对抗真菌酸与β-环素复合的辅溶剂作用:一个结合分子动力学和NMR研究
Dragos L Isac1, Petru Tîrnovan1, Alina Nicolescu1
1Center of Advanced Research in Bionanocojugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry Iasi, Grigore Ghica Voda Al. No. 41A, Iasi 700487, Romania.
概括
甲基硫化物 (DMSO) 辅溶剂会影响循环素 (CyD) 药物复合. 在低度的DMSO中发生最佳的酸 (PCZHNO3) 和β- 环氧化 (β- CyD) 复合,而较高的度会使复合物不稳定.
科学领域:
- 物理化学
- 超分子化学
- 制药科学
背景情况:
- 同溶剂显著影响循环素 (CyD) 药物复合,影响溶解性,稳定性和结合性.
- 药物配方的优化需要了解 CyD 综合体内宿主-客体相互作用中的辅溶剂作用.
研究的目的:
- 调查二甲基硫氧化物 (DMSO) /水辅溶剂系统对甲酸盐 (PCZHNO3) 与β-cyclodextrin (β-CyD) 的纳入复合的作用.
- 阐明控制辅溶剂-药物-CyD相互作用的分子机制及其对复合物稳定性的影响.
主要方法:
- 使用分子动力学 (MD) 模拟来建模PCZHNO3,β-CyD和DMSO/水溶剂系统之间的相互作用.
- 使用增强的采样技术和潜在的平均力 (PMF) 计算来量化结合亲和力.
- 使用核磁共振 (NMR) 光谱 (1H-NMR和ROESY) 来实验验证模拟结果.
主要成果:
- MD模拟显示,DMSO与PCZHNO3在β-CyD腔中竞争,即使在低度下也会取代水分子.
- 在大约5%v/v DMSO 的情况下,复合是最有利的,在较高的 DMSO 度下,结合亲和力会降低,复合不稳定.
- 随着DMSO度的增加,NMR数据证实了宿主与客人的相互作用的减弱,与模拟结果一致.
结论:
- 这项研究提供了分子层面的见解,了解辅助溶剂如何调节药物-CyD相互作用.
- 调整溶剂环境对于提高β-CyD包容复合物的稳定性和有效性至关重要.
- 低度的DMSO可能是有益的,但高度会导致PCZHNO3-β-CyD复合物的不稳定.
更多相关视频
10:10Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study
Published on: August 15, 2016
10.4K
10:12Flash NanoPrecipitation for the Encapsulation of Hydrophobic and Hydrophilic Compounds in Polymeric Nanoparticles
Published on: January 7, 2019
22.4K
相关概念视频
02:19Physical Properties Affecting Solubility
28.0K
Solutions of Gases in Liquids
As for any solution, the solubility of a gas in a liquid is affected by the attractive intermolecular forces between solute and solvent species. Unlike solid and liquid solutes, however, there is no solute-solute intermolecular attraction to overcome when a gaseous solute dissolves in a liquid solvent since the atoms or molecules comprising a gas are far separated and experience negligible interactions. Consequently, solute-solvent interactions are the sole...
As for any solution, the solubility of a gas in a liquid is affected by the attractive intermolecular forces between solute and solvent species. Unlike solid and liquid solutes, however, there is no solute-solute intermolecular attraction to overcome when a gaseous solute dissolves in a liquid solvent since the atoms or molecules comprising a gas are far separated and experience negligible interactions. Consequently, solute-solvent interactions are the sole...
28.0K
03:24Common Ion Effect
48.3K
Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Châtelier’s principle. Consider the dissolution of silver iodide:
48.3K
02:30Stability of Substituted Cyclohexanes
17.5K
This lesson discusses the stability of substituted cyclohexanes with a focus on energies of various conformers and the effect of 1,3-diaxial interactions.
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
17.5K
02:12Solvating Effects
9.2K
An understanding of the solvating effect helps rationalize the relation between solvation and acidity of the compound. In addition, this also explains the relative stability of conjugate bases for compounds with different pKa values. This lesson details, in-depth, the principle of solvating effects. The strength of an acid and the stability of its corresponding conjugate base are determined using pKa values. This observed relationship is a consequence of solvation, which is the interaction...
9.2K
01:19Complexation Equilibria: The Chelate Effect
1.6K
In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
1.6K
01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
4.3K
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
4.3K