Theoretical Study of Radical and Neutral Intermediates of Artemisinin Decomposition

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• 作者：M&iacute ; rian S. C. Pereira ; Rudolf Kiralj ; M&aacute ; rcia M. C. Ferreira
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：48
• 期：1
• 页码：85 - 98
• 全文大小：397K
• 年卷期：v.48,no.1(January 2008)
• ISSN：1549-960X

文摘

Four artemisinin reductive decomposition routes A, B1, B2, and B3 with 13 species (QHS, 1/2, 3, 4, 5, 5a,6, 7, 18, 18a, 19, 20, and 21) were studied at the B3LYP/6-31G** level. Structures of the species wereanalyzed in terms of geometrical parameters, Löwdin bond orders, partial atomic charges and spin densities,electronic and free energies, and entropy. Searches in the Cambridge Structural Database for high-levelquality artemisinin-related structures were also performed. Principal Component and Hierarchical Clusteranalyses were performed on selected electronic and structural variables to rationalize relationships betweenthe routes. The A and B1 routes are possibly interconnected. Structural and electronic features of all speciesshow that there are two clusters: A-B1 and B2-B3. The latter cluster is thermodynamically more favorable(ges/gifchars/Delta.gif" BORDER=0 >ges/gifchars/Delta.gif" BORDER=0 >G is -64 to -88 kcal mol^-1) than the former (ges/gifchars/Delta.gif" BORDER=0 >ges/gifchars/Delta.gif" BORDER=0 >G is -58 to -59 kcal mol^-1), but kinetical preferencemay be the opposite. Along the artemisinin decomposition routes, especially B2 and B3, larger structuralchanges including formation of branched structures and CO₂ release are related to increased exothermicityof the conversions, weakened attractive oxygen-oxygen interactions, and increased entropy of the formedspecies. The intermediate 4 definitely belongs to some minor artemisinin decomposition route.