Design And Synthesis Of The NIR Chromenylium-cyanine Fluorophore Library And Application In Vivo Imaging

The real-time monitoring of key biospecies in the living systems has received thrusting attention during the past decades.Specifically,fluorescent detection based on near-infrared(NIR)fluorescent probes is highly favorable for live cells,live tissues,and even animal imaging,owing to the substantial merits of the NIR window,such as minimal phototoxicity,deep penetration into tissues,and low autofluorescence background.Nevertheless,developing potent NIR fluorophores are less tunable than visible-wavelength fluorophores.Therefore,developing a tunable NIR fluorescent probe is very meaningful.We report a set of novel NIR hybrid fluorophores,namely,the hybrid chromenylium-cyanine fluorophore with easily synthetic method by the conformational changes and substitution groups in the second chapter.In addition,characteristic of spectrum reveals the structure-optical properties of the new hybrid chromenylium-cyanine fluorophore dyes.Compared to known NIR fluorophores,the new hybrid fluorophores are substantially advantageous for NIR probe development:(1)CC-Fluors display tunable and moderate Stokes shifts and quantum yields;(2)the fluorophores are stable at physiological conditions after long-term incubation;(3)the absorption maxima of CC-Fluors coincide with the common laser spectral lines in mainstream in vivo imaging systems;(4)most importantly,CC-Fluors can be easily modified to prepare NIR probes targeting various biospecies.In the third chapter,based on the above work,we design a ratiometric pH probe based on the protonation/deprotonation of the hydroxyl groups.Moreover,a wonderful ratiometric probe CC33 is standing out by the conformational changes and substitution groups and successfully employed in live animal imaging.In the fourth chapter,we design a turn-on Hg2+ NIR probe based on spiro-lactam ring-opening/-closing process by Hg2+ promoted 1,3,4-oxadiazoles formation from thiospirolactone,and successfully employed in live animal imaging.Conclusively,we are focusing on the design and synthesis novel chromenylium-cyanine dyes to solve the bottle-necks in fluorescent probes based on near infrared dyes,and then develop the pH and Hg2+fluorescent probes for bioimaging.