A dual encapsulation strategy to generate anion-responsive luminescent lanthanide hydrogels.

We report a new method to generate ion-responsive luminescent hydrogels, involving encapsulation of a luminescent lanthanide probe within crosslinked amphiphilic polymer particles and subsequent entrapment within a hydrogel. The resulting hydrogels are capable of reversible bicarbonate sensing, exhibit no leaching, and can be tuned for a range of sensing applications.

Transmembrane Transport of Inorganic Phosphate by a Strapped Calix[4]pyrrole.

Synthetic anion receptors are increasingly being explored for the transport of anions across lipid membranes because of their potential therapeutic applications. A considerable amount of research focuses on the transport of chloride, whereas the transmembrane transport of inorganic phosphate has not been reported to date, despite the biological relevance of this anion. Here we present a calix[4]pyrrole with a bisurea strap that functions as a receptor and transporter for H2PO4-, relying on the formation of eight hydrogen bonds and efficient encapsulation of the anion. Using a phosphate-sensitive lanthanide probe and 31P NMR spectroscopy, we demonstrate that this receptor can transport phosphate into vesicles by H2PO4-/Cl- antiport, H2PO4- uniport, and Cs+/H2PO4- symport mechanisms. This first example of inorganic phosphate transport by a neutral receptor opens perspectives for the future development of transporters for various biological phosphates.

Sterically demanding macrocyclic Eu(iii) complexes for selective recognition of phosphate and real-time monitoring of enzymatically generated adenosine monophosphate.

The design of molecular receptors that bind and sense anions in biologically relevant aqueous solutions is a key challenge in supramolecular chemistry. The recognition of inorganic phosphate is particularly challenging because of its high hydration energy and pH dependent speciation. Adenosine monophosphate (AMP) represents a valuable but elusive target for supramolecular detection because of its structural similarity to the more negatively charged anions, ATP and ADP. We report two new macrocyclic Eu(iii) receptors capable of selectively sensing inorganic phosphate and AMP in water. The receptors contain a sterically demanding 8-(benzyloxy)quinoline pendant arm that coordinates to the metal centre, creating a binding pocket suitable for phosphate and AMP, whilst excluding potentially interfering chelating anions, in particular ATP, bicarbonate and lactate. The sensing selectivity of our Eu(iii) receptors follows the order AMP > ADP > ATP, which represents a reversal of the order of selectivity observed for most reported nucleoside phosphate receptors. We have exploited the unique host-guest induced changes in emission intensity and lifetime for the detection of inorganic phosphate in human serum samples, and for monitoring the enzymatic production of AMP in real-time.

Advances in anion binding and sensing using luminescent lanthanide complexes.

Luminescent lanthanide complexes have been actively studied as selective anion receptors for the past two decades. Ln(iii) complexes, particularly of europium(iii) and terbium(iii), offer unique photophysical properties that are very valuable for anion sensing in biological media, including long luminescence lifetimes (milliseconds) that enable time-gating methods to eliminate background autofluorescence from biomolecules, and line-like emission spectra that allow ratiometric measurements. By careful design of the organic ligand, stable Ln(iii) complexes can be devised for rapid and reversible anion binding, providing a luminescence response that is fast and sensitive, offering the high spatial resolution required for biological imaging applications. This review focuses on recent progress in the development of Ln(iii) receptors that exhibit sufficiently high anion selectivity to be utilised in biological or environmental sensing applications. We evaluate the mechanisms of anion binding and sensing, and the strategies employed to tune anion affinity and selectivity, through variations in the structure and geometry of the ligand. We highlight examples of luminescent Ln(iii) receptors that have been utilised to detect and quantify specific anions in biological media (e.g. human serum), monitor enzyme reactions in real-time, and visualise target anions with high sensitivity in living cells.

A Mycobacterium species for Crohn's disease?

In ruminants Mycobacterium avium subspecies paratuberculosis (MAP) is the causative organism of a chronic granulomatous inflammatory bowel disease called Johne's disease (JD). Some researchers have hypothesised that MAP is also associated with Crohn's disease (CD), an inflammatory bowel disease in humans that shares some histological features of JD. Despite numerous attempts to demonstrate causality by researchers, direct microbiological evidence of MAP involvement in CD remains elusive. Importantly, it has not been possible to reliably and reproducibly demonstrate mycobacteria in the tissue of CD patients. Past attempts to visualise mycobacteria in tissue may have been hampered by the use of stains optimised for Mycobacterium tuberculosis complex (MTB) and the lack of reliable bacteriological culture media for both non-tuberculous mycobacteria (NTM) and cell-wall-deficient mycobacteria (CWDM). Here we describe a Ziehl-Neelsen (ZN) staining method for the demonstration of CWDM in resected tissue from patients with Crohn's disease, revealing the association of CWDM in situ with host tissue reactions, and posit this as a cause of the tissue inflammation. Using the ZN stain described we demonstrated the presence of CWDM in 18 out of 18 excised tissue samples from patients diagnosed as having Crohn's disease, and in zero samples out of 15 non-inflammatory bowel disease controls.

Accessing a Long-Lived 3LC State in a Ruthenium(II) Phenanthroline Complex with Appended Aromatic Groups.

The photophysical properties of a series of heteroleptic Ru(II) complexes of the form [Ru(phen)2(phen-5,6-R2)]2+, where phen = 1,10-phenanthroline and R = phenyl (Ph), p-tert-butylbenzene (p-Ph-tBu), p-methoxybenzene (p-Ph-OMe), and 2-naphthalene (2-naph), have been measured. Variation of the R group does not greatly perturb the electronic properties of the ground state, which were explored with electronic absorption and resonance Raman spectroscopy and are akin to those of the archetypal parent complex [Ru(phen)3]2+. All complexes were shown to possess emissive 3MLCT states, characterized through transient absorption and emission spectroscopy. However, an additional, long-lived excited state was observed in the Ru(II) naphthalene complex. The naphthalene substituents facilitate population of a 40 µs dark state which decays independently to that of the emissive 3MLCT state. This state was characterized as 3LC in nature, delocalized over the naphthalene substituted ligand.

Conformational control of the self-assembly of triple helicates and [2 × 2]-grids from zinc(II) and 3,6-di(2-pyridyl)pyridazine based ligands.

The reaction of symmetrical ligands based on 3,6-di(2-pyridyl)pyridazine () with carbocyclic rings fused to the pyridazine ring; 7,10-di(2-pyridyl)-8,9-diazafluoranthene (), 1,4-di(2-pyridyl)-6,7-dihydro-5H-cyclopenta[d]pyridazine (), 1,4-di(2-pyridyl)-5,6,7,8-tetrahydrophthalazine (), 1,4-di(2-pyridyl)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyridazine () in reactions with zinc perchlorate gave a series of complexes (). Characterisation of these using single crystal X-ray structure determination showed that less sterically hindered and gave saturated triple helicates ( and , respectively), while [2 × 2]-grids were formed with more sterically hindered ligands ( from and from ), or if methanol (rather than acetonitrile) was used as the reaction solvent with (). The most sterically-hindered ligand formed a mononuclear complex (). The structures of these complexes in solution was determined by (1)H-NMR, and found to match their solid-state structures. The [2 × 2]-grids are effective molecular clips able to hold solvent and anions between their arms via hydrogen bonding to a Zn4(H2O)2(OH)2 core.