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A seventh blind test of crystal structure prediction has been organized by the Cambridge Crystallographic Data Centre. The results are presented in two parts, with this second part focusing on methods for ranking crystal structures in order of stability. The exercise involved standardized sets of structures seeded from a range of structure generation methods. Participants from 22 groups applied several periodic DFT-D methods, machine learned potentials, force fields derived from empirical data or quantum chemical calculations, and various combinations of the above. In addition, one non-energy-based scoring function was used. Results showed that periodic DFT-D methods overall agreed with experimental data within expected error margins, while one machine learned model, applying system-specific AIMnet potentials, agreed with experiment in many cases demonstrating promise as an efficient alternative to DFT-based methods. For target XXXII, a consensus was reached across periodic DFT methods, with consistently high predicted energies of experimental forms relative to the global minimum (above 4 kJ mol -1 at both low and ambient temperatures) suggesting a more stable polymorph is likely not yet observed. The calculation of free energies at ambient temperatures offered improvement of predictions only in some cases (for targets XXVII and XXXI). Several avenues for future research have been suggested, highlighting the need for greater efficiency considering the vast amounts of resources utilized in many cases., (open access.)

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures., (open access.)

The complex distribution of functional groups in carbohydrates, coupled with their strong solvation in water, makes them challenging targets for synthetic receptors. Despite extensive research into various molecular frameworks, most synthetic carbohydrate receptors have exhibited low affinities, and their interactions with sugars in aqueous environments remain poorly understood. In this work, we present a simple pyridinium-based hydrogen-bonding receptor derived from a subtle structural modification of a well-known tetralactam macrocycle. This small structural change resulted in a dramatic enhancement of glucose binding affinity, increasing from 56 M -1 to 3001 M -1 . Remarkably, the performance of our synthetic lectin surpasses that of the natural lectin, concanavalin A, by over fivefold. X-ray crystallography of the macrocycle-glucose complex reveals a distinctive hydrogen bonding pattern, which allows for a larger surface overlap between the receptor and glucose, contributing to the enhanced affinity. Furthermore, this receptor possesses allosteric binding sites, which involve chloride binding and trigger receptor aggregation. This unique allosteric process reveals the critical role of structural flexibility in this hydrogen-bonding receptor for the effective recognition of sugars. We also demonstrate the potential of this synthetic lectin as a highly sensitive glucose sensor in aqueous solutions., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The one-step synthesis of tetra-substituted benzenes was accomplished via gold-catalyzed diyne-ene annulation. Distinguished from prior modification methods, this novel strategy undergoes formal [3+3] cyclization, producing polysubstituted benzenes with exceptional efficiency. The critical factor enabling this transformation was the introduction of amides, which were reported for the first time in gold catalysis as covalent nucleophilic co-catalysts. This interesting protocol not only offers a new strategy to achieve functional benzenes with high efficiency, but also enlightens potential new reaction pathways within gold-catalyzed alkyne activation processes., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Hydrogen bonding is prevalent in biological systems, dictating a myriad of life-sustaining functions in aqueous environments. Leveraging hydrogen bonding for molecular recognition in water encounters significant challenges in synthetic receptors on account of the hydration of their functional groups. Herein, we introduce a water-soluble hydrogen bonding cage, synthesized via a dynamic approach, exhibiting remarkable affinities and selectivities for strongly hydrated anions, including sulfate and oxalate, in water. We illustrate the use of charge-assisted hydrogen bonding in amide-type synthetic receptors, offering a general molecular design principle that applies to a wide range of amide receptors for molecular recognition in water. This strategy not only revalidates the functions of hydrogen bonding but also facilitates the effective recognition of hydrophilic anions in water. We further demonstrate an unconventional catalytic mechanism through the encapsulation of the anionic oxalate substrate by the cationic cage, which effectively inverts the charges associated with the substrate and overcomes electrostatic repulsions to facilitate its oxidation by the anionic MnO 4 - . Technical applications using this receptor are envisioned across various technical applications, including anion sensing, separation, catalysis, medical interventions, and molecular nanotechnology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The design and synthesis of polyhedra using coordination-driven self-assembly has been an intriguing research area for synthetic chemists. Metal-organic polyhedra are a class of intricate molecular architectures that have garnered significant attention in the literature due to their diverse structures and potential applications. Hereby, we report Cu-MOP, a bifunctional metal-organic cuboctahedra built using 2,6-dimethylpyridine-3,5-dicarboxylic acid and copper acetate at room temperature. The presence of both Lewis basic pyridine groups and Lewis acidic copper sites imparts catalytic activity to Cu-MOP for the tandem one-pot deacetalization-Knoevenagel/Henry reactions. The effect of solvent system and time duration on the yields of the reactions was studied, and the results illustrate the promising potential of these metal-organic cuboctahedra, also known as nanoballs for applications in catalysis., (© 2024 Wiley-VCH GmbH.)

An increased interest to expand three-dimensional chemical space for the design of new materials and medicines has created a demand for isosteric replacement groups of commonly used molecular functionality. The structural and chemical properties of chiral S(VI) functional groups provide unique spatial and electronic features compared with their achiral sulfur- and carbon-based counterparts. Manipulation of the S(VI) centre to introduce structural variation with stereochemical control has remained a synthetic challenge. The stability of sulfonimidoyl fluorides and the efficiency of sulfur fluorine exchange chemistry has enabled the development of the enantiopure bifunctional S(VI) transfer reagent t-BuSF to overcome current synthetic limitations. Here, we disclose a reagent platform that serves as a chiral sulfur fluorine exchange template for the rapid asymmetric synthesis of over 70 sulfoximines, sulfonimidoyl fluorides and sulfonimidamides with excellent enantiomeric excess and good overall yields. Furthermore, the practical utility of the bifunctional S(VI) transfer reagent was demonstrated in the syntheses of enantiopure pharmaceutical intermediates and analogues., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Chiral hybrid metal-halide semiconductors (MHS) pose as ideal candidates for spintronic applications owing to their strong spin-orbit coupling (SOC), and long spin relaxation times. Shedding light on the underlying structure-property relationships is of paramount importance for the targeted synthesis of materials with an optimum performance. Herein, we report the synthesis and optical properties of 1D chiral ( R -/ S -THBTD)SbBr 5 (THBTD = 4,5,6,7-tetrahydro-benzothiazole-2,6-diamine) semiconductors using a multifunctional ligand as a countercation and a structure directing agent. ( R -/ S -THBTD)SbBr 5 feature direct and indirect band gap characteristics, exhibiting photoluminescence (PL) light emission at RT that is accompanied by a lifetime of a few ns. Circular dichroism (CD), second harmonic generation (SHG), and piezoresponse force microscopy (PFM) studies validate the chiral nature of the synthesized materials. Density functional theory (DFT) calculations revealed a Rashba/Dresselhaus (R/D) spin splitting, supported by an energy splitting ( E R ) of 23 and 25 meV, and a Rashba parameter (α R ) of 0.23 and 0.32 eV·Å for the R and S analogs, respectively. These values are comparable to those of the 3D and 2D perovskite materials. Notably, ( S -THBTD)SbBr 5 has been air-stable for a year, a record performance among chiral lead-free MHS. This work demonstrates that low-dimensional, lead-free, chiral semiconductors with exceptional air stability can be acquired, without compromising spin splitting and manipulation performance.

The isoguanosine self-assembled pentamer (isoG-star) has exhibited remarkable selectivity for Cs + binding over competing alkali and alkali earth metal cation, rendering it a promising extractor for radioactive waste 137 Cs separation. However, to make isoG-star a pracrtical material for Cs + isolation, the development of recyclable isoG-star material is required. In this study, a systematic screening of functional isoG derivatives was performed. By employing well-defined complex formation and post-assembly modification, a covalently tethered isoG 5 -star was prepared through olefin metathesis, utilizing a designed isoG monomer. The application of this newly developed covalently linked isoG-star enabled selective Cs + extraction, followed by controled solvent-induced H-bond dessociation. This resulted in the creation of a recyclable Cs + extractor, demonstrating excellent cation selectivity and good reusability (over seven cycles) the first time. Consequently, this new supramolecular macrocycle offers a practical new platform for the treatment of radiocesium ( 134 Cs and 137 Cs) in an environmentally friendly and highly effective manner., Competing Interests: Conflicts of interest There are no conflicts to declare.

A series of oligothiophene bis(dioxolene) complexes, SQ-Th n -SQ (SQ = S = ½Tp Cum,Me Zn II (3- tert -butyl-orthosemiquinonate); Tp Cum,Me = tris(5-cumenyl-3-methylpyrazolyl)borate anion) have been synthesized, structurally characterized, and studied as a function of the number of thiophene bridging units, n ( n = 0-3) using a combination of variable-temperature (VT) electronic absorption and EPR spectroscopies, and VT magnetic susceptibility measurements. The thiophene bridge bond lengths determined by X-ray crystallography display dramatic differences across the SQ-Th n -SQ series. Bridge bond deviation values (Σ| Δ i |) display a progressive change in the nature of the bridge fragment bonding as the number of thiophene groups increases, with quinoidal bridge character for n = 1 (SQ-Th-SQ) and biradical character with "aromatic" bridge bond lengths for n = 3 (SQ-Th 3 -SQ). Remarkably, for n = 2 (SQ-Th 2 -SQ) the nature of the bridge fragment is intermediate between quinoid and biradical aromatic, which we describe as having open-shell character as opposed to biradicaloid since the open-shell biradical configuration does not have the correct symmetry to mix with the quinoidal ground-state configuration. This bridge bonding character is reflected in the energies of the lowest lying open-shell states for these three molecules. The SQ-Th-SQ molecule is diamagnetic at all temperatures studied, and we provide evidence for SQ-SQ antiferromagnetic exchange coupling and population of triplet states in SQ-Th 2 -SQ and SQ-Th 3 -SQ, with J SQ-SQ (ave) = -279 cm -1 (VT EPR/electronic absorption/magnetic susceptibility) and J SQ-SQ = -117 cm -1 (VT EPR/electronic absorption/magnetic susceptibility), respectively. The results have been interpreted in the context of state configurational mixing within a simplified 4-electron, 3-orbital model that explicitly contains contributions of a bridge fragment. Variable-temperature spectroscopic- and magnetic susceptibility data are consistent with two low-lying open-shell states for SQ-Th 3 -SQ, but three low-lying states (one closed-shell and two open-shell) for SQ-Th 2 -SQ. This model provides a simple symmetry-based framework to understand the continuum of electronic and geometric structures of this class of molecules as a function of the number of thiophene units in the bridge., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Hybrid metal halide semiconductors are a unique family of materials with immense potential for numerous applications. For this to materialize, environmental stability and toxicity deficiencies must be simultaneously addressed. We report here a porous, visible light semiconductor, namely, (DHS)Bi 2 I 8 (DHS = [2.2.2] cryptand), which consists of nontoxic, earth-abundant elements, and is water-stable for more than a year. Gas- and vapor-sorption studies revealed that it can selectively and reversibly adsorb H 2 O and D 2 O at room temperature (RT) while remaining impervious to N 2 and CO 2 . Solid-state NMR measurements and density functional theory (DFT) calculations verified the incorporation of H 2 O and D 2 O in the molecular cages, validating the porous nature. In addition to porosity, the material exhibits broad band-edge light emission centered at 600 nm with a full width at half-maximum (fwhm) of 99 nm, which is maintained after 6 months of immersion in H 2 O. Moreover, (DHS)Bi 2 I 8 exhibits bacteriocidal action against three Gram-positive and three Gram-negative bacteria, including antibiotic-resistant strains. This performance, coupled with the recorded water stability and porous nature, renders it suitable for a plethora of applications, from solid-state batteries to water purification and disinfection.

The 1,2,3-triazole coordinated ruthenium carbene complexes (TA-Ru) were reported for the first time as a new class of modified Grubbs catalyst to achieve challenging olefin metathesis at higher temperatures without catalyst decomposition. Previously reported N-tethered Ru-carbene complexes all suffered from rapid cis/trans isomerization, causing significantly reduced catalyst reactivity. These new TA-Ru complexes hold the active trans -dichloro conformation even at 80 °C, allowing effective olefin metathesis for challenging substrates. With this new TA-Ru catalyst, cross-metathesis (CM), ring-closing metathesis (RCM) and dynamic covalent chemistry (DCvC) were achieved. Excitingly, the reactivity of TA-Ru prevails all previously reported N-coordinated Ru-carbene precatalysts, Grubbs II, and Hoveyda-Grubbs, making the TA-Ru a transformative catalytic system in olefin catalysis., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl-gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a "base-free" approach to β-hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac) 3 was used as the critical co-catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee)., (© 2023 Wiley-VCH GmbH.)

With the well-documented chemical and biological applications, piperidine and pyridine are among the most important N-heterocycles, and a new synthetic strategy, especially one with an alternative bond-forming design, is of general interest. Using the gold-catalyzed intermolecular condensation of amine and diyne-ene, we report herein the first example of enantioselective 1,2-dihydropyridine synthesis through a formal [3+2+1] fashion (up to 95 % yield, up to 99 % e.e.)., (© 2023 Wiley-VCH GmbH.)

One striking feature of enzyme is its controllable ability to trap substrates via synergistic or cooperative binding in the enzymatic pocket, which renders the shape-selectivity of product by the confined spatial environment. The success of shape-selective catalysis relies on the ability of enzyme to tune the thermodynamics and kinetics for chemical reactions. In emulation of enzyme's ability, we showcase herein a targeting strategy with the substrate being anchored on the internal pore wall of metal-organic frameworks (MOFs), taking full advantage of the sterically kinetic control to achieve shape-selectivity for the reactions. For this purpose, a series of binding site-accessible metal metalloporphyrin-frameworks (MMPFs) have been investigated to shed light on the nature of enzyme-mimic catalysis. They exhibit a different density of binding sites that are well arranged into the nanospace with corresponding distances of opposite binding sites. Such a structural specificity results in a facile switch in selectivity from an exclusive formation of the thermodynamically stable product to the kinetic product. Thus, the proposed targeting strategy, based on the combination of porous materials and binding events, paves a new way to develop highly efficient heterogeneous catalysts for shifting selectivity., (© 2023 Wiley-VCH GmbH.)

A biomimetic receptor for glucose has been developed with high affinity and selectivity. The receptor was efficiently synthesized in three steps through dynamic imine chemistry followed by imine-to-amide oxidation. The receptor features two parallel durene panels, forming a hydrophobic pocket for [CH⋅⋅⋅π] interactions, and two pyridinium residues directing four amide bonds towards the pocket. These pyridinium residues not only improve solubility but also provide polarized C-H bonds for hydrogen bonding. Experimental data and DFT calculations show that these polarized C-H bonds significantly enhance substrate binding. These findings demonstrate the power of dynamic covalent chemistry for creating molecular receptors and using polarized C-H bonds for boosted carbohydrate recognition in water, providing a foundation for developing glucose-responsive materials and sensors., (© 2023 Wiley-VCH GmbH.)

In this work we report a strategy for generating porosity in hybrid metal halide materials using molecular cages that serve as both structure-directing agents and counter-cations. Reaction of the [2.2.2] cryptand (DHS) linker with Pb II in acidic media gave rise to the first porous and water-stable 2D metal halide semiconductor (DHS) 2 Pb 5 Br 14 . The corresponding material is stable in water for a year, while gas and vapor-sorption studies revealed that it can selectively and reversibly adsorb H 2 O and D 2 O at room temperature (RT). Solid-state NMR measurements and DFT calculations verified the incorporation of H 2 O and D 2 O in the organic linker cavities and shed light on their molecular configuration. In addition to porosity, the material exhibits broad light emission centered at 617 nm with a full width at half-maximum (FWHM) of 284 nm (0.96 eV). The recorded water stability is unparalleled for hybrid metal halide and perovskite materials, while the generation of porosity opens new pathways towards unexplored applications (e.g. solid-state batteries) for this class of hybrid semiconductors., (© 2023 Wiley-VCH GmbH.)

Fluorescence (FL) active 8-aryl guanosine derivatives were prepared and applied for cation mediated self-assembly to form the H-bonded G 8 -quadruplexes. The p -cyano ( p -CN) and 8-anthracene (8-An) substituted guanosines were identified to give the strongest fluorescence with the formation of G 8 -octamers (G 8 ) both in solution (NMR) and solid state (X-ray). This well-defined G 8 -octamer system has provided the first direct evidence on the self-assembled G-quadruplex fluorescence emission with aggregation-induced emission (AIE), which could be applied as the foundation for FL molecular probe design toward G-quadruplex recognition.

Porphyrins and phthalocyanines are ideal candidates for the development of photoactive porous metal organic frameworks (MOFs) due to their broad absorption spectra in the visible and near UV regions, high molar extinction coefficients and long triplet state lifetimes. An important factor in the development of porphyrin/phthalocyanine based MOFs is the extent to which the pore modulates the photophysical properties of the guest. Here, two structurally related guests, Zn(II)tetra(4-sulfonatophenyl)porphyrin (Zn4SP) and Zn(II)phthalocyanine tetrasulfonate (ZnPcS4) have been encapsulated within the pores of the MOF HKUST-1(Zn). Both the ZnPcS4@HKUST-1(Zn) and Zn4SP@HKUST-1(Zn) display bathochromic shifts in the Soret absorption band and steady state emission spectra as well as biphasic emissions lifetimes, relative to the chromophores in solution. These results are consistent with the pore modulating the excited state conformations of both chromophores. Interestingly, rotational control of the phenyl groups associated with Zn4SP@HKUST-1(Zn) appears to have a moderate impact on the photophysics.

Six new halogenated butenolides, tongalides A-C ( 1 - 3 ) and their acetylated congeners ( 4 - 6 ), were isolated from an extract of the Antarctic rhodophyte Delisea sp. that displayed significant antibiotic activity. The structures of the compounds were determined by analysis of data acquired by spectroscopic and spectrometric techniques including NMR, HRESIMS, optical rotation, and X-ray diffraction studies. The newly isolated compounds were assayed for antibacterial activity, but exhibited no growth inhibition of ESKAPE pathogens. The extract bioactivity was attributed to the previously reported Z -acetoxyfimbrolide A also isolated from the extract, providing further evidence that the exocyclic double bond is essential to the antibacterial activity of the structurally related fimbrolide class of metabolite.

Chirality is one of the most important intrinsic properties of (supra)molecules. In this study, we obtained enantiomeric metallo-supramolecular octahedra without using any chiral sources. Such cages were self-assembled by prochiral trispyridine ligand L based on a C 3h truxene core and Cu II salts. Crystallization of the cages with BF 4 - as counterions afforded racemate crystals; while crystallizations of cages with ClO 4 - and OTf - as counterions resulted in conglomerates with spontaneous resolution. Three types of chirality were observed in each cage, including planar chirality of the truxene core, axial chirality from the pyridyl and truxene moieties, and propeller chirality of the pyridyl-Cu II coordination sites. The cages reported here are among the largest discrete synthetic metallo-supramolecules ever reported with chiral self-sorting behavior. Remarkably, the chiral cages exhibited very slow racemization even at low concentrations, suggesting their high stability in solution., (© 2022 Wiley-VCH GmbH.)

Enantioselective, intermolecular alkene arylamination was achieved through gold redox catalysis. Screening of ligands revealed chiral P,N ligands as the optimal choice, giving alkene aminoarylation with good yields (up to 80 %) and excellent stereoselectivity (up to 99 : 1 er). As the first example of enantioselective gold redox catalysis, this work confirmed the feasibility of applying a chiral ligand at the gold(I) stage, with the stereodetermining step (SDS) at the gold(III) intermediate, thus opening up a new way to conduct gold redox catalysis with stereochemistry control., (© 2022 Wiley-VCH GmbH.)

A new class of stable four-coordinated benzotriazole-borane compounds was developed via gold-catalyzed alkyne hydroboration. The application of polymeric (BH 2 CN) n reagent gave the formation of cyano-amine-boranes (CAB) complexes with less basic N-heterocyclic amines and anilines. Various new CABs were investigated in catalytic hydroboration to synthesize N-B cycles. The 1,2,3-benzotriazoles were identified as the only feasible N-source, giving the four coordinated borane N-B cycles (BTAB) in excellent yields (up to 90%) with good functional group tolerability. This new class of polycyclic N-B compounds showed excellent stability toward acid, base, high temperature, and photo-irradiation. The facile synthesis, excellent stability, strong and tunable fluorescence emission make BTAB interesting new fluorescent probes for future chemical and biological applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Ceftibuten, C 15 H 14 N 4 O 6 S 2 , with the systematic name (6 R ,7 R )-7-{[( Z )-2-(2-amino-1,3-thia-zol-4-yl)-4-carb-oxy-but-2-eno-yl]amino}-8-oxo-5-thia-1-aza-bicyclo-[4.2.0]oct-2-ene-2-carb-oxy-lic acid, is a third generation, orally administered cephalosporin anti-biotic with broad anti-microbial activity and stability against extended spectrum β-lactamases. Ceftibuten can exist in various hydration states and to better understand the location of the water mol-ecules of crystallization and their effect on the structure, the crystal structures of anhydrous (I) and hydrated (II) ceftibuten were determined and both occur as zwitterions with proton transfer from the carboxyl-ate group adjacent to the β-lactam ring to the N atom of the thia-zole ring. The β-lactam ring in (I) is almost planar but the equivalent grouping in (II) is slightly buckled. In the extended structure of (I), O-H⋯O and N-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network. In (II), O-H⋯O c , N-H⋯O c , O-H⋯O w , N-H⋯O w and O w -H⋯O w (c = ceftibuten, w = water) hydrogen bonds link the components into a three-dimensional network. A large void space is present within the anhydrous crystal structure that can accommodate between two and three mol-ecules of water., (© Nisbet et al. 2022.)

Five new alkaloids have been isolated from the lipophilic extract of the Antarctic tunicate Synoicum sp. Deep-sea specimens of Synoicum sp. were collected during a 2011 cruise of the R/V Nathanial B. Palmer to the southern Scotia Arc, Antarctica. Crude extracts from the invertebrates obtained during the cruise were screened in a zebrafish-based phenotypic assay. The Synoicum sp. extract induced embryonic dysmorphology characterized by axis truncation, leading to the isolation of aminopyrimidine substituted indolone ( 1 - 4 ) and indole ( 5 - 12 ) alkaloids. While the primary bioactivity tracked with previously reported meridianins A-G ( 5 - 11 ), further investigation resulted in the isolation and characterization of australindolones A-D ( 1 - 4 ) and the previously unreported meridianin H ( 12 ).

Malaria is a prevalent and lethal disease. The fast emergence and spread of resistance to current therapies is a major concern and the development of a novel line of therapy that could overcome, the problem of drug resistance, is imperative. Screening of a set of compounds with drug/natural product-based sub-structural motifs led to the identification of spirocyclic chroman-4-one 1 with promising antimalarial activity against the chloroquine-resistant Dd2 and chloroquine-sensitive 3D7 strains of the parasite. Extensive structure-activity and structure-property relationship studies were conducted to identify the essential features necessary for its activity and properties., (Copyright © 2022. Published by Elsevier Ltd.)

The occurrence of sulfoximines and sulfonimidoyl groups in biologically active molecules within pharmaceuticals and agrochemicals has notably increased in the past decade. This increase has prompted a wave of discovery of methods to install S(VI) functionality into complex organic molecules. Traditional synthetic methods to form α-substituted sulfonimidoyl motifs rely on S-C bond disconnections and typically require control of the stereogenic S-centre or late-stage modification at sulfur, and comprise multistep routes. Here, we report the development of a stereospecific, modular S N Ar approach for the introduction of sulfonimidoyl functional groups into heterocyclic cores. This strategy has been demonstrated across 85 examples, in good to excellent yield, of complex and diverse heterocycles. Sulfoximines, sulfonimidamides and sulfondiimines are all compatible nucleophiles in the S N Ar reaction and hence, the methodology was applied to the synthesis of four sulfoximine-containing pharmaceuticals. Of these synthetic applications, most notably ceralasertib, an ATR inhibitor currently in clinical trials, was synthesized in an eight-step procedure on a gram-scale., Competing Interests: Competing interests A provisional patent application naming J.M.L., Z.P.S., and T.S. as inventors has been filed by H. Lee Moffitt Cancer Center & Research Institute, which covers the synthetic methods for the α-(hetero)arylation of sulfonimidoyl functional groups. The remaining authors declare no competing interests.

In nature as well as life systems, the presence of asymmetrical and dissymmetrical structures with specific functions is extremely common. However, the construction of metallo-supramolecular assemblies based on dissymmetrical ligands still remains a considerable challenge for avoiding the generation of unexpected isomers with similar thermodynamic stabilities, especially for three-dimensional supramolecular structures. In this study, a strategy for the conformational control of metallo-supramolecular cages via the enhancement of ligand dissymmetry was proposed. Four dissymmetrical ditopic ligands were designed and synthesized. By increasing the dissymmetry of length or angle, conformations of assemblies were precisely controlled to form discrete cis-Pd n L 2n molecular cages., (© 2021 Wiley-VCH GmbH.)

Diazirines have been recently demonstrated to serve as electrophilic amination reagents that afford diaziridines, versatile heterocycles that are readily transformed into amines, hydrazines, and nitrogen-containing heterocycles. Here, we report the photodecarboxylative amination of redox-active esters with diazirines using inexpensive photoactivators under mild conditions with an enhanced scope for primary substrates. The stability of diazirines to blue light is demonstrated, paving the way for further research into other photochemical amination methods with these unique heterocycles.

Biomimetic metal-organic frameworks have attracted great attention as they can be used as bio-inspired models, allowing us to gain important insights into how large biological molecules function as catalysts. In this work, we report the synthesis and utilization of such a metal-metalloporphyrin framework (MMPF) that is constructed from a custom-designed ligand as an efficient halogen bond donor catalyst for Diels-Alder reactions under ambient conditions. The implementation of fabricated halogen bonding capsule as binding pocket with high-density C-Br bonds enabled the use of halogen bonding to facilitate organic transformations in their three-dimensional cavities. Through combined experimental and computational studies, we showed that the substrate molecules diffuse through the pores of the MMPF, establishing a host-guest system via the C-Br⋅⋅⋅π interaction. The formation of halogen bonds is a plausible explanation for the observed boosted catalytic efficiency in Diels-Alder reactions. Moreover, the unique capability of MMPF highlights new opportunities in using artificial non-covalent binding pockets as highly tunable and selective catalytic materials., (© 2021 Wiley-VCH GmbH.)

Mining uranium from seawater is highly desirable for sustaining the increasing demand for nuclear fuel; however, access to this unparalleled reserve has been limited by competitive adsorption of a wide variety of concentrated competitors, especially vanadium. Herein, we report the creation of a series of uranyl-specific "hooks" and the decoration of them into the nanospace of porous organic polymers to afford uranium nanotraps for seawater uranium extraction. Manipulating the relative distances and angles of amidoxime moieties in the ligands enabled the creation of uranyl-specific "hooks" that feature ultrahigh affinity and selective sequestration of uranium with a distribution coefficient threefold higher compared to that of vanadium, overcoming the long-term challenge of the competing adsorption of vanadium for uranium extraction from seawater. The optimized uranium nanotrap (2.5 mg) can extract more than one-third of the uranium in seawater (5 gallons), affording an enrichment index of 3836 and thus presenting a new benchmark for uranium adsorbent. Moreover, with improved selectivity, the uranium nanotraps could be regenerated using a mild base treatment. The synergistic combination of experimental and theoretical analyses in this study provides a mechanistic approach for optimizing the selectivity of chelators toward analytes of interest., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Extending the structural hierarchy and complexity through small-molecular self-assembly is a powerful way to obtain large discrete, functional molecular architecture. A hydrogen-bonded supramolecular organic framework (H S OF) with nanometer-size pores is constructed in a solid state with simple guanosine-monomer self-assembly. To extend the hierarchy of the G-quartet self-assembly to a higher order thanthatofthetraditionalG-quadruplex,H-bondacceptorsontheC-8 position of guanosine are introduced to establish inter-quadruplex linkage via H bonding to N(2)-H B from the neighboring G-quartet. After screening different C-8 substitution groups and various synthesis conditions, H S OF-G1a' is obtained by solvent evaporation under diluted condition. Single-crystal X-ray structure reveals that cubic repeating units formed by G 8 are the supermolecule secondary building block (SBU) with large pores (d=34A). To our knowledge, this is the first G-quartet self-assembly with an organized structure beyond cylindrical G-quadruplexes., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

A helical metal-organic framework was prepared by using a conformationally rigid tetratopic benzoic acid ligand with binding units pointing toward each other (concave ligand). To avoid the obvious intramolecular interactions between binding units, matching spacing groups were applied to introduce atropic repulsion, thereby allowing the formation of extended frameworks for the first time. With this new ligand design, a helical-shaped MOF with significantly improved air and moisture stability was successfully prepared, thus providing a new strategy for ligand design toward porous material constructions., (© 2021 Wiley-VCH GmbH.)

Various robust, crystalline, and porous organic frameworks based on in situ-formed imine-linked oligomers were investigated. These oligomers self-assembled through collaborative intermolecular hydrogen bonding interactions via liquid-liquid interfacial reactions. The soluble oligomers were kinetic products with multiple unreacted aldehyde groups that acted as hydrogen bond donors and acceptors and directed the assembly of the resulting oligomers into 3D frameworks. The sequential formation of robust covalent linkages and highly reversible hydrogen bonds enforced long-range symmetry and facilitated the production of large single crystals, with structures that were unambiguously determined by single-crystal X-ray diffraction. The unique hierarchical arrangements increased the steric hindrance of the imine bond, which prevented attacks from water molecules, greatly improving the stability. The multiple binding sites in the frameworks enabled rapid sequestration of micropollutant in water., (© 2021 Wiley-VCH GmbH.)

The discovery and application of new types of helical peptidic foldamers have been an attractive endeavor to enable the development of new materials, catalysts and biological molecules. To maximize their application potential through structure-based design, it is imperative to control their helical handedness based on their molecular scaffold. Herein we first demonstrate the generalizability of the solid-state right-handed helical propensity of the 4 13 -helix of L-α/L-sulfono-γ-AA peptides that as short as 11-mer, using the high-resolution X-ray single crystallography. The atomic level folding conformation of the foldamers was also elucidated by 2D NMR and circular dichroism under various conditions. Subsequently, we show that the helical handedness of this class of foldamer is controlled by the chirality of their chiral side chains, as demonstrated by the left-handed 4 13 -helix comprising 1:1 D-α/D-sulfono-γ-AA peptide. In addition, a heterochiral coiled-coil-like structure was also revealed for the first time, unambiguously supporting the impact of chirality on their helical handedness. Our findings enable the structure-based design of unique folding biopolymers and materials with the exclusive handedness or the racemic form of the foldamers in the future., (© 2021. The Author(s).)

Systematic investigations were performed with various substituted groups at C8 purine and ribose. A series of isoG analogs, C8-phenyl substituted isoG were synthesized and applied for Cs + coordination. The structural proximity between purine and ribose limited pentaplex formation for C8-phenyl substituted isoG derivatives. Based on this observation, deoxy isoG derivative with modification on ribose ( tert -butyldimethylsilyl ether) was applied to assemble with the Cs + cation. Critical solvent (CDCl 3 and CD 3 CN) and anion (BPh 4 - , BARF - , and PF 6 - ) effects were revealed, leading to the controllable formation of various stable isoG pentaplexes, including singly charged decamer, doubly charged decamer, and 15-mer, etc. Finally, the X-ray crystal structure of [isoG 20 Cs 3 ] 3+ (BARF - ) 3 was successfully obtained, which is the first example of multiple-layer deoxy isoG binding with the Cs + cation, providing solid evidence of this new isoG ionophore beyond two-layer sandwich self-assembly., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)