Theoretical studies on the pK~a~ values of perfluoroalkyl carboxylic acids

Sierra Rayne,Kaya Forest

doi:10.1038/npre.2010.3829.2

Abstract

AbstractComputational studies were conducted using the major levels of semiempirical, ab initio, density functional theory (DFT), and the CBS-Q//B3 method and various solvation models on a homologous series of straight chain perfluoroalkyl carboxylic acids (PFCAs) ranging in chain length from C~1~ (trifluoroacetic acid) to C~9~ (n-perfluorodecanoic acid) as well as the monomethyl branched C~7~ (n-perfluorooctanoic acid; n-PFOA) isomers. Regardless of perfluoroalkyl chain length and theoretical method employed, application of a computational thermodynamic cycle indicated no significant change in the estimated aqueous monomeric pK~a~ values between C~1~ and C~9~, all having a relatively constant pK~a~ of about 0 that is in agreement with earlier predictions and recent experimental evidence. Perfluoroalkyl chain helicity does not appear to result in increased monomeric PFCA pK~a~ values at chain lengths greater than 5. Increasing chain length does not substantially influence the structural or electronic character of the carboxylic acid head group. A MMFF94 conformational search yielded 2915 separate low- through high-energy conformers of n-PFOA. Ranking of these structures gave the 94 lowest MMFF94 energy conformations that were subjected to DFT investigations. Application of a thermodynamic cycle approach, coupled with aqueous and gas phase DFT calculations on the molecular and anionic forms for each of the conformers, gave conformationally averaged pK~a~ values for n-PFOA equal to the global minimum helical conformer pK~a~. The conformational populations under study occupy about 100 percent of the global n-PFOA conformational space, indicating no higher energy/low acidity conformations remain unexamined that could influence the predicted composite aqueous monomeric pK~a~ of zero for this compound.

Highlights

Perfluoroalkyl carboxylic acids (PFCAs; Figure 1) are widespread environmental contaminants that are persistent to natural degradation processes, can undergo long-range transport by both aquatic and atmospheric pathways, and are of toxicological concern [1,2,3]
Goss has argued that based on analogy considerations using other highly fluorinated carboxylic acids, as well as computational data obtained from the COSMOtherm and SPARC software programs, the monomeric pKa of n-perfluorooctanoic acid (n-PFOA) should be about 0 [11, 12]
In order to help resolve the current controversy in this field, and to shed light on the likely true pKa values of monomeric long-chain PFCAs, we have undertaken comprehensive theoretical studies at all major levels of computational theory on a homologous series of straight chain PFCAs and the monomethyl branched n-PFOA isomers in order to better understand what role, if any, that perfluoroalkyl chain conformations may play in the acidity constants of these important environmental contaminants

Summary

Introduction

Perfluoroalkyl carboxylic acids (PFCAs; Figure 1) are widespread environmental contaminants that are persistent to natural degradation processes, can undergo long-range transport by both aquatic and atmospheric pathways, and are of toxicological concern [1,2,3]. Recent experimental evidence by Cheng et al [10] using electrospray ionization mass spectrometry has provided an upper limit boundary for a monomeric n-PFOA pKa at ≤1, consistent with the prediction of Goss [11, 12]. As part of their studies into the air-water partitioning constant of n-PFOA, Kutsuna and Hori proposed a pKa of 1.3 from the best fit of their experimental data [14]. Burns et al [8] used a potentiometric titration

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Materials and Methods

Results and Discussion