Conformational and electrostatic properties of naphthazarin, juglone, and naphthoquinone: an ab initio theoretical study.
Conformational and electrostatic properties of naphthazarin, juglone, and naphthoquinone: an ab initio theoretical study.
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萘扎林、胡桃醌和萘醌的构象和静电性质：从头算理论研究。
作者：
A. Bhattacharjee;S. S. Pundlik;S. Gadre
萘扎林、胡桃醌和萘醌的构象特征已通过从头计算 (Hartree-Fock) SCF 计算在 3-21G 水平进行了检查。结果表明，所有三个分子均具有平面结构，而萘沙林和胡桃醌的内部氢键结构是它们的首选构象。优化后的结构特征与其晶体几何形状基本相同。使用从头开始 SCF 方法从 3-21G 到 6-31G 水平进行分子静电势 (MEP) 计算，以可视化其三维药效团模式和形貌。结果表明，两个因素——（i）羟基和醌类氧周围负电势的深度、范围和相对位置，以及（ii）由于分子酚部分中羟基的存在和方向而导致分子平面上负电势的逐渐损失——对于化合物与其受体的识别相互作用至关重要。水溶剂化似乎对分子的 MEP 曲线有显着影响。尽管由于水溶剂化，所有化合物（包括不同构象异构体）的固有亲核性都增加，但所有化合物的固有亲电性均显着下降。看来这些化合物和构象异构体中氢的酸性性质随着从气相到水相的位置移动而急剧降低。这些观察结果可能有助于解释细胞毒性抗生素蒽环类抗生素的作用机制。
Conformational features of naphthazarin, juglone, and naphthoquinone have been examined via ab initio (Hartree-Fock) SCF calculations at 3-21G level. The results suggest a planar structure for all the three molecules and internally hydrogen-bonded structure for naphthazarin and juglone to be their preferred conformation. The optimized structural features are essentially the same as their crystal geometries. Molecular electrostatic potential (MEP) calculations using ab initio SCF methods ranging from 3-21G to 6-31G levels have been performed to visualize their three-dimensional pharmacophoric patterns and topography. The results indicate that two factors--(i) the depth, extent, and relative location of negative potential around hydroxyl and quinonoid oxygens, and (ii) a gradual loss of negative potential over the molecular plane due to the presence and orientation of the hydroxyl groups in the phenolic part of the molecules--are crucial for recognition interaction of the compounds with their receptors. Aqueous solvation seems to have significant influence on the MEP profiles of the molecules. Although intrinsic nucleophilicity increases for all the compounds, including the different conformers, due to aqueous solvation, the intrinsic electrophilicity shows remarkable decrease for all. It appears that the acidic nature of the hydrogens in these compounds and conformers decreases sharply along with shifts of positions while going from the gas phase to the aqueous phase. These observations may help to explain the mechanism of action(s) of the anthracyclin family of cytotoxic antibiotics.
DOI：
--
发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
K. Davies;J. Doroshow
通讯作者：
K. Davies;J. Doroshow