Proton dissociation properties of arylphosphonates: Determination of accurate Hammett equation parameters

Gergő Dargó; Adrienn Bölcskei; Alajos Grün; Szabolcs Béni; Zoltán Szántó; Antal Lopata; György Keglevich; György T Balogh

doi:10.1016/j.jpba.2017.05.038

Proton dissociation properties of arylphosphonates: Determination of accurate Hammett equation parameters

J Pharm Biomed Anal. 2017 Sep 5:143:101-109. doi: 10.1016/j.jpba.2017.05.038. Epub 2017 May 27.

Authors

Gergő Dargó¹, Adrienn Bölcskei², Alajos Grün², Szabolcs Béni³, Zoltán Szántó⁴, Antal Lopata⁴, György Keglevich², György T Balogh⁵

Affiliations

¹ Compound Profiling Laboratory, Gedeon Richter Plc., Gyömrői út. 19-21., 1107, Budapest, Hungary; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rakpart 3., 1111, Budapest, Hungary.
² Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rakpart 3., 1111, Budapest, Hungary.
³ Department of Pharmacognosy, Semmelweis University, Üllői út 26, 1085, Budapest, Hungary.
⁴ CheMicro Ltd., Károly körút 1., 1075, Budapest, Hungary.
⁵ Compound Profiling Laboratory, Gedeon Richter Plc., Gyömrői út. 19-21., 1107, Budapest, Hungary. Electronic address: gy.balogh@richter.hu.

PMID: 28578253
DOI: 10.1016/j.jpba.2017.05.038

Abstract

Determination of the proton dissociation constants of several arylphosphonic acid derivatives was carried out to investigate the accuracy of the Hammett equations available for this family of compounds. For the measurement of the pK_a values modern, accurate methods, such as the differential potentiometric titration and NMR-pH titration were used. We found our results significantly different from the pK_a values reported before (pK_a1: MAE = 0.16 pK_a2: MAE=0.59). Based on our recently measured pK_a values, refined Hammett equations were determined that might be used for predicting highly accurate ionization constants of newly synthesized compounds (pK_a1=1.70-0.894σ, pK_a2=6.92-0.934σ).

Keywords: Arylphosphonic acids; Hammett equation; NMR-pH titration; pH-metric pK(a) measurements; pK(a) predictors.

MeSH terms

Acids
Hydrogen-Ion Concentration
Magnetic Resonance Spectroscopy
Organophosphonates / chemistry*
Protons

Substances

Acids
Organophosphonates
Protons