9,9-bis(4-hydroxyphenyl)fluorene is a member of the class of fluorenes that is 9H-fluorene in which both of the hydrogens at position 9 have been replaced by p-hydroxyphenyl groups. It has a role as an anti-estrogen. It is a member of fluorenes and a polyphenol. It has a structure of multiple hydroxyphenyl groups, and this structure gives it some special properties and applications:Material Synthesis: 9,9-bis(4-hydroxyphenyl)fluorene can be used as an intermediate in organic synthesis, involved in condensation reactions, the synthesis of aromatic compounds, etc., for the preparation of polymers, compounds and other materials with specific structure and properties. Optoelectronic functional materials: Because it contains fluorene group and hydroxyphenyl group, 9,9-bis(4-hydroxyphenyl)fluorene may have good photoelectric properties, can be used in the preparation of optoelectronic devices, organic semiconductor materials.

Synthesis of 9,9-bis(4-hydroxyphenyl)fluorene

Bisphenol compounds are produced from the condensation reaction of aldehydes (or ketones) and phenol. 9,9-bis(4-hydroxyphenyl)fluorene (BHPF) is a compound with a cardo-ring structure and it is an important raw material to produce epoxy resin, polycarbonate, acrylic resin and other materials with high thermal stability and good optical properties. In this work, in view of the need for acid-thiol synergistic catalysis in the synthesis of BHPF, we introduced sulfonic acid groups (–SO3H) into the cationic structure of the ILs, and the sulfhydryl groups (–SH) were introduced into the cationic and/or anionic structure of ILs. To screen BFIL catalysts and get the relationship among the structure of the BFILs with the conversion of fluorenone and the selectivity of 9,9-bis(4-hydroxyphenyl)fluorene, the reaction parameter on the condensation of fluorenone with phenol was optimized firstly. The crucial reaction parameters include catalyst amount, reaction temperature, reaction time and the molar ratio of phenol and 9-fluorenone.[1]

With 110 °C or higher temperature, 100% conversion of 9-fluorenone can be obtained, while the selectivity of 9,9-bis(4-hydroxyphenyl)fluorene became worse with increasing temperature. To compare the catalytic performance of BFILs with different structures (so as their acidity and electronic properties of –SH), the reaction time was 4 hours. At that point, not only condensation reactions with different ILs could reach the equilibrium state (usually within 0.5–1 h), but also the selectivity of BHPF was good. It is clear that IL 6c is the best catalyst among the thirteen BFILs for the condensation reaction, the conversion of 9-fluorenone is 100%, and the selectivity of BHPF is 91.8%.It is clear that IL 6c is the best catalyst among the thirteen BFILs for the condensation reaction, the conversion of 9-fluorenone is 100%, and the selectivity of 9,9-bis(4-hydroxyphenyl)fluorene is 91.8%.The part of intermediate IV coming from IL 6c is a large structural item, so it's the spatial effect that make the p-carbon in phenol rather than the o-carbon in phenol to attack the reactive center. So that the –SH group in some BFILs can influence the ration of BHPF and the by-product 1. Therefore, IL 6c increased the yield of BHPF and also the selectivity of BHPF.

The toxic effects of Fluorene-9-bisphenol on porcine oocyte

Bisphenol A (BPA) substitutes have been applied in the synthesis of plastic products due to the restricted use of BPA. Fluorene-9-bisphenol, also known as 9,9-bis(4-hydroxyphenyl)fluorene (BHPF), is a substitute of BPA used in the synthesis of polyester polymers such as PC, epoxy resins, polyesters, and polyurethanes. BHPF (1000?nM) delayed the development, increased mortality and surface tension of embryonic chorions, caused aberrant expression of the key genes in early development, and damaged the CaP motor neurons. Our study suggests that BHPF inhibits the cumulus expansion and disrupts porcine oocyte maturation and reduces oocyte quality through impairing spindle assembly, declining ATP content, elevating ROS level, inducing apoptosis and impeding CGs distribution.[2]

In conclusion, the present study demonstrated that 9,9-bis(4-hydroxyphenyl)fluorene impaired oocyte maturation even in the presence of dense cumulus layers. 9,9-bis(4-hydroxyphenyl)fluorene led to the PBE failure and reduced oocyte quality in porcine oocytes by affecting spindle assembly, ATP production, ROS accumulation, apoptosis, and CGs distribution. Our study reports the toxic effects on cumulus expansion and oocyte maturation in pig, and raises the concerns about the safety of BPA substitutes.

References

[1]Wei J, Yu L, Yan L, Bai W, Lu X, Gao Z. Synthesis of 9,9-bis(4-hydroxyphenyl) fluorene catalyzed by bifunctional ionic liquids. RSC Adv. 2021 Oct 4;11(52):32559-32564. doi: 10.1039/d1ra05967j. PMID: 35493579; PMCID: PMC9041788.

[2]Jiao, Xiaofei et al. “The toxic effects of Fluorene-9-bisphenol on porcine oocyte in vitro maturation.” Environmental toxicology vol. 35,2 (2020): 152-158. doi:10.1002/tox.22851