Aim To compare lipophilicity measuring scale stemmed from immobilized artificial membrane chromatography and n octanol/buffer systems. Methods A test set consisted of 27 structurally diverse compounds. The lipophilici...Aim To compare lipophilicity measuring scale stemmed from immobilized artificial membrane chromatography and n octanol/buffer systems. Methods A test set consisted of 27 structurally diverse compounds. The lipophilicity of these were evaluated by both immobilized artificial memberane chromatography (IAMC) and n octanol/buffer systems, which were expressed as lg k IAM and lg D O/W,7 4 , respectively. Results With regard to each individual group, good correlation coefficient ( r 2) over 0 81 was obtained (0 82 for acid, 0 88 for neutral, 0 81 for base and 0 92 for ampholyte, respectively). However, a smaller r 2 (0 62) was acquired for all compounds studied than that of each individual group. Conclusion IAMC and n octanol/buffer systems were shown to be different in lipophilicity.展开更多
The thermodynamic partitioning behavior of solutes into immobilized artificial membrane(IAM) and n-octanol/water systems was investigated, including acidic,basic,and amphoteric substances.In an n-octanol/buffer system...The thermodynamic partitioning behavior of solutes into immobilized artificial membrane(IAM) and n-octanol/water systems was investigated, including acidic,basic,and amphoteric substances.In an n-octanol/buffer system,partitioning process was entropy-dominated for the most studied drugs,while partitioning of oxolinic and nalidixic acids into n-octanol phase was enthalpy-driven.In IAM chromatography,partitioning into membrane for the studied solutes was enthalpy-driven and an exothermal process.In conclusion,there is a significant difference of solutes′ partitioning mechanism into either IAM or an n-octanol phase,therefore,presenting the theoretical basis for differing lipophilicity measuring scale.展开更多
In this paper the effect of the unusual molecular charge property of amphoteric quinolones,including grepafloxacin and olamufloxacin,on the binding to the negatively charged lipid membrane under the physiological cond...In this paper the effect of the unusual molecular charge property of amphoteric quinolones,including grepafloxacin and olamufloxacin,on the binding to the negatively charged lipid membrane under the physiological conditions was investigated.The subtle pH variation around 7.4 can significantly change the molecular charge property of the two amphoteric quinolones,which results in a significant change of the electrostatic forces.The liposome/water system was undertaken to measure the drug-phospholipid membrane interactions.In the liquid-crystal liposome,the binding to membrane of the two quinolones was increased in the negatively charged liposome while decreased in the neutral liposome,with pH from 7.4 to 6.8.Similarly,the same tendency occurred in the gel-state liposome,that the binding to membrane increased in the negatively charged liposome from 7.4 to 6.8,mimicking drug transfer process from extracellular into intracellular fluid.In conclusion,the molecular electrical charge for amphoteric quinolones was very sensitive to pH variation around physiological pH,which may play an important role in the in vivo drug pharmacokinetics.展开更多
文摘Aim To compare lipophilicity measuring scale stemmed from immobilized artificial membrane chromatography and n octanol/buffer systems. Methods A test set consisted of 27 structurally diverse compounds. The lipophilicity of these were evaluated by both immobilized artificial memberane chromatography (IAMC) and n octanol/buffer systems, which were expressed as lg k IAM and lg D O/W,7 4 , respectively. Results With regard to each individual group, good correlation coefficient ( r 2) over 0 81 was obtained (0 82 for acid, 0 88 for neutral, 0 81 for base and 0 92 for ampholyte, respectively). However, a smaller r 2 (0 62) was acquired for all compounds studied than that of each individual group. Conclusion IAMC and n octanol/buffer systems were shown to be different in lipophilicity.
文摘The thermodynamic partitioning behavior of solutes into immobilized artificial membrane(IAM) and n-octanol/water systems was investigated, including acidic,basic,and amphoteric substances.In an n-octanol/buffer system,partitioning process was entropy-dominated for the most studied drugs,while partitioning of oxolinic and nalidixic acids into n-octanol phase was enthalpy-driven.In IAM chromatography,partitioning into membrane for the studied solutes was enthalpy-driven and an exothermal process.In conclusion,there is a significant difference of solutes′ partitioning mechanism into either IAM or an n-octanol phase,therefore,presenting the theoretical basis for differing lipophilicity measuring scale.
文摘In this paper the effect of the unusual molecular charge property of amphoteric quinolones,including grepafloxacin and olamufloxacin,on the binding to the negatively charged lipid membrane under the physiological conditions was investigated.The subtle pH variation around 7.4 can significantly change the molecular charge property of the two amphoteric quinolones,which results in a significant change of the electrostatic forces.The liposome/water system was undertaken to measure the drug-phospholipid membrane interactions.In the liquid-crystal liposome,the binding to membrane of the two quinolones was increased in the negatively charged liposome while decreased in the neutral liposome,with pH from 7.4 to 6.8.Similarly,the same tendency occurred in the gel-state liposome,that the binding to membrane increased in the negatively charged liposome from 7.4 to 6.8,mimicking drug transfer process from extracellular into intracellular fluid.In conclusion,the molecular electrical charge for amphoteric quinolones was very sensitive to pH variation around physiological pH,which may play an important role in the in vivo drug pharmacokinetics.
