A complete series of sulfur-substituted fluoresceins: synthesis and position-dependent optical properties

A complete series of sulfur-substituted fluoresceins was synthesized by systematically replacing the bridging oxygen atom at the 10-position of the xanthene core and/or the phenolic oxygen atoms at the 3- and 6-positions with sulfur. The optical properties of the five sulfur-substituted derivatives were compared with those of parent fluorescein to elucidate the effects of the number and position of sulfur atoms. Sulfur substitution induced systematic bathochromic shifts in the UV-vis absorption spectra, with central, single-terminal, and dual-terminal substitution producing shifts of approximately 20, 35-40, and 120 nm, respectively. Single-terminal sulfur substitution also red-shifted the fluorescence maxima by approximately 55-65 nm, whereas terminal sulfur substitution markedly suppressed fluorescence, and the doubly terminally substituted derivatives were only very weakly emissive. DFT calculations reproduced the position-dependent bathochromic shifts and revealed progressive stabilization of the LUMO upon sulfur substitution. TD-DFT calculations further showed that terminal sulfur substitution introduces a low-lying n-π* excited state with negligible oscillator strength below the bright π-π* state, providing a plausible explanation for the markedly reduced fluorescence. These results demonstrate that both the number and position of sulfur atoms critically govern the electronic and optical properties of the fluorescein framework.