LogP determination as part of biocompatibility screening

Area of Science:

• Toxicology
• Environmental Science
• Materials Science

Background:

• The octanol-water partition coefficient (logP) is vital for predicting bioaccumulation and environmental risk.
• Accurate logP determination is essential for assessing the biocompatibility of composite monomers.

Purpose of the Study:

• To experimentally determine the logP of composite monomers using the shake-flask method.
• To compare experimental logP values with those predicted by in-silico models.
• To evaluate the reliability of in-silico models for logP prediction.

Main Methods:

• Composite monomers (BisEMA3, BisEMA6, BisEMA10, BisGMA, HEMA, TEGDMA, UDMA) were subjected to the shake-flask method for logP determination.
• Equilibration was performed over 24, 48, and 72 hours, followed by UHPLC-MS/MS analysis.
• In-silico logP predictions were generated using KOWWIN, ACD/LogP, and XLogP3 models.

Main Results:

• No significant difference in logP was observed between time points (p > 0.05), indicating equilibrium after 24 hours.
• Experimental logP values at 72 hours ranged from 4.05 ± 0.09 (BisEMA10) to 0.09 ± 0.03 (HEMA).
• In-silico models consistently overpredicted logP values, particularly for more hydrophobic monomers.

Conclusions:

• In vitro logP determination is recommended due to the unreliability of current in-silico models.
• Experimentally determined logP values were lower than in-silico predictions, suggesting lower bioaccumulation potential.
• Further development of in-silico models requires large datasets of experimentally validated logP values.