Design, synthesis, and characterization of porphyrin derivatives for biological applications

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.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

Chemistry

Year dc:date.available

2013

Author dc:creator

• Jinadasa, Raja Gabadage Waruna Eranga

• PDT
• Amino acid coupling
• Chemical degradation of chlorophylls
• hydroporphyrins
• Gouterman four-orbital model
• photosensitizers
• Conformational analysis of chlorin derivatives
• oxidative cyclization
• Aminolysis of the β-keto ester
• Vilsmeier-Haack reaction
• Trichlorotriazine
• a c-Biladiene
• Pyrrole

Statement dc:rights

• unrestricted
• Release the entire work immediately for access worldwide.

Identifier

etd-11152013-105517
https://repository.lsu.edu/gradschool_dissertations/1482

OAI identifier oai:identifier

oai:repository.lsu.edu:gradschool_dissertations-2481