Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, 420088 Kazan, Russia.
Department of Organic and Medical Chemistry, Kazan Federal University, 420008 Kazan, Russia.
Molecules. 2023 Jan 4;28(2):466. doi: 10.3390/molecules28020466.
Hypoxia accompanies many human diseases and is an indicator of tumor aggressiveness. Therefore, measuring hypoxia in vivo is clinically important. Recently, complexes of calix[4]arene were identified as potent hypoxia markers. The subject of this paper is new hypoxia-sensitive host-guest complexes of thiacalix[4]arene. We report a new high-yield synthesis method for thiacalix[4]arene with four anionic carboxyl azo fragments on the upper rim (thiacalixarene ) and an assessment of the complexes of thiacalixarene with the most widespread cationic rhodamine dyes (6G, B, and 123) sensitivity to hypoxia. Moreover, 1D and 2D NMR spectroscopy data support the ability of the macrocycles to form complexes with dyes. Rhodamines B and 123 formed host-guest complexes of 1:1 stoichiometry. Complexes of mixed composition were formed with rhodamine 6G. The association constant between thiacalixarene and rhodamine 6G is higher than for other dyes. Thiacalixarene -dye complexes with rhodamine 6G and rhodamine B are stable in the presence of various substances present in a biological environment. The UV-VIS spectrometry and fluorescence showed hypoxia responsiveness of the complexes. Our results demonstrate that thiacalixarene has a stronger binding with dyes compared with the previously reported azo-calix[4]arene carboxylic derivative. Thus, these results suggest higher selective visualization of hypoxia for the complexes with thiacalixarene .
缺氧伴随着许多人类疾病，是肿瘤侵袭性的指标。因此，在体内测量缺氧具有重要的临床意义。最近，杯[4]芳烃的配合物被鉴定为有效的缺氧标志物。本文的主题是新型硫代杯[4]芳烃的缺氧敏感主体-客体配合物。我们报道了一种新的高产合成方法，用于在上边缘带有四个阴离子羧基偶氮片段的硫代杯[4]芳烃（硫代杯芳烃），并评估了硫代杯芳烃与最广泛的阳离子罗丹明染料（6G、B 和 123）形成的复合物对缺氧的敏感性。此外，1D 和 2D NMR 光谱数据支持大环形成与染料配合物的能力。罗丹明 B 和 123 形成了 1:1 化学计量比的主客体配合物。罗丹明 6G 形成了混合组成的配合物。硫代杯芳烃与罗丹明 6G 的缔合常数高于其他染料。在存在生物环境中存在的各种物质的情况下，硫代杯芳烃-染料与罗丹明 6G 和罗丹明 B 的复合物是稳定的。紫外-可见光谱和荧光显示了这些复合物的缺氧响应性。我们的结果表明，与以前报道的偶氮杯[4]芳烃羧酸衍生物相比，硫代杯芳烃与染料的结合更强。因此，这些结果表明，对于与硫代杯芳烃形成的复合物，缺氧的选择性可视化能力更高。
