TY - JOUR
T1 - LogP determination for highly lipophilic hydrogen-bonding anion receptor molecules
AU - Tshepelevitsh, Sofja
AU - Kadam, Sandip
AU - Darnell, Astrid
AU - Bobacka, Johan
AU - Rüütel, Alo
AU - Haljasorg, Tõiv
AU - Leito, Ivo
PY - 2020/10/2
Y1 - 2020/10/2
N2 - Lipophilicity, usually expressed as octanol-water partition coefficient (logP
o/w), is an important property in biomedical research, drug design and technology. However, high logP
o/w values of complex hydrogen-bonding molecules are not easy to measure or calculate. Exemplary problematic molecules are prospective active components (ionophores) of polymeric sensor membranes – the working elements of ion-selective electrodes. High lipophilicities of the membrane components are crucial for the sensor lifetime. In this work, lipophilicities of a wide range of urea-, carbazole- and indolocarbazole-based anion receptor molecules (some newly synthesized) and two common plasticizers were determined using a chromatography-based approach and/or the COSMO-RS method. Very high logP
o/w values, up to around 20, i.e. far beyond directly experimentally accessible range, were obtained. The agreement between the two approaches ranged from very good to satisfactory. Based on these results, simple fragment-based equations were developed for quick lipophilicity estimation without any specialized software. Membrane-water partition coefficients for the studied compounds were modeled. Limitations and biases of the used methods are discussed.
AB - Lipophilicity, usually expressed as octanol-water partition coefficient (logP
o/w), is an important property in biomedical research, drug design and technology. However, high logP
o/w values of complex hydrogen-bonding molecules are not easy to measure or calculate. Exemplary problematic molecules are prospective active components (ionophores) of polymeric sensor membranes – the working elements of ion-selective electrodes. High lipophilicities of the membrane components are crucial for the sensor lifetime. In this work, lipophilicities of a wide range of urea-, carbazole- and indolocarbazole-based anion receptor molecules (some newly synthesized) and two common plasticizers were determined using a chromatography-based approach and/or the COSMO-RS method. Very high logP
o/w values, up to around 20, i.e. far beyond directly experimentally accessible range, were obtained. The agreement between the two approaches ranged from very good to satisfactory. Based on these results, simple fragment-based equations were developed for quick lipophilicity estimation without any specialized software. Membrane-water partition coefficients for the studied compounds were modeled. Limitations and biases of the used methods are discussed.
U2 - 10.1016/j.aca.2020.07.024
DO - 10.1016/j.aca.2020.07.024
M3 - Article
SN - 0003-2670
VL - 1132
SP - 123
EP - 133
JO - Analytica Chimica Acta
JF - Analytica Chimica Acta
ER -