The first modification made to the HD involves replacing the endocyclic oxygen atom with an electrondeficient functional group. Heteroatom substitution is a versatile strategy employed to shift the absorbance and emission profile of various dye platforms to longer wavelengths, with fluorescein and related molecules being the most notable examples. Substitutions include oxygen to boron, carbon, silicon, phosphorus, sulfur, as well as several other group 14 elements. From this list, we identified silicon as the most optimal heteroatom for our dye remodeling campaign. First, it has been shown that regardless of the scaffold being modified, replacing the endocyclic oxygen with a silicon group (i.e., SiMe2) reliably red shifts the λmax by ~90 nm. Second, unlike elements such as boron which can decompose in the presence of ROS, the SiMe2 group is remarkably stable under oxidative conditions. Third, on the contrary to heavy-atoms such as selenium, silicon-based dyes are not known to generate singlet oxygen upon irradiation, which is important to limit unnecessary phototoxicity. Moreover, the inability to generate substantial levels of singlet oxygen likely contributes to the outstanding photostability exhibited by silicon-substituted dyes. Unfortunately, the canonical synthetic route utilized to access the HD core is incompatible with silicon incorporation (Scheme 1 (top)). Specifically, the crucial carbon-oxygen bond that is formed between the cyanine (e.g., Cy7-Cl) and resorcinol (or 3-(diethylamino)phenol) precursors involve a conjugated substitution reaction where the latter acts as a nucleophilic species. However, silicon typically behaves as an electrophile, although strategies have been conceived to reverse this reactivity. We hypothesized it would be possible to employ organolithium chemistry to incorporate the requisite SiMe2 group (Scheme 1 (bottom)). Once attached, we would employ a non-templated vinylogous aldol condensation reaction to yield the dye backbone, which could be further extended using a Knoevenagel condensation reaction. The absorbance and emission can be further tuned at this stage by varying the acceptor.