Cruz Állefe Barbosa, Ciribelli Nicolas Nascimento, Cunha Camila Luiza, Nascimento Isabele Rodrigues, Holzbach Juliana Cristina, Pereira Douglas Henrique
Collegiate of Exact Sciences and Biotechnology, Universidade Federal do Tocantins, 77 402-970, Gurupi, Tocantins, Brazil.
Institute of Chemistry, Universidade Estadual Paulista (Unesp), Araraquara, SP, 14800-060, Brazil.
J Mol Model. 2023 Feb 25;29(3):77. doi: 10.1007/s00894-023-05482-y.
In this work the diastereoisomers (2S) and (2R)-naringenin-6-C-β-D-glucopyroside, isolated for the first time from Clitoria guianensis, were studied using the density functional theory. The frontier molecular orbitals and structural properties showed that the diastereoisomers exhibit the same energy gap 166.61 kcal mol and structural properties different, where in the S diastereoisomer, the bond length between the chiral carbon and the phenolic group is greater (difference of 0.0126 Å). The HPLC data showed that the retention time of the S-diastereoisomer (16.7 min) is shorter than that of R, suggesting that the S compound is more polar than R. The HPLC results corroborates with the molecular electrostatic potential which showed that in the S configuration, the electronegative density was more intense overall, particularly in the glucose molecule. The reactivity indices showed that the diastereoisomers are good electrophiles and reactive species. Finally, the absolute configuration of the diastereoisomers were determined using electronic circular dichroism (ECD) spectroscopy and the theoretical spectra were similar to the experimental. METHODS : All calculations of Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) were performed using the program Gaussian 09 and the structures of the diastereoisomers were generated and analyzed using the GaussView program. The optimization and vibrational frequency calculations were performed using the functional CAM-B3LYP and 6-311 + + G(2d,2p) basis set. Conformational searches were performed for R configuration, by molecular mechanics using the MM + , MMFF, and OPLS05 force fields; the entire molecular mechanics simulation was performed using the Maestro/MacroModel software. The calculations for the simulations of the ECD spectra were performed for the eight lowest energy conformers obtained in the geometric optimization step, and the TDDFT at the CAM-B3LYP/6-311 + + G(2d,2p) theory level used. The effects of methanol and chloroform were calculated using the SMD implicit solvent model.
在本研究中，首次从圭亚那蝶豆中分离出的非对映异构体（2S）和（2R）-柚皮素-6-C-β-D-吡喃葡萄糖苷，使用密度泛函理论进行了研究。前沿分子轨道和结构性质表明，这些非对映异构体具有相同的能隙166.61千卡/摩尔，但结构性质不同，其中在S非对映异构体中，手性碳与酚羟基之间的键长更长（相差0.0126埃）。高效液相色谱数据表明，S-非对映异构体的保留时间（16.7分钟）比R-非对映异构体短，这表明S化合物比R化合物极性更强。高效液相色谱结果与分子静电势结果相符，分子静电势结果表明，在S构型中，整体负电密度更强，尤其是在葡萄糖分子中。反应性指数表明，这些非对映异构体是良好的亲电试剂和反应物种。最后，使用电子圆二色光谱（ECD）确定了非对映异构体的绝对构型，理论光谱与实验光谱相似。方法：所有密度泛函理论（DFT）和含时密度泛函理论（TDDFT）计算均使用Gaussian 09程序进行，非对映异构体的结构使用GaussView程序生成和分析。优化和振动频率计算使用CAM-B3LYP泛函和6-311++G(2d,2p)基组。通过使用MM+、MMFF和OPLS05力场的分子力学对R构型进行构象搜索；整个分子力学模拟使用Maestro/MacroModel软件进行。对几何优化步骤中获得的八个最低能量构象异构体进行ECD光谱模拟计算，并使用CAM-B3LYP/6-311++G(2d,2p)理论水平的TDDFT。使用SMD隐式溶剂模型计算甲醇和氯仿的影响。
