Studies On The Synthesis Of Nitrosyl Metalloporphyrins And Application As NO Donors

Objective:The nitrosyl metalloporphyrin complexes were designed, synthesized and considered as NO donor drugs. The nitric oxide released efficiency and the bioactivities of the notrosyl metalloporphyrins were studied. To provide theoretical and experimental value for studying novel NO donors further.Methods:1. Two porphyrin ligands (a, b) were synthesised by different function groups—hydroxy, amino attaching to the phenyl groups on the meso-positions ring. The yields increased in the mixed of sovlents (propionic acid, acetic acid and nitro-benzene). Porphyrins ligand was converted into corresponding metal complexes on treatment with excess of M(OAc)2 (M=Co, Mn, Cu, Fe). The nitrosyl metalloporphyrin complexes were synthesized by metalloporphyrin complexe treating with nitric oxide.2. The nitric oxide released process of nitrosyl metalloporphyrins in vitro was detected with diazotization assay at room temperature.3. The first function, scavenging O2-, has been proved by using riboflavine-methionine photoreduction methods. The second function, scavenging H2O2, has been demonstrated by using the oxidating Vit C. The third function, scavenging HO·, has been demonstrated by using Fenton reaction. The complexes were measured by the liver homogenate technique of mice.4.To investigate the relaxation of nitrosyl metalloporphyrins on isolated aorta pectoralis circle in the rabbit.5. Eighteen rats were randomized into two groups. The treatment group was injected venously with 0.5mL TAPP-Co-NO mixed DMSO, and the control group was given with 0.5mL DMSO. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rates ( HR) were investigated before and after administration.Results: 1. The structures of the above synthetic products were characterized by IR, MS, UV-vis, 1HNMR and elemental analysis.2.The nitric oxide released efficiency of the notrosyl metalloporphyrins were 38.98% for THPP-Cu-NO, 35.22% for THPP-Mn-NO, 59.48% for THPP-Co-NO, 66.42% for THPP- Fe -NO, 38.37% for TAPP-Cu-NO, 35.61% for TAPP-Mn-NO, 63.17% for TAPP-Co-NO, 62.04% for TAPP-Fe-NO, respectively.3. Sixteen target complexes could scavenge O2- in the range of 1. 0×10-5~10–6mol·L-1, decompose H2O2 in the concentration of 7.50×10-7 mol·L-1, scavenge HO·in the concentration of 5. 0×10-7 mol·L-1. All showed that they had obvious action of decreasing the lipid peroxidation in the concentration of 1. 0×10-7 mol·L-1.4.TAPP-Fe-NO and TAPP-Co-NO shifted Methoxamine cumulative dose- respo -nse curves rightward im-paralleled and reduced the Max, the reduced percentage were 14.9%and 29.0% respectively.5. For the treament group, the blood pressure of rats began to decrease at the time of 5sec after the administration. The blood pressure of rats reached to minimum at the time of 10sec, then increased gradually; finally, approached to normal blood pressure at 60sec. For the control group, the blood pressure of the rats was no change after employing the DMSO.Conclusions:1. Eight novel nitrosyl metalloporphyrins were synthesised.2. These notrosyl metalloporphyrins are useful as NO donor drugs.3. Sixteen complexes were considered to be qualified analogous enzymes of anti-active oxygen.4. TAPP-Fe-NO and TAPP-Co-NO shifted Methoxamine cumulative dose- respo -nse curves rightward im-paralleled and reduced the Max.5. TAPP-Co-NO can decrease blood pressure instantaneously, but had no effect on heart rates, anapnea and ECG. Perhaps it will be used as ideal emergency hypotensive drugs.