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Applications of Small Heterocycles: Oxetanes as Additives and Cosolvents and Oxazolines as Linkers for Controlled Release from Silica Nanoparticles

Sprachman, Melissa M (2014) Applications of Small Heterocycles: Oxetanes as Additives and Cosolvents and Oxazolines as Linkers for Controlled Release from Silica Nanoparticles. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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In the first chapter of this dissertation, the design and synthesis of bifunctional additives and cosolvents containing an oxetane moiety are described. The use of dimeric oxetanes as additives for reactions involving organometallic agents—namely, organolithium, organozirconium, and organomagnesium reagents was studied. A dimeric bisoxetanyl ether showed promise for solvating organolithium aggregates, but dimeric oxetanyl ethers were not useful additives in hydrozirconation reactions. A bisoxetanyl sulfide is being investigated further as an additive for Grignard reactions. A bisoxetanyl sulfoxide (MMS350) was developed as a dimethylsulfoxide substitute that showed utility for enhancing the aqueous solubility of small organic molecules.

In the second chapter, efforts toward the development of agents for protection and mitigation of ionizing radiation damage are outlined. It was discovered that administration of MMS350 prolonged survival in irradiated mice. Moreover, mice given MMS350 in their drinking water had lower incidences of pulmonary fibrosis. Additional analogs of MMS350 were synthesized for further investigation of the molecular and structural requirements for successful sulfoxide-containing radiation protectors.

In the third chapter, the design and proof-of-concept study of using an oxazoline linker for functionalization and pH-dependent release of reactive oxygen species (ROS) scavengers from silica nanoparticles is discussed. pH-Dependent hydrolysis of model oxazolines was achieved by modulating the substitution on the oxazoline moiety. Moreover, functionalized silica nanoparticles were successfully endocytosed by macrophages. Our studies have laid the groundwork for the design of covalently modified nanoparticles for delivery of ROS.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Sprachman, Melissa Mmms79@pitt.eduMMS79
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWipf, Peterpwipf@pitt.eduPWIPF
Committee MemberCurran, Dennis Pcurran@pitt.eduCURRAN
Committee MemberWilcox, Craig Sdaylite@pitt.eduDAYLITE
Committee MemberYang, Judith Cjudyyang@pitt.eduJUDYYANG
Date: 31 January 2014
Date Type: Publication
Defense Date: 12 November 2012
Approval Date: 31 January 2013
Submission Date: 9 November 2012
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 346
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: oxetane, azetidine, solvent effects, dimethylsulfoxide substitute, radiation mitigation, silica nanoparticle, oxazoline
Date Deposited: 31 Jan 2014 06:00
Last Modified: 15 Nov 2016 14:06


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