Interactions of DNA with H2TMPyP4+and Ru(II)TMPyP4+: Probable Lead Compounds for African Sleeping Sickness

Abstract

Interactions of DNA with free base porphyrin, tetrakis(1-methylpyridium-4-yl)porphyrin (H 2 TMPyP 4+ ) and its metallo-derivative of ruthenium(II) have been investigated by UV-Vis, fluorescence and circular dichroism (CD) spectroscopy at 0.1 M NaCl, 7.5 pH and 25 °C. The results suggest that Ru(II)TMPyP 4+ interacts with DNA via outside binding in self-stacking manner as indicated by UV-Vis data, a small red shift (∆λ = 3 nm) and a minimal hypochromicity (10%) upon addition of DNA. CD spectra showed the presence of a new peak in the Soret region on addition of Ru(II)TMPyP 4+ to DNA solution. On the other hand, the interaction of free base porphyrin, H 2 TMPyP 4+with DNA revealed a significant hypochromicity (30%) and a large red shift (∆λ = 20 nm) in the UV-Vis results which conforms intercalation of free base porphyrin with DNA. In this case, the CD results showed only a negative peak developed in the Soret region during titration with DNA. Fluorescence spectroscopy revealed that initially aggregated porphyrin species were de-aggregated after addition of DNA. This phenomenon has been verified with the fluorescence experiments for the porphyrins in the presence of different concentrations of NaCl and ethanol. Ru(II)TMPyP 4+ showed enhanced DNA cleavage in the presence of EcoR1 restriction enzyme, where the enzyme did not cleave DNA. Metallo-porphyrins having the ability to cleave DNA could be used as chemotherapeutic agents for the treatment of African sleeping sickness (Trypanosomiasis).

Formation of Nickel(II)Porphyrin and Its Interaction with DNA in Aqueous Medium

“…The addition of nitrate ion reduces the positive charge of the cationic porphyrin at the transition state through formation of anion-cation-porphyrin adducts that causes the decreasing the reaction rates for negatively charged nickel species [18,58,65]. In our previous study, we also found weak intensities from the Ru 2+ -, Pd 2+ -, Pt 2+ -and [Au(III)TMPyP] 5+ porphyrins in aqueous solution because of the heavy atom effect [40,41]. The fluorescence intensity for the [Ni(II)TMPyP] 4+ complex is significantly decreased upon addition of a low concentration of DNA, and then increased with further addition of DNA (supplementary Figure S-2a).…”

“…The intensity of the hump increases with addition of DNA and the fluorescence spectrum is finally centered at 630 nm (supplementary Figure S-2b). These results suggested that the cationic free base porphyrin initially interacts with DNA via negatively charged phosphate network in the presence of a low concentration of DNA, and then de-stacking occurs upon further addition of DNA [40,41]. From the UV-vis and fluorescence spectral results, it is confirmed that both the metalloporphyrin, [Ni(II)TMPyP] 4+ , and the free base porphyrin interact with DNA but their modes of interaction are different.…”

“…The porphyrin molecules aggregate on the negatively charged phosphate network of the DNA molecules through self-stacking in the presence of low concentration of DNA, however, de-aggregation occurs upon addition of additional DNA. This causes the increasing the fluorescence intensity of the metalloporphyrin [40,41]. On the other hand, the intensity of the fluorescence centered at 660 nm did not change but the intensity of the hump appeared at ~628 nm is increased with a low concentration of DNA into the [H2TMPyP] 4+ solution.…”

“…Much attention has been paid to explore the interaction between the cationic porphyrins and nucleic acids, such as DNA and RNA because of promising properties of the porphyrins in medical as well as in biological applications [2,3,[5][6][7][9][10][11][12][13][14][15][16][39][40][41][42][43][44][45]. The potential uses of the porphyrins in medical and biological fields are due to their anticancer [11,12,16], antiviral and/or antibacterial/anti-inflammatory [4,6,10,[13][14][15] and antifungal [6,46] activities.…”

“…Cationic porphyrins interact with DNA in various modes where substituents of the porphyrins and/or central metal ions play vital roles. The three major modes of interaction between porphyrins and DNA are intercalation, outside binding without self-stacking, and outside binding with self-stacking along the DNA surface [38][39][40][41]50,51]. Partial intercalation has also been suggested [40].…”