The structure of streptonigrin semiquinone in solution.
Streptonigrin semiquinone (SQ.), a free radical intermediate implicated in the biological functioning of the antitumor antibiotic streptonigrin has been prepared and its structural properties in solution have been characterized. Through the use of electron paramagnetic resonance spectroscopy, the spin densities of the unpaired electron have been determined, indicating that the unpaired electron is largely confined to the quinolinesemiquinone moiety of the antibiotic. Unambiguous assignment of the hyperfine coupling constants was achieved employing isotopically labeled semiquinone radical, INDO molecular orbital calculations, and the study of unsubstituted 5,8-quinolinesemiquinone as a reference system. The assignments point to a negative spin density at the carbon para to the pyridine nitrogen in the radicals derived from both streptonigrin and the unsubstituted 5,8-quinolinequinone. Characterization of the properties of the streptonigrin semiquinone in solution indicate that the radical is stable in solution: it can be conveniently studied in 0.1 M methanolic lithium hydroxide or in aqueous organic solvent mixtures buffered with 0.06 M K3PO4 at pH 12.0. Under these conditions, the semiquinone shows completely reversible spectral changes between -10 to 60 degrees C. Lowering the pH from 12.0 to 7.0 in aqueous DMSO decreases the lifetime of the radical from two weeks to a few minutes. Changes in structural properties of streptonigrin semiquinone in solution have been found to occur mainly due to variation in solvation and freedom of rotation of the amino group. Decreasing the temperature of SQ. solution in methanol from 60 to -10 degrees C leads to an increase in the hyperfine coupling constant to the amino nitrogen from 1.28 to 1.40 G, and those of the two amino protons from 0.73 and 0.73 to 1.02 and 1.11 G respectively, while the other coupling constants change less than 3%. Greater electron spin delocalization onto the -NH2 group has been found throughout the solvent systems examined, yet the temperature at which
Soedjak
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Department of Chemistry, California State University, Northridge 91330, USA.
Hajdu
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Raffetto
J D
JD
Cano
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R
Bales
B L
BL
Prasad
L S
LS
Kispert
L D
LD
D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D004121:Dimethyl Sulfoxide; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D007211:Indoles; D000432:Methanol; D012996:Solutions; D012997:Solvents; D013308:Streptonigrin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D007211:Indoles; D012996:Solutions; D012997:Solvents; D013308:Streptonigrin; C048960:indo-1; D000432:Methanol; D004121:Dimethyl Sulfoxide