Fragmental Method KowWIN as the Powerful Tool for Prediction of Chromatographic Behavior of Novel Bioactive Urea Derivatives

Abstract

A series of the new urea derivatives with antinociceptive activity has been chromatographically evaluated using reversed phase materials: Zorbax Extend-C18, Cogent UDC Cholesterol with organic-aqueous eluent systems with two organic modifiers (methanol and acetonitrile). The chromatographic lipophilicity parameters: log k w , S and j 0 were determined basing on linear relationship between log k values and concentration of organic mobile phase modifier. The structure-retention studies revealed that the retention mechanism for all studied urea derivatives is uniform for the proposed chromatographic systems. However, a few exceptions were noticed. Derivatives containing nonpolar substituents in the imidazole ring acted as outliers for cholesterol column. In turn, the derivative containing ester polar substituent acted as an outlier in conventional reversed-phase system. Quantitative relationships based on a wide set of established computational molecular descriptors and experimental chromatographic data were also developed. Through a systematic study, by using the principal component analysis, fragmental method KowWIN appeared to be the most powerful software to produce reliable estimations of experimental retention parameters obtained on cholesterol column.

Recent applications of retention modelling in liquid chromatography

“…The extent to which a drug can penetrate biological membranes, such as the blood–brain barrier, cell membranes, and skin, depends heavily on the . A number of groups publish the lipophilicity parameters of many newly synthesized drug candidates [167–180]. In drug discovery research, the LSS model is often used to obtain the , but Hawrył et al.…”

Affinity of Compounds for Phosphatydylcholine-Based Immobilized Artificial Membrane—A Measure of Their Bioconcentration in Aquatic Organisms

“…Total energy (E t ), energy of the highest occupied molecular orbital (E HOMO ), energy of the lowest unoccupied molecular orbital (E LUMO ), dipole point charge (DiPCh), dipole hybrid (DipH) and dipole sum (DipS) were of Mopac 2016 type and were calculated using the OCHEM platform [57]. Octanol-water partition coefficient (log K ow ) was calculated according to the KOWWIN algorithm [58] using EPI Suite TM software [42] (Table S2).…”