title: Bioorthogonal Labeling, Bioimaging, and Photocytotoxicity Studies of Phosphorescent Ruthenium(II) Polypyridine Dibenzocyclooctyne Complexes.
abstract: The synthesis, characterization, photophysics, lipophilicity, and cellular properties of new phosphorescent ruthenium(II) polypyridine complexes functionalized with a dibenzocyclooctyne (DIBO) or amine moiety [Ru(N^N)2 (L)](PF6 )2 are reported (L=4-(13-N-(3,4:7,8-dibenzocyclooctyne-5-oxycarbonyl) amino-4,7,10-trioxa-tridecanyl-aminocarbonyl-oxy-methyl)-4'-methyl-2,2'-bipyridine bpy-DIBO, N^N=2,2'-bipyridine bpy (1 a), 1,10-phenanthroline phen (2 a); L=4-(13-amino-4,7,10-trioxa-tridecanylaminocarbonyl-oxy-methyl)-4'-methyl-2,2'-bipyridine bpy-NH2 , N^N=bpy (1 b), phen (2 b)). The strain-promoted alkyne-azide cycloaddition (SPAAC) reaction of the DIBO complexes 1 a and 2 a with benzyl azide were studied. Also, the DIBO complexes 1 a and 2 a can selectively label N-azidoglycans located on the surface of CHO-K1 and A549 cells that were pretreated with 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-D-mannosamine (Ac4 ManNAz). Additionally, the intracellular trafficking and localization of these biomolecules were monitored using laser-scanning confocal microscopy. Interestingly, the biolabeling and cellular uptake efficiency of the DIBO complexes 1 a and 2 a were cell-line dependent, as revealed by flow cytometry and ICP-MS. Furthermore, the complexes showed good biocompatibility toward the Ac4 ManNAz-pretreated cells in the dark, but exhibited photoinduced cytotoxicity due to the generation of singlet oxygen.
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (P. R. China).
authors.forename: Tommy Siu-Ming
authors.initials: TS
authors.lastname: Tang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (P. R. China).
authors.forename: Alex Man-Hei
authors.initials: AM
authors.lastname: Yip
authors.affiliation: Key Laboratory for Organic Electronics and Information Displays and Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023 (P. R. China).
authors.forename: Kenneth Yin
authors.initials: KY
authors.lastname: Zhang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (P. R. China).
authors.forename: Hua-Wei
authors.initials: HW
authors.lastname: Liu
authors.affiliation: Department of Physics and Institute of Advanced Materials, Hong Kong Baptist University, Kowloon, Hong Kong (P. R. China).
authors.forename: Po Lam
authors.initials: PL
authors.lastname: Wu
authors.affiliation: Department of Physics and Institute of Advanced Materials, Hong Kong Baptist University, Kowloon, Hong Kong (P. R. China).
authors.forename: King Fai
authors.initials: KF
authors.lastname: Li
authors.affiliation: Department of Physics and Institute of Advanced Materials, Hong Kong Baptist University, Kowloon, Hong Kong (P. R. China).
authors.forename: Kok Wai
authors.initials: KW
authors.lastname: Cheah
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (P. R. China). bhkenlo@cityu.edu.hk.|State Key Laboratory of Millimeter Waves, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (P. R. China). bhkenlo@cityu.edu.hk.
authors.forename: Kenneth Kam-Wing
authors.initials: KK
authors.lastname: Lo
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D000480:Alkynes / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry* / Q000633:toxicity; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry*; D003412:Cricetulus; D006801:Humans; D049408:Luminescent Agents / Q000737:chemistry* / Q000633:toxicity; D018613:Microscopy, Confocal; D061848:Optical Imaging; D009942:Organometallic Compounds / Q000737:chemistry* / Q000633:toxicity; D011134:Polysaccharides / Q000032:analysis*; D013194:Staining and Labeling
chemical_list: D000480:Alkynes; D001555:Benzene Derivatives; D049408:Luminescent Agents; D009942:Organometallic Compounds; D011134:Polysaccharides; C103599:bis(bipyridyl)ruthenium(II); D015082:2,2'-Dipyridyl; C042001:1-octyne
keywords: bioorthogonal labeling; cell-surface glycan recycling; imaging agents; photocytotoxicity; ruthenium