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To elucidate the involvement of individual and inter-related pathological factors [i.e., amyloid-β (Aβ), metals, and oxidative stress] in the pathogenesis of Alzheimer's disease (AD), chemical tools have been developed. Characteristics required for such tool construction, however, have not been clearly identified; thus, the optimization of available tools or new design has been limited. Here, key structural properties and mechanisms that can determine tools' regulatory reactivities with multiple pathogenic features found in AD are reported. A series of small molecules was built up through rational structural selection and variations onto the framework of a tool useful for in vitro and in vivo metal-Aβ investigation. Variations include: (i) location and number of an Aβ interacting moiety; (ii) metal binding site; and (iii) denticity and structural flexibility. Detailed biochemical, biophysical, and computational studies were able to provide a foundation of how to originate molecular formulas to devise chemical tools capable of controlling the reactivities of various pathological components through distinct mechanisms. Overall, this multidisciplinary investigation illustrates a structure-mechanism-based strategy of tool invention for such a complicated brain disease. [ABSTRACT FROM AUTHOR]

Aggregates of amyloidogenic peptides are involved in the pathogenesis of several degenerative disorders. Herein, an iridium(III) complex, Ir-1, is reported as a chemical tool for oxidizing amyloidogenic peptides upon photoactivation and subsequently modulating their aggregation pathways. Ir-1 was rationally designed based on multiple characteristics, including 1) photoproperties leading to excitation by low-energy radiation; 2) generation of reactive oxygen species responsible for peptide oxidation upon photoactivation under mild conditions; and 3) relatively easy incorporation of a ligand on the IrIII center for specific interactions with amyloidogenic peptides. Biochemical and biophysical investigations illuminate that the oxidation of representative amyloidogenic peptides (i.e., amyloid-β, α-synuclein, and human islet amyloid polypeptide) is promoted by light-activated Ir-1, which alters the conformations and aggregation pathways of the peptides. Additionally, their potential oxidation sites are identified as methionine, histidine, or tyrosine residues. Overall, our studies on Ir-1 demonstrate the feasibility of devising metal complexes as chemical tools suitable for elucidating the nature of amyloidogenic peptides at the molecular level, as well as controlling their aggregation. [ABSTRACT FROM AUTHOR]

Curcuma longa, C. wenyujin and C. phaeocaulis are important herbal medicine which of rhizomatous herbaceous perennial plant of the family Zingiberaceae. This study generated a complete chloroplast genome sequence of three medicinal species were characterized by de novo assembly with whole genome sequencing data. The length of complete chloroplast genome were 162,180 bp (C. longa), 162,266 bp (C. wenyujin), and 162,133 bp (C. phaeocaulis), respectively, with four structures that were included in large single copy region (87,001 bp, 87,042 bp, and 87,013 bp), small single copy region (15,681 bp, 15,710 bp, and 15,622 bp), and duplicated inverted regions (29,749 bp, 29,757 bp and 29,749 bp of each). Based on phylogenetic trees, C. longa, C. wenyujin, and C. phaeocaulis were grouped by high bootstrap value with Curcuma species. This result approved that C. longa, C. wenyujin and C. phaeocaulis were comprised in Alpinia and Wurfbainia. Therefore, this chloroplast genome data firstly generated valuable genetic resource in discrimination of herbal materials, phylogeny and development DNA marker. [ABSTRACT FROM AUTHOR]

A new metal ion sensor that contains quinoline and pyridylaminophenol has been synthesized. In acetonitrile and in the presence of Zn2+, the sensor fluoresces. In contrast, in aqueous solutions the sensor fluoresces in the presence of Cd2+. The fluorescence of the molecule is selective for Zn2+ or Cd2+ and shows no fluorescence with other metal ions. The crystal structure of the Cd2+ complex shows coordination through the amide and phenol oxygens, as well as the amine nitrogen of the sensor. The sensor also acts as a colorimetric sensor for Co2+ by changing color from colorless to yellow. The color change is selective for Co2+ and is not observed with other metal ions. The unique combination of pyridine and phenol groups with quinoline results in the properties of this sensor. [ABSTRACT FROM AUTHOR]

In this study, an assay to quantify the presence of magnesium ions with a chemosensor of bispicolylamine covalently attached to coumarin as a fluorephore was developed using a ratiometric fluorescence enhancement approach. Upon treatment with magnesium ions, the fluorescence wavelength of the chemosensor at 367 nm was shifted to 413 nm and the intensity was also enhanced. The formation of a 1:2 complex between the chemosensor and magnesium ions was confirmed based on the spectral changes of UV–vis, fluorescence and NMR as well as Job's plot. An appreciable enhancement in the luminescence intensity for the emission band at 413 nm was evident when magnesium ions were added progressively. The maximum wavelength and intensity of the emission of the complex with Mg2+were discriminated from those of other metal ions, such as Ca2+and Zn2+. [ABSTRACT FROM PUBLISHER]