Determination of dissociation constants of p-hydroxybenzophenone in aqueous organic mixtures - Solvent effects

Canadian Journal of Chemistry (Impact Factor: 1.06). 05/2008; 86(5):462-469. DOI: 10.1139/v08-040


The apparent acidity constant of p-hydroxybenzophenone, which is a practically insoluble drug in water but of great pharmaceutical interest, was determined by reversed-phase high-performance liquid chromatography in organic solvent - water mixtures (acetonitrile-water, ethanol-water, and methanol-water), varying the reaction medium permittivity in the interval 56 to 70, at constant ionic strength (0.050) and temperature (30 °C). A combined glass electrode calibrated with aqueous standard buffers was used to obtain pH readings based on the concentration scale (swpH). The pKa values from chromatographic data were obtained using the Hardcastle-Jano equation. Moreover, excellent linear relationships between the pKa values and solvation properties of the reaction medium (relative permittivity and Acity) were used to derive acid dissociation constants in aqueous solution. It has been concluded that the pKa values extrapolated from such solvent-water mixtures are consistent with each other and with previously reported measurements. In addition, the molecular structures of all the chemical species involved in the acid-base dissociation equilibrium studied were calculated with a B3LYP/6-311++G(d,p) method that makes use of the polarizable continuum model (PCM). Taking into account the theoretical pKa values, the conclusions obtained match our experimental determinations.

Download full-text


Available from: Matias I. Sancho,
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The survey is dedicated to the critical analysis of different experimental methods of determining the dissociation constants (Ka) of organic acids in solutions. Advantages and disadvantages of the contemporary methods of rapid analysis used in biochemistry are considered. Special attention is paid to the problems of measurements in the nonaqueous media and to the reasons for possible incorrect results. The processes in solutions that should be taken into account for obtaining the correct values of dissociation constant are analyzed. On the basis of the consideration the recommendations directed toward an increase in the accuracy of measurements are given.
    Russian Journal of General Chemistry 09/2009; 79(9):1859-1889. DOI:10.1134/S1070363209090138 · 0.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The need to have a measure of the strength of some substituted benzoic acids in ionic liquid solution led us to use the protonation equilibrium of sodium p-nitrophenolate as a probe reaction, which was studied by means of spectrophotometric titration at 298 K. In order to evaluate the importance of electronic effect of the substituents present on the aromatic ring, both electron-withdrawing and -donor substituents were taken into account. Furthermore, to have a measure of the importance of the steric effect of the substituents both para- and ortho-substituted benzoic acids were analyzed. The probe reaction was studied in two ionic liquids differing for the ability of the cation to give hydrogen bond and pi-pi interactions, namely [bm(2)im][NTf(2)] and [bmpyrr][NTf(2)]. Data collected show that benzoic acids are less dissociated in ionic liquid than in water solution. Furthermore, the equilibrium constant values seem to be significantly affected by both the nature of ionic liquid cation and the structure of the acid. In particular, the ortho-steric effect seems to operate differently in water and in the aromatic ionic liquid, determining in this solvent medium a particular behavior for ortho-substituted benzoic acids.
    The Journal of Organic Chemistry 07/2010; 75(14):4828-34. DOI:10.1021/jo100914p · 4.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this paper we have studied the 4-hydroxyl-2,5dimethylphenyl-benzophenone. Also, it was analyzed the vibrational assignment (FT-IR and Raman) in conjunction with computational results. The conformational analysis showed three barrier heights where two are due to the dihedral rotation and the other one is attributed to hydroxyl rotation. While the high dihedral rotational barrier (TS1) is 6.06-7.22kcalmol(-1), the lower one (TS2) is almost three times smaller. The variations with the change of basis set is 5-8% to TS1, and 3-15% in the values predicted to TS2. In the case of OH rotational barrier, the values range from 3.70 to 4.86kcalmol(-1), and it is also observed that this transition state is less sensitive to the change of basis set and to the method. Two isomers was detected due to the changes in the OH rotation with the gap energy lower than 0.7kcalmol(-1), and at this point is seen that semi-empirical methods fail into describe the most stable conformation which may be due to the small energy gap. The enthalpy formation at 0K and 298K was 111.71 and 102.20kcalmol(-1), respectively.
    Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy 10/2012; 102C:386-392. DOI:10.1016/j.saa.2012.09.094 · 2.35 Impact Factor
Show more