A fluorescent ammonia sensor based on a porphyrin cobalt(II)-dansyl complex

Detecting and measuring the concentration of ammonia is of interest in many scientific and technological areas. A porphyrin based cobalt(II) complex with a dansyl fluorophore has been synthesized and investigated as a ‘turn-on’ fluorescent ammonia sensor. Over sixfold increase in fluorescence emission occurs upon the treatment of NH₃ to [Co(TPP)(Ds-pip)] sensor solution, resulting from NH₃-induced displacement of the axially coordinated fluorophore.     

First X-ray structural characterisation of host-guest interactions in tetra-tetrazole macrocycles

The syntheses of tetra-tetrazole macrocycles, containing two 1,3-bis(tetrazole)benzene units linked by a variety of n-alkyl (n=3, 5, 7 or 9 carbon atoms) chain lengths, are described. The crystal structures of two 1,3-bis(tetrazole)benzenes containing pendant bromoalkyl chains (n=3 or 5) are reported. A tetra-tetrazole macrocycle has also been structurally characterised and contains an unexpected ‘host-guest’ interaction through binding of a chloroform solvent molecule. The resulting deviation of the macrocycle from planarity results from a combination of the ‘host-guest’ interaction and strong intermolecular interactions between adjacent tetrazole and phenylene rings.     

Formal synthesis of the piperidine alkaloid (±)-prosophylline using polymer-supported dihydro-2H-pyridin-3-one

The use of polymer-supported 2,6-disubstituted-dihydro-2H-pyridin-3-one, as the ‘polymorphic’ core molecule for the formal synthesis of the piperidine alkaloid (±)-prosophylline is presented.     

Solid-phase synthesis of polyfunctional polylysine dendrons using aldehyde linkers

A straightforward method for the solid-phase synthesis of C-terminally modified polylysine dendrons has been developed by applying bisalkoxybenzaldehyde and trisalkoxybenzaldehyde linkers. The method has been used for the synthesis of polylysine dendrons with a variety of C-terminal ‘tail groups’ such as alkyl, propargyl, and dansyl to give dendrons in high crude purity. Furthermore, the method was successful for the synthesis of dendrons with multiple N-terminal pentapeptide groups together with C-terminal alkyl and propargyl tail groups. Finally, the method was shown to be well-suited for automated synthesis.     

Toehold-mediated DNA displacement-based surface-enhanced Raman scattering DNA sensor utilizing an Au–Ag bimetallic nanodendrite substrate

A simple and sensitive surface enhanced Raman scattering (SERS)-based DNA sensor that utilizes the toehold-mediated DNA displacement reaction as a target-capturing scheme has been demonstrated. For a SERS substrate, Au–Ag bimetallic nanodendrites were electrochemically synthesized and used as a sensor platform. The incorporation of both Ag and Au was employed to simultaneously secure high sensitivity and stability of the substrate. An optimal composition of Ag and Au that satisfied these needs was determined. A double-strand composed of ‘a probe DNA (pDNA)’ complementary to ‘a target DNA (tDNA)’ and ‘an indicator DNA tagged with a Raman reporter (iDNA)’ was conjugated on the substrate. The conjugation made the reporter molecule close to the surface and induced generation of the Raman signal. The tDNA released the pre-hybridized iDNA from the pDNA via toehold-mediated displacement, and the displacement of the iDNA resulted in the decrease of Raman intensity. The variation of percent intensity change was sensitive and linear in the concentration range from 200 fM to 20 nM, and the achieved limit of detection (LOD) was 96.3 fM, superior to those reported in previous studies that adopted different signal taggings based on such as fluorescence and electrochemistry.     

Triangle-shaped polycyclic aromatics based on tribenzocoronene: facile synthesis and physical properties

A series of triangle-shaped polycyclic aromatics have been developed according to a facile synthetic protocol with high yields. As revealed by X-ray single crystal data, their molecular conformation and packing arrangement are significantly influenced by the electronic properties and steric bulk of peripheral subunits. The ‘saddle’-shaped hexahalotribenzocoronenes (ClTBC and FTBC) possess C₂ symmetric structures and can self-assemble into well-defined columnar structures, dramatically different from hexabutyoxytribenzocoronene (TBC), which adopts a C₃ symmetric ‘double-concave’ structure and less efficient packing arrangement. In the compound trithiophenocoronene (TTC), the five-membered corner rings produce a more open bay-region periphery alleviating intramolecular steric congestion. As a result, the molecule adopts an almost planar conformation.     

Microchip device for rapid screening and fingerprint identification of phenolic pollutants

A new microchip protocol has been developed for rapid measurements of the ‘total’ content of phenolic compounds, as well as for a detailed fingerprint identification of the ‘individual’ ones. The protocol involves the use of a microchip flow-injection analysis for fast screening and early detection of phenols and switching to the separation (fingerprint) mode once such compounds are detected. This is readily accomplished by exchanging the run buffers in the separation channel. While operating with an acidic run buffer (pH 5) offers high speed flow-injection measurements of the ‘total’ phenolic content, on chip switching to a basic buffer (pH 8) leads to ionization of the phenolic compounds and to their effective separation and detection. Under optimum conditions, assay rates of about 120 and 18 samples/h can be realized for the ‘total’ and ‘individual’ measurements, respectively. The effect of the buffer pH, switching (washing) time, applied voltages and other relevant variables, is described. The concept is illustrated in connection to amperometric detection and is attractive for a wide range of environmental-monitoring applications.     

Fully automated immunoassay for detection of prostate-specific antigen using nano-magnetic beads and micro-polystyrene bead composites, 'Beads on Beads'

Magnetic beads have served as a conventional bioassay platform in biotechnology. In this study, a fully automated immunoassay was performed using novel nano- and microbead-composites constructed by assembling nano-magnetic beads onto polystyrene microbeads, designated ‘Beads on Beads’. Nano-sized bacterial magnetic particles (BacMPs) displaying the immunoglobulin G (IgG)-binding domain of protein A (ZZ domain) were used for the construction of ‘Beads on Beads’ via the interaction of biotin-streptavidin. The efficient assembly of ‘Beads on Beads’ was performed by gradual addition of biotin-labeled BacMPs onto streptavidin-coated polystyrene microbeads. Approximately 2000 BacMPs were uniformly assembled on a single microbead without aggregation. The constructed ‘Beads on Beads’ were magnetized and separated from the suspension by using an automated magnetic separation system with a higher efficiency than BacMPs alone. Furthermore, fully automated detection of prostate-specific antigens was performed with the detection limit of 1.48 ng mL⁻¹. From this preliminary assay, it can be seen that ‘Beads on Beads’ could be a powerful tool in the development of high-throughput, fully automated multiplexed bioassays.     

Temperature-driven on/off fluorescent indicator of pH window: an anthracene-conjugated thermoresponsive polymer

A simple copolymer, poly(NIPAM-co-N_AN), consisting of N-isopropylacrylamide (NIPAM) and 9-aminomethylanthracene (N_AN) units behaves as a temperature-driven on/off fluorescence indicator of pH window (2-12): showing an ‘on-off’ fluorescence intensity profile against the pH window at 15 °C, while showing an ‘off-on-off’ profile at 34 °C.     

An efficient synthesis of l-allono-1,4-lactone from 2,3:5,6-di-O-isopropylidene-d-mannono-1,4-lactone

We reported herein an efficient synthesis of l-allono-1,4-lactone from 2,3:5,6-di-O-isopropylidene-d-mannono-1,4-lactone in five steps. The key feature of this method involved a one-pot, ‘double inversion’ procedure at the stereocenters of C-4 and C-5 of d-mannono-1,4-lactone to afford the target molecule.     

Pre-analytical method for NMR-based grape metabolic fingerprinting and chemometrics

Although metabolomics aims at profiling all the metabolites in organisms, data quality is quite dependent on the pre-analytical methods employed. In order to evaluate current methods, different pre-analytical methods were compared and used for the metabolic profiling of grapevine as a model plant. Five grape cultivars from Portugal in combination with chemometrics were analyzed in this study. A common extraction method with deuterated water and methanol was found effective in the case of amino acids, organic acids, and sugars. For secondary metabolites like phenolics, solid phase extraction with C-18 cartridges showed good results. Principal component analysis, in combination with NMR spectroscopy, was applied and showed clear distinction among the cultivars. Primary metabolites such as choline, sucrose, and leucine were found discriminating for ‘Alvarinho’, while elevated levels of alanine, valine, and acetate were found in ‘Arinto’ (white varieties). Among the red cultivars, higher signals for citrate and GABA in ‘Touriga Nacional’, succinate and fumarate in ‘Aragonês’, and malate, ascorbate, fructose and glucose in ‘Trincadeira’, were observed. Based on the phenolic profile, ‘Arinto’ was found with higher levels of phenolics as compared to ‘Alvarinho’. ‘Trincadeira’ showed lowest phenolics content while higher levels of flavonoids and phenylpropanoids were found in ‘Aragonês’ and ‘Touriga Nacional’, respectively. It is shown that the metabolite composition of the extract is highly affected by the extraction procedure and this consideration has to be taken in account for metabolomics studies.     

Dipyridinocalixcrown/diiodoperfluorocarbon binary host systems for CsI: structural studies and fluorous phase extraction of caesium

A mixture of partial cone 2,4-bis[(2-pyridylmethyl)oxy]-(1,3)-p-tert-butylcalix[4]crown-6, hexadecafluoro-1,8-diiodooctane and CsI in EtOH produces a crystalline ‘supramolecular salt’. In the solid state the caesium ion of the ‘supercation’ is encapsulated inside the cavity created by the crown ether loop, the picolyl and the inverted phenyl moieties, while the two iodide ions of the ‘superanion’ form a discrete five-component aggregate held together by co-existing hydrogen and halogen bonds. Similar calix/CsI/iodofluorocarbon adducts are shown to exist also in solution. In a prototypical study, a combination of this calixcrown and liquid octafluoro-1,4-diiodobutane acts as an effective ‘binary host’ system for the selective extraction of CsI from aqueous to fluorous phase.     

Dispersive kinetic models for isothermal solid-state conversions and their application to the thermal decomposition of oxacillin

The authors recently published works in which the use of two novel equations for modeling the dispersive kinetics observed in various solid-state conversions are described. These equations are based on the assumptions of a ‘Maxwell-Boltzmann (M-B)-like’ distribution of activation energies and a first-order rate law. In the present work, it is shown that it may be possible to expand the approach to include mechanisms other than first-order, i.e. some of those commonly encountered in the field of thermal analysis, thus obtaining ‘dispersive versions’ of these kinetic models. The application of these dispersive kinetic models to the slightly sigmoidal, isothermal conversion-time (x-t) data of Rodante and co-workers for the degradation of the antibiotic, oxacillin, is described. This is done in an effort to test the limitations of the proposed dispersive models in describing kinetic data which is not clearly sigmoidal (i.e. as shown in previous works). Finally, it is demonstrated that, using graphical analysis, the typically sigmoidal x-t plots of first-order dispersive processes are the direct result of (asymmetric) activation energy distributions that are either ‘∩-shaped’ (for heterogeneous conversions) or ‘∪-shaped’ (for homogeneous conversions) in appearance, i.e. when the activation energy is plotted as a function of conversion. This finding lends support to the founding hypothesis of the authors’ approach for modeling dispersive kinetic processes: the existence of ‘M-B-like’ distributions of activation energies.     

A practical synthesis of carbamates using an ‘in-situ’ generated polymer-supported chloroformate

A versatile method for the synthesis of carbamates from an ‘in-situ’ generated polymer-supported chloroformate resin is presented. BTC (bis-trichloromethyl carbonate) is used as phosgene equivalent to afford a supported chloroformate, which, by sequential ‘one-pot’ reaction with a variety of alcohols and amines, furnishes the corresponding carbamates in high yields and purities.     

A ‘one-pot’ synthesis of α-1,2,4-oxadiazolo esters from malonic diesters and amidoximes under solvent-free conditions

A ‘one-pot’ procedure for synthesis of α-1,2,4-oxadiazolo esters from malonic diesters and amidoximes under solvent-free conditions is described. It is likely that this reaction goes through a ketene intermediate generated from the malonic diester by elimination of a molecule of alcohol.     

Synthesis of a cytisine/epibatidine hybrid: a radical approach

With the aim of developing a new ligand of neuronal nicotinic receptors (nAChRs), ionic, and radical routes to the synthesis of a cytisine/epibatidine hybrid were studied. The key step of the convergent synthesis was an unprecedented intramolecular coupling between a primary radical and a pyridine heterocycle. The target compound ‘6,11-diaza’ was formed with its ‘4,11-diaza’ regioisomer (‘6,11″/’4,11″: 70/30). Both compounds exhibited a nanomolar affinity at the α₄β₂ nAChR subtype, slightly better for the unexpected regioisomer [K_i (nM) target compound and its regioisomer: 3.5 and 0.5 nM, respectively].     

‘Two-point’-bound supramolecular complexes from semi-rigidified dipyridine receptors and zinc porphyrins

Two linear compounds 1 and 2 have been designed and synthesized as new receptors for zinc porphyrins. Both compounds consist of two folded aromatic amide moieties, which are connected with an acetylene linker in 1 or directly in 2. The rigid conformations of their folded moieties are stabilized by intramolecular tri-centered hydrogen bonding, while the whole molecule adopts a ‘S’- or ‘C’-styled conformation depending on the relative orientation of the two rigid moieties. Two pyridine units are introduced at the ends of 1 and 2 for the complexation of zinc porphyrin guests. Although the ¹H NMR investigation indicated that both compounds can bind two zinc porphyrin guests at high concentrations (≥5 mM) in chloroform, the UV-vis studies revealed that, at low concentration of 1 and 2 (4 μM), both compounds complex one zinc porphyrin guest to form structurally unique ‘two-point’-bound 1:1 complexes. The association constants of the 1:1 complexes have been determined with the UV-vis titration experiments.     

Synthesis and biological evaluation of anthranilamide-based non-peptide mimetics of ω-conotoxin GVIA

Non-peptide mimetics based on an anthranilamide ‘scaffold’ possessing fragments that mimic Lys2, Tyr13 and Arg17 in ω-conotoxin GVIA have been prepared. Compounds were assayed for binding to the voltage-gated calcium channels Ca_v2.2 (‘N-type’) and Ca_v2.1 (‘P/Q-type’) in rat brain. The primary synthetic target, 2-(6-amino-hexanoylamino)-5-(3-guanidino-propoxy)-N-[4-(4-hydroxyphenoxy)-phenyl]-benzamide (2a), exhibited low μM binding to Ca_v2.2 and was more than 30-fold selective for Ca_v2.2 over Ca_v2.1.     

Dansylated aminopropyl controlled pore glass: a model for silica-liquid solvation

We have prepared a series of aminopropyl controlled pore glass (CPG) particles that have been labeled with a solvatochromic fluorescent probe molecule (dansyl). We report on the behavior of the attached dansyl reporter as a function of dansyl-to-amine molar ratio (i.e., dansyl loading), solvent dipolarity, and surface-residue end capping. In these experiments, we systematically adjust the dansyl loading by 10(5); a range much larger than ever explored. The dansylated CPG particles were also end capped with trimethylchlorosilane to derivatize most of the residual silanol and/or aminopropyl groups. The attached dansyl molecules can be surrounded by other dansyl molecules; they can be distributed within an ensemble of sites with differing physicochemical properties, and/or they can be distributed in sites that are restrictive to dansyl motion and/or solvent inaccessible. At high dansyl loadings, the majority of the dansyl groups are solvated by other dansyl moieties and solvent does not significantly alter the local microenvironment surrounding the average dansyl molecule (i.e., the cybotactic region) to any significant level. At intermediate dansyl loadings, the average distance between the dansyl groups increases and solvent is able to access/solvate/wet the dansyl groups and alter their cybotactic region to a greater extent. At the lowest dansyl loadings studied, the results suggest that these dansyl moieties are localized within solvent inaccessible/restrictive SiO2 sites (e.g., small pores).