Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India.
Org Biomol Chem. 2012 Oct 21;10(39):7933-43. doi: 10.1039/c2ob26156a.
In this paper, the synthesis, characterization and glutathione peroxidase and peroxynitrite scavenging activities of a series of stable spirodiazaselenuranes are described. The spiro compounds were synthesized in good yields by oxidative cyclization of diaryl selenides bearing amide moieties. All the selenides and spiro derivatives were characterized by (1)H, (13)C and (77)Se NMR spectroscopy, mass spectral techniques and the structures of some of the spirodiazaselenuranes were confirmed by single crystal X-ray crystallography. The structures reveal that the selenium atom occupies the center of a distorted trigonal bipyramid core with two nitrogen atoms occupying the apical positions and two carbon atoms and the selenium lone pair occupying the equatorial positions. Mechanistic investigations indicate that the spirocyclization occurs via the formation of selenoxide intermediates. The new compounds were evaluated for their glutathione peroxidase (GPx) mimetic activity by using H(2)O(2) as a substrate and glutathione (GSH) as a co-substrate. It was found that the substituents attached to the nitrogen atom of the selenazole ring have a significant effect on the GPx activity. While the introduction of electron withdrawing groups such as -Cl, -Br etc. to the phenyl ring decreases the activity, the introduction of electron donating groups such as -OH, -OMe significantly enhances the GPx activity of both diaryl selenides and spirodiazaselenuranes. In addition to GPx activity, the selenides and spiro derivatives were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. These studies indicate that the diarylselenides effectively inhibit the PN-mediated nitration and oxidation reactions by reacting with PN to produce the corresponding spirodiazaselenuranes.
本文描述了一系列稳定的螺环二氮杂硒烷的合成、表征及谷胱甘肽过氧化物酶和过氧亚硝酸盐清除活性。通过含酰胺部分的二芳基硒醚的氧化环化，以良好的产率合成了螺化合物。所有的硒化物和螺衍生物均通过（1）H、（13）C 和（77）Se NMR 光谱、质谱技术进行了表征，部分螺环二氮杂硒烷的结构通过单晶 X 射线晶体学得到了证实。结构表明，硒原子占据扭曲的三角双锥核心的中心，两个氮原子占据顶点位置，两个碳原子和硒孤对占据赤道位置。机理研究表明，螺环化是通过硒氧化物中间体的形成来实现的。新化合物通过使用 H2O2 作为底物和谷胱甘肽（GSH）作为共底物，评估其作为谷胱甘肽过氧化物酶（GPx）模拟物的活性。研究发现，连接到硒唑环氮原子上的取代基对 GPx 活性有显著影响。虽然在苯环上引入吸电子基团如-Cl、-Br 等会降低活性，但在苯环上引入供电子基团如-OH、-OMe 则会显著增强二芳基硒醚和螺环二氮杂硒烷的 GPx 活性。除了 GPx 活性外，还研究了硒化物和螺衍生物抑制过氧亚硝酸盐（PN）介导的牛血清白蛋白（BSA）硝化和二氢罗丹明 123 氧化的能力。这些研究表明，二芳基硒化物通过与 PN 反应生成相应的螺环二氮杂硒烷，有效地抑制 PN 介导的硝化和氧化反应。
