Protolitičke ravnoteže bromazepama

The protolytic equilibria of bromazepam, an ampholyte sparingly soluble in water, in homogeneous and heterogeneous systems were studied in the pH range 0–14 at 25ºC and at ionic strength of 0.1 mol/dm3 (NaCl). On the basis of 13C-NMR spectra, the protonation site was predicted – in acidic media the pyridine nitrogen of bormazepam is protonated. The acidity constants of bromazepam were determined spectrophotometrically (pKa1 2.83 and pKa2 11.60) and potentiometrically (pKa1 2.99). In the heterogeneous system the following equilibrium constants were determined: Ks0 =[HA](pKs0 3.44), Ks1 =[H2A+]/[H3O+](pKs1 0.61), and Ks2 =[A-][H3O+](pKs2 15.04). Proučavane su protolitičke ravnoteže bromazepama, amfolita iz klase 1,4-benzodiazepina, slabo rastvornog u vodi. Ispitivanja su vršena u homogenom i heterogenom sistemu u pH intervalu 0–14, na temperaturi 25ºC i pri jonskoj sili 0,1 mol/dm3 (NaCl). Na osnovu 13C-NMR spektara pretpostavljeno je da do protonovanja u molekulu bromazepama dolazi na piridinskom atomu azota. Kiselinske konstante određene su spektrofotometrijski (pKa1 2.83 and pKa2 11.60) i potenciometrijski (pKa1 2,99). U heterogenom sistemu određene su sledeće ravnotežne konstante Ks0 =[HA](pKs0 3.44), Ks1=[H2A+]/[H3O+](pKs1 0.61), and Ks2 =[A-][H3O+](pKs2 15.04).