Elinova V I, Bobko A A, Mazhukin D G, Markel' A L, Khramtsov V V
Institute of Chemical Kinetics and Combustion, Siberian Division, Russian Academy of Sciences, ul. Institutskaya 3, Novosibirsk, 630090 Russia.
Bioorg Khim. 2003 Jul-Aug;29(4):434-41.
The synthesis of new donors and acceptors of nitrogen oxide is described. New lipophilic nitronylnitroxyl radicals (NNR) that act as paramagnetic scavengers of nitrogen oxide are synthesized and characterized. The purity of the preparations is determined, and their structures are confirmed. The lipophilicity of the radicals is tested by ESR spectroscopy. The incorporation into lipid multilayers is shown to protect NNR from reduction in biological samples, while their ability to scavenge nitrogen oxide and form iminonitroxyl radicals is retained. A decreased rate of NNR reduction under these conditions substantially enhances their effectiveness as paramagnetic acceptors of nitrogen oxide in biological systems. The synthesis of a new hydrophilic NO donor, 3-bromo-3,4-dihydro-4,4-dimethyl-4-(2-pyridyl)-diazet-1,2-dioxide (DDpyr), is described. The constants of DDpyr decomposition in tris-HCl buffer (pH 7.5) and in DMSO are determined (4.5 x 10(-6) and 0.5 x 10(-6) s-1, respectively). A substantially higher rate of of DDpyr decomposition in buffer, compared with the decomposition rates determined previously for some diazetines, makes DDpyr a prospective candidate for the use in aqueous media. It is found in experiments on perfused rat caudal artery that DDpyr is an effective vasodilator. Intraperitoneal injection of DDpyr to hereditarily hypertensive rats (ISIAH line) at doses of 100-200 micrograms/kg body mass considerably diminishes their systolic arterial pressure.
描述了新型氮氧化物供体和受体的合成。合成并表征了作为氮氧化物顺磁清除剂的新型亲脂性硝酮氮氧自由基（NNR）。测定了制剂的纯度并确认了其结构。通过电子自旋共振光谱测试了自由基的亲脂性。结果表明，将其掺入脂质多层膜可保护NNR在生物样品中不被还原，同时保留其清除氮氧化物并形成亚氨基氮氧自由基的能力。在这些条件下，NNR还原速率的降低显著提高了它们作为生物系统中氮氧化物顺磁受体的有效性。描述了一种新型亲水性NO供体3-溴-3,4-二氢-4,4-二甲基-4-(2-吡啶基)-重氮-1,2-二氧化物（DDpyr）的合成。测定了DDpyr在三羟甲基氨基甲烷盐酸盐缓冲液（pH 7.5）和二甲基亚砜中的分解常数（分别为4.5×10⁻⁶和0.5×10⁻⁶ s⁻¹）。与先前测定的一些重氮嗪的分解速率相比，DDpyr在缓冲液中的分解速率显著更高，这使得DDpyr成为在水性介质中使用的潜在候选物。在灌注大鼠尾动脉的实验中发现，DDpyr是一种有效的血管扩张剂。以100 - 200微克/千克体重的剂量向遗传性高血压大鼠（ISIAH品系）腹腔注射DDpyr可显著降低其收缩压。
