NEW NITRIC OXIDE-RELEASING ZWITTERIONS DERIVED FROM POLYAMINES
NEW NITRIC OXIDE-RELEASING ZWITTERIONS DERIVED FROM POLYAMINES
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DOI：
10.1021/jo00058a030
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发表时间：
1993-03-12
影响因子：
3.6
通讯作者：
KEEFER, LK
中科院分区：
文献类型：
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作者：
HRABIE, JA;KLOSE, JR;KEEFER, LK
研究了一氧化氮 (NO) 与多胺的反应，发现了一种新型的释放 NO 的化合物，其结构为 RN[N(O)NO]-(CH2)xNH2+R' (3)。已经制备了这些两性离子多胺/NO加合物的许多实例，并且发现它们是非常稳定的固体，其在溶液中释放NO。这些新化合物含有高达 45% 重量的 NO，并且能够以可预测的随结构变化的速率释放全部 NO。在 pH 7.4 和 22 摄氏度的缓冲水溶液中，半衰期从极短（二胺 8、MeN[N(O)NO]-(CH2)4NH2+Me 为 1.3 分钟）到非常长（三胺 18、H2NCH2CH2N[N(O)NO]-CH2CH2NH3+ 为 56 小时）不等。一般来说，三胺/NO 加合物和乙二胺衍生物 (x = 2) 实现了最长的半衰期。对于任何给定的 x 值，R 大小的小幅增加会导致半衰期相对较大的增加，但 R' 的变化似乎影响不大。所提供的数据应允许选择适当的化合物以实现各种所需的 NO 生成速率。这些含 NO 的两性离子应该被证明是 NO 生物学研究的重要资源，并且还可能具有重要的制药和化学应用。
The reaction of nitric oxide (NO) with polyamines has been studied, resulting in the discovery of a new type of NO-releasing compound having the structure RN[N(O)NO]-(CH2)xNH2+R' (3). Numerous examples of these zwitterionic polyamine/NO adducts have been prepared and found to be very stable solids which release NO in solution. The new compounds contain as much as 45% NO by weight and are capable of releasing it all at rates which have been shown to vary in a predictable way with structure. The half-lives in buffered aqueous solution at pH 7.4 and 22-degrees-C were shown to vary from extremely short (1.3 min for diamine 8, MeN[N(O)NO]-(CH2)4NH2+Me) to very long (56 h for triamine 18, H2NCH2CH2N[N(O)NO]-CH2CH2NH3+). In general, the longest half-lives were achieved by triamine/NO adducts and derivatives of ethylenediamine (x = 2). For any given value of x, a small increase in the size of R resulted in a relatively large increase in half-life but changes in R' appeared to have little effect. Data are presented which should allow the selection of the proper compounds to achieve a wide range of desired NO generation rates. These NO-containing zwitterions should prove to be important resources in studies of the biology of NO and may also have important pharmaceutical and chemical applications.