Computational Study on the Effect of Exocyclic Substituents on the Ionization Potential of Primaquine: Insights into the Design of Primaquine-Based Antimalarial Drugs with Less Methemoglobin Generation.

ABSTRACT: The effect of an exocyclic substituent on the ionization potential of primaquine, an important antimalarial drug, was investigated using density functional theory methods. It was found that an electron-donating group (EDG) makes the ionization potential decrease. In contrast, an electron-withdrawing group (EWG) makes the ionization potential increase. Among all the exocyclic positions, a substituent at the 5- or 7-position has the largest effect. This can be explained by the contribution of the atomic orbitals at those positions to the highest occupied molecular orbital (HOMO). In addition, a substituent at the N8-position has a considerably large effect on the ionization potential because this atom makes the second largest contribution to the HOMO. These findings have potential implicatio

SUBMITTER: Liu H 

PROVIDER: S-EPMC4332040 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature