Chemical Chartographisis: a contemporary perspective in molecular design and synthesis.

The use of flexible molecular systems in solution, without strictly controlling their behaviour, has frequently been productive. Their potential could increase by a more holistic view of the reaction(s) process(es) in which they are involved. In this perspective, we introduce a broader approach - "Chemical Chartographisis" - and discuss three projects in detail to illustrate its potential. The topics involve bimetallic 3d/4f species and coordination compounds built from benzotriazole-based and (a)symmetric salan ligands and focus on catalytic and, in less detail, biological-related examples.

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. Further on, this could lead to loss of reputation, loss of funding, to safety and ethical concerns due to potential in vivo administration of the wrong form of a drug. It is our firm belief that more stringent control of chirality be provided by the supplier and, if needed, requested by the end user, to minimise the potential issues mentioned above. Certification of chirality would bring much needed confidence in chemical structure assignment and could be provided by a variety of techniques, from polarimetry, chiral HPLC, using known chiral standards, vibrational circular dichroism, and x-ray crystallography. A few case studies of our brushes with wrong chirality assignment are shown as well as some examples of what we believe to be good practice.

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 H2O from the atmosphere. In solution (DMSO-H2O) and at the millimolar level, experimental and theoretical studies identify that these complexes exist in a dimeric-monomeric equilibrium. We also investigated their ability to sense amines via19F NMR. In CDCl3 or d6-DMSO, strongly coordinating molecules (H2O or DMSO) are the limiting factor in using these easy-to-make complexes as chemosensory platforms since their exchange with analytes requires an extreme excess of the latter.

Chiral Co3Y Propeller-Shaped Chemosensory Platforms Based on 19F-NMR.

Two propeller-shaped chiral CoIII3YIII 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 (1H, 13C, and 19F). This work explores the sensing and discrimination abilities of these complexes, thus providing an innovative sensing method using a 19F 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.

Tubular glassy carbon microneedles with fullerene-like tips for biomedical applications.

Glassy carbon, in general, is made by the pyrolysis of polymeric materials and has been the subject of research for at least fifty years. However, as understanding its microstructure is far from straightforward, it continues to be an area of active research. Glassy carbon adopts different allotropes depending on the hybridizations of the C-C bond, that is, sp, sp2, or sp3 . Furthermore, a variety of short-range ordering effects can interact with each other and this, along with the effects of microporosity, grain boundaries, and defects, render this a fascinating material. Following the nanoarchitectonics concept of bottom-up creation of functional materials, we use methane rather than a polymer to form glassy carbon. Here we show that tubular glassy carbon microneedles with fullerene-like tips form when methane undergoes pyrolysis on a curved alumina surface. X-ray diffraction of these glassy carbon tubules shows long-range order with a d-spacing of 4.89 Å, which is indicative of glassy carbon. Raman spectroscopy shows the material to be graphitic in nature, and SEM shows the fullerene-like structure of the material. This work provides new insights into the structure of glassy carbons relevant to the application of glassy carbons as a biomaterial, for example, as a new form of carbon-based microneedles. Since metallic needles can introduce toxic/allergenic species into susceptible subjects, this alternative carbon-based microneedle form has great potential as a replacement biomedical material for metallic needles in the field of neural engineering and as acupuncture needles.

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

A dimeric Cu(II) complex [Cu(II)2L2(µ2-Cl)Cl] (1) built from an asymmetric tridentate ligand (2-(((2-aminocyclohexyl)imino)methyl)-4,6-di-tert-butylphenol) and weakly coordinating anions has been synthesized and structurally characterized. In dichloromethane solution, 1 exists in a monomeric [Cu(II)LCl] (1') (85%)-dimeric (1) (15%) equilibrium, and cyclic voltammetry (CV) and electron paramagnetic resonance (EPR) studies indicate structural stability and redox retention. Addition of phenylacetylene to the CH2Cl2 solution populates 1' and leads to the formation of a transient radical species. Theoretical studies support this notion and show that the radical initiates an alkyne C-H bond activation process via a four-membered ring (Cu(II)-O···H-Calkyne) intermediate. This unusual C-H activation method is applicable for the efficient synthesis of propargylamines, without additives, within 16 h, at low loadings and in noncoordinating solvents including late-stage functionalization of important bioactive molecules. Single-crystal X-ray diffraction studies, postcatalysis, confirmed the framework's stability and showed that the metal center preserves its oxidation state. The scope and limitations of this unconventional protocol are discussed.

Salpyran: A Cu(II) Selective Chelator with Therapeutic Potential.

We report the rational design of a tunable Cu(II) chelating scaffold, 2-(((2-((pyridin-2-ylmethyl)amino)ethyl)amino)methyl)phenol, Salpyran (HL). This tetradentate ligand is predicated to have suitable permeation, has an extremely high affinity for Cu compared to clioquinol (pCu7.4 = 10.65 vs 5.91), and exhibits excellent selectivity for Cu(II) over Zn(II) in aqueous media. Solid and solution studies corroborate the formation of a stable [Cu(II)L]+ monocationic species at physiological pH values (7.4). Its action as an antioxidant was tested in ascorbate, tau, and human prion protein assays, which reveal that Salpyran prevents the formation of reactive oxygen species from the binary Cu(II)/H2O2 system, demonstrating its potential use as a therapeutic small molecule metal chelator.

Skeletally Tunable Seven-Membered-Ring Fused Pyrroles.

We describe a copper-mediated method that enables the synthesis of seven-membered-ring fused pyrroles (7-mrFPs). The protocol proceeds via an in situ spiro-intermediate ring expansion and tolerates a library of 7-mrFP derivatives with a broad range of functional groups in a simple step with tangible parameters and substrate adaptations. These rare 7-mrFPs are now accessible on a millimolar scale, and selected examples exhibit high antioxidant activity.

Breaking the symmetry: C1-salans with (N-H) backbones.

We disclose a synthetic route that providess an unprecedented library of C1 salan ligands endowed with (N-H) backbones, previously limited to N-methylated backbones. Efforts to identify a generic complexation protocol to yield the corresponding Cu(II)-salan complexes demonstrate the scope and limitations of this approach.

Synthesis of trans-Mono(silyl)palladium(II) Bromide Complexes.

The stoichiometric reaction of cis-[Pd(ITMe)2(SiR3)2], where (SiR3 = SiMe3 and SiMe2Ph and ITMe = 1,3,4,5-tetramethylimidazol-2-ylidene) with allyl bromide affords the corresponding allylsilanes along with complexes of the type trans-[Pd(ITMe)2(SiR3)(Br)]. The structure of trans-[Pd(ITMe)2(SiMe2Ph)Br] 2b has been determined in the solid state and displays a slightly distorted square-planar geometry with the two N-heterocyclic carbene ligands in a trans-configuration.

Structural and Electronic Control of the Bidentate 1-(2-pyridyl)benzotriazole Ligand in Copper Chemistry with Application to Catalysis in the A3 Coupling Reaction.

The hybrid bidentate 1-(2-pyridyl)benzotriazole (pyb) ligand was introduced into 3d transition metal catalysis. Specifically, [CuII (OTf)2 (pyb)2 ]⋅2 CH3 CN (1) enables the synthesis of a wide range of propargylamines by the A3 coupling reaction at room temperature in the absence of additives. Experimental and high-level theoretical calculations suggest that the bridging N atom of the ligand imposes exclusive trans coordination at Cu and allows ligand rotation, while the N atom of the pyridine group modulates charge distribution and flux, and thus orchestrates structural and electronic precatalyst control permitting alkyne binding with simultaneous activation of the C-H bond via a transient CuI species.

Exploratory studies on azido-bridged complexes (Ni2+ and Mn2+) as dual colourimetric chemosensors for S2- and Ag+: combined experimental and theoretical outcomes with real field applications.

We report two isostructural dinuclear transition metal complexes [M2(HL)2(N3)4], where M = Ni2+ (BS-1), Mn2+ (BS-2), and HL is (2-methyl-2-((pyridin-2-ylmethyl)amino)propan-1-ol) and investigate them as molecular sensors towards hazardous entities. BS-1 shows high selectivity towards the S2- and Ag+ ions, easily observed by the naked eye colour change and its detection limit in aqueous solutions for the S2- ion was calculated as 0.55 µM with a binding constant of 3.28 × 105 M-1, while the limit for the Ag+ ion is 21.8 µM. Notably, BS-2 shows good selectivity towards the Ag+ ion with a detection limit of 10.84 µM. Spectroscopic and DFT studies shed light on the mechanistic course of interaction between the host and guest entities, suggesting a sulphide-mediated reduction of the azide mechanism. In a nutshell, these simple transition metal complexes were exploited for discriminately detecting hazardous analytes with real field applications in analytical science (via. "Dip-Stick" approach) as well as engineering science, which provides a significant contribution in the recent advancement of supramolecular chemistry.

Selective Photoinduced Reduction of Nitroarenes to N-Arylhydroxylamines.

We report the selective photoinduced reduction of nitroarenes to N-arylhydroxylamines. The present methodology facilitates this transformation in the absence of catalyst or additives and uses only light and methylhydrazine. This noncatalytic photoinduced transformation proceeds with a broad scope, excellent functional-group tolerance, and high yields. The potential of this protocol reflects on the selective and straightforward conversion of two general antibiotics, azomycin and chloramphenicol, to the bioactive hydroxylamine species.

Recent Bio-Advances in Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) have found uses in adsorption, catalysis, gas storage and other industrial applications. Metal Biomolecule Frameworks (bioMOFs) represent an overlap between inorganic, material and medicinal sciences, utilising the porous frameworks for biologically relevant purposes. This review details advances in bioMOFs, looking at the synthesis, properties and applications of both bioinspired materials and MOFs used for bioapplications, such as drug delivery, imaging and catalysis, with a focus on examples from the last five years.

Shedding light on the use of Cu(ii)-salen complexes in the A3 coupling reaction.

One Cu(ii) complex, {Cu(ii)L} (1S), has been synthesised, in two high yielding steps under ambient conditions, and characterised by single-crystal X-Ray diffraction (SXRD), IR, UV-Vis, circular dichroism (CD), elemental analysis, thermogravimetric analysis (TGA) and electron spray ionization mass spectroscopy (ESI-MS). This air-stable compound enables the generation, at room temperature and in open-air, of twenty propargylamines, nine new, from secondary amines, aliphatic aldehydes and alkynes with a broad scope with yields up to 99%. Catalyst loadings can be as low as 1 mol%, while the recovered material retains its structural integrity and can be used up to 5 times without loss of its activity. Control experiments, SXRD, cyclic voltammetry and theoretical studies shed light on the mechanism revealing that the key to success is the use of phenoxido salen based ligands. These ligands orchestrate topological control permitting alkyne binding with concomitant activation of the C-H bond and simultaneously acting as a template temporarily accommodating the abstracted acetylenic proton, and continuously generating, via in situ formed radicals and a Single Electron Transfer (SET) mechanism, a transient Cu(i) active site to facilitate this transformation. The scope and limitations of this protocol are discussed and presented.

Synthesis, structure and electrochemical characterization of an isopolytungstate (W4O16) held by MnII anchors within a superlacunary crown heteropolyanion {P8W48}.

An isopolyanion {W4O16} within an archetypal {P8W48} heteropolyanion assembly [(P8W48O184)(W4O16)K10Li4Mn10Na(H2O)50Cl2]15- (Mn10W4-P8W48) has been synthesized by the reaction of the cyclic superlacunary anion [H7P8W48O184]33- and Mn(ClO4)2·6H2O in 1 M LiCl solution medium at pH 8. The isolated compound has been characterized by single-crystal X-ray crystallography, powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, elemental analysis and thermogravimetric analysis. Electrochemical studies were also performed on Mn10W4-P8W48, which confirmed the presence of Mn centres bonded to the tungstic framework. The novel polyanion [(P8W48O184)(W4O16)K10Li4Mn10Na(H2O)50Cl2]15- is the first example of a macrocyclic complex, where an isopolyanion (W4O16)8- is embedded within the inner cavity of {P8W48} and is placed in position by six MnII cations as anchors, whereas the exocyclic coordination of four further MnII cations to {P8W48} yields an extended structure by linking neighbouring polyanions through {W-O-Mn-O-W} bridges. Furthermore, the polyanion Mn10W4-P8W48 is the first derivative of {P8W48} with six MnII ions (largest) coordinated to the inner side of the crown ring as anchors.

Solvent-Free Synthesis and Key Intermediate Isolation in Ni2Dy2 Catalyst Development in the Domino Ring-Opening Electrocyclization Reaction of Furfural and Amines.

A solvent-free methodology that yields trans-4,5-diaminocyclopent-2-enones, main domains of natural products and a variety of N-heterocycles, is described. The bimetallic catalyst [NiII2DyIII2L4(DMF)6] 2(OTf) 2(DMF) (1) promotes the domino reaction of furfural and amines, with loadings as low as 0.01%, under stirring or microwave-assisted conditions to afford the corresponding frameworks in very good to excellent yields. Crystallographic and theoretical studies shed light on the exclusive formation of the trans-diastereoisomers via a 4π-conrotatory electrocyclization process elucidating the key step in the catalytic process.

Zinc-dysprosium functionalized amyloid fibrils.

The heterometallic Zn2Dy2 entity bearing partially saturated metal centres covalently decorates a highly ordered amyloid fibril core and the functionalised assembly exhibits catalytic Lewis acid behaviour.

Twists to the Spin Structure of the Ln9-diabolo Motif Exemplified in Two {Zn2Ln2}[Ln9]{Zn2} Coordination Clusters.

Two pentadecanuclear Zn4Ln11 [with Ln = Gd(1) or Dy(2)] coordination clusters, best formulated as {Zn2Ln2}[Ln9]{Zn2}, are presented. The central {Ln9} diabolo core has a {Zn2Ln2} handle motif pulling at two outer Ln ions of the central core via two {ZnLn} units, which also invest the system with C2 point symmetry. The resulting cluster motif is supported on two Zn "feet", corresponding to the {Zn2} unit in the formula. A thorough investigation of the magnetic properties in the light of the properties of previously reported {Ln9} diabolo compounds was undertaken. Up to now, the spin structure of such diabolo motifs usually proves ambiguous. Our magnetic studies show that the orientation of the central spin in the {Gd9} diabolo plays a decisive role. In stabilizing the core by attachment of the {Zn}2+ "feet" and using the C2 symmetry related {ZnGd}5+ handles to influence the spin direction of the central Gd of the {Gd9} diabolo, we can understand why the "naked" {Gd9} diabolo shows ambiguous spin structure. This then allowed us to elucidate the single-molecule magnetic (SMM) properties of the Dy-based compound 2 through disentangling the magnetic properties of the isostructural Gd-based compound 1.