Hyun Hoon, Owens Eric A, Narayana Lakshminarayana, Wada Hideyuki, Gravier Julien, Bao Kai, Frangioni John V, Choi Hak Soo, Henary Maged
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 3030.
RSC Adv. 2014 Jan 1;4(102):58762-58768. doi: 10.1039/C4RA11225C.
Functional near-infrared (NIR) fluorophores have played a major role in the recent advances in bioimaging. However, the optical and physicochemical stabilities of NIR fluorophores in the biological and physiological environment are still a challenge. Especially, the ether linkage on the carbon of heptamethine core is fragile when exposed to serum proteins or other amine-rich biomolecules. To solve such a structural limitation, a rigid carbon-carbon bond was installed onto the framework of ether-linked NIR fluorophores through the Suzuki coupling. The robust fluorophores replaced as ZW800-1C and ZW800-3C displayed enhanced optical and chemical stability in various solvents and a 100% warm serum environment (> 99%, 24 h). The biodistribution and clearance of C-C coupled ZW800 compounds were almost identical to the previously developed oxygen-substituted ZW800 compounds. When conjugated with a small molecule ligand, ZW800-1C maintained the identical stable form in warm serum (>98%, 24 h), while ZW800-1A hydrolyzed quickly after 4 h incubation (34%, 24 h).
功能性近红外（NIR）荧光团在生物成像的最新进展中发挥了重要作用。然而，NIR荧光团在生物和生理环境中的光学和物理化学稳定性仍然是一个挑战。特别是，七甲川核心碳上的醚键在暴露于血清蛋白或其他富含胺的生物分子时很脆弱。为了解决这种结构限制，通过铃木耦合在醚连接的NIR荧光团框架上安装了一个刚性碳-碳键。取代为ZW800-1C和ZW800-3C的稳健荧光团在各种溶剂和100%温暖血清环境（>99%，24小时）中显示出增强的光学和化学稳定性。C-C耦合ZW800化合物的生物分布和清除与先前开发的氧取代ZW800化合物几乎相同。当与小分子配体缀合时，ZW800-1C在温暖血清中保持相同的稳定形式（>98%，24小时），而ZW800-1A在孵育4小时后迅速水解（34%，24小时）。
