Hyperpolarization of N‐heterocycles with signal amplification by reversible exchange (SABRE) induces NMR sensitivity gains for biological molecules. Substitutions with functional groups, in particular in the ortho‐position of the heterocycle, however, result in low polarization using a typical Ir catalyst with a bis‐mesityl N‐heterocyclic carbene ligand for SABRE, presumably due to steric hindrance. With the addition of allylamine or acetonitrile as coligands to the precatalyst chloro(1,5‐cyclooctadiene)[4,5‐dimethyl‐1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene] iridium, the ¹H signal enhancement increased in several substrates with ortho NH₂ substitutions. For example, for a proton in 2,4‐diaminopyrimidine, the enhancement factors increased from −7±1 to −210±20 with allylamine or to −160±10 with acetonitrile. CH₃ substituted molecules yielded maximum signal enhancements of −25±7 with acetonitrile addition, which is considerably less than the corresponding NH₂ substituted molecules, despite exhibiting similar steric size. With the more electron‐donating NH₂ substitution resulting in greater enhancement, it is concluded that steric hindrance is not the only dominant factor in determining the polarizability of the CH₃ substituted compounds. The addition of allylamine increased the signal enhancement for the 290 Da trimethoprim, a molecule with a 2,4‐diaminopyrimidine moiety serving as an antibacterial agent, to −70.

中文翻译：

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SABRE对NH2和CH3取代的吡啶和嘧啶部分进行核自旋超极化。

N杂环的超极化与可逆交换（SABRE）的信号放大可诱导生物分子的NMR灵敏度增加。然而，带有功能基团的取代，特别是在杂环的邻位，使用典型的Ir催化剂和SABRE的双-间苯三酚N-杂环卡宾配体会导致低极化，这可能是由于空间位阻。向预催化剂氯（1,5-环辛二烯）[4,5-二甲基-1,3-二双（2,4,6-三甲基苯基）咪唑-2-亚基]铱中加入烯丙胺或乙腈作为大分子配体，在邻位NH _2的几种底物中，¹ H信号增强替换。例如，对于2,4-二氨基嘧啶中的质子，烯丙胺的增强因子从-7±1增加到-210±20，乙腈的增强因子增加到-160±10。CH ₃取代的分子在加入乙腈的情况下产生的最大信号增强值为-25±7 ，尽管显示出相似的空间大小，但其显着小于相应的NH ₂取代的分子。随着给予电子的NH _2的取代度增加，增强效果增强，可以得出结论，位阻不是决定CH ₃极化率的唯一主导因素。取代的化合物。烯丙基胺的添加将290 Da甲氧苄啶的信号增强到-70，该分子具有2,4-二氨基嘧啶部分作为抗菌剂。