Identifier

etd-03262014-133039

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

The improvement and utility of crosslinkers are important topics of molecular imprinting. Crosslinker significance is evident when molecularly imprinted polymer (MIP) composition related to performance as separation media is examined. Crosslinkers account for the bulk of MIP formulations made through traditional imprinting (80-90%) and is even greater when the One Monomer Molecularly Imprinted Polymer (OMNiMIP) approach is utilized (100%.) It is not surprising that alteration of the bulk component will result in different separation performances. Crosslinkers studied in this work were designed, synthesized, and evaluated toward improvement in OMNiMIP selectivity. In particular, functionality and number of polymerizable groups, addition of electron withdrawing groups or stereocenters, and maximization of amide content of OMNiMIP crosslinkers were explored using L-BOC-Tyrosine as a standard template. The separation factors (α’) obtained from chromatographic studies of these OMNiMIPs were compared to results from 2-(methacryloylamino)ethyl-2-methylacrylate (NOBE), the most successful OMNiMIP crosslinking monomer thus far. Although several of these new OMNiMIPs displayed enantiomeric selectivity toward BOC-Tyr, an increased α’ was not observed. Racemic and Scalemic imprinting as well as absolute configuration (AC) determination were also studied throughout this work to improve MIP utility in academia and industry. Chiral OMNiMIP crosslinkers (S)-2-methacrylamidopropyl methacrylate (L-NALA) and N,O-bis-methacryloyl L-serine (NOS) were imprinted with racemic BOC-Tyr and both exhibited partial enantiomeric separation by chromatography. L-NALA was further explored through imprinting scalemic templates, and studies also showed enantiomeric separation. Additionally, L-NALA and NOBE were studied in AC determination. Here, a mnemonic was developed to illustrate template recognition. Limitations on binding factors were also set to determine data reliability in regards to determination of absolute configuration. A chimeric antioxidant composed of vitamin E and carnosine (VECAR) was designed and synthesized to improve drug delivery. VECAR was fabricated based on the lipophilicity and hydrophilicity of its individual components and is expected to have increased permeability in hydrophilic media while maintaining recognition by key proteins in biological pathways. This new compound displayed similar antioxidant activity as vitamin E in vitro and is anticipated to reach more versatile regions of cells, leading to the elimination or reduction of diseases caused by oxidative damage.

Date

2014

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Spivak, David

Included in

Chemistry Commons

Share

COinS