ACD/pKa

ACD/pKa is a program that calculated values at 2SC and zero ionic strength in aqueous solution. It uses a structure fragment approach and takes into account electronic, steric, charge,... 

In certain situations, a computational chemistry approach may be useful. The procedure just described for estimating pKa from similar known compounds has been turned into an algorithm in the program ACD/pKa DB from Advanced Chemical Development (www.acdlabs.com). The program performs reasonably well (average accuracy of 0.2 pKa units for common organic compounds), and its database can be supplemented with pK l values of compounds studied in-house. 

ACD/PhysChem Suite, ACD/pKa DB, Advanced Chemistry Development, Toronto, Canada (see http //www.acdlabs.com/products/phys chem lab/pka/). 

The drawback of the spectrophotometric technique is that it is bound to ionization induced changes in UV spectra. It is difficult to guess whether a particular ionization will induce an change in UV spectra a priory. Practically, one combines this approach with an in silico tool like ACD pKa database, which predicts the number of ionizations and gives estimates of the pKa values. If the number of theoretical ionizations is lower than the number of ionizations obtained from the experimental data, one must reanalyze the sample using the potentiometric titration approach. 

Effect of pH on the Retention/Selectivity of the Isomers. The first step in method development is to understand the effect of pH on the separation characteristics of the method. The pKa values of the ortho and the para isomers was estimated by ACD (Advanced Chemistry Development software) to be 9.0 and 9.5, respectively. Obviously the best pH to carry out the separation would be at pH that is less than 2 units lower than the analyte that has the lowest pKa. This would be at pH values less than 7.0. However, to illustrate the effect of pH on the separation selectivity of the isomers, a controlled pH study at isocratic conditions was conducted. 

An estimate for the differences in basicity between the pyridyl and the benzimidazol-l-yl moieties were obtained by calculating pKa values for the conjugated acids of the two hydrogen-bond acceptors in each SR. 3-(benzimi-dazol-l-yl)methylpyridine pKa = 4.71 + 0.10 and 5.72 +0.30 for pyridyl and benzimidazol-l-yl moieties, respectively. 3-(2-methylbenzimidazol-l-yl)mefhyl-pyridine pKa = 4.72 +0.10 and 5.85 + 0.18 for pyridyl and benzimidazol-l-yl moieties, respectively. Calculations were performed using Advanced Chemistry Development (ACD/Labs) Software Solaris V4.76 ( 1994-2005 ACD/Labs). 

Many drug discovery researchers prefer to use software that can predict aqueous pKa values. For example, the ACD/pk", software program contains a vast library that contains experimental values for over 16,000 compounds in aqueous solutions and over 2000 compounds in nonaqueous solvents [82],... 

CE and for developing methods based on chemical structures and retained chromatographic knowledge. Package is integrated with ACD/Spec Manager (MS, NMR, IR, UV-Vis) and with ACD database for log P, log D, and pKa. Able to import data from major chromatography data systems. HPLC system for automated method development ... 

Wan H, Holmen AG, Wang Y, Lindberg W, Englund M, Nagard MB and Thompson RA, High-throughput screening of pKa values of pharmaceuticals by pressure-assisted capillary electrophoresis and mass spectrometry. Rapid Commun. Mass Spectrom., 17, 2639-2648 (2003). NB Reported a predicted value (ACD Labs) of 9.17. 

Most acidic pKa 14.5 + 0.5, calculated using ACD Labs software. 

TOU 13] ToURfi O., Dussap C.-G., Lebert a., Comparison of predicted pKa values for some amino-acids, dipeptides and tripeptides, using Cosmo-RS, ChemAxon and ACD/labs methods , Oil Gas Science and Technology, vol. 68, no. 2, pp. 178-197, 2013. 

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