European Journal of Chemistry ͷ ȋͳȌ ȋʹͲͳͶȌ ͳ‐ͷ European Journal of Chemistry )SSN ʹͳͷ͵‐ʹʹͶͻ ȋPrintȌ / )SSN ʹͳͷ͵‐ʹʹͷ͹ ȋOnlineȌ  ʹͲͳͶ Eurjchem Publishing ‐ Printed in the USA http://dx.doi.org/ͳͲ.ͷͳͷͷ/eurjchem.ͷ.ͳ.ͳ‐ͷ.ͻͲͳ European Journal of Chemistry Journal homepage: www.eurjchem.com New chemometric strategies in the spectrophotometric determination of pKa Judith Amador‐(ernández a, *, Alberto Rojas‐(ernández b , Edith Madaí Colunga‐Urbina a , )liana Margarita De La Garza‐Rodríguez a , Miguel Velázquez‐Manzanares c , and Luis Felipe Medina‐Vallejo a a Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Blvd. V. Carranza s/n, 25280 Saltillo, Coahuila, México b Departamento de Química, Universidad Autónoma Metropolitana, Apdo. Postal 55‐534, 09340 México, Distrito Federal, México c Instituto de Biotecnología, Universidad del Papaloapan, Circuito Central 200, 68301 San Juan Bautista Tuxtepec, Oaxaca, México *Corresponding author at: Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Blvd. V. Carranza s/n, 25280 Saltillo, Coahuila, México. Tel.: +52.844.4159534 (Ext. 112). Fax: +52.844.4159534. E‐mail address: amadorjudith@live.com.mx (J. Amador). ART)CLE )NFORMAT)ON ABSTRACT DO): ͳͲ.ͷͳͷͷ/eurjchem.ͷ.ͳ.ͳ‐ͷ.ͻͲͳ Received: Ͳͷ August ʹͲͳ͵ Received in revised form: Ͳʹ September ʹͲͳ͵ Accepted: Ͳ͸ September ʹͲͳ͵ Online: ͵ͳ March ʹͲͳͶ KEYWORDS )n this work, principal component regression and partial least squares regression were used for the estimation of acid dissociation constants through UV‐Vis spectrophotometric measurements, considering five well‐known acid‐base indicators as well as two herbicides as analytes. )n each case, an acid‐base titration was carried out. Then, the multivariate calibration model was constructed with a few absorption spectra of the series at extreme p( values, to which values of the dissociation fraction ȋαȌ of ͳ or Ͳ were assigned, in the case of (A or A species. After that, the prediction step consisted in the estimation of α for the rest of the series. Then, distribution diagrams were built up with α vs p(, to find α = Ͳ.ͷ where p( = pKa. The results were compared with those obtained through multivariate curve resolution‐ alternating least squares and program stability quotients from absorbance data ȋSQUADȌ, which showed an excellent correspondence. pKa PLS PCR MCR‐ALS Spectrophotometry Chemometric strategies 1. Introduction The study of acid‐base equilibriums is of great importance, because the ionic and the neutral forms of a compound exhibit different physicochemical properties ȋsolubility, partition coefficient, etc.Ȍ [ͳ,ʹ]. )n other words, the predominance of one of the two forms will condition their distribution in the environment, their biological activity or chemical reactivity, among others. Thus, the determination of acid dissociation constants is a topic of current interest. Several research groups are continuing to look for new methodologies to estimate them, based on techniques such as Nuclear Magnetic Resonance [͵], Electric )mpedance Spectroscopy [Ͷ], Capillary Electrophoresis [ͷ], or Gas Chromatography [͸], to name a few. Furthermore, the use of UV‐Visible spectrophotometry is still common, through new approaches to data processing [͹‐ͳͲ]. Particularly, the technique of Multivariate Curve Resolution‐Alternating Least Squares ȋMCR‐ALSȌ is increasingly used for the analysis of component mixtures, both for quantitative measures and for the study of chemical equilibriums [͹,ͳͳ,ͳʹ]. (owever, Partial Least Squares Regression ȋPLSȌ or Principal Component Regression ȋPCRȌ have not been reported for pKa estimation as far as is known to the authors. )n this work, the techniques of MCR‐ALS, PLS and PCR are used for the estimation of acid dissociation constants through UV‐Vis spectrophotometry. The substances of interest were five acid‐base indicators, whose pKa values are widely reported in the literature, in order to show the applicability of the techniques. Later, the pKa values for isomethiozin and methoprotryne, two triazine herbicides, are reported. )n all cases, the pKa values were compared with those estimated through SQUAD [ͳ͵,ͳͶ], an algorithm that is widely used for this purpose [ͳͷ,ͳ͸]. 1.2. Fundamental considerations Consider the general reaction for an acid dissociation: (A ൅ ( ଶ O⇄( ଷ O ା ൅A  ȋͳȌ where (A and A ‐ represent the acid and its conjugated base, respectively. From the expression of the acid‐base equilibrium, it follows the (enderson‐(asselbalch equation: