Photophysical, Catalytic Properties And Interaction With DNA/HSA Of Manganese N-Confused Porphyrins

Metalloporphyrins have been applied to essentially every field and have significant contribution to the scientific developments. N-confused porphyrin is an isomer of porphyrin. Because of its unique chemical structure and reactivity, N-confused porphyrin has potential applications in coordination chemistry, catalytic chemistry, chemical biology and photodynamic therapy. Studies on the photophysical properties of porphyrins, N-confused porphyrins, related macrocycles and their metal complexes will help to deeply understand life process such as photosynthesis in nature and provide theoretical guidance for the applications in various fields. It has been observed that N-confused porphyrins can bind to DNA and serum albumin, stablize G-quardruplex DNA, effectively generate singlet oxygen. N-confused porphyrins have also been proved efficient photosensitizer against living mice bearing colo26 tumour implantly subcutaneously and breast adenocarcinoma cells without skin phototoxicity. Similar to corroles, N-confused porphyrins can stablize the high oxidant states of metal ions. The metal complexes of N-confused porphryin have been demonstrated to be potent catalysts in oxygen transfer reactions and cyclopropanation of styrene with high trans-slectivity, which is a new kind of catalysts with good development prospects. However, less attention has been paid to the photophysical properties and applied research in various fields for the metal complexes of N-confused porphryin. Further research is to be explored in this area.In this dissertation, a series of N-confused porphyrins with different substituents and their manganese complexes were prepared and their photophysical properties were studied. The catalytic application in the oxidation of alkene and interaction with DNA/HSA of manganese N-confused porphyrins were discussed for the first time.(1) A series of N-confused porphyrins with different electron-donating and withdrawing effects(1~6) have been designed and prepared, namely N-confused 5,10,15,20-tetrakisphenylporphyrin(1), N-confused 5,10,15,20-tetrakis(2-methoxyphenyl)por-phyrin(2), N-confused 5,10,15,20-tetrakis(3-methoxyphenyl)porphyrin(3), N-confused 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin(4), N-confused 5,10,15,20-tetrakis(4-methylp-henyl)porphyrin(5), N-confused 5,10,15,20-tetrakis(4-chlorophenyl) porphyrin(6). The corresponding methylated N-confused porphyrins(7~12) and their manganese complexes(7-Mn~12-Mn) were also synthesized. Their structures of all the compounds(1~12-Mn) and valence states of manganese were correctly characterized by UV-Vis, 1HNMR, 13 CNMR, MS, XPS spectra and Cyclic Voltammetry. All results indicated these compounds were identified as the target complexes and the valence state of manganese was trivalence.(2) The steady-state spectra of N-confused porphyrins and their manganese complexes has been investigated with UV-Vis absorption spectroscopy. Methyl substitution and metallization have obvious effect on the steady-state spectra of N-confused porphyrins. The excited-state spectra and relaxation dynamics of manganese N-confused porphyrins 7-Mn and 8-Mn have been measured firstly using femtosecond transient absorption spectroscopy. The transient absorption kinetics of have been found to be well global-fitted to a three-exponential function(τ1, τ2 and τ3). τ1, τ2 and τ3 of 7-Mn(8-Mn) are 0.370 ps(0.270 ps),8.55 ps(5.32 ps) and 21.28 ps(14.28 ps), which may be assigned to the lifetimes of the second excited singlet state(5S2), the first excited singlet state(5S1) and the first excited triplet state, respectively.(3) The first catalytic oxidation of alkene by manganese N-confused porphyrins with six different substituents(7-Mn~12-Mn) are presented. The influence of reaction time, solvents and oxidants on the catalytic reaction were also investigated. The experimental results showed that these manganese N-confused porphyrins can catalyze the oxidation of styrene in the presence of iodosylbenzene to yield styrene oxide as the major product. Among all investigated manganese N-confused porphyrins, the most electron deficient 12-Mn exhibited the best catalytic activity for the alkene oxidation. It turned out their catalytic activities were comparable with manganese tetraphenylporphyrin(Mn TPP). The proposed mechanism for the catalytic oxidation has also been described based on UV-Vis spectral changes for the reaction between 12-Mn(Mn TPP) and Ph IO. Similar spectral changes suggest similar meachnism in both cases and the existence of MnV=O moiety.(4) The ct-DNA binding and chemical nuclease activity of manganese N-confused porphyrin 12-Mn were investigated by UV-Vis absorption spectroscopy, fluorescence spectroscopy, viscosity experiments, circular dichroism spectroscopy, molecular docking and agarose gel elctrophoresis experiments. The DNA binding experimental results showed that 12-Mn bound to ct-DNA via an outside groove binding mode with the binding constant of 4.144×105 M-1. The fluorescence quenching experiments showed that the competition of 12-Mn and ethidium bromide(EB) with ct-DNA was a static process. The binding process of 12-Mn and ct-DNA was spontaneous. The main driven forces were the hydrogen bond and van der Waals for the former, which were further confirmed by molecular docking modeling. Manganese N-confused porphyrin 12-Mn could cleave the supercoiled plasmid DNA efficiently in the presence of hydrogen peroxide. Hydroxyl radical(?OH) was found the active species for oxidative damage of DNA.(5) The interaction of 12-Mn with human serum albumin(HSA) under simulative physiological conditions was investigated by(synchronous) fluorescence spectroscopic, circular dichroism(CD) spectroscopic and molecular docking methods. The fluorescence of HSA might be quenched by 12-Mn via a static process. The HSA binding was a spontaneous process mainly driven by hydrophobic interaction with the binding constant and binding distance of about 106 M-1 and 3.74 nm, respectively. 12-Mn bound preferably to site I of HSA in accord with molecular docking modeling. CD spectroscopy and synchronous fluorescence measurements showed that the interaction of HSA with 12-Mn induced the change of the secondary structure of HSA and microenvironment of tryptophane residue.