Self-Threaded Fluorescent Probes for Biological Imaging and Self-Assembly

Fluorescence imaging plays an important role in fundamental research and disease diagnosis because it is non-toxic and inexpensive compared to other imaging technologies. Near-infrared (NIR) fluorescence imaging has the advantages of the lower scattering, minimized autofluorescence, and deeper tissue penetration. However, one drawback of deep-red/NIR fluorophores is that the large amount of hydrophobic surface area can overwhelm an appended bioactive targeting motif and reduce the targeting performance of the probe. Thus, it is necessary to develop new classes of fluorescent probes.

This thesis focuses on the development of a new class of covalently connected, self-threaded, fluorescent molecular probes with figure-eight architecture, which we call squaraine figure-eight (SF8). The probe structure contains a deep-red squaraine dye encapsulated inside a tetralactam macrocycle, and two peripheral alkyl or peptide loops. The first part describes the general strategy to prepare the SF8 probes and demonstrates their applications in biological imaging. The second part focuses on the engineering of SF8 probes by introducing chirality, incorporating a cancer cell targeting peptide RGD motif onto the loops, or preparing unsymmetric SF8 probes. The last part describes the unusual self-assembly properties of SF8 probes in aqueous media where rigid well-ordered aggregates produce coexisting H- and J-aggregate bands with large fluorescence Stokes shifts.