Controlling the Helical Pitch of Foldamers Through Terminal Functionality: A Solid State Study.

Developing new methods to control the size and shape of the helical structures adopted by foldamers is highly important as the secondary structure displayed by these supramolecular scaffolds often dictates their activity and function. Herein, we report on a systematic study demonstrating that the helical pitch of ortho-azobenzene/2,6-pyridyldicarboamide foldamers can be readily controlled through the nature of the terminal functionality. Remarkably, simply through varying the end group of the foldamer, and without modifying any other structural features of the scaffold, the helical pitch can be over doubled in magnitude (from 3.4 Å to 7.3 Å). Additionally, crystallographic analysis of a library ten foldamers has identified general trends in the influence of a range of terminal functionalities, including carboxylbenzyl (Cbz), diphenylcarbamyl (N(Ph)2), ferrocene (Fc) and tert-butyloxycarbonyl (Boc), in controlling the folding behaviour of these supramolecular scaffolds. These studies could prove useful in the future development of functional foldamers which adopt specific sizes and shapes.

Dual, Photo-Responsive and Redox-Active Supramolecular Foldamers.

We report on dual, light-responsive and redox-active foldamers that demonstrate reversible and robust stimuli-induced behaviour. Herein, UV/Vis, 1H NMR and circular dichroism (CD) spectroscopy and cyclic voltammetry have been used to establish the reversibility and highly robust nature of the light- and redox-driven behaviour of these new foldamers with minimal levels of fatigue observed even upon multiple cyclic treatments with irradiative/non-irradiative and oxidative/reductive conditions. This proof-of-concept work paves the way towards the creation of novel stimuli-responsive foldamers of increasing sophistication capable of demonstrating reversible and robust responses to multiple distinct stimuli.

Regiodivergent Synthesis of 4- and 5-Sulfenyl Oxazoles from Alkynyl Thioethers.

The regiodivergent synthesis of 4- and 5-sulfenyl oxazoles from 1,4,2-dioxazoles and alkynyl thioethers has been achieved. Gold-catalysed conditions are used to favour the formation of 5-sulfenyl oxazoles via ß-selective attack of the nitrenoid relative to the sulfenyl group. In contrast, 4-sulfenyl oxazoles are formed by α-selective reaction under Brønsted acid conditions from the same substrates. The nature of stabilising gold-sulfur interactions have been investigated by natural bond orbital analysis, showing that the S→Au interactions are significantly stronger in the intermediate that favours the 5-sulfenyl oxazoles. A kinetic survey identifies catalyst inhibition processes. This study into the regiodivergent methods includes the development of telescoped annulation-oxidation protocols for regioselective access to oxazole sulfoxides and sulfones.

Azophosphines: Synthesis, Structure and Coordination Chemistry.

The conceptual replacement of nitrogen with phosphorus in common organic functional groups unlocks new properties and reactivity. The phosphorus-containing analogues of triazenes are underexplored but offer great potential as flexible and small bite-angle ligands. This manuscript explores the synthesis and characterisation of a family of air-stable azophosphine-borane complexes, and their subsequent deprotection to the free azophosphines. These compounds are structurally characterised, both experimentally and computationally, and highlight the availability of the phosphorus lone pair for coordination. This is confirmed by demonstrating that neutral azophosphines can act as ligands in Ru complexes, and can coordinate as monodentate or bidentate ligands in a controlled manner, in contrast to their nitrogen analogues.

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts.

A polysubstituted 3-aminoimidazo[5,1-b]oxazol-6-ium framework has been accessed from a new nitrenoid reagent by a two-step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions.

Reversible conformational switching of a photo-responsive ortho-azobenzene/2,6-pyridyldicarboxamide heterofoldamer.

We report on a convenient synthetic route to rapidly access a new photo-responsive ortho-azobenzene/2,6-pyridyldicarboxamide heterofoldamer. The adoption of a stable helical conformation has been established for this scaffold in both the solid state and in solution using single crystal X-ray diffraction and circular dichroism (CD) spectroscopy respectively. Reversible control over the stimuli-driven structural re-ordering of the supramolecular scaffold, from a stable helical conformation under non-irradiative conditions, to a less well-ordered state under irradiative conditions, has been identified. The robust nature of the responsive, conformational, molecular switching behaviour has been determined using UV/Vis, 1H NMR and CD spectroscopy. Minimal loss in the efficiency of the stimuli-driven, structural re-ordering processes of the foldamer scaffold is observed, even upon multiple cyclic treatments with irradiative/non-irradiative conditions.

Diastereoselective Self-Assembly of Low-Symmetry Pdn L2n Nanocages through Coordination-Sphere Engineering.

Metal-organic cages (MOCs) are popular host architectures assembled from ligands and metal ions/nodes. Assembling structurally complex, low-symmetry MOCs with anisotropic cavities can be limited by the formation of statistical isomer libraries. We set out to investigate the use of primary coordination-sphere engineering (CSE) to bias isomer selectivity within homo- and heteroleptic Pdn L2n cages. Unexpected differences in selectivities between alternative donor groups led us to recognise the significant impact of the second coordination sphere on isomer stabilities. From this, molecular-level insight into the origins of selectivity between cis and trans diastereoisomers was gained, highlighting the importance of both host-guest and host-solvent interactions, in addition to ligand design. This detailed understanding allows precision engineering of low-symmetry MOC assemblies without wholesale redesign of the ligand framework, and fundamentally provides a theoretical scaffold for the development of stimuli-responsive, shape-shifting MOCs.

Studies towards the Synthesis of (+)-Dictyoxetane.

The dolabellane-type diterpene dictyoxetane represents a significant challenge to synthetic organic chemistry. Methodology directed towards the total synthesis of naturally occurring (+)-dictyoxetane is reported. Catalytic asymmetric synthesis of the trans-hydrindane ring system is achieved through chemoselective deoxygenation of the Hajos-Parrish ketone. An alternative to the Garst-Spencer furan annulation is developed for the synthesis of a 2,5-dimethyl, tetrasubstituted furan, employing a tandem 5-exo-dig alcohol to alkyne cyclisation/aromatisation reaction as a key step. The (4+3) cycloaddition reaction of an oxyallyl cation with a tetrasubstituted furan is established on a cyclohexanone-derived model system, and a range of related (4+3) cycloadditions investigated on a homochiral, trans-hydrindane-fused furan, where regio- and diastereoselectivity is required for the natural product synthesis. In an alternative (4+2) Diels-Alder approach, a C2 -symmetric vinyl sulfoxide-based chiral ketene equivalent is used to prepare oxanorbornenes with the same oxygen bridge stereochemistry found in the 2,7-dioxatricyclo[4.2.1.03,8 ]nonane ring system of the natural product.

Enhancing Dual-State Emission in Maleimide Fluorophores through Fluorocarbon Functionalisation.

Herein, a library of trifluoroethyl substituted aminomaleimide derivatives are reported with small size and enhanced emissions in both solution and solid-state. A diCH2 CF3 substituted aminochloromaleimide exhibits the most efficient dual-state emission (Φf >50 % in solution and solid-state), with reduced quenching from protic solvents. This is attributed to the reduction of electron density on the maleimide ring and suppressed π-π stacking in the solid-state. This mechanism was explored in-depth by crystallographic analysis, and modelling of the electronic distribution of HOMO-LUMO isosurfaces and NCI plots. Hence, these dual-state dyes overcome the limitations of single-state luminescence and will serve as an important step forward for this rapidly developing nascent field.

Photo- and Electrochemical Dual-Responsive Iridium Probe for Saccharide Detection.

Dual detection systems are of interest for rapid, accurate data collection in sensing systems and in vitro testing. We introduce an IrIII complex with a boronic acid receptor site attached to the 2-phenylpyridine ligand as an ideal probe with photo- and electrochemical signals that is sensitive to monosaccharide binding in aqueous solution. The complex displays orange luminescence at 618 nm, which is reduced by 70 and 40 % upon binding of fructose and glucose, respectively. The electro-chemiluminescent signal of the complex also shows a direct response to monosaccharide binding. The IrIII complex shows the same response upon incorporation into hydrogel matrices as in solution, thus demonstrating the potential of its integration into a device, as a nontoxic, simple-to-use tool to observe sugar binding over physiologically relevant pH ranges and saccharide concentrations. Moreover, the complex's luminescence is responsive to monosaccharide presence in cancer cells.

Glutathione peroxidase mimics based on conformationally-restricted, peri-like, 4,5-disubstituted fluorene dichalcogenides.

Glutathione peroxidase (GPx) regulates cellular peroxide levels through glutathione oxidation. GPx-mimics based on 4,5-disubstituted fluorene diselenides, their oxides, and ditellurides show catalytic activities consistent with conformational restriction about the dichalcogen bond.

Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding.

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.

Effect of Regiochemistry and Methylation on the Anticancer Activity of a Ferrocene-Containing Organometallic Nucleoside Analogue.

Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,Rp ), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1-(S,Rp ), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20 times less cytotoxic. On the other hand, methylated derivatives of 1-(S,Rp ) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,Rp ) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.

Aniline-containing derivatives of parthenolide: Synthesis and anti-chronic lymphocytic leukaemia activity.

Parthenolide exhibits anti-leukaemia activity, whilst its synthetic modification to impart improve drug-like properties, including 1,4-conjugate addition of primary and secondary amines, have previously been used, 1,4-addition of aniline derivatives to parthenolide has not been fully explored. A protocol for such additions to parthenolide is outlined herein. Reaction conditions were determined using tulipane as a model Michael acceptor. Subsequently, aniline-containing parthenolide derivatives were prepared under the optimised conditions and single crystal X-ray diffraction structures were resolved for three of the compounds synthesised. The synthesised derivatives, along with compounds resulting from a side reaction, were tested for their in vitro anti-leukaemia activity using the chronic lymphocytic leukaemia (CLL) MEC1 cell line. Computational studies with the 2RAM protein structure suggested that the activity of the derivatives was independent of their in silico ability to dock with the Cys38 residue of NF-κB.

An Ion-Exchangeable MOF with Reversible Dehydration and Dynamic Structural Behavior (NH4 )2 [Zn2 (O3 PCH2 CH2 COO)2 ]⋠5 H2 O (BIRM-1).

(NH4 )2 [Zn2 (O3 PCH2 CH2 COO)2 ]⋅5 H2 O (BIRM-1) is a new metal phosphonate material, synthesized through a simple hydrothermal reaction between zinc nitrate and 3-phosphonopropionic acid, using urea and tetraethylammonium bromide as the reaction medium. In common with other metal-organic framework materials, BIRM-1 has a large three-dimensional porous structure providing potential access to a high internal surface area. Unlike most others, it has the advantage of containing ammonium cations within the pores and has the ability to undergo cation exchange. Additionally, BIRM-1 also exhibits a reversible dehydration behavior involving an amorphization-recrystallization cycle. The ability to undergo ion exchange and dynamic structural behavior are of interest in their own right, but also increase the range of potential applications for this material. Here the crystal structure of this new metal phosphonate and its ion exchange behavior with K+ as an exemplar are studied in detail, and its unusual structure-reviving property reported.

Synthesis and Characterization of a Series of Bis-homoleptic Cycloruthenates with Terdentate Ligands as a Family of Panchromatic Dyes.

A series of six homoleptic bis-cyclometalated ruthenium complexes, Ru(N^N^C)2, is reported where N^N^C is a 6-(2,4-difluoro-3-R3-phenyl)-4-R2-4'-R1-2,2'-bipyridine with R3 = -H or -CF3 and R2 and R1 = -COOEt or -CF3. An effective synthesis of the ligands and the complexes is described. The UV-visible absorption studies demonstrate that these complexes are panchromatic dyes absorbing up to 900 nm. Importantly, the onset of absorption depends only on the substitution on the metalated phenyl, whereas the intensity of absorption throughout the spectra is a function of substituents on both the phenyl and the bipyridine moieties. The same trend is observed in electrochemistry as the redox gap depends only on the substitution on the metalated phenyl, whereas the oxidation and reduction potentials are a function of substituents on both the phenyl and the bipyridine moieties. Preliminary tests as sensitizer for dye-sensitized solar cells demonstrate that the number of anchoring groups on the dye has a major influence on the device efficiency.

Tris-heteroleptic Iridium Complexes Based on Cyclometalated Ligands with Different Cores.

A series of tris-heteroleptic iridium complexes of the form [Ir(C^N1)(C^N2)(acac)] combining 2-phenylpyridine (ppy), 2-(2,4-difluorophenyl)pyridine (dFppy), 1-phenylpyrazole (ppz), and 1-(2,4-difluorophenyl)pyrazole (dFppz) as the C^N ligands have been synthesized and fully characterized by NMR, X-ray crystallography, UV-vis absorption and emission spectroscopy, and electrochemical methods. It is shown that "static properties" (e.g., absorption and emission spectra and redox potentials) are primarily dictated by the overall architecture of the complex, while "dynamic properties" (e.g., excited-state lifetime and radiative and nonradiative rate constants) are, in addition, sensitive to the specific positioning of the substituents. As a result, the two complexes [Ir(dFppy)(ppz)(acac)] and [Ir(ppy)(dFppz)(acac)] have the same emission maxima and redox potentials, but their radiative and nonradiative rate constants differ significantly by a factor ∼2. Then acetylacetonate (acac) was replaced by picolinate (pic), and two pairs of diastereoisomers were obtained. As expected, the use of pic as the ancillary ligand results in blue-shifted emission, stabilization of the oxidation potential, and improvement of the photoluminescence quantum yield, and only minor differences in the optoelectronic properties are found between the two diastereoisomers of each pair.

Blue and Green Phosphorescent Liquid-Crystalline Iridium Complexes with High Hole Mobility.

Blue- and green-emitting cyclometalated liquid-crystalline iridium complexes are realized by using a modular strategy based on strongly mesogenic groups attached to an acetylacetonate ancillary ligand. The cyclometalated ligand dictates the photophysical properties of the materials, which are identical to those of the parent complexes. High hole mobilities, up to 0.004 cm(2) V(-1) s(-1), were achieved after thermal annealing, while amorphous materials show hole mobilities of only approximately 10(-7) -10(-6) cm(2) V(-1) s(-1), similar to simple iridium complexes. The design strategy allows the facile preparation of phosphorescent liquid-crystalline complexes with fine-tuned photophysical properties.

Intercepting the Gold-Catalysed Meyer-Schuster Rearrangement by Controlled Protodemetallation: A Regioselective Hydration of Propargylic Alcohols.

The regioselective gold-catalysed hydration of propargylic alcohols to ß-hydroxy ketones can be achieved by diverting the gold-catalysed Meyer-Schuster rearrangement through the addition of a protic additive with a pKa of 7-9 such as p-nitrophenol, boric acid or a boronic acid. This provides an interesting alternative to an aldol reaction when combined with the straightforward addition of an alkyne to an aldehyde or ketone. The gold-catalysed reaction of an electron-deficient, sterically hindered propargylic alcohol with a boronic acid led to the formation of an unusually stable cyclic boron enolate.

High performance optical oxygen sensors based on iridium complexes exhibiting interchromophore energy shuttling.

A doubly pyrene-grafted bis-cyclometallated iridium complex with engineered electronically excited states demonstrates reversible electronic energy transfer between adjacent chromophores giving rise to extremely long-lived red luminescence in solution (τ = 480 µs). Time-resolved spectroscopic studies afforded determination of pertinent photophysical parameters including rates of energy transfer and energy distribution between constituent chromophores in the equilibrated excited molecule (ca. 98% on the organic chromophores). Incorporation into a nanostructured metal-oxide matrix (AP200/19) gave highly sensitive O2 sensing films, as the detection sensitivity was 200-300% higher than with the commonly used PtTFPP and approaches the sensitivity of the best O2-sensing dyes reported to date.