School of Chemistry, University of East Anglia, Norwich, NR4 7TJ, UK.
Dalton Trans. 2017 Oct 10;46(39):13397-13408. doi: 10.1039/c7dt02804k.
A series of cyclometallated gold(iii) complexes supported by pyrazine-based (C^N^C)-type pincer ligands were synthesized via two different pathways. Nucleophilic attack on the isocyanide complex [(C^N^C)Au(C[triple bond, length as m-dash]NCHMe-2,6)]SbF (2) gave [(C^N^C)Au(ACC)]SbF complexes with aniline (4·SbF), adamantylamine (5), glycine ethyl ester (6), alanine methyl ester (7), valine methyl ester (8), phenylglycine methyl ester (9) and methionine methyl ester (10) substituents (ACC = acyclic carbene). The pathway via isocyanide insertion into gold-amide bonds was also investigated; e.g. the reaction of xylyl isocyanide with (C^N^C)AuNHPh followed by protonation with HBF·OEt gave the acyclic carbene complex 4·BF. To the best of our knowledge compounds 6-10 represent the first examples of gold(iii) acyclic carbene complexes bearing amino acid functions. The compounds provide a versatile platform for the study of the anti-proliferative properties of gold(iii) complexes. Tests against human adenoma-type lung cancer cells identified 5, 6, 7 and 10 as particularly promising and demonstrate the synthetic flexibility of acyclic carbene complexes and the potential of that class of compounds for anticancer applications. Compared to cisplatin, amino ester-containing ACC complexes showed improved selectivity for MCF-7 breast cancer cells over that for healthy fibroblasts.
一系列基于吡嗪的（C^N^C）-型三齿配体稳定的金（III）配合物通过两种不同的途径合成。亲核进攻异氰化物配合物[(C^N^C)Au(C[三重键，长度为 m-dash]NCHMe-2,6)]SbF（2）得到了具有苯胺（4·SbF）、金刚烷胺（5）、甘氨酸乙酯（6）、丙氨酸甲酯（7）、缬氨酸甲酯（8）、苯甘氨酸甲酯（9）和蛋氨酸甲酯（10）取代基的[(C^N^C)Au(ACC)]SbF 配合物（ACC = 无环卡宾）。还研究了通过异氰化物插入金酰胺键的途径；例如，用 xylyl 异氰化物与（C^N^C）AuNHPh 反应，然后用 HBF·OEt 质子化得到无环卡宾配合物 4·BF。据我们所知，化合物 6-10 代表了首例具有氨基酸功能的金（III）无环卡宾配合物。这些化合物为研究金（III）配合物的抗增殖性质提供了一个通用平台。针对人腺瘤型肺癌细胞的测试确定了 5、6、7 和 10 是特别有前途的，这证明了无环卡宾配合物的合成灵活性以及该类化合物在抗癌应用中的潜力。与顺铂相比，含有氨基酸酯的 ACC 配合物对 MCF-7 乳腺癌细胞的选择性优于健康成纤维细胞。
