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Electronic structure and conformational analysis of P218: An antimalarial drug candidate
Author(s) -
Abbat Sheenu,
Bharatam Prasad V.
Publication year - 2016
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.25189
Subject(s) - dimer , protonation , chemistry , molecule , solvent , conformational isomerism , quantum chemical , computational chemistry , zwitterion , ring (chemistry) , solvent effects , electronic structure , stereochemistry , crystallography , organic chemistry , ion
P218 is one of the very important and recent lead compounds for antimalarial research. The 3D structural and electronic details of P218 are not available. In this article, quantum chemical studies to understand the possible 3D structures of P218 are reported and compared with 3D structures from the active site cavities of h DHFR and Pf DHFR. The neutral P218, can adopt open chain as well as cyclic arrangements. Under implicit solvent condition a zwitterionic‐cyclic conformer is found to be quite possible. Microsolvation studies using explicit water molecules indicate that one water molecule may bridge the two ends of zwitterionic‐cyclic P218. It was observed that the protonation occurs preferentially at N 1 position of the 2,4‐diaminopyrimidine ring, with a proton affinity of 274.49 kcal/mol (implicit solvent phase) and 236.35 kcal/mol (gas phase). A dimer of P218 may be zwitterionic dimer, the dimer formation can release upto ∼28.60 kcal/mol (implicit solvent phase).