Rozvadovskaia A O, Evstigneev V P, Davies D B, Evstigneev M P
Biofizika. 2006 Mar-Apr;51(2):214-24.
The interaction between anthracycline antitumor antibiotics daunomycin and novatrone and the vitamin nicotinamide has been investigated by one- and two-dimensional 1H NMR spectroscopy (500 MHz). Due to significant differences in structures of the chromophores of interacting molecules, a two-site heteroassociation model has been developed, allowing the arrangement of one and two nicotinamide molecules on the chromophore of the antibiotic. The equilibrium association constant, thermodynamical parameters (deltaH, deltaS) of the heteroassociation of nicotinamide with daunomycin and novatrone and the induced proton chemical shifts in the heterocomplexes have been determined from the concentration and temperature dependences of proton chemical shifts of interacting molecules. The most favorable structures of 1:1 nicotinamide--daunomycin and nicotinamide-novatrone heteroassociation complexes have been determined using both the molecular mechanics methods (X-PLOR software) and the calculated values of induced proton chemical shifts. Analysis of the results obtained allows one to conclude that two nicotinamide molecules cannot simultaneously bind on one side of the chromophore of antibiotic. Heterocomplexes of the vitamin with the antibiotics with a stoichiometry 1:1 are mainly stabilized by the stacking of aromatic chromophores.
利用一维和二维氢核磁共振波谱（500兆赫）研究了蒽环类抗肿瘤抗生素柔红霉素和去甲柔红霉素与维生素烟酰胺之间的相互作用。由于相互作用分子发色团结构存在显著差异，已建立了一个双位点异质缔合模型，该模型可确定一个和两个烟酰胺分子在抗生素发色团上的排列方式。根据相互作用分子质子化学位移的浓度和温度依赖性，已确定了烟酰胺与柔红霉素和去甲柔红霉素异质缔合的平衡缔合常数、热力学参数（ΔH、ΔS）以及异质复合物中诱导的质子化学位移。使用分子力学方法（X-PLOR软件）和诱导质子化学位移的计算值，已确定了1:1烟酰胺 - 柔红霉素和烟酰胺 - 去甲柔红霉素异质缔合复合物的最有利结构。对所得结果的分析表明，两个烟酰胺分子不能同时结合在抗生素发色团的一侧。化学计量比为1:1的维生素与抗生素的异质复合物主要通过芳香发色团的堆积而稳定。
