Department of Chemistry, University of Nebraska , Lincoln, Nebraska 68588-0304, United States.
Department of Chemistry and Biochemistry, University of Denver , Denver, Colorado 80208-2436, United States.
J Org Chem. 2017 Feb 3;82(3):1538-1544. doi: 10.1021/acs.joc.6b02737. Epub 2017 Jan 13.
We report the design, synthesis, and electron spin relaxation properties of hydrophilic tetracarboxylate ester pyrroline nitroxides 1 and 2, which serve as models in the search for new spin labels for DEER distance measurement at room temperature. The nitroxides are designed to have the methyl groups further away from the N-O spin site to decrease the inequivalent couplings of the unpaired electron to the methyl protons that shorten T at T > 70 K in currently used labels. The key step in the synthesis of 1 and 2 is the reaction of the dianion of pyrrole-1,2,5-tricarboxylic acid tert-butyl ester dimethyl ester with electrophiles such as methyl chloroformate and methyl bromoacetate. Structures of 1 and 2 are confirmed by X-ray crystallography. Studies of electron spin relaxation rates in rigid trehalose/sucrose matrices reveal approximately temperature independent values of 1/T for 1 and 2 up to about 160 K and modest temperature dependence up to 295 K, demonstrating that increasing the distance between the nitroxide moiety and methyl groups is effective in lengthening T at T > 70 K.
我们报告了亲水性四羧酸酯吡咯啉氮氧自由基 1 和 2 的设计、合成和电子自旋弛豫性质，它们是在室温下进行 DEER 距离测量的新型自旋标记物研究的模型。这些氮氧自由基的设计目的是使甲基远离 N-O 自旋位，以减少未配对电子与甲基质子的不等价耦合，从而缩短目前使用的标记物中 T > 70 K 时的 T。1 和 2 的合成的关键步骤是吡咯-1,2,5-三羧酸叔丁酯二乙酯的二阴离子与亲电试剂（如氯甲酸甲酯和溴乙酸甲酯）的反应。1 和 2 的结构通过 X 射线晶体学得到证实。在刚性海藻糖/蔗糖基质中电子自旋弛豫率的研究表明，1 和 2 的 1/T 值在约 160 K 以下几乎与温度无关，在 295 K 以下略有温度依赖性，这表明增加氮氧自由基部分和甲基之间的距离在 T > 70 K 时有效延长 T。
