Empirical,thermodynamic and quantum-chemical investigations of inclusion complexation between flavanones and (2-hydroxypropyl)-cyclodextrins

The inclusion complexation of (2-hydroxypropyl)-cyclodextrins with flavanones was investigated by phase solubility measurements, as well as thermodynamic and quantum chemical methods. Inclusion complexes were formed between (2-hydroxypropyl)-α-cyclodextrin (HP-α-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD) and β-cyclodextrin (β-CD) and four flavanones (naringenin, naringin, hesperetin and dihydromyricetin) in aqueous solutions and their phase solubility was determined. For all the flavanones, the stability constants of their complexes formed with different CDs followed the rank order: HP-β-CD (MW 1540) > HP-β-CD (MW 1460) > HP-β-CD (MW 1380) > β-CD > HP-γ-CD > HP-α-CD. Experimental results and quantum chemical calculations showed that the ability of flavanones to form inclusion complex with (2-hydroxypropyl)-cyclodextrins was determined by both the steric effect and hydrophobicity of the flavanones. For flavanones that have similar molecular volumes, the hydrophobicity of the molecule was the main determining factor of its ability to form inclusion complexes with HP-β-CD, and the hydrophobicity parameter Log P is highly correlated with the stability constant of the complexes. Results of thermodynamic study demonstrated that hydrophobic interaction is the main driving force for the formation process of the flavanone–CD inclusion complexes. Quantum chemical analysis of the most active hydroxyl groups and HOMO (the highest occupied molecular orbital) showed that the B ring of the flavanones was most likely involved in hydrogen bonding with the side groups in the cavity of the CDs, through which the inclusion complex was stabilised.     

Physicochemical characterisation of the supramolecular structure of luteolin/cyclodextrin inclusion complex

The formation of supramolecular inclusion complexes between luteolin and five cyclodextrins namely β-cyclodextrin (β-CD), methyl-β-cyclodextrin (M-β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and glucosyl-β-cyclodextrin (G-β-CD) was investigated. Results from phase-solubility studies showed that luteolin formed 1:1 stoichiometric inclusion complexes with these cyclodextrins with the G-β-CD complex displaying the greatest stability constant. The supramolecular structure of the luteolin/G-β-CD complex was investigated by ultraviolet–visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Results showed clearly the formation of a supramolecular complex in which the guest molecule, luteolin, was entrapped inside the cavity of the host, G-β-CD. The close association between luteolin and G-β-CD resulted in changes in some of the characteristic spectral, phase transitional and morphological properties of luteolin. Furthermore, molecular docking study showed that the complex was formed with the B ring of luteolin inserted into the cavity of G-β-CD.     

青藤碱- 环糊精包合工艺的优化及包合常数测定

目的：考察青藤碱与环糊精形成包合物的最佳条件,测定青藤碱与不同环糊精的包合常数并进行体外释放研究。方法：通过单因素及正交试验确定青藤碱与不同环糊精形成包合物的最佳条件,并在此条件下利用相溶解度法测定青藤碱与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数,对包合物进行体外释放试验研究。结果：青藤碱与不同环糊精形成包合物的最佳条件为物质的量的1:1、包合温度50℃、包合反应3h、包合反应时溶液pH7,青藤碱与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数分别为501.1、150.0、600.3L/mol。结论：青藤碱与环糊精可以形成1:1型稳定的包合物,以环糊精为载体制备的不同青藤碱-环糊精包合物相对于青藤碱具有明显的缓释作用。     

环糊精对青蒿素的包合工艺研究

通过单因素及正交试验确定青蒿素与3种环糊精形成包合物的最佳条件,在此条件下利用相溶解度法测定青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数并计算包合反应前后的吉布斯自由能。结果表明：青蒿素与环糊精形成包合物的最佳条件为配比1:1(mol/mol)、包合温度40℃、包合时间5h、包合反应时溶液pH7,青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数分别为80.06、58.68、116.96L/mol,反应前后的吉布斯自由能变化分别为－11.76、－10.93、－12.78kJ/mol。表明青蒿素与环糊精可以形成1:1型稳定的包合物,环糊精可以增大青蒿素的溶解度。     

四种β-环糊精制备鞣花酸包合物的抗氧化性研究

利用鞣花酸（EA）与β-环糊精（β-CD）、羟丙基-β-环糊精（HP-β-CD）、二甲基-β-环糊精（DM-β-CD）、磺丁基-β-环糊精（SBE-β-CD）制备鞣花酸包合物,并使用高效液相色谱测定鞣花酸包合物的包合率,然后采用傅里叶红外光谱、X-射线衍射、扫描电镜对包合物进行表征,同时通过自由基清除能力评价鞣花酸包合物的抗氧化性。结果表明,EA/β-CD、EA/HP-β-CD、EA/DM-β-CD、EA/SBE-β-CD包合物的表观溶解度分别为0.037 3 mg/mL、0.123 2 mg/mL、0.093 8 mg/mL、0.095 6 mg/mL,包合率分别为82.58%、89.80%、87.42%、84.64%。鞣花酸与四种鞣花酸包合物清除DPPH自由基的半数清除率（EC50）值分别为6.47 μg/mL、6.31 μg/mL、3.45 μg/mL、3.63 μg/mL、3.92 μg/mL;清除ABTS自由基的EC50值分别为13.53 μg/mL、12.11 μg/mL、7.00 μg/mL、7.66 μg/mL、7.77 μg/mL;清除羟基自由基的EC50值分别为0.133 6 μg/mL、0.136 3 μg/mL、0.108 2 μg/mL、0.108 3 μg/mL、0.105 5 μg/mL;清除超氧阴离子自由基的EC50值分别为89.41 μg/mL、59.71 μg/mL、55.20 μg/mL、58.32 μg/mL、55.29 μg/mL。结果表明包合技术可以提高鞣花酸的溶解度与抗氧化能力。     

Preparation and properties of phytosterols with hydroxypropyl β-cyclodextrin inclusion complexes

In order to enhance the solubility and bioavailability of phytosterols (PS), cyclodextrin–PS (CD–PS) inclusion complexes were prepared and the properties of PS-β-cyclodextrin (PS-β-CD) and the inclusion mechanism of its derivative hydroxypropyl β-cyclodextrin (PS-HP-β-CD) in solution were also evaluated. The effects of crucial parameters on cyclodextrin–sterol inclusion efficiency were optimized, including solvent type, β-CD/PS molar ratio, temperature, PS content and reaction time; 92–98?% inclusion efficiency was achieved under the conditions of HP-β-CD/PS ratio 3:1–4:1, PS concentration 15–20?mM, temperature 50–55?°C, reaction time 12?h. For β-CD host, butanol was a good solvent for PS inclusion reaction. The properties of CD–PS inclusion complexes were characterized by differential scanning calorimetric, scanning electron microscopy, UV–Vis scanning spectrophotometer (UV–Vis) and fourier transform infrared spectroscopy (FT-IR), which demonstrated that there are intermolecular hydrogen bonds between PS and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. To clarify the mechanism of the increase in the solubility and bioactivity of HP-β-CD–PS inclusion complexes, the structure of CD as well as the interaction of the HP-β-CD–PS inclusion formation was elucidated. The conclusions indicated that PS-HP-β-CD showed higher water solubility with greater solubilizing and complexing capabilities than PS-β-CD and PS itself.     

茶多酚-β-环糊精包合物对羊肚冷藏期间肌原纤维蛋白氧化的影响

本实验将茶多酚（tea polyphenol,TP）与2-羟丙基-β-环糊精（2-hydroxypropyl-β-cyclodextrin,HP-β-CD）通过共沉积法制备出不同物质的量之比（n（HP-β-CD）∶n（TP）＝1∶0.5、1∶1和1∶2）的包合物,利用傅里叶变换红外光谱、热重分析和扫描电子显微镜对TP及其包合物的结构进行分析,研究表明,HP-β-CD/TP包合物被成功制备,且物质的量之比为1∶2的包合物DPPH自由基清除能力最好。此外,以新鲜绵羊羊肚为研究对象,选取0（对照）、0.1、0.5 mg/mL和1.0 mg/mL HP-β-CD/TP包合物（1∶2）对羊肚进行浸泡处理,于4 ℃条件下贮藏,研究7 d内其对肌原纤维蛋白（myofibrillar protein,MP）氧化的影响。结果显示,包合物处理能显著抑制羊肚中MP羰基含量、表面疏水性、浊度的上升和总巯基含量、游离氨基质量分数、溶解度的下降（P＜0.05）,十二烷基硫酸钠-聚丙烯酰胺凝胶电泳结果也表明HP-β-CD/TP包合物对MP的降解有一定的抑制作用,且包合物质量浓度越高,效果越明显,1 mg/mL处理效果最佳。因此,HP-β-CD/TP包合物与MP的相互作用可以有效延缓其变性和降解程度,抑制羊肚功能性质的劣变。     

Physicochemical properties and mechanism of solubilised neohesperidin system based on inclusion complex of hydroxypropyl-β-cyclodextrin

A solvent method was used to prepare the inclusion compound of neohesperidin (NH) and hydroxypropyl-β-cyclodextrin (HP-β-CD) to improve the water solubility and thermal stability of NH. The physical and chemical properties and supramolecular structure of the inclusion complex were investigated by UV–vis spectroscopy, FTIR, SEM, TG-DTG, PXRD, NMR and molecular docking techniques. The results showed that the C-ring of NH was embedded in the cavity of HP-β-CD to form an inclusion complex. The phase has changed significantly, NH is completely dispersed in HP-β-CD in an amorphous state, and the two are combined in the form of non-covalent bonds such as hydrogen bonds or van der Waals forces. Through inclusion of HP-β-CD, the solubility of NH in water at 37 °C increased from 161.81 μg ml⁻¹ to 1927.12 μg ml⁻¹, and its stability was also significantly improved.     

Physical and light oxidative properties of eugenol encapsulated by molecular inclusion and emulsion–diffusion method

The aim of this research was to study the encapsulation of eugenol as a volatile active substance by inclusion with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), and by an emulsion–diffusion method with polycaprolactone (PCL). After formulation of each type of complex, size, zeta-potential, and thermal properties were determined by using Nanosizer®, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Overall, the mean sizes of encapsulated eugenol were the same at 320 nm. However, the size distribution of the β-CD and 2-HP-β-CD inclusion complex was poly-disperse as compared with eugenol encapsulated with polycaprolactone (PCL). TGA analysis revealed the encapsulation efficiency of PCL, β-CD eugenol and 2-HP-β-CD eugenol inclusion complexes were 100%, 90.9% and 89.1%, respectively. The study of oxidation stability revealed the emulsion–diffusion method was more efficient than the molecular inclusion method resulting from high stability depending on storage time. On the other hand, β-CD was more effective than 2-HP-β-CD for eugenol encapsulation. It is supposed that the side chain of hydroxypropyl group of 2-HP-β-CD might interrupt eugenol inclusion within the cavity of 2-HP-β-CD molecule. From our experiments, we concluded that the emulsion–diffusion method was the most effective for eugenol encapsulation to protect from light oxidation during storage time due to their complete wrapping of eugenol by PCL layer from TEM analysis.     

Preparation,characterisation and activity of the inclusion complex of paeonol with β-cyclodextrin

The inclusion complex of β-cyclodextrin (β-CD) and paeonol (2′-hydroxy-4′-methoxyacetophenone, PAE) was synthesised and characterised by thermal gravimetric analysis (TGA) and two-dimensional rotating frame spectroscopy (2D ROESY). The antioxidant activity and tyrosinase inhibition activity were also studied. The TGA results indicated that the thermal stability of PAE was improved when it was included with β-CD. Based on the 2D ROESY analysis, an inclusion structure of the PAE–β-CD complex was proposed, in which PAE penetrated β-CD in a tilted manner due to the interaction of intermolecular hydrogen bonds between PAE and β-CD. The complex of PAE with β-CD increased the antioxidant activity and tyrosinase-inhibiting activity of PAE.     

β-酸-番茄红素/HP-β-CD复合包合物的制备及稳定性

研磨法制备β-酸-番茄红素/羟丙基-β-环糊精(hydroxypropyl-β-cyclodextrin,HP-β-CD)复合包合物,采用紫外-可见光谱、傅里叶变换红外光谱、X射线粉末衍射、扫描电镜及核磁共振等方法对其结构进行表征,评价该复合包合物溶液中β-酸和番茄红素在光、热和酸碱性环境下的稳定性.结果表明,成功制备...     

黄曲霉毒素G1与β-环糊精及其衍生物超分子体系的荧光光谱研究

研究β-环糊精及其衍生物对AFG1的超分子包合作用及反应体系荧光响应值的影响。经研究:AFG1-HE-β-CD二元包合物反应体系荧光响应值大幅提高,在溶剂为2%的甲醇溶液,HE-β-CD浓度0.05mol/L、反应时间3min时体系可以达到最大的荧光值。根据Benesi-Hildebrand法确定HE-β-CD与AFG1形成1:1包络物。紫外吸收光谱、荧光光谱、KI淬灭实验以及热力学参数表明,AFG1进入HE-β-CD空腔从而荧光得到保护。AFG1在2～40μg/kg范围内与体系荧光呈良好线性关系,相关系数为0.9998,检出限为0.079μg/kg。将HE-β-CD应用于花生样品AFG1分析,准确度和精密度良好。     

Characterisation of inclusion complex of trans-ferulic acid and hydroxypropyl-β-cyclodextrin

The inclusion complex of trans-ferulic acid (FA) with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared by the freeze-drying method and its characterisation was investigated by different analytical techniques including UV–visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. All these approaches indicated that FA was able to form an inclusion complex with HP-β-CD, and the FA/HP-β-CD inclusion compounds exhibited different spectroscopic features and properties from FA. The stoichiometry of the complex was 1:1. The calculated apparent stability constant of the FA/HP-β-CD complex was 166.3 M⁻¹, and the water solubility of FA was significantly improved by phase solubility studies. Moreover, the irradiation-induced decomposition of FA in aqueous solution was markedly reduced by complexation with HP-β-CD. The results showed that HP-β-CD was a proper excipient for increasing solubility and stability of FA.     

高良姜油-羟丙基-β-环糊精包合物的抗氧化活性及抑制亚硝胺合成作用

采用饱和水溶液法和超声法制备高良姜油的羟丙基-β-环糊精（hydroxypropyl-β-cyclodextrin,HP-β-CD） 包合物,以包合率和得率为指标筛选出较优的方法,通过显微镜观察、薄层色谱分析、傅里叶变换红外光谱分 析、紫外光谱分析等对包合物的结构进行表征,并测定高良姜油及其包合物对羟自由基、1,1-二苯基-2-三硝基苯肼 （1,1-diphenyl-2-picrylhydrazyl,DPPH）自由基的清除能力和还原能力、对DNA氧化损伤的保护作用、对紫外线诱 导红细胞溶血的影响以及在模拟胃液条件下其阻断亚硝胺合成作用的变化。结果表明：饱和水溶液法制备高良姜 油-HP-β-CD包合物优于超声法,高良姜油能被有效包合,且对其化学成分几乎无影响;高良姜油及其包合物具有 较好的清除羟自由基、DPPH自由基的能力和较高的还原能力,对DNA氧化损伤具有保护作用,能抑制紫外线诱导 的红细胞溶血,并且可有效抑制亚硝胺的合成;包合后高良姜油的抗氧化活性及抑制亚硝胺合成的能力得到显著提 升（P＜0.05）。     

叶黄素浸膏的环糊精包合作用研究

目的:研究环糊精包合时叶黄素浸膏性能的改进效果.方法:HSCCC及HPLC分析浸膏成分,紫外法测定表观包合常数,研磨法制备包合物,以溶解性及稳定性指标考察包合效果.结果:色谱分析表明,叶黄素浸膏为成分复杂的混合物;叶黄素浸膏与环糊精存在较强的包合作用,且混合环糊精优于单一环糊精;单一环糊精的包合改进效果各异,p一环糊精的增溶效果较差,但稳定性好于羟丙基-β-环糊精;混合环糊精包舍的改进效果明显,尤以β-环糊精/羟丙基-β-环糊精9:1的混合包合性能效果最佳.结论:混合环糊精包合成分复杂的叶黄素浸膏可弥补单一环糊精的不足,包舍物的溶解度和稳定性均能得到明显改善.     

Physicochemical and release characterisation of garlic oil-β-cyclodextrin inclusion complexes

Garlic oil (GO), rich in organosulphur compounds, has a variety of antimicrobial and antioxidant activities, however, its volatility and low physicochemical stability limit its application as food functional ingredients. The aim of this study was to investigate the physicochemical and release characterisation of inclusion complexes of GO in β-cyclodextrin (β-CD). The formation of GO/β-CD inclusion complex was demonstrated by different analytical techniques including Fourier transform-infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry. The stoichiometry of the complex was 1:1. The calculated apparent stability constant of GO/β-CD complex was 1141 M⁻¹, and the water solubility of GO was significantly improved by the phase solubility study. Furthermore, the release of GO from the inclusion complex was determined at a temperature range from 25 to 50 °C and in an acidic dissolution medium (pH 1.5), respectively. The release rate of GO from the inclusion complex was controlled.     

Inclusion complexes of β-cyclodextrin with chlorogenic acids (CHAs) from crude and purified aqueous extracts of green Robusta coffee beans (Coffea canephora L.)

The initial aim of the study was to purify the crude aqueous coffee bean extract, containing CHAs and caffeine with the use of the centrifugal partition chromatography (CPC) technique to obtain a higher concentration of CHAs with a simultaneous decrease of caffeine quantity. As a result of extract purification CHA content was increased by about 50% and caffeine was completely eliminated. CHAs were identified by the LC-ESI–MS/MS technique. A further aim was to obtain inclusion complexes of both crude and purified extracts with β-cyclodextrin (β-CD). The highest obtained concentration of CHAs in a complex with β-CD amounted to 19 g/100 g. The formation of inclusion complexes was confirmed with the use of ESI-MS/MS and differential scanning calorimetry (DSC) techniques. The analysis of antioxidant capacity of inclusion complexes with β-CD revealed that crude and purified extracts showed about 2-fold higher antioxidant capacity than the obtained complex.     

肉桂醛-羟丙基-β-环糊精包合物的喷雾干燥法制备及表征

为了提高肉桂醛的稳定性,采用喷雾干燥法制备羟丙基-β-环糊精-肉桂醛包合物,并对包合物的结构、热稳定性及缓释特性进行研究。结果表明,当肉桂醛和羟丙基-β-环糊精质量比为1:2、进料速度20 mL/min、进风温度180℃时包合率达到77.6%。红外光谱、差示扫描量热、热重以及扫描电镜分析,证实了肉桂醛包合物的形成,被包埋后肉桂醛的热稳定性得到显著提高。释放特性表明,肉桂醛包合物在模拟海水中的释放率显著低于在纯水中的释放率,有望应用于海产品保鲜领域。     

六氢β-酸环糊精包合物与食品添加剂的协同抗氧化活性

以羟自由基（·OH）和1,1-二苯基-2-三硝基苯肼（1,1-diphenyl-2-picrylhydrazyl,DPPH）自由基清除活性 为考察指标,考察α、β、γ-环糊精及2-甲基、2,6-二甲基、2,3,6-三甲基及羟丙基等β-环糊精的衍生物与啤酒花中重 要树脂成分的氢化衍生物六氢β-酸所形成的环糊精包合物的抗氧化活性。结果表明：上述六氢β-酸环糊精包合物均 具有不同程度清除·OH和DPPH自由基的活性,且清除活性均好于同浓度下未包合的六氢β-酸。在此基础上,以 协同系数为指标,苯甲酸钠为对照,研究六氢β-酸-2-甲基-β-环糊精、六氢β-酸-γ-环糊精、六氢β-酸-羟丙基-β-环糊 精、六氢β-酸-2,3,6-三甲基-β-环糊精包合物与食品添加剂VC、NaCl、柠檬酸、蔗糖在·OH和DPPH自由基体系的 协同抗氧化作用。结果表明：·OH体系中,各种包合物/柠檬酸的双组分体系和包合物/VC-NaCl-蔗糖的多组分体 系均无协同抗氧化性;而包合物/VC、包合物/NaCl、包合物/蔗糖的双组分体系有较好的协同抗氧化性。DPPH自由 基体系中,除包合物/蔗糖的双组分体系外,其他双组分和多组分体系均具有较好的协同抗氧化作用。而对照品苯 甲酸钠与4 种食品添加剂所形成的双组分体系中均无协同抗氧化作用。