Synthesis And Interfacial Assembly Of Chiral Macrocyclic Polyamine-Mn(Ⅱ) Complexes And Their Superoxide Dismutation Ability

Superoxide dismutase (SOD) is a common metalloenzyme in organism for the effective mediation and maintaniance of biological superoxide concentration. Superoxide dismutase mimics (MSOD) by rational design and synthesis are expected to have the advantages of high stability, low toxicity, low cost for production and small molecular weight, etc., over natural SODs, and it is significant for these MSOD to be used in clinic. Design and synthesis of chiral macrocyclic polyamine-metal complexes with SOD-like activity will be very useful for their immobilization on electrodes for the detectation of superoxide in vivo and in vitro. It is expected that this kind biosensors with SOD mimics modified electrodes will possess long lifetime in use and high reproducibility in production, etc., and have impotant application in clinic diagnosis for the diseases related to superoxide.In this thesis, we designed and synthesized a new group of chiral macrocyclic polyamine-Mn(â…¡) complexes as superoxide dismutase mimics, and constructed them on the surface of gold substrates for the application of superoxide detection. The main contents are listed as the following:1. A group of chiral macrocyclic polyamine-Mn(â…¡) complexes based on the substituted [15]-ane-N₅ backbone and a axial ligand N-(2-(1H-imidazol-5-yl)ethyl)-5-(1,2-dithiolan-3-yl) pentanamide (imid-2S) were synthesized. The molecular structures of the target compounds and some intermediates were confirmed by ¹HNMR,GC-MS,ESI-MS,IR,UV, etc.2. Macrocyclic polyamine-metal complexes were attempted to immobilize on a self-assembled monolayer (SAM) of imid-2S on gold electrode by exchange of axial ligand Cl^-1 of Mn-01 with the terminal imidazolyl of imid-2S SAM and the exchang procedure was investigated by the electrochemical cyclic voltammetry and electrochemical impendence spectra. The result showed that immobilization of macrocyclic polyamine-metal complexes on a self-assembled monolayer via axial ligand exchange had been achieved, and the surface concentration of Mn-01 reached 1.45×10^-11mol·cm^-2. However, the UV-Vis spectra was not obvious for the axial ligand exchange and maybe it can be attributed to the week coordination ability of Cl^-1 and imidazole group to Mn²⁺, for the change of the coordination field of the metal ion via ligand exchange. 3. Macrocyclic polyamine manganese(â…¡) complex linked withα-lipoic acid as headgroup (Mn-07) had been constructed on gold electrodes by self-assembly technology. The surface coverage of the SAMs is up to 99.65%, and the surface concentration of Mn-07 is 1.32×10^-10 mol·cm^-2. Upon the change of potential scan rate, the redox potential position of Mn-07/Au modified electrodes remained unchanged and the anodic peak currents augmented linearly with potential scan rate, implifying Mn-07 has formed well packed SAM on gold electrodes. This conclusion could been further confirmed by the X-ray photoelectron spectra(XPS) of Mn-07/Au modified electrodes.4. Xanthine and xanthine oxidase system was used to generate O₂^.- and its dimutation on Mn-07/Au were investigated. The result demonstrated that these MSOD molecular self-assembly systems promoted the disproportionation of superoxide obviously, and the plausible mechanism was established. For those Macrocyclic polyamine manganese(â…¡) complex without the self-assembly ability on gold electrodes directly, Mn-02, Mn-04 and Mn-06 were tested their SOD-like activity by the method of pyrogallol autoxidation, and afforded the inhibition rate 14.75%, 9.01%, 0.82% respectively.