β-环糊精与巴西木素的主-客体体系研究
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摘要
制备了β-环糊精与巴西木素的主-客体包合物,并对其包合行为和性能进行研究.采用紫外可见光谱滴定法确定了包合物的包合比和稳定常数;利用X射线粉末衍射(XRD)、量热分析(DSC)和热重分析(TG)对包合物进行了表征;运用量子化学计算和分子对接模拟研究了主-客体的包合机制.结果显示,β-环糊精与巴西木素的包合量比为1∶1;包合物形成后,巴西木素的热稳定性得到了显著改善;量子化学计算表明,巴西木素以单羟基苯环一侧进入β-环糊精空腔时结合能最低,并以氢键作用形成包合物;分子对接模拟表明,结合能最低时优化的构象为巴西木素以单羟基一侧从大口端进入β-环糊精空腔,与量子化学计算结果一致.
The host-guest inclusion complex of β-cyclodextrin and brazilin was prepared and its inclusion behavior and properties were explored. The inclusion ratio and stability constant of the inclusion complex were determined with UV-visible spectroscopy. The inclusion complex was characterized by means of XRD, DSC and TG. The inclusion mechanism of host-guest was studied by quantum chemical calculation and molecular docking simulation. The results showed that inclusion ratio of β-cyclodextrin and brazilin inclusion complex was 1:1. After the formation of the inclusion complex, the thermal stability was improved. Quantum chemical calculations showed that brazilin has the lowest binding energy when it entered the β-cyclodextrin cavity by the side of monohydroxy benzene ring, and formed complex by hydrogen bonding. The molecular docking simulation showed that the optimized conformation of lowest binding energy is brazilian from the large end by the monohydroxy side enters the β-cyclodextrin cavity, which is consistent with the quantum chemical calculation results.
The host-guest inclusion complex of β-cyclodextrin and brazilin was prepared and its inclusion behavior and properties were explored. The inclusion ratio and stability constant of the inclusion complex were determined with UV-visible spectroscopy. The inclusion complex was characterized by means of XRD, DSC and TG. The inclusion mechanism of host-guest was studied by quantum chemical calculation and molecular docking simulation. The results showed that inclusion ratio of β-cyclodextrin and brazilin inclusion complex was 1:1. After the formation of the inclusion complex, the thermal stability was improved. Quantum chemical calculations showed that brazilin has the lowest binding energy when it entered the β-cyclodextrin cavity by the side of monohydroxy benzene ring, and formed complex by hydrogen bonding. The molecular docking simulation showed that the optimized conformation of lowest binding energy is brazilian from the large end by the monohydroxy side enters the β-cyclodextrin cavity, which is consistent with the quantum chemical calculation results.
引文
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[19]王淑慧,杨云汉,常清,等.长春胺/β-环糊精衍生物包合物的制备及水溶性研究[J].云南民族大学学报:自然科学版,2017,26(3):179-184.DOI:12.3969/j.issn.1672-8513.2017.03.09.Wang S H,Yang Y H,Chang Q,et al.A study of the preparation and water solubility of the inclusion compounds of vincamine withβ-cyclodextrin derivatives[J].Journal of Yunnan Minzu University:Natural Sciences Edition,2017,26(3):179-184.
[20]Siva S,Kothai N S,Rajendiran N.Spectral and molecular modeling investigations of supramolecular complexes of mefenamic acid and aceclofenac withα-andβ-cyclodextrin[J].Spectrochimica Acta Part A,2017,174:349-362.DOI:10.1016/j.saa.2014.12.002.
[21]Rajendiran N,Siva S.Inclusion complex of sulfadimethoxine with cyclodextrins:Preparation and characterization[J].Carbohydrate Polymers,2014,101(101):828-836.DOI:10.1016/j.carbpol.2013.10.016.
[22]Abdelmalek L,Fatiha M,Leila N,et al.Computational study of inclusion complex formation between carvacrol andβ-cyclodextrin in vacuum and in water:Charge transfer,electronic transitions and NBO analysis[J].Journal of Molecular Liquids,2016,224:62-71.DOI:10.1016/j.molliq.2016.09.053.
[23]Frisch M J,Trucks G W,Schlegel H B,et al.Gaussian03,revision C.02[Z].Wallingford,CT:Gaussian,Inc.;2004.
[24]Morris G M,Huey R,Lindstrom W,et al.AutoDock4and AutoDockTools4:Automated docking with selective receptor flexibility[J].Journal of Computational Chemistry,2010,30(16):2 785-2 791.DOI:10.1002/jcc.21256.
[25]Steiner T,Saenger W.Geometry of oxygen hydrogen bonds in carbohydrate crystal structures.Analysis of neutron diffraction data[J].Journal of the American Chemical Society,1992,114(26):10 146-10 154.DOI:10.1021/ja00052a009.
[26]Gejji S P,Taurian O E,Lunell S.Theoretical study of the short asymmetric[O.H.O]hydrogen bond in solid potassium hydrogen diformate,including electron correlation[J].Journal of Physical Chemistry,1990,94 (11):4 449-4 452.DOI:10.1021/j100374a018.
[27]Nakamoto K,Margoshes M,Rundle R E.Stretching frequencies as a function of distances in hydrogen bonds[J].Journal of the American Chemical Society,1955,77(24):6 480-6 486.DOI:10.1021/ja01629a013.
[2]Puchtler H,Meloan S N,Waldrop,F S.Application of current chemical concepts to metal-hematein and brazilein stains[J].Histochemistry,1986,85(5):353-364 .DOI:10.1007/BF00982665.
[3]Yang L J,Chang Q,Zhou S Y,et al.Host-guest interaction between brazilin and hydroxypropyl-β-cyclodextrin:Preparation,Inclusion mode,molecular modelling and characterization[J].Dyes and Pigments,2018,150:193-201.DOI:10.1016/j.dyepig.2017.12.010.
[4]Moon C K,Lee S H,Lee M O,et al.Effects of Brazilin on glucose oxidation,lipogenesis and therein involved enzymes in adipose tissues from diabetic KK-mice[J].Life Sciences,1993,53(16):1 291-1 297.DOI:10.1016/0024-3205(93)90574-M.
[5]Moon C K,Park K S,Kim S G,et al.Brazilin protects cultured rat hepatocytes from BrCCl3-induced toxicity[J].Drug and Chemical Toxicology,1992,15(1):81-91.DOI:10.3109/01480549209035174.
[6]Mok M S,Jeon S D,Yang K M,et al.Effects of Brazilin on induction of immunological tolerance by sheep red blood cells in C57BL/6 female mice[J].Archives of Pharmacal Research,1998,21(6):769-773.DOI:10.1007/BF02976774.
[7]Kim S G,Kim Y M,Khil L Y,et al.Brazilin inhibits activities of protein kinase C and insulin receptor serine kinase in rat liver[J].Archives of Pharmacal Research,1998,21(2):140-146.DOI:10.1007/BF02974018.
[8]Hwang G S,Kim J Y,Chang T S,et al.Effects of Brazilin on the phospholipase A2 activity and changes of intracellular free calcium concentration in rat platelets[J].Archives of Pharmacal Research,1998,21(6):774-778.DOI:10.1007/BF02976775.
[9]Xu H X,Lee S F.The antibacterial principle of Caesalpina sappan[J].Phytotherapy Research,2004,18(8):647-651.DOI:10.1002/(ISSN)1099-1573.
[10]Hiking H,Taguchi T,Fujmura H,et al.Antiinflammatory principles of Caesalpinia sappan wood and of Haematoxylon campechianum wood[J].Planta Medica,1977,31(3):214-220.DOI:10.1055/s-0028-1097516.
[11]Kim B,Kim S H,Jeong S J,et al.Brazilin induces apoptosis and G2/M arrest via inactivation of histone deacetylase in multiple myeloma U266 cells[J].Journal of Agricultural and Food Chemistry,2012,60(39):9 882-9 889.DOI:10.1021/jf302527p.
[12]Hu C M,Kang J J,Chen C L,et al.Induction of vasorelaxation through activation of nitric oxide synthase in endothelial cells by brazilin[J].European Journal of Pharmacology,2003,468(1):37-45.DOI:10.1016/S0014-2999(03)01639-X.
[13]俞强.巴西苏木素类化合物在制备抗肿瘤药物中的用途.CN101045046[P].2007.Yu Q.Use of Brazilian hematoxylin compounds in the preparation of antitumor drugs.CN101045046[P].2007.
[14]Lee Y R,Noh E M,Han J H,et al.Brazilin inhibits UVB-induced MMP-1/3 expressions and secretions by suppressing the NF-κB pathway in human dermal fibroblasts[J].European Journal of Pharmacology,2012,674(2/3):80-86.DOI:10.1016/j.ejphar.2011.10.016.
[15]Bae I K,Min H Y,Han A R,et al.Suppression of lipopolysaccharide-induced expression of inducible nitric oxide synthase by brazilin in RAW 264.7 macrophage cells[J].European Journal of Pharmacology,2005,513(3):237-242.DOI:10.1016/j.ejphar.2005.03.011.
[16]赵芳,杨云汉,赵雪秋,等.延胡索乙素与β-环糊精及其衍生物的包合行为研究[J].中草药,2018,49(15):3 609-3 618.DOI:10.7501/j.issn.0253-2670.2018.15.020.Zhao F,Yang Y H,Zhao X Q,et al.Study on the inclusion behavior and properties of tetrahydropalmatine withβ-cyclodextrin and its derivatives[J].Chinese Traditional an Herbal Drugs,2018,49(15):3 609-3 618.
[17]赵雪秋,王淑慧,周树娅,等.紫外光谱法研究鬼臼毒素与环糊精及其衍生物的包合行为[J].云南大学学报:自然科学版,2016,38(4):645-651.DOI:10.7540/j.ynu.20150704.Zhao X Q,Wang S Y,Zhou S H,et al.Studies on the inclusion behavior of podophyllotoxin with cyclodextrin and its derivatives by ultraviolet spectroscopy[J].Journal of Yunnan University:Natural Sciences Edition,2016,38(4):645-651.
[18]Ma S X,Chen W,Yang X D,et al.Alpinetin/hydroxypropyl-β-cyclodextrin host-guest system:preparation,characterization,inclusion mode,solubilization and stability[J].Journal of Pharmaceutical&Biomedical Analysis,2011,84(4):1 321-1 328.DOI:10.1016/j.jpba.2012.04.038.
[19]王淑慧,杨云汉,常清,等.长春胺/β-环糊精衍生物包合物的制备及水溶性研究[J].云南民族大学学报:自然科学版,2017,26(3):179-184.DOI:12.3969/j.issn.1672-8513.2017.03.09.Wang S H,Yang Y H,Chang Q,et al.A study of the preparation and water solubility of the inclusion compounds of vincamine withβ-cyclodextrin derivatives[J].Journal of Yunnan Minzu University:Natural Sciences Edition,2017,26(3):179-184.
[20]Siva S,Kothai N S,Rajendiran N.Spectral and molecular modeling investigations of supramolecular complexes of mefenamic acid and aceclofenac withα-andβ-cyclodextrin[J].Spectrochimica Acta Part A,2017,174:349-362.DOI:10.1016/j.saa.2014.12.002.
[21]Rajendiran N,Siva S.Inclusion complex of sulfadimethoxine with cyclodextrins:Preparation and characterization[J].Carbohydrate Polymers,2014,101(101):828-836.DOI:10.1016/j.carbpol.2013.10.016.
[22]Abdelmalek L,Fatiha M,Leila N,et al.Computational study of inclusion complex formation between carvacrol andβ-cyclodextrin in vacuum and in water:Charge transfer,electronic transitions and NBO analysis[J].Journal of Molecular Liquids,2016,224:62-71.DOI:10.1016/j.molliq.2016.09.053.
[23]Frisch M J,Trucks G W,Schlegel H B,et al.Gaussian03,revision C.02[Z].Wallingford,CT:Gaussian,Inc.;2004.
[24]Morris G M,Huey R,Lindstrom W,et al.AutoDock4and AutoDockTools4:Automated docking with selective receptor flexibility[J].Journal of Computational Chemistry,2010,30(16):2 785-2 791.DOI:10.1002/jcc.21256.
[25]Steiner T,Saenger W.Geometry of oxygen hydrogen bonds in carbohydrate crystal structures.Analysis of neutron diffraction data[J].Journal of the American Chemical Society,1992,114(26):10 146-10 154.DOI:10.1021/ja00052a009.
[26]Gejji S P,Taurian O E,Lunell S.Theoretical study of the short asymmetric[O.H.O]hydrogen bond in solid potassium hydrogen diformate,including electron correlation[J].Journal of Physical Chemistry,1990,94 (11):4 449-4 452.DOI:10.1021/j100374a018.
[27]Nakamoto K,Margoshes M,Rundle R E.Stretching frequencies as a function of distances in hydrogen bonds[J].Journal of the American Chemical Society,1955,77(24):6 480-6 486.DOI:10.1021/ja01629a013.