clears the visible part of the electromagnetic spectrum from emission arising from low‐energy ligand‐based excited states. [ABSTRACT FROM AUTHOR]

Here we describe the story behind the link between molecular chirality and macroscopic phenomena, the latter being a probe for the direct assignment of absolute configuration of chiral molecules. First, a brief tour of the history of molecular stereochemistry, starting with the classic experiment reported by Pasteur in 1848 on the separation of enantiomorphous crystals of a salt of tartaric acid, and his conclusion that the molecules of life are chiral of single‐handedness. With time, this study raised, inter alia, two fundamental questions: the absolute configuration of chiral molecules and how a molecule of given configuration shapes the enantiomorphous morphology of its crystal. As for the first question, following the beginning of crystal structure determination by X‐ray diffraction in 1912, it took almost 40 years before Bijvoet assigned molecular chirality through the esoteric method involving anomalous X‐ray scattering. We have been able to address and link both questions through 'everyday concepts of left and right' (in the words of Jack Dunitz) by the use of 'tailor‐made' auxiliaries. By such means, it proved possible to reveal, through morphology, etch patterns, epitaxy and symmetry reduction of both chiral and, paradoxically, centrosymmetric crystals, the basic chiral symmetry of the molecules of life, the α‐amino acids and sugars. [ABSTRACT FROM AUTHOR]

We describe convenient preparations of N,N′‐dialkyl‐1,3‐propanedialdiminium chlorides, N,N′‐dialkyl‐1,3‐propanedialdimines, and lithium N,N′‐dialkyl‐1,3‐propanedialdiminates in which the alkyl groups are methyl, ethyl, isopropyl, or tert‐butyl. For the dialdiminium salts, the N2C3 backbone is always in the trans‐s‐trans configuration. Three isomers are present in solution except for the tert‐butyl compound, for which only two isomers are present; increasing the steric bulk of the N‐alkyl substituents shifts the equilibrium away from the (Z,Z) isomer in favor of the (E,Z), and (E,E) isomers. For the neutral dialdimines, crystal structures show that the methyl and isopropyl compounds adopt the (E,Z) form, whereas the tert‐butyl compound is in the (E,E) form. In aprotic solvents all four dialdimines (as well as the lithium dialdiminate salts) adopt cis‐s‐cis conformations in which there presumably is either an intramolecular hydrogen bond (or a lithium cation) between the two nitrogen atoms. [ABSTRACT FROM AUTHOR]

We report the synthesis of coordinatively unsaturated cationic rhodium complexes bearing the sterically encumbered electron‐rich NHC ligand IPr*OMe. The COD (1,5‐cyclooctadiene) complex [Rh(IPr*OMe)(COD)]BF4 adopts a tilted, pseudo‐square planar coordination geometry, where bonding to the ipso‐carbon of the NHC aryl substituent was observed in the solid state. Hydrogenation of this complex afforded a metastable dihydride complex [Rh(IPr*OMe)(H)2]BF4 with an unusual internal coordination to an arene of the ligand. In the absence of a hydrogen atmosphere, spontaneous reductive elimination of H2 afforded a rhodium complex [Rh(IPr*OMe)]BF4 with a single chelating ligand that stabilizes the highly unsaturated metal by two‐fold π‐face donation as suggested by NMR spectroscopy and computational studies. This unusual complex might serve as a versatile precatalyst for a variety of transformations. [ABSTRACT FROM AUTHOR]

Embedding seven‐membered rings into polycyclic aromatic molecules is attractive as they can exert an influence on molecular conformation that ultimately changes the solubility and π‐electronics. The considerations in designing and synthesizing a highly strained azatriseptane framework are discussed herein. We employ a twofold macrocyclization strategy to form the [7,7,7]‐system and through scoping various strategies identify that the Friedel–Crafts approach is the key. In addition to the successes presented here, the synthetic limitations we have identified highlight the key challenges in forming triseptane frameworks and pave the way for second‐generation analogues that may have various applications in optical and electronic organic materials. [ABSTRACT FROM AUTHOR]

The exploration of new materials is timeless. Especially 2D‐materials have gotten much interest in the last decades. This work proposes a new route towards a fascinating class of 2D materials: molecular textiles. The suggested bottom‐up approach focuses on the 2D self‐assembly of a cross‐shaped monomer at the water/air interface. A 3D cross‐shaped motive was designed, synthesized, and characterized, which exhibits the required structural features, i. e., static and dynamic control. Analysis of the cross‐shaped motive by 1H‐NMR spectroscopy, X‐ray structure, and chiral stationary phase HPLC proved the rigidity and stability of the system, and thus also its potential for the here suggested new strategy towards molecular textiles. Three variants of a Schiff‐base precursor pair functionalized monomer were synthesized and characterized by 1H‐NMR spectroscopy, 13C‐NMR spectroscopy, and mass spectrometry. Finally, the network formation of the monomer is shown to be triggered by deprotonation of its ammonium salt, corroborated with FT‐IR analysis. [ABSTRACT FROM AUTHOR]

2,4‐Diaryl‐2,3‐dihydro‐1H‐1,5‐benzodiazepines readily undergo a ring contraction to generate 2‐aryl‐1‐styrylbenzimidazoles in the presence of some Lewis acids. Copper acetate shows high efficiency compared with other Lewis acids. The ring contraction includes Lewis acid‐catalyzed intramolecular addition, ammonium‐induced ring‐opening of the generated four‐membered azetidine ring, deprotonation, and amine‐promoted nucleophilic styryl 1,2‐shift and elimination. Copper acetate serves as Lewis acid, base, and oxidant. The current reaction provides an efficient method for the convenient synthesis of 2‐aryl‐1‐styrylbenzimidazole derivatives from readily available 2,4‐diaryl‐2,3‐dihydro‐1H‐1,5‐benzodiazepines. [ABSTRACT FROM AUTHOR]

Recent years have witnessed a considerable progress in research aimed at merging transition metal catalysis with chemical and cell biology. Therefore, a crescent number of metal‐catalyzed transformations have been shown compatible with biological media and even with living settings. Of the different transition metals used to build these biocompatible catalysts, ruthenium has demonstrated to be particularly powerful, in part because the resulting complexes exhibit a very good balance between reactivity and biological stability. Indeed, ruthenium complexes have demonstrated utility to promote a great variety of reactions in biologically relevant contexts, from deprotection and redox processes to cycloadditions or photocatalytic transformations. Many of these reactions may enable the development of new type of biological tools and pharmacological strategies. [ABSTRACT FROM AUTHOR]

In this synthetic procedure, a seven‐step protocol for the preparation of monosubstituted 3‐bromo‐1,2,4,5‐tetrazine is presented. The procedure features efficient transformations and purification methods starting from commercially readily available starting materials and affords the title compound on a gram scale with 13 % overall yield in reliable purity (>97 %). Detailed experimental procedures, supported by images and additional notes, allow the preparation of a valuable advanced building block, enabling further applications in bioconjugation, protein labelling, bio‐orthogonal chemistry, heterocycle syntheses, high energy materials, and drug release, among others. [ABSTRACT FROM AUTHOR]

The synthesis of four clickable sydnone‐heptamethine cyanine derivatives is described in this article. The synthetic route is based on a palladium‐cross coupling reactions of sydnone boronates affording the desired sydnone‐cyanine conjugates in only five steps. These compounds were shown to react smoothly with cyclooctynes to form the corresponding pyrazoles clicked products quantitatively at room temperature and with rate constants up to 18 m−1 ⋅ s−1, affording interesting new tools for biorthogonal fluorescent labelling of (bio)molecules. Fluorescence properties of both sydnone‐ and pyrazole‐cyanines are described, as well. [ABSTRACT FROM AUTHOR]

We review in this short perspective the history of cholesterol crystals and crystal structures. We address in particular the helical crystals that form in vitro and in pathology from environments rich in bile acids or from phospholipid membranes. We review the known mechanisms leading to crystals with chiral morphology, from screw‐dislocation mediated growth to mechanisms involving asymmetric mechanical strain. We propose a mechanism for cholesterol helical crystal development based on the monoclinic cholesterol monohydrate crystal structure. We suggest that curvature arises in few layers thick crystals due to the tension induced between the hydrophobic layer and the ice‐like H‐bonded lattice of the water molecules with the cholesterol hydroxy groups. Helicity would ensue through a combination of the curvature and the fast growth of a thin ribbon in one crystal direction. [ABSTRACT FROM AUTHOR]

In an article published by Helvetica Chimica Acta in 1995, chemist P. Martin describes the synthesis of 2′‐O‐alkylated ribonucleosides for use in therapeutic antisense oligonucleotides (ASOs). This work was motivated by the need for a modified ribose structure that was compatible with solid‐phase synthesis protocols and that, when incorporated into an oligonucleotide, would render it resistant to nucleases without attenuating its ability to hybridize to a complementary RNA target. Martin described a robust route to 2′‐O‐alkylribonucleosides in which the ribose 2′‐OH group is substituted with 2′‐ethylene glycol derivatives. Oligonucleotides containing these modifications displayed überraschende Eigenschaften – 'surprising properties' – notably, higher affinity and specificity for RNA substrates and greater stability to nucleases relative to their unmodified counterparts. Today, the 2′‐ethylene glycol modification is universally known in the field as the 2′‐O‐methoxyethyl (MOE) modification. The chemistry features in four ASO drugs and many others in clinical trials. Here, we 1) summarize the synthesis of the MOE‐modified ribose; 2) outline the properties of MOE‐modified oligonucleotides as reported in Martin's article; 3) highlight the first approved MOE‐modified ASO drugs, mipomersen and nusinersen; and 4) survey MOE‐modified ASOs in clinical development. In the outlook, we put these developments into context and consider future possibilities for the MOE modification. [ABSTRACT FROM AUTHOR]

This publication promotes the increased necessity for strain management in topochemical reactions with an enlarged structural extension of the molecular products formed, i. e., when going from small molecule dimerizations, through linear polymerizations to the formation of 2D polymers. Further, it promotes to combine the trap model for photon absorption with concrete molecular scale consequences of this absorption on topochemical transformations and briefly discusses the expected consequences topological dimensionality of the forming (macro)molecular products has on trap location. The time appears ripe for going in this direction because local information concerning structural changes within single crystals is now accessible by the 3D‐ΔPDF method. This method greatly facilitates the analysis of diffuse X‐ray scattering providing access to concrete values of pair distribution functions and, thus, factual information on which and how distances change near a reaction site. Although only based on a first case where distance changes could be quantified in a lateral polymerization, the thoughts put forward may ignite more research towards a full understanding of all the action that occurs when a photochemically triggered topochemical reaction takes place. The 3D‐ΔPDF method is so attractive for this purpose because it provides otherwise inaccessible local information in pair correlation functions rather than average structure information, which is used through the ubiquitous Bragg scattering. [ABSTRACT FROM AUTHOR]

The magnetic properties of noble‐metal nanoparticles are a puzzling phenomenon, tentatively often explained as a size effect or a ligand effect. Many experimental studies performed to date have attempted to vary these readily available parameters without reaching a definitive conclusion. In an attempt at better understanding the role of core crystallinity on these magnetic properties, we have compared the behavior of silver nanoparticles, which were either single‐crystalline or multi‐twinned, of almost identical sizes and with the same ligand coating. Our results indicate that single‐crystalline nanoparticles tend to behave as classical paramagnetic materials, whereas multi‐twinned ones exhibit a combination of para‐ and ferro‐magnetic behaviors. Our hypothesis is that lattice defects within the core bear magnetic moments which couple through conduction electrons, with dipolar interactions also playing a local and macroscopic role. [ABSTRACT FROM AUTHOR]

Structural analysis using powder X‐ray diffraction data has overcome many obstacles and nowadays is readily applicable for structural analysis of all types of compounds and materials. Being less straightforward than single crystal diffraction, it requires significant users' input and consequently, implementation of standardized tools to assess the accuracy of crystal structures. This article discusses potential errors in crystal structure solution and refinement of small‐molecule structures obtained from PXRD data. Moreover, it proposes how accuracy of these structures can be improved by using high‐quality PXRD data, complementary external analytical techniques, knowledge stored in crystal structure databases, as well as an approach to search the parameter space to avoid local minima in testing different sets of geometry restraints. [ABSTRACT FROM AUTHOR]

The C−F bond activation of pentafluoropyridine and 2,3,5,6‐tetrafluoropyridine at [Ni(cod)2] (cod=1,5‐cyclooctadiene) in the presence of the phosphine PPh2(Ind) (Ind=3‐methyl‐2‐indolyl) led to the formation of the nickel(II) fluorido bis(phosphine) complexes trans‐[Ni(F)(2‐C5NF4){PPh2(Ind)}2] and trans‐[Ni(F)(2‐C5HNF3){PPh2(Ind)}2]. The complexes are characterized by the presence of intramolecular hydrogen bonds between the NH group of the phosphine ligands and the fluorido ligand. Stochiometric model reactions of nickel(II) fluorido complexes with PhB(OH)2 revealed that the former can be considered as intermediates in Suzuki–Miyaura cross coupling reactions. Catalytic experiments were attempted using 10 mol‐% of trans‐[Ni(F)(2‐C5NF4){PPh2(Ind)}2] as catalyst and the activities of the PPh2(Ind) complex were compared to the ones of an analogous nickel(II) fluorido complex, bearing PPh3 instead of PPh2(Ind) as ligands. The latter exhibited a somewhat lower catalytic activity suggesting a slight influence of the H‐bonds in the outer coordination sphere. [ABSTRACT FROM AUTHOR]

Stimulated by a suggestion of the late Professor Jack D. Dunitz, that perdeuterated Janus face cycloalkanes may be more polar than their unlabelled forms, the deuterated isotopologue of all cis‐1,2,3,4,5,6‐hexafluorocyclohexane ([2H6]‐1a) and all cis‐1,2,3,4‐tetrafluorocyclopentane ([2H6]‐3a) were prepared. Computation at the B3LYP−D3 level indicated that [2H6]‐1a is not more polar than its protio form 1, however perdeuterated cyclopentane [2H6]‐3a may indeed be more polar than 3, although the magnitude is predicted to be small. None‐the‐less retention time analysis on a reverse phase GC/MS column of an add‐mix of 3 and [2H6]‐3a gave some indication that the per‐deuterated isotopologue 3a was detected marginally before the unlabelled compound consistent with increased polarity associated with perdeuteration. [ABSTRACT FROM AUTHOR]

Ko143 is a tetracyclic, synthetic analog of the fungal metabolite fumitremorgin C. Ko143 is a potent and specific inhibitor of the membrane‐bound efflux transporter ABCG2, and it reverses ABCG2‐mediated drug resistance in cancer cells. Here, we describe an improved synthesis of Ko143 that relies on the highly selective, substrate‐controlled reduction of an imine that is formed in a Bischler–Napieralski reaction with the amide derived from 6‐methoxy‐l‐tryptophan methyl ester and isovaleric acid as a key step. We have also developed a new route to 6‐methoxy‐l‐tryptophan methyl ester from Cbz‐l‐aspartic acid methyl ester, m‐anisidine and differently substituted benzaldehydes. With p‐nitrobenzaldehyde as one of the starting materials, this route gave access to 6‐methoxy‐l‐tryptophan methyl ester in five steps and 20 % overall yield; however, it is less efficient than a previously reported synthesis of 6‐methoxy‐l‐tryptophan methyl ester from 6‐methoxy indole. [ABSTRACT FROM AUTHOR]

A survey has been made of the well determined (R≤0.050) organic crystal structures that have only a single glide plane (e. g., are in space group Pc) and that have more than one crystallographically independent formula unit (Z′>1); the goal was to discover what fraction have additional approximate symmetry. Of the 377 unique structures examined 8 % should almost certainly been refined in a higher‐symmetry unit cell; 86 % of the remaining 347 have approximate symmetry that is periodic in at least one dimension. While these percentages are similar to those found for P1 structures (C. P. Brock, Acta Crystallogr., Sect. B2022, 78, 576–588), the types of approximate symmetry differ because 89 % of the P1, Z′>1 structures were composed of enantiopure material. The 347 reliable Pc structures include 118 that are slightly distorted or mimicked Cc and P21/c structures, 15 of which were reported as having been determined at room temperature. The distortions in another 72 are so large that the approximate symmetry must be seen as periodic in two dimensions only. These results suggest that symmetry lowering may accompany transformation of a crystal nucleus to a macroscopic crystal. [ABSTRACT FROM AUTHOR]