Photolariats: synthesis, metal ion complexation and photochromism

International audiencePhotolariat development, as an extension to the family of synthetic photochromic crown ether receptors, or photocrowns, is reported. Incorporated additional chelating groups, namely two anisoles or thioanisoles, contribute in completing the metal ion coordination sphere with different affinities and selectivities for a range of ions. Single-crystal X-ray diffraction analysis suggests that the thermally stable trans-form of the receptor is unsuitable for ion binding, consistent with spectrophotometric and NMR titration results, which is largely improved in the cis-form as the basis for the photocontrolled ion coordination/ejection. In terms of the azobenzene-containing receptor photochemistry, a photostationary state highly enriched in the cis-form (94:6, cis-/trans-) is reached, with slow thermal return (1.1-1.4 × 10− 5 s− 1) in the dark, which can undergo multiple cycles without discernable photodegradation

Ultrasensitive electrochemical genosensor for direct detection of specific RNA sequences derived from avian influenza viruses present in biological samples

An electrochemical genosensor based on an epoxyphenanthroline–Fe(III)–NH2-ssDNA layer for the detection of RNA derived from Avian Influenza is presented. The biosensor preparation consists of: (I) modification of gold electrodes with aminoethanethiol, (II) modification of the self-assembled monolayer of aminoethanethiol with 5,6-epoxy-5,6-dihydro-[1,10]-phenanthroline using “click” chemistry, (III) a first step of complexation of Fe(III) by 5,6-epoxy-5,6-dihydro-[1,10]-phenanthroline, (IV) a second step of complexation of Fe(III) by 5,6-epoxy-5,6-dihydro-[1,10]-phenanthroline, (V) immobilization of the single stranded amino-DNA probe via “click” chemistry between epoxy and amino groups. The interactions between the ssDNA probe and RNA targets were explored with Osteryoung Square Wave Voltammetry. The genosensor showed a remarkable detection limit of 3 copies/μL (5 aM) for RNA extracted from A/swan/Poland/305/06 (H5N1) containing a fully complementary sequence. A linear dynamic range for this sequence was observed from 3.0×103 to 3.0×105 [copies/μl]. RNA extracted from A/mallard/Poland/446/09 (H7N7), containing a non-complementary sequence, generated a much weaker response. Moreover, the developed genosensor allows to distinguish RNA present in biological samples having 2, 3 and 4 mismatches. This biosensing approach can become a potential alternative tool for detecting RNA samples in biomedical research and early clinical diagnosis of avian influenza viruses

Teaching Story without Struggle: Using Graded Readers and Their Audio Packs in the EFL Classroom

In recent years the support for extensive reading (ER) in English as a second or foreign language (ESL/EFL) programs has been compelling. When practicing extensive reading, the learner reads a wide variety of texts for pleasure and achieves a general understanding of the content while deciphering unknown words through context. This approach contrasts with intensive reading, a more traditional approach based on a slow, careful reading of a text, with goals of complete comprehension and the identification of specific details and information

The application of the click reaction in the synthesis of targeted drugs and MRI contrast agents.

The click reaction is a versatile tool in synthetic chemistry and in this thesis, the applicability of this reaction in the synthesis of targeted drugs and MRI contrast agents has been assessed. In the first part of the research, the reaction was used to construct conjugates of targeting agents and cytotoxic drugs, with applications in cancer treatment. The conclusions in this first part are dual, on one hand, the reaction, on one hand the reaction prevented the synthesis of a number of tirapazamine analogues (most likely due to the formation of insoluble copper complexes), on the other hand, the modular nature of the reaction and its orthogonality with most other reactions proved to enable and facilitate the synthesis of conjugates of RGD mimetics with tubuline polymerization inhibitors and conjugates of an NLS-peptide with a BODIPY PDT probe.In the second part of the thesis, the click reaction as a tool in the synthesis of specific MRI contrast agents has been evaluated. Firstly, the click reaction was used to demonstrate the ease and feasibility of the synthesis of small molecular weight target specific MRI contrast agents. Here, azide substituted target specific probes were fused to an alkyne bearing GdDOTA analogue and the physical and biological properties of the contrast agent proved its effectiveness in vitro.A second type of contrast agents, consisting of a Ru2+ based metallostar contrast agent decorated with RGD-peptides, was constructed. Here, the click reaction s orthogonality enabled the decoration to be postponed to the final step, thus allowing the introduction of the peptides under relatively mild conditions. Due to the modular nature of the click reaction, the scaffold used here could be used as a building block of analogous metallostars decorated with different specific probes.status: publishe

Preorganisation in bistriazolyl anion receptors

A series of 4,6-bis-(1,2,3-triazolyl)-pyrimidine and 4,6-bis-(1,2,3-triazolyl)-pyridine anion receptors were synthesized and the effect of the pyrimidine and pyridine moieties on their binding properties was examined. We found that intramolecular interactions preorganize the 4,6 bis (1,2,3-triazolyl)-pyridine receptors resulting in higher anion binding constants in comparison with the non-preorganized 4,6-bis-(1,2,3-triazolyl)-pyrimidine receptor.status: publishe

The role of copper ions in pathophysiology and fluorescent sensors for the detection thereof

Copper ions are indispensible to life and maintaining tight control over the homeostasis of copper ions in the body is a prerequisite to sustaining health. Aberrations in normal copper levels, both systemic as well as on a tissue or cellular scale, are implicated in a wide range of diseases, such as Menkes disease, Wilson's disease, Alzheimer's disease, Parkinson's disease and transmissible spongiform encephalopathy (prion diseases). The current understanding of how copper influences these diseases is described. The field of fluorescent copper sensors both functioning via a reaction based mechanism as well as by directly binding copper ions has known an inflation in recent years, and the importance of this field to elucidating the role of copper in cell biology is pointed out. Progress in these tightly interwoven fields has resulted in a better understanding of a number of diseases related to copper imbalances and current developments might open the path for novel and innovating therapies to address these diseases.status: publishe

Immobilization of His-tagged kinase JAK2 onto the surface of a plasmon resonance gold disc modified with different copper (II) complexes.

New surface plasmon resonance (SPR) sensing platforms which consists of copper (II) complexes of a pentetic acid thiol ligand (DPTA-Cu(II)) and of a thiol derivative of dipyrromethene (DPM-Cu(II) created on the surface of gold SPR disc were applied to oriented immobilization of His-tagged Janus kinase 2 (GST-His6-JAK2). This method is based on the covalent bond formation between histidine from a His-tag chain of a protein and Cu(II) centres from the complexes. The kinetic and thermodynamic parameters of the oriented immobilization of GST-His6-JAK2 protein to DPTA-Cu(II) and DPM-Cu(II) complexes attached to the Au surface of a SPR disc were discussed

Recent advances in Gd-chelate based bimodal optical/MRI contrast agents

Research on bimodal contrast agents in general and optical/MRI contrast agents in particular has attracted increased attention from the scientific community in recent years. Whereas optical contrast agents reveal pathologies at the cellular or sub-cellular level, MRI contrast agents generally report physiological differences at the level of tissues and organs. The complementary information obtained from these two techniques allows for a more precise diagnosis. Furthermore the emergence of near-infrared luminophores accommodates the simultaneous detection of optical and MRI signals. The current multitude and diversity in molecular architectures mirrors the ever increasing interest in the field. In this review the developments between 2010 and mid-2014 are highlighted.status: publishe

Pentetic acid (DPTA) Cu(II) monolayer deposited on gold electrode—The base of biosensors for electrochemical screening of kinase JAK2 and potential inhibitor interactions

Here, the new biosensor destined for screening of interactions between kinase JAK2 and compounds which may act as inhibitors was presented. The Cu(II) complex of pentetic acid thiol ligand was applied for immobilization of kinase JAK2 on the gold electrode surface through his-tagged chemistry. The base of the biosensor response was the change of the electrochemical properties of the Cu(II) redox centres upon formation of the kinase JAK2–potential inhibitor complex. The increasing inhibitor concentration caused the decrease of reduction/oxidation Cu(II) current observed with Osteryoung square wave voltammetry. The biosensor usability was checked using known inhibitors, berberines–isoquinolone alkaloids, as well as caffeic acid—a control compound which has no affinity to kinase JAK2. The possible parameters suitable for estimation of the strength of the interactions between kinase JAK2 covalently attached to the Cu(II) complex of pentetic acid thiol ligand deposited on the gold electrode surface and potential inhibitors present in the solution were presented

In Vitro Activation of Cytochrome P450 46A1 (CYP46A1) by Efavirenz-Related Compounds

Cytochrome P450 46A1 (CYP46A1) is a central nervous system-specific enzyme, which catalyzes cholesterol 24-hydroxylation. Currently CYP46A1 is being evaluated in a clinical trial for activation by small doses of the anti-HIV drug efavirenz. Eight efavirenz-related compounds were investigated for CYP46A1 activation in vitro, induction of a CYP46A1 spectral response, spectral Kd values, interaction with the P450 allosteric sites, and a model of binding to the enzyme active site. We gained insight into structure-activity relationships of efavirenz for CYP46A1 activation and found that the investigated efavirenz primary metabolites are stronger and better activators of CYP46A1 than efavirenz. We also established that CYP46A1 is activated by racemates and that a conformational-selection mechanism is operative in CYP46A1. The results suggest structural modifications of efavirenz to further increase CYP46A1 activation without inhibition at high compound concentrations. It is possible that not only efavirenz but its metabolites activate CYP46A1 in vivo.status: publishe