Tarasov S G, Casas-Finet J R, Cholody W M, Michejda C J
Molecular Aspects of Drug Design, MSL, ABL-Basic Research Program, SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.
Photochem Photobiol. 1999 Oct;70(4):568-78.
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.
双咪唑吖啶酮（BIA）是高度选择性的抗肿瘤和抗病毒药物。进行了紫外可见光谱、稳态和时间分辨荧光光谱研究，以探究BIA在水性和非水性（有机溶剂、胶体微团）溶液中的行为。揭示了三个荧光寿命范围：约0.2 - 0.5纳秒（可能反映发色团 - 发色团相互作用）、约1 - 5纳秒（解释为连接基扰动的发色团衰减）和约6 - 12纳秒（未扰动的发色团衰减）。这些组分对衰减信号的指数前和稳态贡献以及稳态荧光强度、波长最大值和带宽的数据表明，溶液中BIA的构象对环境敏感，并受到其最小化疏水相互作用倾向的强烈影响。在水中，分子倾向于采取使两个咪唑吖啶酮部分紧密靠近的凝聚构象（导致分子内荧光能量转移），而在非水体系中构象变得更加松弛。大分子从极性环境向更亲脂性环境的转变被认为是BIA与生物大分子如核酸结合的主要驱动力。
