Iron chelators of the pyridoxal 2-pyridyl hydrazone class. Part 4. pK a values of the chelators and their relevance to biological properties

Doungdee, Prayong; Sarel, Shalom; Wongvisetsirikul, Nipon; Avramovici-Grisaru, Shelly

doi:10.1039/p29950000319

Iron chelators of the pyridoxal 2-pyridyl hydrazone class. Part 4. pK a values of the chelators and their relevance to biological properties

Author(s)

Doungdee, Prayong

Sarel, Shalom

Wongvisetsirikul, Nipon

Avramovici-Grisaru, Shelly

Date Issued

January 1, 1995

Type

Article

DOI

10.1039/p29950000319

Abstract

The proton binding constants (pKa) and species distribution over pH range 1.5-12.0 of two types of biologically active iron chelators (a) pyridoxal type (Lx)-pyridoxal 2-pyridyl hydrazone (PPH) and pyridoxal isonicotinoyl hydrazone (PIH); (b) pyridoxal-betaine type (Ly) - 1 -[N- methylpyridoxylidenium]-2-[2′-pyridyl]hydrazine iodide (MPH) and 1-[N-ethoxy-carbonylmethylpyridoxylidenium]-2-[2′-pyridyl]hydrazine bromide (EPH] have been determined by glass electrode potentiometry. The lowest pK value in type (a), in the range 2.62 (PPH)-2.45 (PIH) was assigned to pyridinium protonation; the following ionization constants. pKa2 = 4.63 (PPH)-4.54 (PIH), to pyridoxylidenium protonation; pKa1 = 7.96 (PPH)-7.44 (PIH), to phenolate protonation, and pKa4 = 9.96 (PIH)-9.84 (PPH) to amine-hydrazone protonation. At pH<2, all ligands exist in the respective protonated forms (H4Lx²⁺, H3Ly²⁺ and H3Lx ⁺) and at pH > 11, in the fully deprotonated forms (L x²⁺, and Ly^-). At pH ca. 5.0, the pyridoxal-betaines, MPH and EPH, exist predominantly as zwitterions, whereas PPH and PIH are present at that pH predominantly in the neutral, non-zwitterionic, H2Lx form. At higher pH (7.2), PPH and PIH, are present as mixtures of the neutral and the negatively charged monodeprotonated forms (IV).

Citation

Journal of the Chemical Society Perkin Transactions 2, 319-323, 1995