Redetermination of the crystal and molecular structure of the antimalarial chloroquine bis(dihydrogenphosphate) dihydrate.

N4-(7-Chloro-4-quinolinyl)-N',N'-diethyl-1,4-pentanediamine bis(dihydrogenphosphate) dihydrate, C18H28ClN2+(3).2H2PO-4-2H2O, Mr = 551.8, monoclinic, P2(1)/c, a = 9.830 (2), b = 16.879 (3), c = 15.783 (4) A, beta = 105.51 (2) degrees, V = 2523.2 A3, Z = 4, Dx = 1.452 g cm-3, Mo K alpha, lambda = 0.71073 A, mu = 2.78 cm-1, F(000) = 1168, room temperature, final R = 5.5% for 2431 reflections with [F0] greater than 3 sigma. The chloroquine molecule is a dication with a hydrogen atom from each of the phosphate moieties residing on the quinoline and the terminal chain nitrogen atoms. Neighboring phosphate chains are bridged by chloroquine molecules via hydrogen bonding. Each hydrogen atom on each nitrogen atom, on each phosphate oxygen atom, and in each water molecule participates in hydrogen bonding. The helical manner in which the side chains of the chloroquine molecules wrap around phosphate chains and the stacking interval of the quinoline rings between the phosphate groups may be indicative of the interaction of chloroquine molecules with cellular constituents important to antimalarial action.