Iron chelators of the pyridoxal 2-pyridyl hydrazone class. part III.1 Ionisation and conformational characteristics of the ligands

Doungdee, Prayong; Sarel, Shalom; Ringel, Israel; Gibson, Dan; Wongvisetsirikul, Nipon; Avramovici-Grisaru, Shelly

doi:10.3987/com-94-s16

Iron chelators of the pyridoxal 2-pyridyl hydrazone class. part III.1 Ionisation and conformational characteristics of the ligands

Author(s)

Doungdee, Prayong

Sarel, Shalom

Ringel, Israel

Gibson, Dan

Wongvisetsirikul, Nipon

Avramovici-Grisaru, Shelly

Date Issued

January 1, 1995

Type

Article

DOI

10.3987/com-94-s16

Abstract

pKa values of three biologically active iron chelators: pyridoxal 2-pyridyl hydrazone (PPH), 1-[N-methylpyridoxylidenium]-2-[2′-pyridyl]hydrazineiodide (MPH), 1-[N-elhoxycar-bonylmethylpyridoxylidenium]-2-[2′-pyridyl]hydrazine bromide (EPH) have been determined by a combination of ab initio calculations and pH-dependence of ¹³C nmr spectroscopy. In conformity with pyridoxal isonicotinoyl hydrazone (PIH), all ligands included in this study the pKa values invariably increase in the ordering: pyridinium protonation < pyridoxylidenium protonation < phenolate protonation < amine-hydrazone protonation < alkoxide protonation. Identical ordering was obtained by ab initio calculations, based on STO-3G set. Mulliken population analysis indicates that the conformer of the lowest energy of PPH, (I), contains an internal 6-membered-ring H-bond. Rotation about C³ - C⁸ bond in (I), to yield conformer (IV), requires 8.8 kcal/mol, whereas its internal H-bonding (I → II) accounts for 5.8 kcal/mol. Protonation of (I) lowers significantly energies both of I → V (6.5 kcal), and I → VI (2.5 kcal) transitions. © 1995.

Citation

Heterocycles, 40(1), 241-248, 1995