Miguel-Ávila Joan, Tomás-Gamasa María, Olmos Andrea, Pérez Pedro J, Mascareñas José L
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS) , Departamento de Química Orgánica , Universidade de Santiago de Compostela , 15782 Santiago de Compostela , Spain . Email:
Laboratorio de Catálisis Homogénea , Unidad Asociada al CSIC , CIQSO-Centro de Investigación en Química Sostenible , Departamento de Química , Universidad de Huelva , Campus de El Carmen s/n , 21007 Huelva , Spain . Email:
Chem Sci. 2018 Jan 15;9(7):1947-1952. doi: 10.1039/c7sc04643j. eCollection 2018 Feb 21.
The archetype reaction of "click" chemistry, namely, the copper-promoted azide-alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interior of mammalian cells, are essentially unknown. Herein we demonstrate that isolated, well-defined copper(i)-tris(triazolyl) complexes featuring designed ligands can readily enter mammalian cells and promote intracellular CuAAC annulations of small, freely diffusible molecules. In addition to simplifying protocols and avoiding the addition of "non-innocent" reductants, the use of these premade copper complexes leads to more efficient processes than with the alternative, made copper species prepared from Cu(ii) sources, tris(triazole) ligands and sodium ascorbate. Under the reaction conditions, the well-defined copper complexes exhibit very good cell penetration properties, and do not present significant toxicities.
“点击”化学的原型反应，即铜促进的叠氮化物-炔烃环加成反应（CuAAC），已在生物化学领域得到了大量应用。然而，在哺乳动物细胞复杂的内部环境中促进外源小分子叠氮化物和炔烃分子间环化反应的方法基本上还不为人知。在此，我们证明了具有设计配体的分离、明确的铜（I）-三（三唑基）配合物能够轻易进入哺乳动物细胞，并促进小分子、可自由扩散分子的细胞内CuAAC环化反应。除了简化实验方案并避免添加“非无害”还原剂外，使用这些预制的铜配合物比使用由铜（II）源、三（三唑）配体和抗坏血酸钠制备的替代铜物种能产生更高效的反应过程。在反应条件下，这些明确的铜配合物表现出非常好的细胞穿透性能，且不会产生显著毒性。
