title: Extreme Basicity of Biguanide Drugs in Aqueous Solutions: Ion Transfer Voltammetry and DFT Calculations.
abstract: Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution. Measurements gave the pKa1 values for MFH(+), PFH(+), and PBH(+) characterizing the basicity of MF, PF, and PB, which are significantly higher than those reported in the literature. As a result, the monoprotonated forms of these biguanides should prevail in a considerably broader range of pH 1-15 (MFH(+), PFH(+)) and 2-13 (PBH(+)). DFT calculations with solvent correction were performed for possible tautomeric forms of neutral, monoprotonated, and diprotonated species. Extreme basicity of all drugs is confirmed by DFT calculations of pKa1 for the most stable tautomers of the neutral and protonated forms with explicit water molecules in the first solvation sphere included.
authors: J. Heyrovský Institute of Physical Chemistry, v.v.i., Academy of Sciences of the Czech Republic , Dolejškova 3, 182 23 Prague 8, Czech Republic.
authors: Jan
authors: J
authors: Langmaier
authors: J. Heyrovský Institute of Physical Chemistry, v.v.i., Academy of Sciences of the Czech Republic , Dolejškova 3, 182 23 Prague 8, Czech Republic.|Department of Inorganic Chemistry, University of Chemistry and Technology , Prague 6, Technická 5, 166 28, Czech Republic.
authors: Martin
authors: M
authors: Pižl
authors: J. Heyrovský Institute of Physical Chemistry, v.v.i., Academy of Sciences of the Czech Republic , Dolejškova 3, 182 23 Prague 8, Czech Republic.
authors: Zdeněk
authors: Z
authors: Samec
authors: J. Heyrovský Institute of Physical Chemistry, v.v.i., Academy of Sciences of the Czech Republic , Dolejškova 3, 182 23 Prague 8, Czech Republic.
authors: Stanislav
authors: S
authors: Záliš
mesh_terms: D001645:Biguanides / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008687:Metformin / Q000737:chemistry*; D008958:Models, Molecular; D010629:Phenformin / Q000737:chemistry*; D011789:Quantum Theory; D012996:Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D001645:Biguanides; D012996:Solutions; D014867:Water; D008687:Metformin; D010629:Phenformin; C008846:phenyl biguanide