Bisimidazoacridones: effect of molecular environment on conformation and photophysical properties.
Bisimidazoacridones (BIA) are highly selective antineoplastic and antiviral agents. Ultraviolet-visible spectroscopy and steady-state and time-resolved fluorescence spectroscopy studies were carried out to probe the behavior of BIA in aqueous and nonaqueous (organic solvents, colloid micelles) solutions. Three ranges of fluorescence lifetimes were revealed: approximately 0.2-0.5 ns (presumably reflecting the chromophore-chromophore interaction), approximately 1-5 ns (interpreted as linker-perturbed chromophore decay) and approximately 6-12 ns (nonperturbed chromophore decay). The pre-exponential and steady-state contributions of these components to the decay signal as well as the data on steady-state fluorescence intensities, wavelength maxima and bandwidths showed that the BIA conformations in solution were sensitive to the environment and influenced strongly by their propensity to minimize hydrophobic interactions. In water, the molecules tend to adopt condensed conformations that bring the two imidazoacridone moieties into close proximity (resulting in intramolecular fluorescence energy transfer), while in nonaqueous systems the conformations become more relaxed. The transfer from a polar to more lipophilic environment of macromolecules is suggested to be the main driving force for binding of BIA to biomacromolecules, such as nucleic acids.
Tarasov
S G
SG
Molecular Aspects of Drug Design, MSL, ABL-Basic Research Program, SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. tarasovs@ncifcrf.gov
Casas-Finet
J R
JR
Cholody
W M
WM
Michejda
C J
CJ
D000166:Acridines / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D066298:In Vitro Techniques; D008968:Molecular Conformation; D010777:Photochemistry; D012997:Solvents; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
D000166:Acridines; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D005456:Fluorescent Dyes; D012997:Solvents