The octanol-water partition
1) A paper published earlier this year by Berens et al., (2020, EST) examined the reduction of 2,4-dinitroanisole (DNAN) one of the new generation of insensitive munitions explosives that has become an environmental problem at many Department of Defense facilities. They report that DNAN forms two isomers, 6-methoxy, 3-nitroaniline (also known as 2-amino-4-nitroanisole) and 4-methoxy, 5-nitroaniline (also known as 4-amino-2-nitroanisole). Please answer the following questions.
• Calculate the octanol-water partition coefficient using the atom/fragment contribution method. Note that you need to only do this once because they are structural isomers. (10)
• There is no “experimental” pKa values for both isomers. Please estimate their pKa values using the Hammett-Taft model. (15)
• A different paper by Li et al., (2013, J. Haz. Materials) examined the oxidation of DNAN by ultrasound and the Fenton reaction. They ran their experiments at a pH of 2.7.
i. Determine the speciation of both compounds at this pH i.e., what fraction is protonated vs. neutral. (10)
ii. Recalculate the octanol-water partition coefficients for both isomers at this pH. What is the principal reason behind any difference in your calculated values given that the isomers have the same calculated Kow? (5)
2) A paper by Rudel et al. (EST 2003, 4543) measured the concentration of various pollutants in indoor air. They report respective average levels of 1560 and 426 ng/M3 for diethyl phthalate (DEP) and di-n-butyl phthalate (DBP), which are both present in most plastics (use Chemspider to get additional data).
• If these levels are present in your house and you have a bottle of extra virgin olive oil open to the air at 30o C (its summertime), how much of each compound will be in the oil phase (mol/L)? You can assume Raoult’s Law is obeyed and a respective molecular weight and density for the olive oil of 160 g/mol and 0.9 g/ml. (25)
• What is the air-olive oil partition coefficient for these two compounds at 25 C based upon:
o The assumption that Raoult’s Law is obeyed (15)
o Estimated based upon the pp-LFER provided in the book (Table 10.2) and the UFZ database. Is the assumption that Raoult’s Law is obeyed a reasonable one? If not what is the activity coefficient for each compound in olive oil? (20)
Sample Solution
Octanol-water partition ratio is the most common way of expressing the lipophilicity of a compound, and it is defined as the ratio of the concentration of a solute in a water-saturated octanolic phase to its concentration in an octanol-saturated aqueous phase. In the early stage of the drug discovery process, lipophilicity is often ranked as one of the most important physicochemical properties to screen lead compounds, and it is also widely used in environmental risk assessment and agricultural fields. In addition, the correlation between lipophilicity and biological activity has provoked the extensive use of the octanol-water partition ratio, among others, as a descriptor in quantitative structure-activity/property relationships.
