Solid-Phase Synthesis of Dyes and their Application as Sensors and Bioimaging Probes

Solid-phase methodologies have been widely used in the context of sensor development. Initial applications came after the expansion of solid-phase peptide synthesis and primarily made use of the immobilization process to facilitate the screening of potential peptide-based sensors in a high-throughput manner. Their subsequent adjustment to nonpeptidic biomolecules considerably spread out their scope from the preparation of resins to label bioactive molecules to combinatorial approaches to accelerate the derivatization of fluorescent scaffolds. Once combinatorial chemists succeeded in adapting fluorescent heterocycles to solid-phase synthesis, small molecule fluorescent dyes started to be increasingly implemented in sensor discovery programs as powerful bioimaging probes (Figure 14.1). Diversity-oriented fluorescent libraries (DOFLs) have been successfully prepared by solid-phase synthesis and demonstrated that subtle structural modifications within a fluorescent core can be distinguishable by largemacromolecules and hence lead to selective fluorescent probes. This chapter will review the progress of solid-phase approaches for the preparation of sensors over the last years and outlook the role that these methodologies will play in probe development in the near future.