| It is very important to investigate the interaction between drug molecules and biological related material. With the improvement of researchers to study, analytical instrument unceasing renewal and the new drugs coming out constantly, the research methods of interactions between drugs and biological molecules are increasing and being updated. In this thesis the interactions between drugs (curcumin, tamsulosin, diacerein, alkaloids and benzoic acid drugs) and some substances (DNA, bovine serum albumin, cyclodextrins and metal ions) are studied by the methods such as ultraviolet-visible spectrophotometry, fluorescence spectrometry, capillary electrophoresis method and partial filling technique, computer molecular modeling, etc. The binding constant and related thermodynamics parameters are determined. And the mechanism of interactions is speculated at the certain conditions. The certain improvement and expansion are applied in research methods. In additional, these methods are applied in the corresponding analysis of drugs, including drug quality control and separation of chiral drugs enantiomer.This thesis includes two parts. Part one is an introduction, which reports in detail the development and important significance of the interactions, methods and their application, the present study about drugs and biological material by citing with lots of references. Part two is a research report. And the specific research contents are listed as follows:1. Investigation on the interaction between curcumin and related substances by spectroscopic methods and their applicationsThe stability constant of curcumin-Fe2+complex is determined by spectrophotometric dual isosbestic points when the value of pH is6.5in buffer solution. And the new improvement is put forward in experimental design. Excel is used in the iteration data processing, greatly simplifying the experiment and data processing. The curcumin-spectrophotometry is applied to determine Fe2+in compound ferrous sulfate folic acid tablets, and this method is simple and reliable. The binding constant of the curcumin-Fe2+complex with salmon sperm DNA (ssDNA) is determined by double multiplicative inverse curve, and its mechanism is discussed. By fluorescence combined with Excel iteration method in data processing and ultraviolet spectrum are applied to investigate in detail the interactions between curcumin and bovine serum albumin (BSA), beta-cyclodextrin (β-CD), hycroxypropyl-beta-cyclodextrin (HP-(3-CD). The curcumin-HP-(3-CD complex is prepared and its properties are investigated such as infrared spectrum, water-solubility and stability, etc.2. Methodology study on the interaction between three alkaloids with BSA/CDs and applicationFirstly, classical fluorescence spectroscopy is used to study the interaction mechanism between BSA and drugs (caffeine, theobromine and theophylline). Secondly, affinity capillary electrophoresis (ACE) is also used for investigation the interactions through two modes:"Dp" for drugs as additive and "PD" for BSA as additive, respectively. Their experimental results are consistent. Thirdly, the interactions between three alkaloids with β-CD are analyzed by UV spectrometer. Finally, based on their recognition function, the quantitative analysis is established for determining three alkaloids in samples (tea, cola drink, coffee and drugs) by capillary zone electrophoresis (CZE) with β-CD as additive in the buffer solution.3. Methodology study on the interaction between tamsulosin with BSA/CDs and applicationThe interactions between tamsulosin with β-CD and HP-P-CD are investigated by spectrophotometry combined with molecular modeling. Then using the recognition, CZE method is established for simultaneous separation and determination tanmulosin in its bulk drug and sustained-release capsule. Based on the principles of CZE and ACE, the enantioseparation of tamsulosin and the interactions between the enantiomers with chiral selectors are investigated, the chiral selectors including β-CD, HP-β-CD, BSA, dextran, etc. Additionally, in experimental investigation the interactions tamsulosin and intermediates with BSA, the background interference problem is solved successfully by using partial filling technique and drugs instead of neutral markers in capillary electrophoresis.4. Interactions between benzoic acid drugs with BSA by spectrophotometry and their quantitative analysis by high performance capillary electrophoresis (HPCE)The electrostatic mode is applied to study the interactions between benzoic acids and BSA by spectrophotometry. BSA solution is used as reference solution in experimental process to determine the absorbance of drug-BSA system, which can eliminate the interference about residual BSA on absorbance measure of drugs. This method can be extended to other similar spectrum overlapping interaction system. In additional, five benzoic acids are separated simultaneously by micellar electrokinetic capillary chromatography (MECC) modified with β-CD. Then the MECC-internal standard method is applied to separate and determine aromatic acid compounds in the radix isatidis, the results are feasible and satisfactory.5. Interactions between diacerein and CDs/BSA by spectroscopic methodDiacerein is a kind of new anti-inflammatory. It can ease and improve significantly the patients'arthralgia with osteoarthritis. The inclusion interactions between diacerein with β-CD and HP-β-CD are observed by simple UV spectrophtotometry. The results show the inclusion is feasible and its degradation will be improved. The interaction of diacerein-BSA system is investigated by using fluorescence analysis. The results show that diacerein can quench the fluorescence of BSA with a static quenching mechanism. At the same time Excel iterative method is used to data processing in determining the binding constant of diacerein-BSA complex at different temperature. Then the interactional type is speculated from the relevant thermodynamic parameters, which is mainly hydrophobic interaction and electrostatic effect. |
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