SiR-DNA is a commercially-available Si-rhodamine dye with the DNA-targeting ligand Hoechst 33258 attached to the pendant phenyl ring, allowing specific labeling of the nucleus in live cells (Figure ). We synthesized two Hoechst 33258-modified Si-Bridge isomers via direct reaction of the phenol of Hoechst 33258 with the isomeric Si-iodopropyl dyes 52a and 52b, and then assessed their ability to label the nucleus in live HeLa cells compared to SiR-DNA (Figure , Figure ). We found that 68b is highly fluorogenic, labeling only the nucleus in live cells (Figure ). This importantly demonstrates that the valued fluorogenic effect seen in traditional Si-rhodamine dyes modified on the pendant phenyl ring can also translate to Si-rhodamine dyes modified on the silyl group. Interestingly, however, the isomeric compound 68a labeled internal membranes and yielded no labeling of the nucleus (Figure ). To gain more insight into the molecular basis for this difference, we evaluated the photophysical properties of 68a-b in vitro in the presence and absence of a hairpin DNA oligonucleotide (hpDNA). Like SiR-DNA, these dyes are quenched and virtually nonfluorescent in PBS, with quantum yields <0.02 and brightness of <130 M -1 cm -1 (SI).