Glassy Fluorene and Sulfone Polyesters with High Refractive Index and Thermal Stability Whose Monomers Induce Estrogenic Bioactivity

Abstract

Two new diacid monomers containing either fluorene or sulfone moieties polymerize via step-growth polymerization in the presence of their diol counterparts or alkyl diols (ethylene glycol and 1,6-hexanediol), forming eight new cardo structure polyesters. The polymers exhibit high optical transparency in the thin-film form with refractive indices ranging from 1.56 to 1.69, tunable glass transition temperatures from ca. 40 to 116 °C with no melting temperature, and resistance to thermal degradation in a nitrogenous atmosphere, reaching 350-398 °C before observing 10% weight loss. Their molecular weights, M _w , range from ca. 17 to 77 kDa, with an average polydispersity, Đ, of 1.5, and average purified yields of 82%. The polymers absorb light primarily in the UV region from ca. 228 to 320 nm with no absorption from 320 to 800 nm. A critical finding is that some of the fluorene and sulfone monomers induce negative bioactivity and even cell death in T47D-KBLuc cells, a breast cancer cell line, at high concentrations. This report details the project inspiration, monomer synthesis, polymerization steps, structural confirmation, material characterization, and the impact of the new monomer's estrogenic and antiestrogenic bioactivity.

Figure 1

Estrogen hormone, estradiol (pink). Endocrine disruptors, BPA, BHPF, and BPS (blue), overlaid on estradiol.⁻

Scheme 1. Synthesis of Monomers

Top: F-diacid and S-diacid. Bottom: F-diol and S-diol.

Figure 2

T47D-KBLuc cell response to increasing F-diol (A–C) or S-diacid (D–F) monomer concentrations. Dashed lines represent cell numbers without a monomer in growth media alone (black dashes) and estradiol media alone (pink dashes). Symbols with error bars represent the mean ± SD. The asterisks signify a statistically significant difference vs estradiol medial alone (pink *), or vs growth media alone (black *).

Figure 3

Estrogen-driven luminescence of cells treated with increasing F-diol (A–C) or S-diacid (D–F) monomer concentrations on day 1 (A and D), day 2 (B and E), and day 3 (C and F). The dashed lines represent luminescence in the absence of monomer in growth media alone (black dashes) or estradiol media alone (pink dashes). Symbols with error bars represent the mean ± SD. The asterisks signify a statistically significant difference vs estradiol media alone (pink *) or vs growth media alone (black *).

Figure 4

F1–4 and S1–4 polymer structures (NMR in the Supporting Information, Figures S7–S14), and optical image of typical FBP and SBP samples' appearance in the powder form.

Figure 5

TGA of representative FBP and SBP. (A) Polymers F1–4. (B) Polymers S1–4.

Figure 6

Normalized DSC curves of representative FBP and SBP. (A) Polymers F1–4. (B) Polymers S1–4.

Figure 7

UV–vis of representative FBP and SBP samples in CHCl₃ at room temperature. (A) Polymers F1–4. (B) Polymers S1–4.