作为生物相容性查的一部分,LogP的确定
Marko Turkalj1, Siemon De Nys1, Jeroen Vanoirbeek2
1KU Leuven, Department of Oral Health Sciences, BIOMAT & UZ Leuven, Dentistry, Leuven, Belgium.
概括
复合单体的经验确定的八醇-水分区系数 (logP) 值对于评估生物积累风险至关重要. 在体外测量比目前的in-silico模型更可靠,这些模型往往会过度预测logP.
科学领域:
- 毒理学 毒理学 毒理学
- 环境科学 环境科学
- 材料科学 材料科学 材料科学
背景情况:
- 八醇-水分区系数 (logP) 对于预测生物积累和环境风险至关重要.
- 准确的logP测定对于评估复合单体的生物相容性至关重要.
研究的目的:
- 通过shake-flask方法实验确定复合单体的logP.
- 将实验logP值与in-silico模型预测的值进行比较.
- 评估用于logP预测的in-silico模型的可靠性.
主要方法:
- 复合单体 (BisEMA3,BisEMA6,BisEMA10,BisGMA,HEMA,TEGDMA,UDMA) 经过摇法进行了对logP的确定.
- 在24小时,48小时和72小时内进行平衡,随后进行UHPLC-MS/MS分析.
- 使用KOWWIN,ACD/LogP和XLogP3模型生成了in-silico logP预测.
主要成果:
- 在时间点之间没有观察到logP的显著差异 (p > 0.05),表明在24小时后处于平衡状态.
- 72小时后的实验logP值在4.05 ± 0.09 (BisEMA10) 到0.09 ± 0.03 (HEMA) 之间.
- 无模型始终预测过多的logP值,特别是对于更多的疏水性单体.
结论:
- 由于当前in-silico模型的不可靠性,建议进行体外logP测定.
- 实验确定的logP值低于in-silico预测值,这表明生物积累潜力较低.
- 进一步开发in-silico模型需要大量实验验证的logP值数据集.
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