Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration.

Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro-d-mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospecific manner using inversion via a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro-d-mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding d-glucoside with TBAF.

Reduction of hexaazatrinaphthylenes by divalent lanthanocenes leads to ligand-based multiconfigurational properties.

Reduction of hexaazatrinaphthylene (HAN) and its hexamethyl derivative with [Cp*Sm(THF)] or [Cp*Yb(OEt)] produces [(Cp*Ln)(RHAN)] (Ln = Sm, Yb; R = H, Me), where the heterocyclic ligand forms as a trianion. The magnetism and electronic structure of these compounds reflect unusual multiconfigurational character within the reduced ligand but not the lanthanide ions.

Discovery and optimization of narrow spectrum inhibitors of Tousled like kinase 2 (TLK2) using quantitative structure activity relationships.

The oxindole scaffold has been the center of several kinase drug discovery programs, some of which have led to approved medicines. A series of two oxindole matched pairs from the literature were identified where TLK2 was potently inhibited as an off-target kinase. The oxindole has long been considered a promiscuous kinase inhibitor template, but across these four specific literature oxindoles TLK2 activity was consistent, while the kinome profile was radically different ranging from narrow to broad spectrum kinome coverage.

Facial Selectivity in Mechanical Bond Formation: Axially Chiral Enantiomers and Geometric Isomers from a Simple Prochiral Macrocycle.

In 1971, Schill recognized that a prochiral macrocycle encircling an oriented axle led to geometric isomerism in rotaxanes. More recently, we identified an overlooked chiral stereogenic unit in rotaxanes that arises when a prochiral macrocycle encircles a prochiral axle. Here, we show that both stereogenic units can be accessed using equivalent strategies, with a single weak stereodifferentiating interaction sufficient for moderate to excellent stereoselectivity.

A redox switch allows binding of Fe(II) and Fe(III) ions in the cyanobacterial iron-binding protein FutA from .

The marine cyanobacterium is a main contributor to global photosynthesis, whilst being limited by iron availability. Cyanobacterial genomes generally encode two different types of FutA iron-binding proteins: periplasmic FutA2 ABC transporter subunits bind Fe(III), while cytosolic FutA1 binds Fe(II). Owing to their small size and their economized genome ecotypes typically possess a single gene.

A Platform Approach to Cleavable Macrocycles for the Controlled Disassembly of Mechanically Caged Molecules.

Inspired by interlocked oligonucleotides, peptides and knotted proteins, synthetic systems where a macrocycle cages a bioactive species that is "switched on" by breaking the mechanical bond have been reported. However, to date, each example uses a bespoke chemical design. Here we present a platform approach to mechanically caged structures wherein a single macrocycle precursor is diversified at a late stage to include a range of trigger units that control ring opening in response to enzymatic, chemical, or photochemical stimuli.

Discovery and Optimization of Narrow Spectrum Inhibitors of Tousled Like Kinase 2 (TLK2) Using Quantitative Structure Activity Relationships.

The oxindole scaffold has been the center of several kinase drug discovery programs, some of which have led to approved medicines. A series of two oxindole matched pairs from the literature were identified where TLK2 was a potent off-target kinase. The oxindole has long been considered a promiscuous inhibitor template, but across these 4 specific literature oxindoles TLK2 activity was consistent, while the kinome profile was radically different from narrow to broad spectrum coverage.

Chirality: a key parameter in chemical probes.

Many small molecule bioactive and marketed drugs are chiral. They are often synthesised from commercially available chiral building blocks. However, chirality is sometimes incorrectly assigned by manufacturers with consequences for the end user ranging from: experimental irreproducibility, wasted time on synthesising the wrong product and reanalysis, to the added cost of purchasing the precursor and resynthesis of the correct stereoisomer.

Machine Learning-Guided Development of Trialkylphosphine Ni Dimers and Applications in Site-Selective Catalysis.

Owing to the unknown correlation of a metal's ligand and its resulting preferred speciation in terms of oxidation state, geometry, and nuclearity, a rational design of multinuclear catalysts remains challenging. With the goal to accelerate the identification of suitable ligands that form trialkylphosphine-derived dihalogen-bridged Ni dimers, we herein employed an assumption-based machine learning approach. The workflow offers guidance in ligand space for a desired speciation without (or only minimal) prior experimental data points.

Synthesis and Structural Characterization of Copper Complexes Containing "R-Substituted" Bis-7-Azaindolyl Borate Ligands.

The coordination chemistry of scorpionate ligands based on borates containing the 7-azaindole heterocycle is relatively unexplored. Thus, there is a requirement to further understand their coordination chemistry. This article outlines the synthesis and characterization of a family of complexes containing anionic flexible scorpionate ligands of the type [(R)(bis-7-azaindolyl)borohydride] ([]), where R = Me, Ph or naphthyl.

A catenane that is topologically achiral despite being composed of oriented rings.

Catenanes-molecules comprising two interlocking rings held together like links in a chain-are topologically non-trivial: a catenane is a topological isomer of its separated rings, but the rings cannot be disconnected without bond scission. Catenanes can exist as topological enantiomers if both rings have directionality conferred by a defined atom sequence, but this has led to the assumption that the stereochemistry of chiral catenanes composed of oriented rings is inherently topological in nature. Here we show that this assumption is incorrect by synthesizing an example that contains the same fundamental stereogenic unit but whose stereochemistry is Euclidean.

Fluorine-based Zn salan complexes.

We synthesised and characterised the racemic and chiral versions of two Zn salan fluorine-based complexes from commercially available materials. The complexes are susceptible to absorbing HO from the atmosphere. In solution (DMSO-HO) and at the millimolar level, experimental and theoretical studies identify that these complexes exist in a dimeric-monomeric equilibrium.

Chiral CoY Propeller-Shaped Chemosensory Platforms Based on F-NMR.

Two propeller-shaped chiral CoY complexes built from fluorinated ligands are synthesized and characterized by single-crystal X-ray diffraction (SXRD), IR, UV-vis, circular dichroism (CD), elemental analysis, thermogravimetric analysis (TGA), electron spray ionization mass spectroscopy (ESI-MS), and NMR (H, C, and F). This work explores the sensing and discrimination abilities of these complexes, thus providing an innovative sensing method using a F NMR chemosensory system and opening new directions in 3d/4f chemistry. Control experiments and theoretical studies shed light on the sensing mechanism, while the scope and limitations of this method are discussed and presented.

Fe in the high-spin state in dimethylammonium bis[3-ethoxysalicylaldehyde thiosemicarbazonato(2-)-κO,N,S]ferrate(III).

The synthesis and crystal structure (100 K) of the title compound, [(CH)NH][Fe(CHONS)], are reported. The asymmetric unit consists of an octahedral [Fe(L)] fragment, where L is 3-ethoxysalicylaldehyde thiosemicarbazonate(2-), and a dimethylammonium cation. Each L ligand binds with the thiolate S, the imine N and the phenolate O atoms as donors, resulting in an FeSNO chromophore.

Synthesis and Kr NMR spectroscopy of Kr@C.

Synthesis of Kr@C is achieved by quantitative high-pressure encapsulation of the noble gas into an open-fullerene, and subsequent cage closure. Krypton is the largest noble gas entrapped in C using 'molecular surgery' and Kr@C is prepared with >99.4% incorporation of the endohedral atom, in 4% yield from C.

Solvent-Free Synthesis of Core-Functionalised Naphthalene Diimides by Using a Vibratory Ball Mill: Suzuki, Sonogashira and Buchwald-Hartwig Reactions.

Solvent-free synthesis by using a vibratory ball mill (VBM) offers the chance to access new chemical reactivity, whilst reducing solvent waste and minimising reaction times. Herein, we report the core functionalisation of N,N'-bis(2-ethylhexyl)-2,6-dibromo-1,4,5,8-naphthalenetetracarboxylic acid (Br -NDI) by using Suzuki, Sonogashira and Buchwald-Hartwig coupling reactions. The products of these reactions are important building blocks in many areas of organic electronics including organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs) and organic photovoltaic cells (OPVCs).

Scale-up and optimization of the synthesis of dual CBP/BRD4 inhibitor ISOX-DUAL.

ISOX-DUAL is a dual inhibitor of CBP/p300 (IC = 0.65 μM) and BRD4 (IC = 1.5 μM) bromodomains, and a useful chemical probe for epigenetic research.

Reversible P-P bond cleavage at an iridium(III) metal centre.

Treatment of a κ-P-monodentate bicyclic diphosphane iridium(III) complex with a labile gold(I) precursor afforded an unusual Ir/Au complex in which the P-P single bond has been cleaved. This reaction was cleanly reversed upon addition of tertiary phosphine. Carbon-carbon bond activation, across neighbouring PCN rings of the coordinated bicyclic diphosphane, occurred upon thermolysis of the Ir/Au complex.

Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds.

The pentafluorosulfanyl (-SF ) functional group is of increasing interest as a bioisostere in medicinal chemistry. A library of SF -containing compounds, including amide, isoxazole, and oxindole derivatives, was synthesised using a range of solution-based and solventless methods, including microwave and ball-mill techniques. The library was tested against targets including human dihydroorotate dehydrogenase (HDHODH).

Fe in a high-spin state in bis(5-bromosalicylaldehyde 4-ethylthiosemicarbazonato-κO,N,S)ferrate(III) nitrate monohydrate, the first example of such a cationic Fe complex unit.

The synthesis and crystal structure (100 K) of the title compound, [Fe(CHBrNOS)]NO·HO, is reported. The asymmetric unit consists of an octahedral [Fe(HL)] cation, where HL is H-5-Br-thsa-Et or 5-bromosalicylaldehyde 4-ethylthiosemicarbazonate(1-) {systematic name: 4-bromo-2-[(4-ethylthiosemicarbazidoidene)methyl]phenolate}, a nitrate anion and a noncoordinated water molecule. Each HL ligand binds via the thione S, the imine N and the phenolate O atom, resulting in an FeSNO chromophore.

A chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes.

Rotaxanes can display molecular chirality solely due to the mechanical bond between the axle and encircling macrocycle without the presence of covalent stereogenic units. However, the synthesis of such molecules remains challenging. We have discovered a combination of reaction partners that function as a chiral interlocking auxiliary to both orientate a macrocycle and, effectively, load it onto a new axle.

Room-Temperature Cu(II) Radical-Triggered Alkyne C-H Activation.

A dimeric Cu(II) complex [Cu(II)L(μ-Cl)Cl] () built from an asymmetric tridentate ligand (2-(((2-aminocyclohexyl)imino)methyl)-4,6-di--butylphenol) and weakly coordinating anions has been synthesized and structurally characterized. In dichloromethane solution, exists in a monomeric [Cu(II)LCl] () (85%)-dimeric () (15%) equilibrium, and cyclic voltammetry (CV) and electron paramagnetic resonance (EPR) studies indicate structural stability and redox retention. Addition of phenylacetylene to the CHCl solution populates and leads to the formation of a transient radical species.

Electrochemical oxidative -selective C(sp)-H chlorination of acrylamides.

An electrochemical method for the oxidative -selective C(sp)-H chlorination of acrylamides has been developed. This catalyst and organic oxidant free method is applicable across various substituted tertiary acrylamides, and provides access to a broad range of synthetically useful -β-chloroacrylamides in good yields (22 examples, 73% average yield). The orthogonal derivatization of the products was demonstrated through chemoselective transformations and the electrochemical process was performed on gram scale in flow.