Lian-Cai Xu

Tricationic pyridium porphyrins appending different peripheral substituents: Experimental and DFT studies on their interactions with DNA

Four tricationic pyridium porphyrins appending hydroxyphenyl, methoxyphenyl, propionoxyphenyl or carboxyphenyl group at meso-20-position of porphyrin core have been synthesized and their abilities to bind and cleave DNA have been investigated. Using a combination of absorption, fluorescence, circular dichroism (CD) spectra, thermal DNA denaturation as well as viscosity measurements, their binding modes and intrinsic binding constants (K(b)) to calf DNA (CT DNA) were comparatively studied and also compared with those of 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP). The results suggest that the K(b) values of these porphyrins are greatly influenced by the number of positive charges and steric hindrance. Theoretical calculations applying the density functional theory (DFT) have been carried out and explain their DNA-binding properties reasonably. The efficiency of DNA photocleavage by these porphyrins shows high dependence on the values of K(b).

DNA-binding and photocleavage properties of cationic porphyrin-anthraquinone hybrids with different lengths of links.

Four cationic porphyrin-anthraquinone (Por-AQ) hybrids differing in lengths of flexible alkyl linkage, 5-[4-(1-N-anthraquinonon-yl)-L-oxophenyl]-10,15,20-tris(N-methylpyridinium-4-yl)porphyrin triiodide, (L = acetyl, pentanoyl, octanoyl, undecanoyl, designed as [AQATMPyP]I3, [AQPTMPyP]I3, [AQOTMPyP]I3 and [AQUTMPyP]I3, respectively, see Fig. 1), were synthesized and their interactions with DNA were investigated. The results of spectroscopic, denaturation and viscosity measurements suggest that [AQATMPyP]I3 binds to DNA through non-intercalative mode while the other three hybrids with longer links bind via bis-intercalative mode. Ethidium bromide (EB) competition experiment was carried out to determine the binding constants (Kb) of these compounds for CT DNA, and [AQPTMPyP]I3 shows the largest Kb among these hybrids. The photocleavage mechanism and wavelength-dependent cleaving abilities of these hybrids to pBR322 plasmid DNA were also comparably investigated.

DNA binding and photocleavage properties of a novel cationic porphyrin-anthraquinone hybrid.

A novel cationic porphyrin-anthraquinone (Por-AQ) hybrid has been synthesized and characterized. Using the combination of absorption titration, fluorescence spectra, circular dichroism (CD) as well as viscosity measurements, the binding properties of the hybrid to calf thymus (CT) DNA have been investigated compared with its parent porphyrin. The experimental results show that at low [Por]/[DNA] ratios, the parent porphyrin binds to DNA in an intercalative mode while the hybrid binds in a combined mode of outside binding (for porphyrin moiety) and partial intercalation (for anthraquinone). Ethidium bromide (EB) competition experiment determined the binding affinity constants (K(app)) of the compounds for CT DNA. Theoretical calculational results applying the density functional theory (DFT) can explain the different DNA binding behaviors reasonably. (1)O(2) was suggested to be the reactive species responsible for the DNA photocleavage of porphyrin moieties in both two compounds. The wavelength-depending cleavage activities of the compounds were also investigated.

A combined computational and experimental study on DNA-photocleavage of Ru(II) polypyridyl complexes [Ru(bpy)2(L)]2+ (L = pip, o-mopip and p-mopip)

A combined computational and experimental study on DNA-photocleavage by Ru(II) polypyridyl complexes [Ru(bpy)2(L)]2+ 1-3 (bpy = 2,2-bipyridine; L: pip = 2-phenylimidazo[4,5-f]1,10-phenanthroline, o-mopip = 2-(2-methoxyphenyl)imidazo[4,5-f]1,10-phenanthroline and p-mopip = 2-(4-methoxyphenyl)imidazo[4,5-f]1,10-phenanthroline) has been carried out. The DNA-photocleavage behavior of these complexes was comparably measured by the gel electrophoresis experiments. The experimental results show that they can induce considerable DNA-photocleavage, and have different DNA-photocleavage efficiencies (phi) following the order phi (1) < phi (2) < phi (3). In order to understand their DNA-photocleavage mechanism and trend, the theoretical studies on the geometric and electronic structures of these complexes in the ground state (S0), the first singlet excited state (S1) and triplet excited states (T1), have been carried out using the density functional theory (DFT/TD-DFT), Hartree-Fock (HF) and configuration interaction singles (CIS) methods. In particular, the reduction potentials (E*red) of the excited complexes in aqueous solution, which seem to be closely responsible for the DNA-photocleavage behavior, were calculated to be 0.966 V (vs. SCE) for complex , 1.024 V (vs. SCE) for complex and 1.030 V (vs. SCE) for complex , respectively. Such computational results show that the reduction potentials of the excited complexes reach the theoretical range for oxidizing some DNA-bases, and follow the order E*red (1) < E*red (2) < E*red (3). Therefore, here, in addition to the general theoretical explanation of their DNA-photocleavage mechanism according to our recent report, a further explanation on the trend of their DNA-photocleavage efficiencies, i.e., phi (1) < phi (2) < phi (3), was reasonably carried out, on the basis of the calculated electrochemical properties in the excited states as well as general photochemical insights.

Experimental and DFT studies on DNA binding and photocleavage of two cationic porphyrins. Effects of the introduction of a carboxyphenyl into pyridinium porphyrin.

The DNA-binding affinities and DNA photocleavage abilities of cationic porphyrin, 5-(4-carboxyphenyl)-10,15,20-tris(4-methylpyridiniumyl)porphyrin (CTMPyP), and its reference compound meso-tetrakis(N-methyl-4-pyridiniumyl)porphyrin (H2TMPyP) have been investigated. The DNA-binding behaviors of the two compounds in NaH2PO4 buffer were compared systematically by using absorption, fluorescence and circular dichroism (CD) spectra, thermal denaturation as well as viscosity measurements. The experimental results show that CTMPyP binds to DNA in an outside binding mode, while H2TMPyP in an intercalative mode. Photocleavage experiments reveal that both two compounds employ 1O2-mediated mechanism in cleaving DNA and H2TMPyP can cleave DNA more efficiently than CTMPyP. Theoretical calculations were carried out with the density functional theory (DFT), and the calculated results indicate that the character and energies of some frontier orbitals of CTMPyP are quite different from those of H2TMPyP. These theoretical results can be used to explain their different DNA-binding modes and affinities to a certain extent.