Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
J Org Chem. 2023 Aug 18;88(16):11694-11701. doi: 10.1021/acs.joc.3c00982. Epub 2023 Aug 2.
Oxoanions such as carboxylates, phosphates, and sulfates play important roles in both chemistry and biology and are abundant on the cell surface. We report on the synthesis and properties of a rationally designed guanidinium-containing oxoanion binder, 1-guanidino-8-amino-2,7-diazacarbazole (GADAC). GADAC binds to a carboxylate, phosphate, and sulfate in pure water with affinities of 3.6 × 10, 1.1 × 10, and 4.2 × 10 M, respectively. Like 2-azacarbazole, which is a natural product that enables scorpions to fluoresce, GADAC is fluorescent in water (λ = 356 nm, λ = 403 nm, ε = 13,400 M cm). The quantum yield of GADAC is pH-sensitive, increasing from Φ = 0.12 at pH 7.4 to Φ = 0.53 at pH 4.0 as a result of the protonation of the aminopyridine moiety. The uptake of GADAC into live human melanoma cells is detectable in the DAPI channel at low micromolar concentrations. Its properties make GADAC a promising candidate for applications in oxoanion binding and fluorescence labeling in biological (e.g., the delivery of cargo into cells) and other contexts.
氧阴离子，如羧酸盐、磷酸盐和硫酸盐，在化学和生物学中都起着重要作用，并且在细胞表面大量存在。我们报告了一种合理设计的胍基氧阴离子结合物，1-胍基-8-氨基-2,7-二氮杂咔唑（GADAC）的合成和性质。GADAC 在纯水中与羧酸盐、磷酸盐和硫酸盐的亲和力分别为 3.6×10、1.1×10 和 4.2×10 M。像 2-氮杂咔唑一样，它是一种使蝎子发光的天然产物，GADAC 在水中具有荧光（λ = 356nm，λ = 403nm，ε = 13400 M cm）。GADAC 的量子产率对 pH 敏感，由于氨基吡啶部分的质子化，其在 pH 7.4 时的 Φ = 0.12 增加到 pH 4.0 时的 Φ = 0.53。在低微摩尔浓度下，GADAC 进入活的人类黑色素瘤细胞的摄取可在 DAPI 通道中检测到。其性质使 GADAC 成为在生物（例如，将货物递送到细胞中）和其他环境中氧阴离子结合和荧光标记的有前途的候选物。
