Linked Life Data

18693050

Source:http://linkedlifedata.com/resource/pubmed/id/18693050

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-10-22
pubmed:abstractText
Quantum chemical methods were used to obtain a structure for the peroxide-iron intermediate complex required for the inner-sphere reduction of dispiro-1,2,4-trioxolane antimalarials. Investigation of this biologically important interaction with iron(II) allows further understanding of the mechanisms of action and clearance of this promising new class of fully synthetic peroxide antimalarials. UHF, B3LYP and B3LYP//MP2 calculations were undertaken to provide structural and energetic information about the coordination complex of iron(II) with five representative trioxolanes, ranging in both iron-mediated reactivity and antimalarial activity. Significant energy differences were observed between the conformational isomers of these trioxolanes, indicating the importance of steric interactions between the iron complex ligands and the trioxolane substituents. These calculations may explain the slower iron-mediated reaction rates of trioxolanes that preferentially adopt a conformation that sterically shields the peroxide bond. The relationship between antimalarial activity and accessibility of the peroxide bond to iron has also been demonstrated for these trioxolanes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1873-4243
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
394-400
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Quantum chemical study of the intermediate complex required for iron-mediated reactivity and antimalarial activity of dispiro-1,2,4-trioxolanes.
pubmed:affiliation
Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't