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Advancements in transition metal catalyzed C-H activation/functionalization cascades have allowed the synthetic chemist's toolbox to be significantly expanded. Despite this, protocols for the remote alkynylation of linear aliphatic amines still remain limited. Herein, a palladium-catalyzed directing-group approach to alkynylation of aliphatic amines is disclosed. The synthetic utility was demonstrated with a gram-scale reaction and a functional group compatibility test.

As part of a much larger study on non-covalent interactions in binary adducts, we have explored the solid-state structures of bromopentafluorobenzene (C 6 F 5 Br) using differential scanning calorimetry (DSC), variable-temperature powder X-ray diffraction (VT-PXRD), and single-crystal X-ray diffraction (SXD). DSC data initially indicated a single solid-state phase below the freezing point, but revealed additional weak transitions upon heating. The crystal structures of three solid-state phases have been solved. The SXD data showed that phases I and IV are centrosymmetric, whilst phase II is polar. However, the structure of phase III remains elusive due to the changing phase behaviour of C 6 F 5 Br that is determined as much as by kinetics as thermodynamics. The results underline the need for multiple analytical techniques to study non-covalent interactions and offer valuable data for refining computational models in crystal structure prediction and machine learning. A comparison with the iodinated counterpart is also made., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The development of oxidation catalysts that are resistant to sulfur poisoning is crucial for extending the lifespan of catalysts in real-working conditions. Herein, we describe the design and synthesis of oxide-metal interaction (OMI) catalyst under oxidative atmospheres. By using organic coated TiO 2 , an oxide/metal inverse catalyst with non-classical oxygen-saturated TiO 2 overlayers were obtained at relatively low temperature. These catalysts were found to incorporate ultra-small Pd metal and support particles with exceptional reactivity and stability for CO oxidation (under 21 vol % O 2 and 10 vol % H 2 O). In particular, the core (Pd)-shell (TiO 2 ) structured OMI catalyst exhibited excellent resistance to SO 2 poisoning, yielding robust CO oxidation performance at 120 °C for 240 h (at 100 ppm SO 2 and 10 vol % H 2 O). The stability of this new OMI catalyst was explained through density functional theory (DFT) calculations that interfacial oxygen atoms at Pd-O-Ti sites (of oxygen-saturated overlayers) serve as non-metal active sites for low-temperature CO oxidation, and change the SO 2 adsorption from metal(d)-to-SO 2 (π*) back-bonding to much weaker σ(Ti-S) bonding., (© 2023 Wiley-VCH GmbH.)

Lipopolyplexes (LPDs) are of considerable interest for use as gene delivery vehicles. Here LPDs have been prepared from cationic vesicles (composed of a 1 : 1 molar ratio of DOTMA with the neutral helper lipid, DOPE), singly branched cationic peptides and plasmid DNA. All peptides contained a linker sequence (cleaved by endosomal furin) attached to a targeting sequence selected to bind human airway epithelial cells and mediate gene delivery. The current study investigates the effects of novel Arg-containing cationic peptide sequences on the biophysical and transfection properties of LPDs. Mixed His/Arg cationic peptides were of particular interest, as these sequences have not been previously used in LPD formulations. Lengthening the number of cationic residues in a homopolymer from 6 to 12 in each branch reduced transfection using LPDs, most likely due to increased DNA compaction hindering the release of pDNA within the target cell. Furthermore, LPDs containing mixed Arg-containing peptides, particularly an alternating Arg/His sequence exhibited an increase in transfection, probably because of their optimal ability to complex and subsequently release pDNA. To confer stability in serum, LPDs were prepared in 0.12 M sodium chloride solution (as opposed to the more commonly used water) yielding multilamellar LPDs with very high levels of size reproducibility and DNA protection, especially when compared to the (unilamellar) LPDs formed in water. Significantly for the clinical applications of the LPDs, those prepared in the presence of sodium chloride retained high levels of transfection in the presence of media supplemented with fetal bovine serum. This work therefore represents a significant advance for the optimisation of LPD formulation for gene delivery, under physiologically relevant conditions, in vivo .

We report the evaluation of density-functional-theory (DFT) based procedures for predicting 19 F NMR chemical shifts at modest computational cost for a range of molecules with fluorine bonds, to be used as a tool for assisting the characterisation of reaction intermediates and products and as an aid to identifying mechanistic pathways. The results for a balanced learning set of molecules were then checked using two further testing sets, resulting in the recommendation of the ωB97XD/aug-cc-pvdz DFT method and basis set as having the best combination of accuracy and computational time, with a RMS error of 3.57 ppm. Cationic molecules calculated without counter-anion showed normal errors, whilst anionic molecules showed somewhat larger errors. The method was applied to the prediction of the conformationally averaged 19 F chemical shifts of 2,2,3,3,4,4,5,5-octafluoropentan-1-ol, in which gauche stereoelectronic effects involving fluorine dominate and to determining the position of coordination equilibria of fluorinated boranes as an aid to verifying the relative energies of intermediate species involved in catalytic amidation reactions involving boron catalysts.

The prospect of eradicating malaria continues to be challenging in the face of increasing parasite resistance to antimalarial drugs so that novel antimalarials active against asexual, sexual, and liver-stage malaria parasites are urgently needed. In addition, new antimalarials need to be affordable and available to those most in need and, bearing in mind climate change, should ideally be sustainable. The West African climbing shrub Cryptolepis sanguinolenta is used traditionally for the treatment of malaria; its principal alkaloid, cryptolepine ( 1 ), has been shown to have antimalarial properties, and the synthetic analogue 2,7-dibromocryptolepine ( 2 ) is of interest as a lead toward new antimalarial agents. Cryptolepine ( 1 ) was isolated using a two-step Soxhlet extraction of C. sanguinolenta roots, followed by crystallization (yield 0.8% calculated as a base with respect to the dried roots). Semi-synthetic 7-bromo- ( 3 ), 7, 9-dibromo- ( 4 ), 7-iodo- ( 5 ), and 7, 9-dibromocryptolepine ( 6 ) were obtained in excellent yields by reaction of 1 with N -bromo- or N -iodosuccinimide in trifluoroacetic acid as a solvent. All compounds were active against Plasmodia in vitro , but 6 showed the most selective profile with respect to Hep G2 cells: P. falciparum (chloroquine-resistant strain K1), IC 50 = 0.25 µM, SI = 113; late stage, gametocytes, IC 50 = 2.2 µM, SI = 13; liver stage, P. berghei sporozoites IC 50 = 6.13 µM, SI = 4.6. Compounds 3 - 6 were also active against the emerging zoonotic species P. knowlesi with 5 being the most potent (IC 50 = 0.11 µM). In addition, 3 - 6 potently inhibited T. brucei in vitro at nM concentrations and good selectivity with 6 again being the most selective (IC 50 = 59 nM, SI = 478). These compounds were also cytotoxic to wild-type ovarian cancer cells as well as adriamycin-resistant and, except for 5 , cisplatin-resistant ovarian cancer cells. In an acute oral toxicity test in mice, 3 - 6 did not exhibit toxic effects at doses of up to 100 mg/kg/dose × 3 consecutive days. This study demonstrates that C. sanguinolenta may be utilized as a sustainable source of novel compounds that may lead to the development of novel agents for the treatment of malaria, African trypanosomiasis, and cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abacha, Forkuo, Gbedema, Mittal, Ottilie, Rocamora, Winzeler, van Schalkwyk, Kelly, Taylor, Reader, Birkholtz, Lisgarten, Cockcroft, Lisgarten, Palmer, Talbert, Shnyder and Wright.)

Sugars are abundant in waste biomass, making them sustainable chiral building blocks for organic synthesis. The demand for chiral saturated heterocyclic rings for pharmaceutical applications is increasing as they provide well-defined three-dimensional frameworks that show increased metabolic resistance. A range of sugar thioacetals can be dehydrated selectively at C-2 under mild basic conditions, and the resulting ketene thioacetals can be applied to the production of useful chiral building blocks via further selective dehydration reactions.

The long-standing crusade searching for efficient photocatalytic materials has resulted in a vast landscape of promising photocatalysts, as reflected by the number of reviews reported in the last decade. Virtually all of these reviews have focused on quantitative approaches aiming at developing an understanding of the underlying mechanisms behind photocatalytic behavior and the parameters that influence structure-function correlation. Less attention has been paid, however, to qualitative measures around the development and assessment of photocatalysts. These measures will contribute toward narrowing the range of potential photocatalytic materials for widespread applications. The current report provides a critical perspective over some of the main factors affecting the assessment of photocatalytic materials as a code of good practice. A case of study is also provided, where this qualitative analysis is applied to one of the most prolific materials of the last-decade, disorder-engineered, black titanium dioxide (TiO 2 )., (Copyright © 2020 Quesada-Cabrera and Parkin.)

Understanding the structure of the stratum corneum (SC) is essential to understand the skin barrier process. The long periodicity phase (LPP) is a unique trilayer lamellar structure located in the SC. Adjustments in the composition of the lipid matrix, as in many skin abnormalities, can have severe effects on the lipid organization and barrier function. Although the location of individual lipid subclasses has been identified, the lipid conformation at these locations remains uncertain. Contrast variation experiments via small-angle neutron diffraction were used to investigate the conformation of ceramide (CER) N -(tetracosanoyl)-sphingosine (NS) within both simplistic and porcine mimicking LPP models. To identify the lipid conformation of the twin chain CER NS, the chains were individually deuterated, and their scattering length profiles were calculated to identify their locations in the LPP unit cell. In the repeating trilayer unit of the LPP, the acyl chain of CER NS was located in the central and outer layers, while the sphingosine chain was located exclusively in the middle of the outer layers. Thus, for the CER NS with the acyl chain in the central layer, this demonstrates an extended conformation. Electron density distribution profiles identified that the lipid structure remains consistent regardless of the lipid's lateral packing phase, this may be partially due to the anchoring of the extended CER NS. The presented results provide a more detailed insight on the internal arrangement of the LPP lipids and how they are expected to be arranged in healthy skin.

Metal oxynitrides adopting the perovskite structure have been shown to be visible light-activated photocatalysts, and therefore, they have potential as self-cleaning materials where surface organic pollutants can be removed by photomineralization. In this work, we establish a route for the deposition of thin films for seven perovskite oxynitrides, CaTaO 2 N, SrTaO 2 N, BaTaO 2 N, LaTaON 2 , EuTaO 2 N, SrNbO 2 N, and LaNbON 2 , on quartz and alumina substrates using dip-coating of a polymer gel to form an amorphous oxide precursor film, followed by ammonolysis. The initially deposited oxide films were annealed at 800 °C, followed by ammonolysis at temperatures from 850 to 1000 °C. The perovskite oxynitride thin films were characterized using XRD and EDX, with band gaps determined using Tauc plots derived from UV-vis spectroscopic data. A cobalt oxide co-catalyst was deposited onto each film by drop casting, and the photocatalytic activity assessed under visible light using dichloroindophenol dye degradation in the presence of a sacrificial oxidant. The light source used was a solar simulator equipped with a 400 nm cut-off filter. The dye degradation test demonstrated photocatalytic activity in all samples except EuTaO 2 N and BaTaO 2 N. The three most active samples were SrNbO 2 N, CaTaO 2 N, and SrTaO 2 N. The cobalt oxide loading was optimized for these three films and found to be 0.3 μg cm -2 . Further, catalytic tests were conducted using stearic acid degradation, and this found the film of SrNbO 2 N with the cobalt oxide co-catalyst to be the most active for complete mineralization of this model pollutant.

When the gas sensor active layer film thickness is decreased, increased sensitivity to changes in the adsorbate concentration is expected when measuring the resistance of the layer, in particular when this thickness is on the order of the Debye length of the material (one-tens of nanometers); however, this is demonstrated only for a limited number of materials. Herein, ultrathin NiO films of different thicknesses (8-21 nm) have been deposited via chemical vapor deposition to fabricate gas sensor devices. Sensor performance for a range of NO 2 concentrations (800 part-per-billion to 7 part-per-million) was evaluated and an optimum operating temperature of 125 °C determined. The dependence of the potential relative changes with respect to the NO 2 concentration and of the sensor signal with respect to the geometrical parameters was qualitatively evaluated to derive a transduction model capable of fitting the experimental results. The selective sensitivity toward NO 2 was confirmed by the limited response for different reducing gases, CO, CH 4 , NH 3 , and SO 2 , under optimum operating conditions, and the sensor signal toward NO 2 increased with decreasing thickness, demonstrating that the concept of a Debye length dependence of sensitivity is applicable for the p-type semiconductor NiO. In addition, these NiO sensors were exposed to different relative levels of humidity over a wide range of operating temperatures and were found to display humidity tolerance far superior to those in previous reports on SnO 2 materials.

A transition metal catalyzed alkylation with an alkyl halide is one of the most difficult reactions to achieve, because of the difficult oxidative addition of an alkyl-halogen bond to a metal, and the tendency of the resulting alkylmetal intermediate to undergo a β-hydride elimination reaction to give an olefin. In this review, we discuss hybrid reaction systems involving Cu catalyzed combination of radicals and organometallic species, which enable facile alkylation reactions to construct C-C and C-heteroatom bonds. This paper highlights recent progress in arylation, alkenylation, alkynylation, cyclization, addition and introduction of heteroatoms via these hybrid reaction systems., (© 2019 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Creams are multi-component semi-solid emulsions that find widespread utility across a wide range of pharmaceutical, cosmetic, and personal care products, and they also feature prominently in veterinary preparations and processed foodstuffs. The internal architectures of these systems, however, have to date been inferred largely through macroscopic and/or indirect experimental observations and so they are not well-characterized at the molecular level. Moreover, while their long-term stability and shelf-life, and their aesthetics and functional utility are critically dependent upon their molecular structure, there is no real understanding yet of the structural mechanisms that underlie the potential destabilizing effects of additives like drugs, anti-oxidants or preservatives, and no structure-based rationale to guide product formulation. In the research reported here we sought to address these deficiencies, making particular use of small-angle neutron scattering and exploiting the device of H/D contrast variation, with complementary studies also performed using bright-field and polarised light microscopy, small-angle and wide-angle X-ray scattering, and steady-state shear rheology measurements. Through the convolved findings from these studies we have secured a finely detailed picture of the molecular structure of creams based on Aqueous Cream BP, and our findings reveal that the structure is quite different from the generic picture of cream structure that is widely accepted and reproduced in textbooks.

A series of potent inhibitors of histone deacetylase-8 (HDAC8) is described that contains an α-amino amide zinc-binding unit and a substituted isoindolinyl capping group. The presence of a 2,4-dichlorophenyl unit located in the acetate-release cavity was shown to confer a gain of approx. 4.3 kJ mol -1 in binding energy compared to a phenyl group, and the isoindoline linker has approx. 5.8 kJ mol -1 greater binding energy than the corresponding tetrahydroisoquinoline ring system. In a series of 5-substituted isoindolin-2-yl inhibitors, a 5-acetylamino derivative was found to be more potent than the 5-unsubstituted lead HDAC8 inhibitor (increase in binding energy of 2.0 kJ mol -1 , ascribed to additional binding interactions within the N ε -acetyl-l-lysine binding tunnel in HDAC8, including hydrogen bonding to Asp101. Tolerance of a 5-substituent (capping group) on the isoindoline ring has been demonstrated, and which in some cases confers improved enzyme inhibition, the HDAC8 substrate-binding region providing a platform for additional interactions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

We present the structure of a novel solvate adduct formed by dissolving ferrocene, FeCp 2 , in hexafluorobenzene, C 6 F 6 . This adduct demonstrates the remarkably strong interactions between the five-membered aromatic rings of FeCp 2 and the six-membered aromatic ring of C 6 F 6 . These molecular interactions are sufficiently strong and anisotropic to change the temperature of the order-disorder transition of the ferrocene molecule from below ca. 164 K to RT. No solvate adduct could be formed between benzene and FeCp 2 . These observations will be of particular relevance to the crystal engineering community, whose goal is the design of solids with bespoke properties.

The monocyclic 1,4-benzoquinone, HU-331, the direct oxidation product of cannabidiol, inhibits the catalytic activity of topoisomerase II but without inducing DNA strand breaks or generating free radicals, and unlike many fused-ring quinones exhibits minimal cardiotoxicity. Thus, monocyclic quinones have potential as anticancer agents, and investigation of the structural origins of their biological activity is warranted. New syntheses of cannabidiol and (±)-HU-331 are here reported. Integrated synthetic protocols afforded a wide range of polysubstituted resorcinol derivatives; many of the corresponding novel 2-hydroxy-1,4-benzoquinone derivatives are potent inhibitors of the catalytic activity of topoisomerase II, some more so than HU-331, whose monoterpene unit replaced by a 3-cycloalkyl unit conferred increased antiproliferative properties in cell lines with IC 50 values extending below 1 mM, and greater stability in solution than HU-331. The principal pharmacophore of quinones related to HU-331 was identified. Selected monocyclic quinones show potential for the development of new anticancer agents., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A homologous series of n-alkyl trimethylammonium bromide surfactants, H(CH2)nN+(CH3)3 Br-, from C10TAB to C18TAB have been studied systematically in the bulk over a wide range of temperatures. Common features in the structures are identified, with packing dominated by the co-ordination of the cationic head groups with bromide anions and interdigitation of the hydrocarbon chains. This arrangement provides an explanation for the thin adsorbed bilayers that have been observed at various hydrophilic surfaces from aqueous solutions in previous studies. The molecular volumes and arrangement are comparable with structures of a number of different self-assembled amphiphiles. For these surfactants with bromide counter-ions, formation of crystal hydrates was not observed. The alkyl chains are highly mobile and at high temperatures a plastic phase is found for all materials with a transition enthalpy that is similar to the melting enthalpy of many long alkyl chains. Other unexpected phase transitions depend more markedly on the hydrocarbon chain length and evidently depend on delicate balances of the various contributions to the free energy.

A versatile approach to the valorization of propargylic alcohols is reported, enabling controlled access to three different products from the same starting materials. First, a general method for the hydroamination of propargylic alcohols with anilines is described using gold catalysis to give 3-hydroxyimines with complete regioselectivity. These 3-hydroxyimines can be reduced to give 1,3-amino alcohols with high syn selectivity. Alternatively, by using a catalytic quantity of aniline, 3-hydroxyketones can be obtained in high yield directly from propargylic alcohols. Further manipulation of the reaction conditions enables the selective formation of 3-aminoketones via a rearrangement/hydroamination pathway. The utility of the new chemistry was exemplified by the one-pot synthesis of a selection of N -arylpyrrolidines and N -arylpiperidines. A mechanism for the hydroamination has been proposed on the basis of experimental studies and density functional theory calculations.

We report a single-step route to co-deposit Cu nanoparticles with a graphitic carbon nitride (gCN) support using nanosecond Ce:Nd:YAG pulsed laser ablation from a Cu metal target coated using acetonitrile (CH 3 CN). The resulting Cu/gCN hybrids showed strong optical absorption in the visible to near-IR range and exhibited surface-enhanced Raman or resonance Raman scattering (SERS or SERRS) enhancement for crystal violet (CV), methylene blue (MB), and rhodamine 6G (R6G) used as probe analyte molecules adsorbed on the surface. We have characterized the Cu nanoparticles and the nature of the gCN support materials using a range of spectroscopic, structural, and compositional analysis techniques.

Following observations of survival of microbes and other life forms in deep subsurface environments it is necessary to understand their biological functioning under high pressure conditions. Key aspects of biochemical reactions and transport processes within cells are determined by the intracellular water dynamics. We studied water diffusion and rotational relaxation in live Shewanella oneidensis bacteria at pressures up to 500 MPa using quasi-elastic neutron scattering (QENS). The intracellular diffusion exhibits a significantly greater slowdown (by -10-30%) and an increase in rotational relaxation times (+10-40%) compared with water dynamics in the aqueous solutions used to resuspend the bacterial samples. Those results indicate both a pressure-induced viscosity increase and slowdown in ionic/macromolecular transport properties within the cells affecting the rates of metabolic and other biological processes. Our new data support emerging models for intracellular organisation with nanoscale water channels threading between macromolecular regions within a dynamically organized structure rather than a homogenous gel-like cytoplasm.

We describe work carried out within our group to explore new transition metal and main group nitride phases synthesized using high pressure-high temperature techniques using X-ray diffraction and spectroscopy at synchrotron sources in the USA, UK and France to establish their structures and physical properties. Along with previously published data, we also highlight additional results that have not been presented elsewhere and that represent new areas for further exploration. We also describe new work being carried out to explore the properties of carbon nitride materials being developed for energy applications and the nature of few-layered carbon nitride nanomaterials with atomically ordered structures that form solutions in polar liquids via thermodynamically driven exfoliation. This article is part of the theme issue 'Fifty years of synchrotron science: achievements and opportunities'.

The formation of a novel trichain (TC) lipid was discovered when a cationic lipid possessing a terminal hydroxyl group and the helper lipid dioleoyl l-α-phosphatidylethanolamine (DOPE) were formulated as vesicles and stored. Importantly, the transfection efficacies of lipopolyplexes comprised of the TC lipid, a targeting peptide and DNA (LPDs) were found to be higher than when the corresponding dichain (DC) lipid was used. To explore this interesting discovery and determine if this concept can be more generally applied to improve gene delivery efficiencies, the design and synthesis of a series of novel TC cationic lipids and the corresponding DC lipids was undertaken. Transfection efficacies of the LPDs were found to be higher when using the TC lipids compared to the DC analogues, so experiments were carried out to investigate the reasons for this enhancement. Sizing experiments and transmission electron microscopy indicated that there were no major differences in the size and shape of the LPDs prepared using the TC and DC lipids, while circular dichroism spectroscopy showed that the presence of the third acyl chain did not influence the conformation of the DNA within the LPD. In contrast, small angle neutron scattering studies showed a considerable re-arrangement of lipid conformation upon formulation as LPDs, particularly of the TC lipids, while gel electrophoresis studies revealed that the use of a TC lipid in the LPD formulation resulted in enhanced DNA protection properties. Thus, the major enhancement in transfection performance of these novel TC lipids can be attributed to their ability to protect and subsequently release DNA. Importantly, the TC lipids described here highlight a valuable structural template for the generation of gene delivery vectors, based on the use of lipids with three hydrophobic chains.

Lipoplexes (LDs) have been prepared from DNA and positively charged vesicles composed of the helper lipid, dioleoyl l-α-phosphatidylethanolamine (DOPE) and either a dichain (DC) oxyethylated cationic lipid or their corresponding novel trichain (TC) counterpart. This is the first study using the TC lipids for the preparation of LDs and their application. Here the results of biophysical experiments characterising the LDs have been correlated with the in vitro transfection activity of the complexes. Photon correlation spectroscopy, zeta potential measurements and transmission electron microscopy studies indicated that, regardless of the presence of a third chain, there were little differences between the size and charge of the TC and DC containing LDs. Small angle neutron scattering studies established however that there was a significant conformational re-arrangement of the lipid bilayer when in the form of a LD complex as opposed to the parent vesicles. This re-arrangement was particularly noticeable in LDs containing TC lipids possessing a third chain of C12 or a longer chain. These results suggested that the presence of a third hydrophobic chain had a significant effect on lipid packing in the presence of DNA. Picogreen fluorescence and gel electrophoresis studies showed that the TC lipids containing a third acyl chain of at least C12 were most effective at complexing DNA while the TC lipids containing an octanoyl chain and the DC lipids were least effective. The transfection efficacies of the TC lipids in the form of LDs were found to be higher than for the DC analogues, particularly when the third acyl chain was an octanoyl or oleoyl moeity. Little or no increase in transfection efficiency was observed when the third chain was a methyl, acetyl or dodecanoyl group. The large enhancement in transfection performance of the TC lipids can be attributed to their ability to complex their DNA payload. These studies indicate that presence of a medium or long third acyl chain was especially beneficial for transfection.

In this paper we outline how dihalohydration reactions of propargylic alcohols can be used to access a wide variety of useful halogenated building blocks. A novel procedure for dibromohydration of alkynes has been developed, and a selection of dichloro and dibromo diols and cyclic ethers were synthesized. The dihalohydration of homo-propargylic alcohols provides a useful route to 3-halofurans, which were shown to readily undergo cycloaddition reactions under mild conditions. Finally, a novel ring expansion of propargylic alcohols containing a cyclopropylalkyne provides access to halogenated alkenylcyclobutanes.

Amidation of unprotected amino acids has been investigated using a variety of 'classical" coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions., (© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Herein, we report a silver-free Pd(II)-catalyzed C(sp 3 )-H arylation of saturated bicyclic and tricyclic amine scaffolds. The reaction provides good yields using a range of aryl iodides and aryl bromides including functionalized examples bearing aldehydes, ketones, esters, free phenols, and heterocycles. The methodology has been applied to medicinally relevant scaffolds. Two of the intermediate palladium complexes in the catalytic cycle have been prepared and characterized, and a mechanism is proposed. Removal of the directing group proceeded with good yield under relatively mild conditions.

Analyte sensitivity for gas sensors based on semiconducting metal oxides should be highly dependent on the film thickness, particularly when that thickness is on the order of the Debye length. This thickness dependence has previously been demonstrated for SnO₂ and inferred for TiO₂. In this paper, TiO₂ thin films have been prepared by Atomic Layer Deposition (ALD) using titanium isopropoxide and water as precursors. The deposition process was performed on standard alumina gas sensor platforms and microscope slides (for analysis purposes), at a temperature of 200 °C. The TiO₂ films were exposed to different concentrations of CO, CH₄, NO₂, NH₃ and SO₂ to evaluate their gas sensitivities. These experiments showed that the TiO₂ film thickness played a dominant role within the conduction mechanism and the pattern of response for the electrical resistance towards CH₄ and NH₃ exposure indicated typical n -type semiconducting behavior. The effect of relative humidity on the gas sensitivity has also been demonstrated., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC 50 values of 11 to 15 nmol/L, is ATP-competitive, and targets these kinases selectively. TAOK inhibition or depletion in centrosome-amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death, and inhibits cell growth. In contrast, nontumorigenic and dividing bipolar MCF-10A breast cells appear less dependent on TAOK activity and can complete mitosis and proliferate in the presence of the TAOK inhibitor. We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. Live cell imaging shows that the TAOK inhibitor prolongs the duration of mitosis in SKBR3 cells, increases mitotic cell death, and reduces the percentages of cells exiting mitosis, whereas MCF-10A cells continue to divide and proliferate. Over 80% of breast cancer tissues display supernumerary centrosomes, and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome-amplified cancer cells preferentially, while sparing normal bipolar cells. Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells, and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur. Mol Cancer Ther; 16(11); 2410-21. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Chemical reactions for the formation of amide bonds are among the most commonly used transformations in organic chemistry, yet they are often highly inefficient. A novel protocol for amidation using a simple borate ester catalyst is reported. The process presents significant improvements over other catalytic amidation methods in terms of efficiency and safety, with an unprecedented substrate scope including functionalized heterocycles and even unprotected amino acids. The method was used to access a wide range of functionalized amide derivatives, including pharmaceutically relevant targets, important synthetic intermediates, a catalyst, and a natural product.

Nanomaterials are at the leading edge of the emerging field of nanotechnology. Their unique and tunable size-dependent properties (in the range 1-100 nm) make these materials indispensable in many modern technological applications. In this Review, we summarize the state-of-art in the manufacture and applications of inorganic nanoparticles made using continuous hydrothermal flow synthesis (CHFS) processes. First, we introduce ideal requirements of any flow process for nanoceramics production, outline different approaches to CHFS, and introduce the pertinent properties of supercritical water and issues around mixing in flow, to generate nanoparticles. This Review then gives comprehensive coverage of the current application space for CHFS-made nanomaterials including optical, healthcare, electronics (including sensors, information, and communication technologies), catalysis, devices (including energy harvesting/conversion/fuels), and energy storage applications. Thereafter, topics of precursor chemistry and products, as well as materials or structures, are discussed (surface-functionalized hybrids, nanocomposites, nanograined coatings and monoliths, and metal-organic frameworks). Later, this Review focuses on some of the key apparatus innovations in the field, such as in situ flow/rapid heating systems (to investigate kinetics and mechanisms), approaches to high throughput flow syntheses (for nanomaterials discovery), as well as recent developments in scale-up of hydrothermal flow processes. Finally, this Review covers environmental considerations, future directions and capabilities, along with the conclusions and outlook.

Polysubstituted pyridinium salts are valuable pharmacophores found in many biologically active molecules. Their synthesis typically involves the use of multistep procedures or harsh reaction conditions. Here, we report water-based phosphate mediated reaction conditions that promote the condensation of arylacetaldehydes with amines to give 1,3,5-pyridinium salts. The reaction, carried out at pH 6, provides conditions suitable for the use of less stable aldehydes and amines in this Chichibabin pyridine condensation. The evaluation of selected 1,3,5-trisubstituted pyridinium salts highlighted that they can inhibit the growth of S. aureus in the low μg/mL range. The synthetic accessibility of these compounds and preliminary growth inhibition data may pave the way towards the discovery of new anti-bacterials based on the 1,3,5-trisubstituted pyridinium scaffold.

In this paper we report on the use of aerosol assisted chemical vapour deposition (AACVD) to form thin films of the zinc titanate phases using zinc acetate and titanium isopropoxide as precursors in methanol solution. Analysis by XRD and XPS found that through variation in experimental conditions we have been able to synthesize films of zinc titanate with composition of Zn 2 TiO 4 or Zn 0.3 Ti 2.7 O 4.94 , which adopt the spinel and pseudobrookite structure respectively. In addition, we have also formed hybrid films of Zn 2 TiO 4 with either ZnTiO 3 or ZnO. Using a technique previously reported with powders, the mixed ZnO and Zn 2 TiO 4 films were treated with acid to produce porous Zn 2 TiO 4 which, through reduction and vapour leaching of zinc, were converted to hierarchically porous thin films of anatase TiO 2 . This conversion was monitored by XRD. Analysis of photocatalytic activity of the hierarchically porous titania, using dye and stearic acid degradation tests, found a factor of 12 to 14 increase in rates of photocatalysis over conventional TiO 2 thin films. Finally we are able to report a maximum formal quantum efficiency for stearic acid degradation of 1.76 × 10 -3 molecules per photon.

Non-destructive pigment analysis by Raman microscopy (RM) and portable X-ray fluorescence (pXRF) has been carried out on some Bolognese illuminations and cuttings chosen to represent the beginnings, evolution and height of Bolognese illuminated manuscript production. Dating to the thirteenth and fourteenth centuries and held in a private collection, the study provides evidence for the pigments generally used in this period. The results, which are compared with those obtained for other north Italian artwork, show the developments in usage of artistic materials and technique. Also addressed in this study is an examination of the respective roles of RM and pXRF analysis in this area of technical art history.This article is part of the themed issue 'Raman spectroscopy in art and archaeology'., (© 2016 The Author(s).)

Two new palladium-catalysed reactions have been developed for the synthesis of stable 4-substituted benzooxaborinin-1-ols. A palladium-catalysed cyclisation of ortho-alkenylbenzene boronic acids can be used to access 4-chlorobenzooxaborinin-1-ols via a Wacker-type oxidation and chlorination. Alternatively, ortho-alkynylbenzene boronic acids undergo a palladium-catalysed oxyallylation reaction to provide 4-allylbenzooxaborinin-1-ols.