US EPA

6848219 

Journal Article 

IRON CHELATORS OF THE PYRIDOXAL 2-PYRIDYL HYDRAZONE CLASS .3. IONIZATION AND CONFORMATIONAL CHARACTERISTICS OF THE LIGANDS 

Doungdee, P; Doungdee, P; Sarel, S; Sarel, S; Ringel, I; Ringel, I; Gibson, D; Gibson, D; Wongvisetsirikul, N; Wongvisetsirikul, N; Avramovicigrisaru, S; Avramovicigrisaru, S 

1995 

Yes 

Heterocycles
ISSN: 0385-5414 

40 

1 

241-248 

WOS:A1995QC65000031 

pKa values of three biologically active iron chelators: pyridoxal 2-pyridyl hydrazone (PPH), 1-[N-methylpyridoxylidenium]-2-[2'-pyridyl]hydrazineiodide (MPH), 1-[N-ethoxycarbonylmethylpyridoxylidenium]-2-[2'-pyridoxyl]hydrazine bromide (EPH) have been determined by a combination of ab initio calculations and pH-dependence of C-13 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 byab 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 C-3 - C-8 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.<