Identifier

etd-11152013-105517

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

Chapter 1 of this Dissertation presents a brief introduction to the basic properties of porphyrins and their derivatives (hydroporphyrins), their abundance and functions in the nature, and their applications in photodynamic therapy. Chapter 2 reports the synthesis, characterization, conformational analysis and cellular studies of novel mono conjugated regioisomers of chlorin e6 derivatives that are promising photosensitizers for photodynamic therapy. All three regioisomers were synthesized from pheophytin a, which was extracted from the alga Spirulina pacifica. In vitro investigations using human carcinoma HEp2 cells show that the 152-lysyl regioisomers accumulate the most within cells, and the most phototoxic are the 131 regioisomers. Cellular studies revealed that the 131-aspartylchlorin e6 conjugate could be a more efficient photosensitizer for PDT than the currently used commercial 152 derivative. Chapter 3 describes the synthesis, characterization and cellular investigation of water soluble regioisomers of di-conjugated chlorin e6 derivatives for photodynamic therapy. New synthetic routes were developed to synthesize all three regioisomes. Both the 152,173-diamino and 131,173,-diamino derivatives were synthesized starting from chlorin e6 and the 131,152-diamino derivatives were synthesized from pheophytin a. The effects of position and number of amino acid substituents on their In vitro photodynamic properties are described. Chapter 4 discussed the design, synthesis and characterization of electron deficient symmetric porphyrin for incorporation into a synthetic cytochrome to mimic the activity of native cytochrome. It also presents a brief introduction of basic synthetic routes to obtain porphyrin macrocycles. The importance of the construction of artificial hemoproteins to understand the cytochromes activity is also discussed. Various synthetic routes and strategies to obtain the symmetric porphyrin are reported in detail.

Date

2013

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Smith, Kevin M.

Included in

Chemistry Commons

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