The Dissociation Constants of Tetrahydrofolic Acid

Abstract

Six dissociable groups exist in tetrahydrofolic acid in the range H0 -3.0 to pH 14. The assignments in tetrahydrofolic acid by titrimetric and spectrophotometric comparisons with model compounds, p-aminobenzoylglutamic acid and 2-amino-6,7-dimethyl-5,6,7,8-tetrahydro-4-pteridinone, are as follows: acidic ionization of amide, pK' 10.5; N5, pK' 4.82; γ-carboxyl, pK' 4.8; α-carboxyl, pK' 3.5; N1, pK' 1.24; and N10, pK' -1.25. These pK' values, with the exception of those of the carboxyl groups, were determined directly for tetrahydrofolic acid at 22–25° and ionic strength 1.0.