平阳霉素与Mn^（2＋）络合物结构的~1H－NMR弛豫研究

Structural study on the proton relaxation of Mn￣(2+)-pingyangmycin complex

为了确证Ｍｎ^（２＋）－ＰＹＭ络合物在溶液中的静态微观结构，本文研究了高自旋顺磁离子Ｍｎ^（２＋）对在Ｍｎ^（２＋）－ＰＹＭ络合物分子中各种质子的纵向弛豫速率的影响。根据这种顺磁效应的大小，计算出各种质子距中心金属离子的相对距离。以嘧啶甲基质子到中心离子的距离６．５×１０^（－１０）ｍ为标准，求得绝对距离。实验发现，分子中的二噻唑基以及末端胺基链上的质子非常靠近中心金属离子，Ｍｎ^（２＋）与二噻唑质子的距离为５．７５×１０（－１０）ｍ，可以认为该基团是作为金属离子的配体而参予成键作用的。结果还表明，β－羟基组氨酸中的咪唑环很可能作为配体而成键，两个氢的距离分别为５．７４×１０^（－１０）和４．９６×１０^（－１０）ｍ。ＰＹＭ的作用机制是：ＰＹＭ在Ｆｅ^（２＋）的络合下激活，当与底物ＤＮＡ靠近时，便会将周围的Ｏ_２变成具有活性的还原态含［Ｏ］基团，进攻ＤＮＡ，使其降解。同时，Ｆｅ^（２＋）－ＰＹＭ转变为Ｆｅ^（３＋）－ＰＹＭ，进而在体内氨基酸、维生素Ｃ等还原剂作用下。重新生成Ｆｅ^（２＋）－ＰＹＭ（诱导一粒子进攻降解机理）。同时，在构象匹配的条件下，也可通过插入方式破坏ＤＮＡ的遗传密码。

In order to define the static microstructure of Mn￣(2+)-PYM comples in the solution,the effect of high spin Mn￣(2+) ion to the longitudinal nucleas relaxation rates of various protons in the Mn￣(2+)-PYM complex was studied. Based on the magnitudes of the paramagnetic effect of Mn￣(2+),the relative distance of central metal ion to the protons could be calculated.When the distance of the pyrimdine methyl proton to the central ion ,6.5×10-10m was taken as standard,the absolute distance could be calculated. Experimental results showed that the protons of bithiazole and amide terminal were very close to the central metal ion.The distance of the Mn￣(2+)and bithiazide was 5. 75 ×10-10m,it could be considered that the functional group was the ligand of the metallic ion bonding and also the imidazole ring in the β-hydroxy histamine is a ligand to form the hydrogen bonding.The distances of the two hydrogen bonding were 5.74 ×10-10 and 4.96× 10-10m respectively.Mode of action of PYM could be postulated as follows:PYM was activated in the present of Fe￣(2+) to become chelate comples with the approaching of the substrate DNA,by activating the surrounding O_2 to become active radical[O] attacking the substrate DNA to promote the degradation. At the same time, Fe￣(2+)- PYM was oxidized to become Fe￣(3+) -PYM.Which is further being reduced to Fe￣(2+) -PYM by some amino acids and vitamin C in the body(that is so called induced-particle degradation attack mechanism),while in some other cases,by confirmational change of the antibiotic, it may intercalate into the backbone to destruet the genetic code of substrate DNA.