title: Central C-C Bonding Increases Optical and Chemical Stability of NIR Fluorophores.
abstract: 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 themesocarbon 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).
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 3030.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Owens
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 3030.
authors.forename: Lakshminarayana
authors.initials: L
authors.lastname: Narayana
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: Julien
authors.initials: J
authors.lastname: Gravier
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: Kai
authors.initials: K
authors.lastname: Bao
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215 ; Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215 ; Curadel, LLC, 377 Plantation Street, Worcester, MA 01605, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 3030.
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
keywords: Image-Guided Surgery; Near-Infrared Fluorescence; Optical Imaging; Signal-to-Background Ratio; Suzuki-coupling