Abstract
Utilizing linear dichroism (LD), circular dichroism (CD), and fluorescence energy transfer, the binding geometries of a series of Co(3+)-porphyrins and their free ligands were examined. The compounds studied were Co-meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (CoTMPyP) and its free ligand (H2-TMPyP), Co-meso-tetrakis(N-n-butylpyridinium-4-yl)porphyrin (CoTBPyP) and its free ligand (H2TBPyP), and Co-meso-tetrakis(N-n-octylpyridinium-4-yl)porphyrin (CoTOPyP). The two non-metalloporphyrins exhibit negative LD, having angles of roughly 75 degrees relative to the DNA helix axis. They also display negative CD and a significant contact energy transfer from the DNA bases. On the other hand, the three metalloporphyrins display orientation angles of roughly 45 degrees between the porphyrin plane and the helix axis of DNA. Furthermore, they exhibit positive CD and no contact energy transfer from DNA bases. These observations show that the metalloporphyrins are not intercalated whereas non-metalloporphyrins having four freely rotating meso-aryl groups intercalate between the base pairs of DNA. In the presence of KHSO5, the cobalt porphyrins cleave closed circular PM2 DNA in a single strand manner, i.e., a single activation event on the porphyrin leads to a break in one of the DNA strands. A kinetic analysis of the cleavage data revealed that cleavage rates are in the order CoTMPyP > CoTBPyP > CoTOPyP with the difference being due to different DNA affinities rather than differences in cleavage rate-constants. Based on these and earlier observations, the metalloporphyrins appear bound to a partially melted region of DNA.
Highlights
The most extensively studied DNA binding porphyrin is meso-tetrakis(N-methylpyridinium-4-yl)porphyrinH, 2TMPyP (Figure 1)
The free bases, H2TMPyP and H2TBPyP, which have no axial ligands show a substantial red-shift at the Soret maximum (Figure 2)
Upon binding to CT DNA they exhibit negative circular dichroism (CD) bands in the visible region (Figure 3). These observations indicated that the unmetallated porphyrins have strong interactions with the bases of DNA
Summary
The most extensively studied DNA binding porphyrin is meso-tetrakis(N-methylpyridinium-4-yl)porphyrinH, 2TMPyP (Figure 1). As was originally demonstrated by Fiel and coworkers (Fiel et al, 1982), FeTMPyP can be chemically activated to produce breaks in DNA. Additionalwork by the groups of Dabrowiak and co-workers (Raner et al, 1989; Ward et al, 1986a,b)and of Bernadou and Meunier and their co-workers (Fouguet et al, 1987; Pratviel et al, 1989; Bernadou et al, 1989)established that M-TMPyP where M is Fe3+,Mn3+,and Co3+can be activated with a variety of oxidizing agents to produce breaks in DNA. A detailed study by Bernadou and Meunier and their coworkers (Pratviel et al, 1991;Gasmi et al, 1991;Piti et al, 1992) showed that MnTMPyP cleaves DNA from its minor grove. The details of the cleavage mechanisms are not known, studies with plasmid DNA indicate that certain metalloporphyrins can cause both single- and double-strand breaks in DNA (Praseuth et al, 1986; Fiel et al, 1981)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
