Quantum chemical calculations for predicting the partitioning of drug molecules in the environment

Regional and temporal trends in legal and illicit drug use can be tracked through monitoring of municipal wastewater, ambient air, indoor air, and house dust. To assess the analytical result for the selected environmental matrix, reliable information on the partitioning of the target substance between the different compartments is required. The logarithmic partition coefficients octanol/water (log KOW), octanol/air (log KOA) and air/water (log KAW) are usually applied for this purpose. Most drug molecules are semi-volatile compounds with complex molecular structures, the handling of which is subject to legal regulations. Chemically, they are often acids, bases, or zwitterions. Consequently, the physical and chemical properties are in most cases not determined experimentally but derived from quantitative structure-activity relationships (QSARs). However, the lack of experimental reference data raises questions about the accuracy of computed values. It therefore seemed appropriate and necessary to calculate partition coefficients using alternative methods and compare them with QSAR results. We selected 23 substances that were particularly prominent in European and US drug reports. Different quantum mechanical methods were used to calculate log KOW, log KOA, and log KAW for the undissociated molecule as a function of temperature. Additionally, the logarithmic hexadecane/air partition coefficient log KHdA h L and the logarithmic vapor pressure of the subcooled liquid log PL were determined in the temperature range 223 < T/K < 333. Despite the sometimes high variability of the parameters, it is possible to estimate how an investigated substance distributes between air, water and organic material.