Publication Details

AFRICAN RESEARCH NEXUS

SHINING A SPOTLIGHT ON AFRICAN RESEARCH

biochemistry, genetics and molecular biology

Linear free energy relationships predict coordination and π-stacking interactions of small molecules with ferriprotoporphyrin IX

Journal of Inorganic Biochemistry, Volume 105, No. 5, Year 2011

In order to better understand the interaction of antimalarial compounds with ferriprotoporphyrin IX (Fe(III)PPIX), association constants of pyridines, imidazoles, amines and phenolates with Fe(III)PPIX and protoporphyrin IX (PPIX) have been measured spectrophotometrically in 40% (v/v) aq. DMSO at pH 7.4. The pH independent log association constants for coordination of nitrogen donor ligands exhibit a linear free energy relationship (LFER) with the pKa of the donor atom. Association through π-stacking interactions (log K π) with PPIX and Fe(III)PPIX increases with the number of π-electrons in the aromatic ring system. These findings indicate that in the aqueous milieu of the malaria parasite digestive vacuole, coordination to the Fe(III) center of the porphyrin is necessarily very weak, while π-stacking interactions will be much stronger. On the other hand, in environments in which proton competition is absent, coordination will dominate, with the most basic donor atoms forming the strongest complexes with Fe(III)PPIX. The lipid nanospheres within the digestive vacuole which are now known to be the location of conversion of Fe(III)PPIX to hemozoin could possibly be such an environment, making both types of interaction relevant to the design of new hemozoin inhibitors. © 2011 Elsevier Inc.

Statistics
Citations: 22
Authors: 3
Affiliations: 1
Research Areas
Infectious Diseases