Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds (original) (raw)
Related papers
Beilstein Journal of Organic Chemistry, 2017
New derivatives of cyclodextrins were prepared in order to determine the relative importance of the structural key elements involved in the degradation of organophosphorus nerve agents. To avoid a competitive inclusion between the organophosphorus substrate and the iodosobenzoate group, responsible for its degradation, the latter group had to be covalently bound to the cyclodextrin scaffold. Although the presence of the α nucleophile iodosobenzoate was a determinant in the hydrolysis process, an imidazole group was added to get a synergistic effect towards the degradation of the agents. The degradation efficiency was found to be dependent on the relative position of the heterocycle towards the reactive group as well as on the nature of the organophosphorus derivative.
European Journal of Medicinal Chemistry, 2005
b-Cyclodextrin was substituted by an iodosobenzoic acid derivative to create a catalytic hydrolytic activity against neurotoxic organophosphorus agents. The catalytic moiety was introduced on a secondary hydroxy group at the position 2 of a glucose unit. Several b-cyclodextrin derivatives were obtained. In these derivatives, the methylene linker occupied all potential positions on the aromatic ring. Kinetic assays were carried out with paraoxon as organophosphate model. Three regioisomers hydrolyzed paraoxon, although the paraoxon-leaving group, paranitrophenol, was not released from the b-cyclodextrin torus.
European journal of medicinal chemistry, 2005
Beta-cyclodextrin was substituted by an iodosobenzoic acid derivative to create a catalytic hydrolytic activity against neurotoxic organophosphorus agents. The catalytic moiety was introduced on a secondary hydroxy group at the position 2 of a glucose unit. Several beta-cyclodextrin derivatives were obtained. In these derivatives, the methylene linker occupied all potential positions on the aromatic ring. Kinetic assays were carried out with paraoxon as organophosphate model. Three regioisomers hydrolyzed paraoxon, although the paraoxon-leaving group, para-nitrophenol, was not released from the beta-cyclodextrin torus.
CYCLODEXTRINS – FIELDS OF APPLICATION. PART II
This paper represents an analysis of potential and current applications of cyclodextrins as biologically active substances in medicine. The main applications described here include use of cyclodextrins as agents that form inclusion complexes with endogenous substances (membrane lipids, cellular cholesterol), agents that form inclusion complexes with exogenous substances with their man role as guest molecules (sugammadex, FBCx), agents that block endogenous and exogenous macromolecules (ion channels, anthrax toxin, α-hemolysin), and agents which activity is based on the chemical nature of them and of their derivatives (cyclodextrin polysulphate derivatives). The first classification for medically important biological activity of cyclodextrins has been proposed.
In vitro detoxification of cyclosarin (GF) by modified cyclodextrins
Toxicology Letters, 2011
Developing potent detoxification strategies for prophylaxis and therapy against organophosphate (OP) intoxication still represents a challenging task. Clinical application of numerous investigated substances including enzymes and low molecular scavengers like metal ions or nucleophiles could not yet be realised due to profound disadvantages. Presenting a promising attempt, cyclodextrins (CDs) efficiently enhance the degradation of some organophosphorus compounds. The present study examined the in vitro GF degradation mediated by three CDs and a nucleophilic precursor performed by mass spectrometric detection with ammonia chemical ionisation. All four compounds caused a notable enhancement of GF detoxification that was synergistically accelerated in the case of 2-O-(3-carboxy-4-iodosobenzyl)-cyclodextrin (IBA--CD) with the alpha-nucleophile 2-iodosobenzoic acid (IBA) grafted on the secondary face of -cyclodextrin (-CD). In vitro toxicokinetic investigations of CD derivatives are needed to evaluate the effect of slow terminal elimination phase of the more toxic (−)-GF shown for two CD-derivatives underlining the necessity of detecting the complete kinetic course of inactivation. The observed effect of fast high affinity binding (20-30%) represents an additional therapeutic option of an extremely rapid reduction of GF concentration in vivo. Distinctive differences in the course of reaction are detected depending on -CD-derivatives, allowing a first inference of possible mechanisms and relevance of attached substituents. However, further profound investigation needs to be done to evaluate the basis of a clinical application of substituted CDs as potential detoxification agents.
Cyclodextrins and their uses: a review
Process Biochemistry, 2004
Cyclodextrins are a family of cyclic oligosaccharides composed of ␣-(1,4) linked glucopyranose subunits. Cyclodextrins are useful molecular chelating agents. They possess a cage-like supramolecular structure, which is the same as the structures formed from cryptands, calixarenes, cyclophanes, spherands and crown ethers. These compounds having supramolecular structures carry out chemical reactions that involve intramolecular interactions where covalent bonds are not formed between interacting molecules, ions or radicals. The majority of all these reactions are of 'host-guest' type. Compared to all the supramolecular hosts mentioned above, cyclodextrins are most important. Because of their inclusion complex forming capability, the properties of the materials with which they complex can be modified significantly. As a result of molecular complexation phenomena CDs are widely used in many industrial products, technologies and analytical methods. The negligible cytotoxic effects of CDs are an important attribute in applications such as rug carrier, food and flavours, cosmetics, packing, textiles, separation processes, environment protection, fermentation and catalysis.