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

Jean M. Karle, Apurba K. Bhattacharjee, Jonathan L Vennerstrom

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalJournal of Chemical Crystallography
Volume32
Issue number5-6
DOIs
StatePublished - Dec 1 2002

Fingerprint

Antimalarials
diamines
Hydrates
hydrates
cyclohexane
Salts
Crystal structure
quinoline
Chloroquine
salts
Static Electricity
nitrogen atoms
crystal structure
Nitrogen
electrostatics
Phototoxic Dermatitis
Atoms
Hemin
Hydrogen Bonding
Coulomb interactions

Keywords

  • Antimalarial agent
  • Bisquinoline
  • Hematin polymerization
  • Phototoxicity

ASJC Scopus subject areas

  • Chemistry(all)
  • Condensed Matter Physics

Cite this

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title = "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",
abstract = "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) {\AA}, b = 15.618(3) {\AA}, c = 20.382(4) {\AA}, 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.",
keywords = "Antimalarial agent, Bisquinoline, Hematin polymerization, Phototoxicity",
author = "Karle, {Jean M.} and Bhattacharjee, {Apurba K.} and Vennerstrom, {Jonathan L}",
year = "2002",
month = "12",
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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 - 2002/12/1

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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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