Title page for ETD etd-04142009-133745


Type of Document Dissertation
Author Manono, Janet
URN etd-04142009-133745
Title Derivatization of Porphyrins for DNA and Metal Ion Binding, Especially by Employing Secondary Sulfonamide Links
Degree Doctor of Philosophy (Ph.D.)
Department Chemistry
Advisory Committee
Advisor Name Title
Luigi G. Marzilli Committee Co-Chair
Anne Grove Committee Member
Jayne Garno Committee Member
Steve Watkins Committee Member
Xu Zhimin Dean's Representative
Keywords
  • Methylcobaloximes
  • Tertiary sulfonamide links
  • Cationic porphyrins
Date of Defense 2009-04-07
Availability restricted
Abstract

Porphyrins are of exceptional importance in nature, science and technology: For instance, as ligands for metals in supramolecular synthesis, as photosenstizers in photodynamic therapy (PDT), and as building blocks for electronic devices. In addition to their application in cancer therapy, porphyrin species also exhibit antiviral activity. New meso-tetraarylporphyrins (TArP, Ar = -C6H4-) of the general formula, T(R1R2NSO2Ar)P, with R1 = N-py-n-CH2 (n = 2, 3 or 4) or SO3- and R2 = H or CH3 were synthesized. These groups were linked to the 4-position of the phenylene group of the porphyrin by a secondary (SO2NHR) or tertiary (SO2NR2) sulfonamide group. The sulfonamide group was found to be a versatile way of expanding the porphyrin. The presence of a tertiary sulfonamide group instead of a dissociable proton improved the solubility of the new class of porphyrin compounds synthesized.

Adducts having four methylcobaloxime unit (CH3Co(DH)2) bound to the pyridyl nitrogens of T(N-py-4-CH2(CH3)NSO2Ar)P or TpyP(4) were synthesized for the first time and their solution properties studied by 1H NMR spectroscopy. The 1H NMR signal of the axial methyl of CH3Co(DH)2L complexes shifts upfield with increasing L basicity, but the signal of the equatorial methyl is insensitive to L basicity. The axial methyl signal was used to examine the effect of coordination of the CH3Co(DH)2 moiety to the N-pyridyl group of the TpyP(4) and of the newly synthesized porphyrin, T(N-py-4-CH2(CH3)NSO2Ar)P.

A new class of water-soluble porphyrins meso-tetraarylporphyrins and some metal derivatives were synthesized from the above class of compounds by simple alkylation and metallation with copper and zinc salt. Interactions of selected porphyrins and metalloporphyrins (Cu(II), Zn(II)) with calf thymus DNA were investigated by visiblr circular dichroism, absorption, and fluorescence spectroscopies. The main aim of studying this class of compounds was to assess whether N-methylpyridinium (N-Mepy) groups must be directly attached to the porphyrin core in order for intercalative binding to DNA to occur.

Porphyrins have been known for some years to show antiviral activity against human immunodeficiency virus (HIV) infection in assays that measured inhibition of virus replication. One promising approach receiving increasing attention is the development of microbicides which, when applied topically, can prevent viral infection. These compounds could directly interact with HIV virions to decrease or prevent infectivity, thus providing a defense against sexual transmission of the virus. Sulfonated derivatives of tetraarylporphyrin have also been shown to exhibit activity HIV. A new class of porphyrins containing sulfonamide links was synthesized and characterized by 1H NMR spectroscopy and mass spectrometry.

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