TY - JOUR
T1 - Crystal structure of the potent bisquinoline antimalarial agent (±)-trans-N1,N2-bis(7-chloroquinolin-4-yl) cyclohexane-1,2-diamine dimethanesulfonate salt hydrate in relation to its biological properties
AU - Karle, Jean M.
AU - Bhattacharjee, Apurba K.
AU - Vennerstrom, Jonathan L.
PY - 2002
Y1 - 2002
N2 - The neighboring 4-aminoquinoline substituents of the bisquinoline (±)-trans-N1,N 2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine dimethanesulfonate salt crystallized in the diequatorial position which is in agreement with quantum chemical calculations. The bisquinoline salt crystallized in the monoclinic C2/c space group with a = 19.328(4) Å, b = 15.618(3) Å, c = 20.382(4) Å, β = 98.84(3)°. The two quinoline nitrogen atoms are protonated by the salt as predicted by calculated electrostatic surface potentials. The -5 kcal/mol isopotential surface of the bisquinoline resembles that of chloroquine, which may explain the potent inhibition of hematin polymerization by both the bisquinoline and chloroquine. The smaller HOMO/LUMO gap of the bisquinoline is consistent with its phototoxicity. The overall conformation, the ability of all nitrogen atoms to participate in hydrogen bonding, and the electrostatic interaction of the quinoline rings in the crystal packing may all aid in the determination of the binding pharmacophore of the bisquinoline.
AB - The neighboring 4-aminoquinoline substituents of the bisquinoline (±)-trans-N1,N 2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine dimethanesulfonate salt crystallized in the diequatorial position which is in agreement with quantum chemical calculations. The bisquinoline salt crystallized in the monoclinic C2/c space group with a = 19.328(4) Å, b = 15.618(3) Å, c = 20.382(4) Å, β = 98.84(3)°. The two quinoline nitrogen atoms are protonated by the salt as predicted by calculated electrostatic surface potentials. The -5 kcal/mol isopotential surface of the bisquinoline resembles that of chloroquine, which may explain the potent inhibition of hematin polymerization by both the bisquinoline and chloroquine. The smaller HOMO/LUMO gap of the bisquinoline is consistent with its phototoxicity. The overall conformation, the ability of all nitrogen atoms to participate in hydrogen bonding, and the electrostatic interaction of the quinoline rings in the crystal packing may all aid in the determination of the binding pharmacophore of the bisquinoline.
KW - Antimalarial agent
KW - Bisquinoline
KW - Hematin polymerization
KW - Phototoxicity
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U2 - 10.1023/A:1015602002694
DO - 10.1023/A:1015602002694
M3 - Article
AN - SCOPUS:0036275729
VL - 32
SP - 133
EP - 139
JO - Journal of Crystallographic and Spectroscopic Research
JF - Journal of Crystallographic and Spectroscopic Research
SN - 0277-8068
IS - 5-6
ER -