Synthesis and iron sequestration equilibria of novel exocyclic 3-hydroxy-2-pyridinone donor group siderophore mimics.
Synthesis and iron sequestration equilibria of novel exocyclic 3-hydroxy-2-pyridinone donor group siderophore mimics.
复制标题
DOI：
10.1021/ic902595c
复制
发表时间：
2010-09-20
影响因子：
4.6
通讯作者：
Crumbliss, Alvin L.
中科院分区：
文献类型：
--
作者：
Harrington, James M.;Chittamuru, Sumathi;Dhungana, Suraj;Jacobs, Hollie K.;Gopalan, Aravamudan S.;Crumbliss, Alvin L.
本文报道了一类新型外环双、三-3,2-羟基吡啶酮（HOPO）螯合剂的合成及其与Fe（III）配合物的热力学表征。本研究用哌嗪或N， N ', N ' ' -1,4,7-三氮杂环壬烷与新型亲电性HOPO铝盐反应制备了螯合剂，收率高。随后用氢解法去除苄基保护基团，得到双hopo螯合剂N2(etLH)2和N2(prLH)2，以及三hopo螯合剂N3(etLH)3，收率很高。用分光光度法、电位法和ESI-MS等方法完成了它们与Fe（III）配合物的溶液热力学表征。用分光光度法和电位法测定了N2(etLH)2、N2(prLH)2和N3(etLH)3的pKas。采用分光光度法、电位滴定法和EDTA竞争法测定了四齿N2(etLH)2、N2(prLH)2和六齿N3(etLH)3的Fe（III）配合物稳定性常数。N3(etLH)3与Fe（III）形成1:1配合物，log β110 = 27.34±0.04。N2(prLH)2与Fe（III）形成3:2 L:Fe络合物，其中对数β230 = 60.46±0.04，对数β110 = 20.39±0.02。虽然N2(etLH)2也与Fe（III）形成3:2 L:Fe络合物，但溶解度问题阻碍了对数β230的测定；对数β110为20.45±0.04。N3(etLH)3的pFe值为26.5,N2(prLH)2的pFe值为24.78，与其他用于铁超载治疗的铁载体分子相当，表明这些羟基吡啶酮配体可用于开发新的螯合治疗剂。
The synthesis of a novel class of exocyclic bis- and tris-3,2-hydroxypyridinone (HOPO) chelators built on N2 and N3 aza-macrocyclic scaffolds and the thermodynamic solution characterization of their complexes with Fe(III) are described. The chelators for this study were prepared by reaction of either piperazine or N, N’, N”-1,4,7-triazacyclononane with a novel electrophilic HOPO iminium salt in good yields. Subsequent removal of the benzyl protecting groups using hydrogenolysis gave bis-HOPO chelators N2(etLH)2 and N2(prLH)2, and tris-HOPO chelator N3(etLH)3 in excellent yields. Solution thermodynamic characterization of their complexes with Fe(III) has been accomplished using spectrophotometric, potentiometric and ESI-MS methods. The pKas of N2(etLH)2, N2(prLH)2, and N3(etLH)3, were determined spectrophotometrically and potentiometrically. The Fe(III) complex stability constants for the tetradentate N2(etLH)2 and N2(prLH)2, and hexadentate N3(etLH)3, were measured by spectrophotometric and potentiometric titration, and by competition with EDTA. N3(etLH)3 forms a 1:1 complex with Fe(III) with log β110 = 27.34 ± 0.04. N2(prLH)2 forms a 3:2 L:Fe complex with Fe(III) where log β230 = 60.46 ± 0.04 and log β110 = 20.39 ± 0.02. While N2(etLH)2 also forms a 3:2 L:Fe complex with Fe(III), solubility problems precluded determining log β230; log β110 was found to be 20.45 ± 0.04. The pFe values of 26.5 for N3(etLH)3 and 24.78 for N2(prLH)2 are comparable to other siderophore molecules used in the treatment of iron overload, suggesting that these hydroxypyridinone ligands may be useful in the development of new chelation therapy agents.
登录
查看更多内容
影响因子：
0.6
作者：
Katoh, A;Kudo, H;Saito, R
通讯作者：
Saito, R
影响因子：
3.5
作者：
Harrington, James M.;Crumbliss, Alvin L.
通讯作者：
Crumbliss, Alvin L.
影响因子：
3.3
作者：
Ambrosi, G;Dapporto, P;Zappia, G
通讯作者：
Zappia, G
影响因子：
6.1
作者：
GAMPP, H;MAEDER, M;ZUBERBUHLER, AD
通讯作者：
ZUBERBUHLER, AD
影响因子：
4.6
作者：
Ambrosi, G;Formica, M;Zappia, G
通讯作者：
Zappia, G