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A Cyclic‐RGD Dinuclear Tb III Macrocyclic Complex as a Tumor Integrin‐Selective Luminescent Probe
Author(s) -
Chang C. Allen,
Chia JuChien,
Lin SyueLiang
Publication year - 2018
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201800568
Subject(s) - chemistry , luminescence , dimer , adduct , titration , binding constant , crystallography , stereochemistry , binding site , organic chemistry , biochemistry , physics , optoelectronics
To develop small molecular integrin‐selective luminescent imaging probes, we have prepared the binary dipicolinate (DPA) Tb III dinuclear macrocyclic complex, Tb 2 (cRGDfK‐ODO2A‐dimer) (DPA) 2 2– or complex I, and reference ligands and Tb III complexes which were purified by HPLC and characterized by NMR, mass spectrometry and luminescence spectroscopy. Luminescence titrations of the structural and bonding model Tb 2 ( m ‐ODO2A‐dimer) 2+ complex by DPA 2– ion confirmed the molecular formula of the adduct was Tb 2 ( m ‐ODO2A‐dimer)(DPA) 2 2– , and the first binary binding constant was determined to be log K 1 = 5.76. At pH 7.4, complex I showed 300 times luminescence enhancement at 544 nm ( λ ex = 278 nm) as compared to that without adding DPA, and was found to bind to α v β 3 integrin and human glioblastoma U87MG tumor cells in both specific and non‐specific modes, via luminescence spectroscopic and confocal cell imaging competition studies. This makes complex I and its future optimized derivatives potentially feasible for preclinical bioimaging applications, particularly in the time‐resolved mode.