Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure

Abstract

Lipophilicity parameters (logP) were determined for thirteen synthesized β-hydroxy-β-arilalkanoic acids using reversed phase high performance liquid chromatography. Anti-inflammatory activity and potential selectivity towards cyclooxygenase-2 inhibition of synthetized compounds was assessed. Stationary phase was octadecyl modified (C-18) silicagel, and four used mobile phases contained different amount of methanol. Both synthetized and standard compounds with known logP values (aspirin, ibuprofen, ketoprofen, naproxen and phenanthrene) were tested in a chromatographic system. Using retention times for each standard and synthesized compound logk values (logarithm of capacity factor) were calculated. Intercept on a graph showing dependency of logk from methanol amount in the mobile phase for each compound represents logKw(capacity factor when organic solvent amount is zero). Graph showing linear dependency of logP of standard compounds from experimentally obtained logKw values was plotted. LogP values for synthetized compounds were obtained by interpolation from the plotted graph. Obtained values are in a range from 2.901 to 3.847. The best correlation between experimentally obtained and predicted logP values was using KOWWIN software (R2=0.8864), which makes this software appropriate for predicting logP values of this type of compounds.

Parametri lipofilnosti (logP) su određeni za trinaest sintetisanih β-hidroksi-β-arilalkanskih kiselina primenom reverzno fazne tečne hromatografije. Ispitivanje je urađeno na derivatima kojima je tokom prethodnih istraživanja okarakterisana antiinflamatorna aktivnost i pretpostavljena je potencijalna selektivnost prema inhibiciji ciklooksigenaze-2. Oktadecil-modifikovani (C-18) silikagel je predstavljao stacionarnu fazu, a korišćene su četiri mobilne faze u kojima je variran udeo metanola. Hromatografski su testirana jedinjenja sa poznatim logP vrednostima (aspirin, ibuprofen, ketoprofen, naproksen i fenantren) i sintetisana jedinjenja. Na osnovu retencionog vremena za svako standardno i sintetisano jedinjenje izračunate su vrednosti logk (logaritam faktora kapaciteta). Odsečak na y osi grafika zavisnosti logk od udela metanola u mobilnoj fazi za svako jedinjenje predstavlja vrednost logKw (vrednost retencionog faktora za hromatografski sistem u kome je sadržaj organske komponente nula) za dato jedinjenje. Konstruisan je grafik zavisnosti logP za standardna jedinjenja od njihovih eksperimentalno dobijenih logKw vrednosti i uspostavljena je linearna zavisnost. Interpolacijom logKw sa grafika su očitane vrednosti logP za sintetisana jedinjenja. Dobijene vrednosti su u opsegu od 2,901 do 3,847. Za predviđanje logP vrednosti korišćeni su računarski programi: AlogPS, Molinspiration, MarvinSketch i KOWWIN. Najbolja korelacija između eksperimentalno određenih i predviđenih rezultata je u programu KOWWIN (R2=0,8864), što čini ovaj program pogodnim za predviđanje logP vrednosti ovog tipa jedinjenja.