Ab initio studies on acidity and tautomeric equilibrium constants of some benzoxa-, benzothia-, benzoselena-zolinone derivatives Murat Duran a,⇑ , Sinem Aydemir b a Department of Chemistry, Faculty of Science & Letters, Eskis ßehir Osmangazi University, 26480 Eskis ßehir, Turkey b Department of Physics, Faculty of Science & Letters, Eskis ßehir Osmangazi University, 26480 Eskis ßehir, Turkey article info Article history: Received 18 November 2011 Received in revised form 7 March 2012 Accepted 9 March 2012 Available online 18 March 2012 Keywords: HF DFT pK a CPCM Thermodynamic abstract This paper presents ab initio procedure to calculate aqueous-phase acid dissociation constants (pK a ) val- ues, accurately. In this work, dissociation and tautomeric equilibrium constants (K T ) of some benzoxa-, benzothia-, benzoselena-zolinone derivatives were studied theoretically. For this purpose, Gibbs free energy values for neutral and deprotonated forms of investigated compounds were calculated at gas and aqueous phase by using Hartree–Fock (HF) and density functional theory (DFT) calculation methods. For both calculation methods it was found that 6-311G(d) basis set is the most convenient method. Sol- vent effects are taken into account by means of conductor-like polarizable continuum model (CPCM). It was shown that, theoretically calculated pK a values are in good agreement with the existing experimental pK a values, which are determined from capillary electrophoresis, potentiometric titration and UV–visible spectrophotometric measurements. Calculated pK a values also revealed that the DFT method (R 2 = 0.92) gave much closed results to experimental values in comparison to Hartree–Fock method (R 2 = 0.86). Due to the all investigated compounds have keto-enol tautomerism, K T and pK T values were calculated with- out need to form model compounds. Theoretically calculated K T values indicated that, keto forms are pre- dominant for all the investigated compounds. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction The computational treatment and the underlying theoretical analysis of molecular properties have shown continuous growth in the degree of molecular complexity since the earliest efforts of chemist to employ computer calculations in advancing understand- ing. This will certainly continue right along with rapid increases in computing power as we have seen over the last decade. Computa- tional investigation has reached a point where it is realistic to dis- play predictive simulations of complex biological molecules [1,2]. Many benzoxazolinone (BOA) derivatives that are products of plant origin possess various biological activities [3]. BOA was first discov- ered in nature by Virtanen and Hietala as an anti-Fusarium factor in rye seedlings [4]. BOA and its biologically active derivatives are also objects of numerous studies aiming to establish possibilities for their application as drugs and pesticides [5]. It is known that halo- gen substituted 2-benzoxazolinones have well expressed for their antibacterial and fungicide properties [6,7]. Benzothiazolinone derivatives have also been reported as potent antidepressant agents [8]. Continuing a systematic investigation in the field of benzoxa-, benzothia- and benzoselena-zolinone and their analogs, we have studied the acidity constants (pK a ). In the field of industrial pharmacy, perhaps the most important physicochemical characteristic property of biologically active mol- ecules is their acidity or basicity expressed by their pK a values. Be- cause most molecules have acidic and/or basic functionalities, relationships between dissociation constants and structure may prove useful in drug design studies and in explaining the biophar- maceutical properties of substances [9–11]. There are large spectra of pK a determination techniques such as capillary electrophoresis (CEs) [12,13], liquid–liquid partitioning [14], ultraviolet–visible (UV–Vis) spectroscopy [15]. Recently, studies involving the acidity constants of benzoxa-, benzothia- and benzoselena-zolinone deriv- atives have been carried out by applying capillary electrophoresis (CEs), potentiometry and spectrophotometry experiments. The theoretical prediction of pK a values has received consider- able attention and there have been many studies on this topic in recent years [16–20]. These studies are related with the use of dif- ferent systems and different aspects of the computational methods used to determine acidity constants. Quantum chemical methods provide reliable pK a values that allow a better understanding of the different factors on pK a values to be obtained, and are essential for interpretation of experimental values in various systems [21]. It was demonstrated that the calculation of pK a values is possible by using simple ab initio methods (DFT and HF). By using these meth- ods it is possible to calculate pK a values with an average error of less than 1 pK a unit [22]. As the DFT calculation includes the effect 2210-271X/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.comptc.2012.03.008 ⇑ Corresponding author. Tel.: +90 222 239 37 50x2868; fax: +90 222 239 35 78. E-mail address: mduran@ogu.edu.tr (M. Duran). Computational and Theoretical Chemistry 989 (2012) 69–74 Contents lists available at SciVerse ScienceDirect Computational and Theoretical Chemistry journal homepage: www.elsevier.com/locate/comptc