Study On The Interaction Between Several Classes Of Nitrogenous Heterocyclic Compounds And Bovine Serum Albumin

Proteins are the material base in organisms and paly an important role in the maintenance of life activities. Serum albumin (SA), the most abundant carrier protein in plasma, which has many essential pharmacological and physiological functions. Study of the interaction on SA and small molecular at the molecular level is of special value in new drug design, toxicology and pharmacokinetics. In the thesis, we study the interaction of nitrogenous heterocyclic compounds and bovine serum albumin (BSA) by fluorescence and UV-vis spectroscopy. The thesis includes four parts:1. The binding characteristics of 3,4-dihydropyrimidin-2(1H)-ones (DHPM) and BSA have been investigated by fluorescence and absorbance spectra. The experimental results showed that DHPM had a quite strong ability to lead to the fluorescence of BSA decrease by a static quenching. The binding constants (KA), number of binding sites (n) and binding distances (r) were calculated. The relationship between different substituents and the binding ability of DHPM with BSA was preliminarily discussed. Moreover, the synchronous fluorescence spectra were used to study the effect of DHPM on the conformation of BSA.2. To further investigate the effects of substituents and molecular volume on the interaction between pyrimidine derivatives and BSA, the interaction of BSA and thiazolo[3,2-a]pyrimidine were studied. The quenching mechanism, binding constants and binding sites of BSA and small molecular were obtained applying fluorescence quenching method. The binding distances were calculated and the values of them were less than 7 nm according to theory of non-radiation energy transfer. What's more, the synchronous fluorescence spectra indicated that the thiazolo[3,2-a]pyrimidine have not affected the conformation of BSA obviously.3. The fluorescence and ultraviolet spectroscopy were explored to study the binding between N-confused porphyrins (NCP) and BSA. The experimental results indicated that the fluorescence quenching mechanism between BSA and NCP was static quenching procedure at 293 K and at low NCP concentration at 305 K or a combined quenching (static and dynamic) procedure at higher NCP concentration at 305 K. The comparison of binding potency of the three NCP to BSA showed that the substituting groups in benzene ring could enhance the binding affinity. From the thermodynamic parameters, we concluded that the action force was mainly hydrophobic interaction. The binding distances between NCP and BSA were calculated using F?rster non-radiation energy transfer theory. In addition, synchronous fluorescence spectroscopy was used to analy the effect of NCP on the conformation of BSA.4. Nitrogened heterocyclic drugs lomefloxacin (LOM) and ofloxacin (OFL) have a powerful ability to quench the fluorescence of BSA. The fluorescence quenching action is much stronger when two drugs coexist. To investigate the interaction between LOM and OFL, the coexistent LOM and OFL binding to BSA were studied using fluorescence and ultraviolet spectroscopy under imitated physiological conditions. The synergism between LOM and OFL results in both the reduction of the binding stability between drugs and BSA and the increase of the free drug concentration, which will increase the efficacy of drugs. The binding distances(r) between drugs and BSA were obtained based on F?rster theory of non-radiation energy transfer. The synchronous fluorescence spectra indicated that the effect of synergism affected the conformation of BSA.