Solvatochromism and time-resolved fluorescence of the antitumor agent mitoxantrone and its analogues in solution and in DNA

Su Lin, Walter S. Struve

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The electronic spectroscopy and fluorescence kinetics of 1,4-dihydroxy-5,8-[2-[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione (mitoxantrone) and three closely related analogues have been studied in several solvents. The small solvatochromic blue shifts of their visible charge-transfer absorption bands in protic solvents are dominated by interactions with a solvent H-bonding donor, rather than by dipole-dielectric solute-solvent electrostatics. These interactions are unrelated to the phenolic hydroxy groups or the distal N atoms on the side chains but must be localized to the carbonyl groups. The fluorescence decays of all four anthraquinones are controlled by subnanosecond nonradiative relaxation in all solvents studied. At least two decay mechanisms contribute to the observed fluorescence kinetics in solution: (a) subnanosecond internal conversion that is accelerated relative to that in 1,4-diaminoanthraquinone by the presence of the flexible 1,4-side chains in mitoxantrone and its analogues; (b) an additional decay mode that is accentuated in H-bonding solvents. A substantial normal isotope effect occurs in the fluorescence lifetimes of mitoxantrone in perdeuterated water and methanol but not in aprotic solvents. When bound to double-stranded calf thymus DNA, mitoxantrone displays a fluorescence lifetime similar to that in aprotic solvents, suggesting that H-bonding interactions with water are precluded by chromophore intercalation. DNA-bound ametantrone exhibits a lifetime longer than that in either H-bonding or aprotic solvents, indicating that immobilization of the side chains through binding of the distal N atoms to the DNA backbone may influence the decay kinetics. This technique therefore shows potential for elucidating the DNA binding modes for a large class of intercalative drugs.

Original languageEnglish (US)
Pages (from-to)2251-2256
Number of pages6
JournalJournal of physical chemistry
Volume95
Issue number6
DOIs
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Engineering(all)
  • Physical and Theoretical Chemistry

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