Date of Award
Master of Science in Chemical Engineering (MSChE)
Comparative investigation of the intermolecular chemical interaction (binding) between bovine serum albumin (BSA) and four polyfluoroalkyl substances (PFOA, PFNA, PFHxS, PFOS) by 19F NMR spectroscopy with synchronous observation of the 19F signals from both ends (head and tail) of the polyfluoroalkyl molecules was performed at three temperatures of 298K, 304K and 310K.
Chemical shifts of 19F NMR peaks in solutions of PFAS with BSA were used for evaluation of the dissociation constants, Kd, for both known mechanisms of PFAS binding with BSA: by hydrophobic interaction of the PFAS molecule tail with hydrophobic pockets in the BSA core (Ω mechanism) and by hydrogen bond and electrostatic interaction of the PFAS molecule head group with charged regions on the BSA surface (α mechanism). It was established that highest affinity of all four PFAS:BSA complexes is provided by Ω mechanism of binding when Kd at 310K is reaching as low values as 3.9 x 10-6, 6.5 x 10-6, 7.7 x 10-6, and 1.9 x 10-5 M for PFOS, PFOA, PFNA, and PFHxS, correspondingly, in comparison with 5.7 x10-5, 5.6 x 10-5, 6.6 x 10-5, and 5.4 x 10-5 M values for α mechanism of their binding.
Evaluation of the thermodynamic parameters (enthalpy ΔH, entropy ΔS, and Gibb’s free energy ΔG) showed that binding of PFOA, PFNA, PFHxS, and PFOS with BSA by both α and Ω mechanisms is accompanied by negative ΔH and ΔS and positive ΔG which are characteristic for binding of two large hydrophobic molecules with each other by weak hydrogen bond and van der Waals’ forces.
Kd for binding of the branched isopropyl isomers of PFHxS and PFOS with BSA were measured at 310K as 8.8 × 10-5 and 7.6 × 10-5 M, correspondingly, which indicated less affinity of isomers with the surface of BSA in comparison with the linear structure of PFHxS and PFOS molecules possibly due to “bulky” structure of the branched isomer head.
Fedorenko, Michael, "MOLECULAR MECHANISMS OF PROTEIN BINDING BY PERFLUOROALKYL SUBSTANCES (PFASs)" (2019). Open Access Master's Theses. Paper 1733.