Glutamate receptor endocytosis and signaling in neurological conditions.

The non-essential amino acid glutamate acts as a major excitatory neurotransmitter and plays a significant role in the central nervous system (CNS). It binds with two different types of receptors, ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs), responsible for the postsynaptic excitation of neurons. They are important for memory, neural development and communication, and learning. Endocytosis and subcellular trafficking of the receptor are essential for the regulation of receptor expression on the cell membrane and excitation of the cells. The endocytosis and trafficking of the receptor are dependent on its type, ligand, agonist, and antagonist present. This chapter discusses the types of glutamate receptors, their subtypes, and the regulation of their internalization and trafficking. The roles of glutamate receptors in neurological diseases are also briefly discussed.

A CuII -Salicylidene Glycinato Complex for the Selective Fluorometric Detection of Homocysteine over 20 Proteinogenic Amino Acids.

Homocysteine (Hcy) is a sulfur-containing α-amino acid that differs by one methylene (CH2 ) subunit from homologous cysteine (Cys). Elevated levels of Hcy are diagnostic markers of cardiovascular disease and other medical conditions. We present a new CuII -salicylidene glycinato complex 1 for the selective fluorometric detection of Hcy in water. In the presence of this analyte, the non-fluorescent copper-complex demetallates and disassembles into its building blocks. This process liberates a 3-chloro-5-sulfosalicylaldehyde signaling unit and is accompanied by a 51-fold turn-on fluorescence at 485 nm (λex =350 nm). Out of twenty proteinogenic amino acids, only histidine (12-fold turn-on fluorescence) and Cys (8-fold turn-on fluorescence) trigger some disassembly of probe 1. In comparison with important pioneering work on the detection of biothiols, this study strikingly demonstrates that structural modifications of chelate core structures steer substrate selectivity of metal-based probes. Importantly, probe 1 has proven suitable for the detection of Hcy in artificial urine.

Induced fit activity-based sensing: a mechanistic study of pyrophosphate detection with a "flexible" Fe-salen complex.

Activity-based sensing of biological targets is attracting increasing attention. In this work, we report detailed UV-Vis and fluorescence mechanistic studies on an Fe-salen based probe, [FeIII{salenMeCl2(SO3)2}OH2]- for pyrophosphate (PPi) detection. In the presence of PPi as an analyte, the probe disassembles into its molecular subunits and releases a fluorescent signal. Our studies illustrate that the aqua form of the complex (1-OH2) is the active species and that upon substitution of Fe-coordinated H2O and an initial end-on coordination of HP2O7 3-, the "trapped" pyrophosphate species switches from a monodentate to a bidentate coordination mode (i.e. linkage isomerism) via a probable equilibrium process. The elusive intermediate is further stabilized by a hydrogen bonding interaction that activates the probe for the subsequent final irreversible rate-limiting step, and allows selective discrimination between the other pyrophosphate (H2P2O7 2- and P2O7 4-) species in favour of the HP2O7 3-. The flexible mode of molecular recognition and binding of HP2O7 3- by the tetradentate probe 1-OH2 is unexpected and most effective at physiological pH, and has precedence in enzymatic catalysis (i.e. induced fit principle). These binding properties explain the previously observed outstanding selectivity of 1-OH2 for pyrophosphate over other (poly)oxophosphates and potentially competing analytes.

Detection of glyphosate with a copper(II)-pyrocatechol violet based GlyPKit.

This paper describes the development of a test kit for the selective detection of glyphosate (GlyP). A copper(II)-pyrocatechol violet complex was selected by a screening approach from a pool of 96 combinations of metal ions and commercially available indicators and subsequently incorporated as a detection zone into a hydrophobic C18 solid support. With this kit, detection of 20 µM GlyP in tap water by the "naked eye" is possible and quantifications by smartphone analysis with a limit of detection as low as 2.66 µM (450 µg L-1) have been demonstrated in a proof-of-principle study.

Metal-Salen-based Probes for the Selective Detection of Phosphates via a Disassembly Approach.

Polyoxophosphates are ubiquitous in nature and play important roles in biological systems and in the environment. Pyrophosphate (PPi), an important member of this family, is produced in over 200 biochemical reactions and is a marker in clinical diagnosis. In addition to its endogenous role, PPi alias E450 is currently used as preservative, emulsifier or taste intensifier in foodstuff. Despite this widespread occurrence and biological importance, it is rather surprising that robust chemical systems that detect selectively and sensitively PPi in challenging matrices are still lacking. This mini review focuses on metal-salen complexes as reaction-based fluorescent sensors for the selective detection of PPi and other phosphates. The mode of detection is based on a novel disassembly approach in which the metal ion is sequestered by the target analyte from the complex and the metal-free ligand hydrolyses spontaneously into its fluorescent subunits. Optimizations of the probe and applications for PPi detection in cells and foodstuff are described.

A Quality Improvement Project Focused on Improving First Dose Antibiotic Timeliness for Pediatric Intensive Care Unit Patients with Severe Sepsis.

Recommended time to start administration of first dose antibiotics for sepsis patients is 60 minutes from time 0. Institution-specific data revealed that only one-quarter of severe sepsis patients were meeting this goal when measured from the time of provider order entry. Reliance on a pneumatic tube system for first-dose antibiotic delivery was deemed largely responsible for this finding. This project aimed to increase the percentage of pediatric intensive care unit patients with severe sepsis receiving first dose antibiotics within 60 minutes of provider order entry to ≥50%. METHODS: Baseline data were collected from May to June 2018 and resulted in the development of a new "antibiotic champion" process, which we piloted for 1 week in early August 2018. The primary outcome measure was the cumulative percentage of patients meeting the 60-minute goal as measured from provider order entry to start of antibiotic administration. A key secondary endpoint was the median time in minutes from provider order entry to antibiotic administration. RESULTS: We included 14 patients in baseline data analysis and 16 patients in the pilot. The overall percentage of patients receiving antibiotics within 60 minutes of order entry increased from 29% to 75% (P-value: 0.026). The median time from provider order entry to antibiotic administration decreased by 36.5 minutes [baseline: 84.5 (range 58.8-117) versus pilot 48 (range 32-65), P-value: 0.0017]. CONCLUSION: The antibiotic champion process significantly increased the total percentage of severe sepsis patients meeting the 60-minute goal and decreased the median time to first-dose antibiotic administration for pediatric intensive care unit patients.

FeIII -Salen-Based Probes for the Selective and Sensitive Detection of E450 in Foodstuff.

Inorganic pyrophosphate (PPi) is considered as a diagnostic marker for various diseases such as cancer and vascular calcification. PPi also plays an important preservative role as an additive E450 in foodstuff. In this work, a selective FeIII -salen-based probe for PPi is described; this probe disassembles in the presence of the target analyte into its molecular blocks, 1,2-propanediamine and 3-chloro-5-formyl-4-hydroxybenzenesulfonic acid. The latter signaling unit leads to a fluorometric response. Compared with a related prototype, the new complex shows a 2.3-times stronger emission at 500 nm and a 155-times better selectivity of PPi over adenosine triphosphate (ATP). Importantly, the new probe was successfully applied for detecting E450 in foodstuff.

Carbatriphyrin(3.1.1)-A Distinct Coordination Approach of BIII to Generate Organoborane and Weak C-H⋠⋠⋠B Interactions.

Carbatriphyrin(3.1.1) is the structural isomer of biphenylcorrole and achieved by switching the bonding mode of biphenyl unit from 3,3' to 2,3' which turns the corrole into a triphyrin analogue. The presence of a m-arene unit in the framework restricts the overall conjugation and thus leads to a nonaromatic macrocycle. The protonation experiments afford a trifluoroacetate ion complex. The coordination chemistry reveals that the bottom approach of boron(III) ion forms weak C-H⋅⋅⋅B interactions, however a top approach stabilizes the organoborane complex and the product distribution relies on the basicity of the proton scavengers. These results are unambiguously confirmed by single-crystal X-ray analyses.

Bipyricorrole: A Corrole Homologue with a Monoanionic Core as a Fluorescence Zn(II) Sensor.

In the corrole homologue, 6,11,16-triarylbipyricorrole, the bipyrrole unit is replaced by a 2,2'-bipyridine unit. This modification effectively alters the corrole N4 coordination sphere from the trianionic [(NH)3 N] to the monoanionic [N3NH] state. The newly formed monoanionic core stabilizes Zn(II) ions with enhanced emission properties. The enhanced emission was further utilized for metal ion sensing studies and exploited for the selective detection of Zn(II) ions.