Presentation Title

Analysis of the Reduction and Oxidation Potentials of BPA-GSH Adducts and Related Structures

Presenter Information

Barbara MullenFollow

Advisor Information

Douglas Stack

Location

Dr. C.C. and Mabel L. Criss Library

Presentation Type

Poster

Start Date

2-3-2018 10:45 AM

End Date

2-3-2018 12:00 PM

Abstract

Bisphenol A (BPA)—a compound heavily used in plastics manufacturing– undergoes cellular oxidation yielding BPA-catechols then BPA-o-quinones. Subsequent conjugation with GSH results in various conjugate additions to form BPA-GSH. The mechanism of this conjugation process is unknown, but kinetic studies have indicated that some of these adducts form reversibly. Using cyclic voltammetry (CV) the oxidation potentials of these BPA-GSH adducts (along with similar BPA sulfur adducts) were identified as a preliminary step in determining their formation mechanism, reversibility, and cellular metabolic fate.

Compounds were dissolved in 30 mL of phosphate-buffered saline electrolyte (0.5 mM final concentration) and CVs were measured using a glassy carbon working electrode, platinum counter electrode, and a Ag/AgCl reference electrode. Half cell oxidation potentials are 94, 88, 155, and 173 mV for 3-OH-5-NAC-BPA, 3-OH-5-GSH- BPA, 3-OH-2,5-diGSH-BPA, and 3-OH-2-GSH-BPA respectively. This demonstrates that 3-OH-5-GSH-BPA is significantly easier to oxidize than other BPA-GSH adducts. This difference in oxidation potentials between the 2 and 5 substituted BPA-GSH adducts explains the variations in proton NMR shifts found in previous studies. Additionally, the slightly higher oxidation potential of the 5-NAC adduct in contrast to 5-GSH adduct is consistent with formation of 2,5-diGSH as opposed to NAC which does not form disulfur adducts. Diadduct formation requires oxidation of the monoadduct by unreacted BPAQ. The more easily oxidized 5-GSH thus reacts further to form the 2,5-diGSH adduct while 5-NAC does not.

Selenium—a growing interest in cancer research for its toxicity to tumors in some chemotherapeutic agents—shares similar chemical properties with sulfur. These oxidation potential results in combination with further testing and synthesis will allow for evaluation of similar BPA-selenium adducts as chemotherapeutic agents. Understanding the electrochemistry is paramount to understanding how this potential compound will behave in vitro and in vivo.

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Mar 2nd, 10:45 AM Mar 2nd, 12:00 PM

Analysis of the Reduction and Oxidation Potentials of BPA-GSH Adducts and Related Structures

Dr. C.C. and Mabel L. Criss Library

Bisphenol A (BPA)—a compound heavily used in plastics manufacturing– undergoes cellular oxidation yielding BPA-catechols then BPA-o-quinones. Subsequent conjugation with GSH results in various conjugate additions to form BPA-GSH. The mechanism of this conjugation process is unknown, but kinetic studies have indicated that some of these adducts form reversibly. Using cyclic voltammetry (CV) the oxidation potentials of these BPA-GSH adducts (along with similar BPA sulfur adducts) were identified as a preliminary step in determining their formation mechanism, reversibility, and cellular metabolic fate.

Compounds were dissolved in 30 mL of phosphate-buffered saline electrolyte (0.5 mM final concentration) and CVs were measured using a glassy carbon working electrode, platinum counter electrode, and a Ag/AgCl reference electrode. Half cell oxidation potentials are 94, 88, 155, and 173 mV for 3-OH-5-NAC-BPA, 3-OH-5-GSH- BPA, 3-OH-2,5-diGSH-BPA, and 3-OH-2-GSH-BPA respectively. This demonstrates that 3-OH-5-GSH-BPA is significantly easier to oxidize than other BPA-GSH adducts. This difference in oxidation potentials between the 2 and 5 substituted BPA-GSH adducts explains the variations in proton NMR shifts found in previous studies. Additionally, the slightly higher oxidation potential of the 5-NAC adduct in contrast to 5-GSH adduct is consistent with formation of 2,5-diGSH as opposed to NAC which does not form disulfur adducts. Diadduct formation requires oxidation of the monoadduct by unreacted BPAQ. The more easily oxidized 5-GSH thus reacts further to form the 2,5-diGSH adduct while 5-NAC does not.

Selenium—a growing interest in cancer research for its toxicity to tumors in some chemotherapeutic agents—shares similar chemical properties with sulfur. These oxidation potential results in combination with further testing and synthesis will allow for evaluation of similar BPA-selenium adducts as chemotherapeutic agents. Understanding the electrochemistry is paramount to understanding how this potential compound will behave in vitro and in vivo.