Show simple item record

dc.contributor.authorKuzmin, Alexander Valeryevich
dc.date.accessioned2014-03-04T18:59:32Z
dc.date.available2014-03-04T18:59:32Z
dc.date.issued2010-12
dc.identifier.otherkuzmin_alexander_v_201012_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/kuzmin_alexander_v_201012_phd
dc.identifier.urihttp://hdl.handle.net/10724/26939
dc.description.abstractThe extreme cytotoxicity of natural enediyne antibiotics is attributed to the ability of (Z)-3-ene-1,5-diyne and (Z)-1,2,4-heptatrien-6-yne fragments to undergo cycloaromatization producing DNA-damaging diradicals. The goal of this dissertation work was to develop photoactivatable precursors of reactive enediynes and enyne-allenes. To achieve this goal, we have designed compounds, which upon irradiation can efficiently generate enediyne and/or enyne-allene moiety, constrained within ten-membered ring. Thus, it was found that ten-membered ring cyclic enediynes that possess a carbonyl group in a β position with respect to the one of acetylenic termini undergo very facile cycloaromatization at ambient temperatures. Kinetic data and deuterium-labeling experiments indicate that this reaction proceeds via rate-determining tautomerization to the enyne-allene form followed by very rapid Myers—Saito cyclization. A reactive ten-membered ring enyne-allene was also developed (τ25 °C = 5–6 min). The cyclic enyne-allene is efficiently generated (Φ300 nm = 0.57) by UV irradiation of a thermally stable precursor in which a triple bond is masked as a cyclopropenone moiety. Moreover, we found that incorporation of an additional endocyclic trans double bond in a ten-membered cyclic enediyne structure increases the activation energy of the cycloaromatization reaction. The rate-limiting step of the thermal cycloaromatization of a dienediyne is apparently the trans-cis isomerization and/or 1,3-hydrogen shift, producing the isomer of dienediyne with the cis double bond. The latter isomer then undergoes facile cycloaromatization. The utility of catalyst-free azide−alkyne [3 + 2] cycloaddition for the immobilization of a variety of molecules onto a solid surface and microbeads was investigated. In this process, the surfaces are derivatized with aza-dibenzocyclooctyne (ADIBO) for the immobilization of azide-tagged substrates via a copper-free click reaction.
dc.languageeng
dc.publisheruga
dc.rightsOn Campus Only
dc.subjectenediyne
dc.subjectenyne-allene
dc.subjectantitumor agent
dc.subjectBergman and Myers—Saito cyclization
dc.subjectphoto-Bergman
dc.subjecttriggering
dc.subjectcyclopropenone
dc.subjectallene
dc.subjectcyclooctyne
dc.subjectazide
dc.subjectdibenzocyclooctyne
dc.subjectcopper-free click reaction
dc.subjectclick chemistry
dc.titlePhotochemical triggering of reactive enyne-allenes and enediynes for the application in anti-cancer drugs
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentChemistry
dc.description.majorChemistry
dc.description.advisorVladimir V. Popik
dc.description.committeeVladimir V. Popik
dc.description.committeeRobert Phillips
dc.description.committeeGeorge Majetich


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record