Synlett 2013; 24(19): 2519-2524
DOI: 10.1055/s-0033-1339545
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© Georg Thieme Verlag Stuttgart · New York

Is the Isodesmic Reaction Approach a Better Model for Accurate Calculation of pK a of Organic Superbases? A Computational Study

Abul Kalam Biswas
a   Computation and Simulation Unit (Analytical Discipline and Centralized Instrument Facility), CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India
b   Academy of Scientific and Innovative Research, CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India   Fax: +91(278)2567562   eMail: ganguly@csmcri.org
,
Rabindranath Lo
a   Computation and Simulation Unit (Analytical Discipline and Centralized Instrument Facility), CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India
,
Bishwajit Ganguly*
a   Computation and Simulation Unit (Analytical Discipline and Centralized Instrument Facility), CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India
b   Academy of Scientific and Innovative Research, CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India   Fax: +91(278)2567562   eMail: ganguly@csmcri.org
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Publikationsverlauf

Received: 16. Juli 2013

Accepted: 18. Juli 2013

Publikationsdatum:
27. August 2013 (online)


Abstract

The acid-base dissociation constant (pK a) can be related to the solubility and binding of drugs. However, measuring accurate pK a values is a challenging task. In this study, we have examined the pK a of various organic superbases: naphthalenes, cyclic guanidines, vinamidines, and acyclic guanidines computationally. We have calculated the pK a of such superbases by employing two methods: a conventional thermodynamic cycle and a second method based on an isodesmic reaction. The thermodynamic cycle involves computation of solvation free energy by using gas-phase free energy and the difference in solvation free energies (∆Gsolv) between products and reactants. Calculations performed with the isodesmic reaction approach do not use the free energy of solvation; hence, the accuracy of the approach is less sensitive to solvent molecules and global charges of the calculated species. The root-mean-square errors (RMSE) predict that the pK a of the studied organic superbases are more accurate when calculated with the isodesmic reaction approach.

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