Interactions of tetracationic mercury(II), cadmium(II) and lead(II) porphyrins with DNA and their effects on DNA cleavage

The effects of tetrakis(1-methylpyridinium-4-yl)porphyrinatomercury(II) [Hg(TMPyP)]⁴⁺ (6) along with [Pb(TMPyP)]⁴⁺ (7), [Cd(TMPyP)]⁴⁺ (8), and [H₂(TMPyP)]⁴⁺ (1) (free base porphyrin) on DNA cleavage by Haemophilus aegyptius (HaeIII) have been studied using gel electrophoresis, UV-vis absorption spectroscopy, and circular dichroism (CD) spectroscopy. The gel electrophoresis results indicate that in the absence of 6, HaeIII restriction enzyme could not cleave plasmid DNA at a low concentration of 0.2 units µl⁻¹ after 1 h incubation at 37 °C. However, DNA cleavage occurred in the presence of 6 at the concentrations of 1.0 × 10⁻⁶ and 1.0 × 10⁻⁷ M and 0.2 units µl⁻¹ of HaeIII under the same conditions. In addition, acceleration of DNA cleavage occurred at a higher concentration of HaeIII (0.4 units µl⁻¹) in the presence of a wider concentration range of 6 from 1.0 × 10⁻⁵ to 1.0 × 10⁻⁷ M. 8, 7, and 1 could not enhance DNA cleavage in the presence of HaeIII (0.2 units µl⁻¹). However, when the concentration of HaeIII was increased to 0.4 units µl⁻¹, only 8 inhibited DNA cleavage by HaeIII at higher concentrations (1.0 × 10⁻⁵–10⁻⁶ M) whereas 6, 7, and 1 did not. The UV-vis and CD spectroscopic results indicate that these porphyrins interact differently with DNA based on their binding modes. 6 enhanced DNA cleavage due to the synergistic effect of the Hg²⁺ ions and the free base porphyrin 1 that dissociated from the mercury(II) porphyrin complex upon binding to DNA which resulted in the enhanced transformation of the DNA conformation from the original B-form to a Z-like conformation, while 8 inhibited HaeIII activity at higher concentrations and 7 and 1 neither enhanced nor inhibited DNA cleavage. A mechanism for this phenomenon is suggested. Copyright © 2001 John Wiley & Sons, Ltd.