Nucleobase (A, T, G and C) appended tri-cationic water-soluble porphyrins: Synthesis, characterization, binding and photocleavage studies with DNA

A series of nucleobase appended tri-cationic porphyrins (AT4, TT4, GT4 and CT4) have been synthesized and their binding and cleaving ability of DNA were investigated in this present study. UV-vis, fluorescence, circular dichroism and thermal melting studies were carried out to investigate binding of the porphyrin with calf thymus DNA (CTDNA). The apparent binding constant (K _app) and the intrinsic binding constant (K_b) values calculated from UV-vis and fluorescence titrations, respectively, were comparable to 5,10,15,20-tetra(N-methylpyridinium-4-yl) porphyrin (H ₂T4) or slightly more for few compounds. Circular dichroism spectra of these porphyrins with DNA show variation in their mode of binding. Among the nucleobase appended tri-cationic porphyrins, the porphyrin in GT4 and TT4 exhibit strong intercalating ability in the DNA duplex whereas the porphyrin in AT4 and CT4 exhibit very less ability for intercalation. The intercalating efficiency of the porphyrin in GT4 is even stronger than that of the H ₂T4. The steric strain exists between the tri-cationic porphyrin moiety and the DNA may decrease depending on (a) the ease to exhibit keto-enol tautomerism due to the more acidic protons in guanine and thymine, (b) extended conjugation and (c) hydrogen bonding capability of the nucleobase moieties. Photocleavage proclivities with pBR322 DNA in the presence of light reveal that AT4, TT4 and CT4 show same amount of cleavage but GT4 shows more cleaving efficiency than H₂T4 due to the stacked guanine moieties those are more reducing than a single guanine residue. The singlet oxygen mechanism that is responsible for the photocleavage was confirmed with various inhibitors and interestingly with Tiron (disodium salt of 1,2-dihydroxy-3,5-benzenedisulfonic acid) the photocleaving efficiency increases due to the inhibition of superoxide formation.