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Encapsulation of oxime acetylcholinesterase reactivators: influence of physiological conditions on the stability of oxime-cucurbit[7]uril complexes

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50016981" target="_blank" >RIV/62690094:18470/20:50016981 - isvavai.cz</a>

  • Alternative codes found

    RIV/60162694:G44__/20:00556107

  • Result on the web

    <a href="https://pubs.rsc.org/en/content/articlelanding/2020/NJ/D0NJ03102J#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2020/NJ/D0NJ03102J#!divAbstract</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1039/d0nj03102j" target="_blank" >10.1039/d0nj03102j</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Encapsulation of oxime acetylcholinesterase reactivators: influence of physiological conditions on the stability of oxime-cucurbit[7]uril complexes

  • Original language description

    Oxime-based acetylcholinesterase reactivators are a specific group of drugs used for the treatment of organophosphate intoxication. However, high hydrophilicity and poor blood-brain barrier penetration limit their physiological potential. Cucurbit[7]urile (CB[7]) was used in this work as a potential carrier of oxime molecules to increase their treatment effectiveness. The host-guest chemistry of CB[7] with five clinically used oximes (trimedoxime, asoxime, obidoxime, pralidoxim and methoxime) and two new pre-clinical oximes (K027 and K048) was characterized under simulated physiological conditions using titration experiments with UV-vis detection. CB[7] forms stable complexes of 1 : 1 stoichiometry with all tested oximes. The decrease of complex stability was observed at a pH above the pK(a)of oxime, which limits the applicability of the complexation for oximes with pK(a)below the physiological pH. The combination of physiological ionic strength and pH causes partial decrease of the complex stability. The effect of organic solvent used in the sample pretreatment step before spectral analysis of oxime-CB[7] complexes in biological samples was demonstrated. Methanol is a more suitable solvent with low effect on complex stability. Finally, the ability of mass spectrometry with electrospray ionization was demonstrated for the analysis of oxime-CB[7] complexes.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30107 - Medicinal chemistry

Result continuities

  • Project

    <a href="/en/project/GA18-08937S" target="_blank" >GA18-08937S: Research of oxime-CB(7) complexes for central nervous system penetration of quaternary acetylcholinesterase reactivator</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2020

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    New journal of chemistry

  • ISSN

    1144-0546

  • e-ISSN

  • Volume of the periodical

    44

  • Issue of the periodical within the volume

    34

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    6

  • Pages from-to

    14367-14372

  • UT code for WoS article

    000564479900005

  • EID of the result in the Scopus database