ADME/Tox WEB in silico predictions of longer chain perfluoroalkyl carboxylic acid pKa values are more accurate than other computational methods
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- University of Winnipeg, Manitoba, Canada
- Okanagan College, Penticton, British Columbia, Canada
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- Received 09 March 2009 03:41 UTC; Posted 10 March 2009
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- Chemistry, Pharmacology, Earth & Environment
- Abstract:
Perfluoroalkyl carboxylates are contaminants whose environmental fate and toxicological effects are of broad interest within the academic, industrial, and governmental science and regulatory communities. In addition, coupled perfluoroalkyl and carboxylate moieties are often used in medicinal chemistry as part of the drug design process. However, to date there has been a notable absence of reliable acidity constant estimation programs for these compounds. Here we report that the ADME/Tox WEB method for in silico pKa value predictions is more accurate than the PM6, SPARC, and COSMOtherm methods for the longer chain perfluoroalkyl carboxylic acids, suggesting this may be a good general acidity constant estimation approach for these compounds.
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Rayne, Sierra and Forest, Kaya. ADME/Tox WEB in silico predictions of longer chain perfluoroalkyl carboxylic acid pKa values are more accurate than other computational methods. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.2936.1> (2009)
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Sierra Rayne on 27 August 2009 18:46 UTC
Since the posting of this document on 10 March 2009, there have been recent developments regarding the monomeric pKa values of perfluoroalkyl carboxylic acids (PFCAs) that warrant discussion. In their original article, Burns et al. (Environ. Sci. Technol., 2008, 42 (24), pp 9283–9288; DOI: 10.1021/es802047v; online 7 November 2008) reported that the monomeric pKa of n-perfluorooctanoic acid (n-PFOA) was 3.8+/-0.1, and that the pKa values of this and other long-chain PFCAs were higher than their monomeric counterparts. This information led to a re-evaluation of the historical PFCA pKa datasets, and suggested that the pKa values of PFCAs increase by up to 3 units from trifluoroacetic acid through to n-PFOA. However, Goss and Arp (Environ. Sci. Technol., 2009, 43 (13), pp 5150–5151; DOI: 10.1021/es900451s; online 28 May 2009) have published reasonable concerns regarding the validity of the data and interpretations published by Burns et al., and have called into question the reported monomeric pKa of 3.8+/-0.1 that Burns et al. published for n-PFOA. Recent experimental work by Cheng et al. (J. Phys. Chem. A, 2009, 113 (29), pp 8152–8156; DOI: 10.1021/jp9051352; online 1 July 2009) has presented strong experimental evidence that the monomeric pKa of n-PFOA is <1, and that the apparent pKa values of long-chain PFCAs increase with increasing concentration (i.e., aggregation), rather than decrease as Burns et al. claimed. As such, there is currently much debate in the scientific community regarding the actual monomeric pKa values of long-chain PFCAs. If the monomeric pKa of n-PFOA is about 0, then current quantum chemical prediction tools would be providing reasonable predictive ability for these important environmental contaminants. If the monomeric pKa of n-PFOA is near 4, then such methods would underestimate the pKa values. Further work is underway in our group and others to better understand which monomeric pKa for n-PFOA is most likely correct.