Elucidation of Reaction Mechanism of Abnormal Heme Metabolism by Synthetic Methods

合成了N_A-乙基和N_B-乙基中卟啉二甲酯（A环和B环上带有乙基的同分异构体）的钴（II）配合物，以阐明血红素代谢异常的反应机理。用1.6当量的N_A-和N_B-乙基中卟啉的Co（II）配合物重构肌红蛋白，得到稳定的肌红蛋白（（N_A-C_2 H_5 Meso）Co（II）和（N_B-C_2 H_5 Meso）Co（II）-Mb）。~ 1H-NMR谱在-34.75ppm、-36.63ppm和-48.61ppm处有三个信号，分别归属于N-乙基的甲基和N-乙基，这些信号的化学位移与（N_A-C_2 H_5 Meso）Co（II）和（N_B-C_2 H_5 Meso）Co（II）重构的肌红蛋白的化学位移一致。N-烷基中卟啉与肌红蛋白以正向或反向配位，因为肌红蛋白的血红素口袋识别肌红蛋白的侧链序列， 关于我们 f N-烷基中卟啉。在-34.75、-36.63和-48.61ppm处的信号分别归属于反向取向的NA-CzH、正向取向的N_A-C_2 H_5和反向取向的N_B-C_2 H_5。肌红蛋白中Na-乙基与瓦尔68的异丙基的空间排斥作用大于N_A-乙基，这可能是导致N_A-和N_B-乙基相对丰度为1：0.4的原因。此外，反取向的N_A-乙基和正取向的N_B-乙基（1：2）依赖于这样的假设，即正常取向的N-乙基中卟啉与肌红蛋白参考重构，因为肌红蛋白的血红素口袋识别N-乙基中卟啉的侧链序列。从这些结果可以看出，脱辅基肌红蛋白通过不对称血红素口袋识别N-烷基中卟啉的一对对映体，N-乙基与瓦尔68的空间排斥作用在不对称识别中起重要作用。这似乎是合理的假设，与肌红蛋白重建的N-烷基中卟啉的区域异构体的相对丰度是倾向于迁移到烷基的吡咯氮原子。少

Cobalt(II)complexes of N_A-ethyl and N_B-ethylmesoporphyrin dimethylester(the isomers with ethyl group on the A ring and B rings) have been prepared to elucidate the reaction mechanism of abnormal heme metabolism. The reconstituted myoglobins with the cobalt(II) complexes of N-ethylmesoporphyrin have been characterized by 1^H-NMR measurements.The reconstitution of apomyoglobin with 1.6 equivalent of Co(II)complexes of N_A-and N_B-ethylmesoporphyrin affordd stable myoglobins ((N_A-C_2H_5Meso)Co(II) and (N_B-C_2H_5Meso)Co(II)-Mb. The 1^H-NMR spectrum showed three signals at -34.75 ppm, -36.63 ppm and -48.61 ppm assigned to the methyl group of N-ethyl group, respectively.The chemical shifts of these signals were agreement with those of myoglobins reconstituted with (N_A-C_2H_5 Meso Co(II) and (N_B-C_2H_5Meso)Co(II), individually. The N-alkylmesoporphyrin coordinates with myoglobin in normal or reverse orientation because the heme pocket of yoglobin recognizes the sequence of side chains o … More f N-alkylmesoporphyrin. The signal at -34.75, -36.63 and -48.61ppm is assigned to the NA-CzHs of reverse orientation, N_A-C_2H_5 of normal orientation and N_B-C_2H_5 of reverse orientation, respectively. It seems that the steric repulsion of Na-ethyl group with isopropyl group of Val 68 in myoglobin is larger than that of N_A-ethyl group is responsible for the relative abundance of N_A-and N_B-ehyl group of reverse orientation(1 : 0.4). In addition, it seems that the relative abundance of N_A-ethyl group of reverse rientation and N_B-ethyl group of normal orientation (1 : 2) is dependent on the assumption that the N-ethylmesoporphyrin of normal orientation is referentially reconstituted with myoglobin because the heme pocket of myoglobin recognize the sequence of side chains of N-alkylmesoporphyrin.It can be seen from these results that the apomyoglobin recognizes a pair of enantiomers of N-alkylmesoporphyrin by the asymmetric heme pocket, and that the steric repulsion of N-ethyl group with Val 68 play an important role in the asymmetric recognition. It seems reasonable to assume that the relative abundance of the regioisomers of N-alkylmesoporphyrin reconstituted with myoglobin is tendency to migrate to pyrolle nitrogen atom of alkyl group. Less