Synthesis, structure, and X-band (9.5 GHz) EPR characterization of the new series of pH-sensitive spin probes: N,N-disubstituted 4-amino-2,2,5,5-tetramethyl-3-imidazoline 1-oxyls.

Synthesis, structure, and X-band (9.5 GHz) EPR characterization of the new series of pH-sensitive spin probes: N,N-disubstituted 4-amino-2,2,5,5-tetramethyl-3-imidazoline 1-oxyls.
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新系列 pH 敏感自旋探针的合成、结构和 X 波段 (9.5 GHz) EPR 表征:N,N-二取代 4-氨基-2,2,5,5-四甲基-3-咪唑啉 1-oxyls

DOI:
10.1021/jo0510890
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发表时间:
2005
期刊:
The Journal of organic chemistry.
影响因子:
--
通讯作者:
Grigor'ev,IgorA
Grigor'ev,IgorA
中科院分区:
--
文献类型:
--
作者:
Voinov,MaximA;Polienko,JulyaF;Schanding,Thomas;Bobko,AndreyA;Khramtsov,ValeryV;Gatilov,YuryV;Rybalova,TatyanaV;Smirnov,AlexI;Grigor'ev,IgorA

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本文报道了一种新的含N ′,N ′-二取代脒基的咪唑啉氮氧化合物的合成方法。该方法基于抗磁性4-R-氨基-1,2,2,5,5-五甲基-3-咪唑啉与溴乙酸乙酯的烷基化反应;烷基化产物进一步氧化为相应的氮氧自由基。该方法允许将各种官能团引入到氮氧分子结构中。用溴乙酸乙酯进行烷基化反应,具有较高的区域选择性,可得到外烷基化产物。根据13 C NMR谱进行了区域化学归属,并通过X射线衍射研究进行了证实。所有的氮氧自由基在这里合成的,显示出具有pH依赖的EPR光谱与pKarranging从3.5到6.2。对于nitroxides 13轴承的羧基远程的氮氧部分,EPR谱的各向同性磁参数的变化,由于可逆的去质子化的羧基被发现是小的。对于这些氮氧自由基,我们证明了一种替代的方法pKa测定的基础上测量的EPR谱的峰-峰线宽的存在下的顺磁性增宽剂铁氰化钾。氮氧自由基在辛醇/水和辛醇/磷酸盐缓冲溶液混合物中的分配系数的测定揭示了它们的亲脂性范围。
An approach to the synthesis of new imidazoline nitroxides bearing anN‘,N‘-disubstituted amidine group is reported. The approach is based on the alkylation of diamagnetic 4-R-amino-1,2,2,5,5-pentamethyl-3-imidazolines with bromoacetic acid ethyl ester; the products of alkylation are further oxidized to the corresponding nitroxides. The approach allows a variety of functional groups to be introduced into the nitroxide molecule structure. Alkylation with bromoacetic acid ethyl ester was found to proceed with high regioselectivity and afford the products ofexo-alkylation. The regiochemical assignment is made on the basis of13C NMR spectra and confirmed by X-ray diffraction study. All of the nitroxides synthesized here were shown to have pH-dependent EPR spectra with pKaranging from 3.5 to 6.2. For nitroxides13bearing the carboxylic group remote to the nitroxide moiety, the changes in isotropic magnetic parameters of EPR spectra due to reversible deprotonation of the carboxylic group were found to be small. For these nitroxides, we demonstrate an alternative approach for pKadetermination that is based on measuring the peak-to-peak line width of the EPR spectrum in the presence of the paramagnetic broadening agent potassium ferricyanide. The partition coefficients of nitroxides in octanol/H2O and octanol/phosphate buffer solution mixtures were measured to reveal a range of their lipophilicities.
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