Veselkov A N, Evstigneev M P, Rozvadovskaia A O, Mukhina Iu V, Davies D B
Bioorg Khim. 2005 Sep-Oct;31(5):503-10. doi: 10.1007/s11171-005-0062-0.
A heteroassociation of antitumor antibiotic novatrone (NOV) and flavin mononucleotide (FMN) in aqueous solution was studied by one- and two-dimentional 1H NMR spectroscopy (500 MHz) to elucidate the molecular mechanism of the possible combined action of the antibiotic and vitamin. The equilibrium reaction constants, induced proton chemical shifts, and the thermodynamic parameters (deltaH and deltaS) of the NOV and FMN heteroassociation were determined from the concentration and temperature dependences of proton chemical shifts of the aromatic molecules. The most favorable structure of the 1 : 1 NOV-FMN complex was determined by both the method of molecular mechanics (X-PLOR software) and the induced proton chemical shifts of the molecules. An analysis of the results suggests that the NOV-FMN intermolecular complexes are mainly stabilized by stacking interactions of their aromatic chromophores. An additional stabilization is possible due to intermolecular hydrogen bonds. It was concluded that the aromatic molecules of vitamins, in particular, FMN, can form energetically favorable heterocomplexes with aromatic antitumor antibiotics in aqueous solutions, which could result in a modulation of their medical and biological action.
通过一维和二维1H NMR光谱（500 MHz）研究了抗肿瘤抗生素新制癌菌素（NOV）与黄素单核苷酸（FMN）在水溶液中的异质缔合，以阐明抗生素与维生素可能的联合作用的分子机制。根据芳香族分子质子化学位移的浓度和温度依赖性，确定了NOV与FMN异质缔合的平衡反应常数、诱导质子化学位移和热力学参数（ΔH和ΔS）。通过分子力学方法（X-PLOR软件）和分子的诱导质子化学位移，确定了1:1 NOV-FMN复合物的最有利结构。结果分析表明，NOV-FMN分子间复合物主要通过其芳香发色团的堆积相互作用而稳定。分子间氢键可能导致额外的稳定作用。得出的结论是，维生素的芳香族分子，特别是FMN，在水溶液中可以与芳香族抗肿瘤抗生素形成能量上有利的异质复合物，这可能导致它们的医学和生物学作用的调节。
