Synthesis And Time-resolved Assay Application Of Novel Lanthanide Luminescence Probes

Time-resolved luminescence bioassay technique based on long-lived luminescence of lanthanide probes is an ultrasenstive bioanalytical method, and has been widely used in clinical diagnostics and biotechnology. In this doctoral dissertation, two novel Tb3+complex-based luminescent probes specific for hydroxyl radical (·OH) and mercury(II) ions (Hg2+) were designed, synthesized and characterized, respectively, and their application methods for highly sensitive time-resolved luminescence assay and bioimaging were established. In addition, a luminescent probe for zinc(II) ions (Zn2+) using2,2':6',2"-terpyridine polyacid-Eu3+complex as the luminescence moiety were designed and primarily synthesized.A unique Tb3+complex-based luminescent probe, N,N,N',N'-[2,6-bis(3'-aminomethyl-1'-pyrazolyl)-4-(p-aminophenoxy)methylene-pyridine] tetrakis(acetate)-Tb3+(BMPTA-Tb3+), was designed and synthesized for highly selective and sensitive time-resolved luminescence detection of·OH. The probe itself is almost non-luminescent, but can selectively react with·OH to cause a49-fold increase in luminescence quantum yield with a long luminescence lifetime (2.76ms). The luminescence response of the probe to·OH is highly selective and sensitive in the physiological pH range. Based on this probe, a time-resolved luminescence imaging method for detecting·OH in living cells was successfully established.A unique Tb3+complex-based luminescent probe, N,N',N',N'-{[2,6-bis(3'-aminomethyl-1'-pyrazolyl)-4-[N,N-bis(3",6"-dithiaoctyl)-aminomethyl]-pyridine]} tetrakis(acetic acid)-Tb3+(BBAPTA-Tb3+), was designed and synthesized for highly selective and sensitive time-resolved luminescence detection of Hg2+. The luminescence of the probe is weak, but can be effectively enhanced upon reaction with Hg2+by the formation of heterobimetallic complex Hg2+-BBAPTA-Tb3+, with a5-fold increase in luminescence quantum yield. Based on this probe, a highly sensitive time-resolved luminescence detection method of Hg2+in aqueous solutions was developed.A synthesis procedure of a Eu3+complex-based luminescent probe for Zn2+using N,N-bis(2-picolyl)amine and tetraethyl (4-bromomethyl-2,2':6',2"-terpyridine-6,6"-diyl) bis(methylenenitrilo) tetrakis(acetate) as the coupling reaction materials was designed, and the new compound tetraethyl (4-bromomethyl-2,2':6',2"-terpyridine-6,"-diyl) bis(methylenenitrilo) tetrakis(acetate) was synthesized. All the synthesis intermediates and final compound were characterized. The synthesis of this compound provides an essential reagent for the further development of functional probes using2,2':6',2"-terpyridine polyacid-Eu3+complex as the luminescence moiety.