THE COMPLEX FORMATION OF PROCAINE AND PROCAINE AMIDE WITH ADENOSINE TRIPHOSPHATE

¹ Department of Medicine, Robinette Foundation, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

Evidence for interactions of procaine and procaine amide with adenosine triphosphate in aqueous solutions was found by means of optical rotation and nuclear magnetic resonance methods. The aromatic components of the drug and nucleotide molecules were shown to associate through hydrophobic bonding with vertical stack formation rather than through horizontal hydrogen bonding. The dependences of the optical activity of the nucleotide and of the chemical shifts of certain nucleotide and drug protons on the nucleotide-drug ratios provided detailed information about the intermolecular relationships, the binding constants and the number of binding sites involved. At pH 7.0, adenosine tniphosphate binds one drug molecule tightly and two molecules weakly. The tight binding parameters obtained from both the optical rotation and the nuclear magnetic resonance data on adenosine triphosphate were in good agreement. A graphical analysis of these parameters gave the following average apparent tight association quotients: procaine, K₁ = 1430 ± 380 M^-1 and procaine amide, K₁ = 360 ± 90 M^-1. The weak association quotients were obtained by a trial-and-error procedure and gave the following values: procaine, K₂ = 1.1 ± 0.7 x 10⁵ M^-2 and procaine amide, K₂ = 4.7 ± 2.8 x 10³ M^-2. The hypothesis is put forward that procaine and procaine amide may act on nerve membranes by complexing with membranebound adenosine tniphosphate and thus interfere with the nucleotide's natural functions.