Our long-term objectives are to develop synthetic methods for creating bioorganic molecules which can be used to provide insight into the relation between molecular structure and biological function. We have developed a room temperature biomimetic synthesis of tetraphenyl-porphyrin in 60% yield. We will expand the scope of this methodology to prepare porphyrins which have previously been unobtainable. This includes the class of meso-alkylporphyrins, some of which should be extremely soluble in lipid media. Amphipathic porphyrins can then be prepared for bilayer studies. Then we will exploit this new methodology in the high yield synthesis of cofacial dimers containing porphyrins and chlorins. We plan an extensive study of the electronic interactions resulting from the juxtaposition of rings. To model the light harvesting apparatus of photosynthesis, we will design and synthesize porphyrins bearing bulky substituents which in the crystalline state will hold the porphyrins at fixed distances apart. Fluorescence measurements in applied electric fields should provide data to distinguish the mechanisms of energy transfer. These new synthetic porphyrins should be of considerable value in extending our understanding of the properties of heme and chlorophyll in biological systems. A more global problem in bioorganic chemistry is the synthesis of model systems having well-defined 3-dimensional structures. We propose to create modular model systems of the photosynthetic process which contain a donor and acceptor covalently linked in a stacked geometry. The spacer groups separating the donor and acceptor are composed of p-aminobenzoic subunits, which are coupled together in a stepwise manner analogous to peptide and DNA synthesis. Three porphyrin-quinone compounds of 5, 10, and 15 A separation will be prepared which have 1, 2, and 3 subunits in their spacer groups. The photochemical characterization of this family of molecules will provide a systematic study of the effect of distances on electron transfer reactions. This modular approach should have broad applicability in the bioorganic field.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM036238-08
Application #
2178230
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1986-12-01
Project End
1995-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Carnegie-Mellon University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Lindsey, Jonathan S (2015) De novo synthesis of gem-dialkyl chlorophyll analogues for probing and emulating our green world. Chem Rev 115:6534-620
Huang, Liyi; Huang, Ying-Ying; Mroz, Pawel et al. (2010) Stable synthetic cationic bacteriochlorins as selective antimicrobial photosensitizers. Antimicrob Agents Chemother 54:3834-41
Mroz, Pawel; Huang, Ying-Ying; Szokalska, Angelika et al. (2010) Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy. FASEB J 24:3160-70
Huang, Ying-Ying; Mroz, Pawel; Zhiyentayev, Timur et al. (2010) In vitro photodynamic therapy and quantitative structure-activity relationship studies with stable synthetic near-infrared-absorbing bacteriochlorin photosensitizers. J Med Chem 53:4018-27
Mroz, Pawel; Bhaumik, Jayeeta; Dogutan, Dilek K et al. (2009) Imidazole metalloporphyrins as photosensitizers for photodynamic therapy: role of molecular charge, central metal and hydroxyl radical production. Cancer Lett 282:63-76
Kee, Hooi Ling; Bhaumik, Jayeeta; Diers, James R et al. (2008) Photophysical Characterization of Imidazolium-Substituted Pd(II), In(III), and Zn(II) Porphyrins as Photosensitizers for Photodynamic Therapy. J Photochem Photobiol A Chem 200:346-355
Borbas, K Eszter; Ruzie, Christian; Lindsey, Jonathan S (2008) Swallowtail bacteriochlorins. Lipophilic absorbers for the near-infrared. Org Lett 10:1931-4
Muresan, Ana Z; Lindsey, Jonathan S (2008) Design and synthesis of water-soluble bioconjugatable trans-AB-porphyrins. Tetrahedron 64:11440-11448
Dogutan, Dilek Kiper; Lindsey, Jonathan S (2008) Investigation of the scope of a new route to ABCD-bilanes and ABCD-porphyrins. J Org Chem 73:6728-42
Borbas, K Eszter; Kee, Hooi Ling; Holten, Dewey et al. (2008) A compact water-soluble porphyrin bearing an iodoacetamido bioconjugatable site. Org Biomol Chem 6:187-94

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