TY - JOUR
T1 - Iron chelators of the pyridoxal 2-pyridyl hydrazone class. part III.1 Ionisation and conformational characteristics of the ligands
AU - Doungdee, Prayong
AU - Sarel, Shalom
AU - Ringel, Israel
AU - Gibson, Dan
AU - Wongvisetsirikul, Nipon
AU - Avramovici-Grisaru, Shelly
PY - 1995/1/1
Y1 - 1995/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33745484074&partnerID=8YFLogxK
U2 - 10.3987/com-94-s16
DO - 10.3987/com-94-s16
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AN - SCOPUS:33745484074
SN - 0385-5414
VL - 40
SP - 241
EP - 248
JO - Heterocycles
JF - Heterocycles
IS - 1
ER -