PROTOLYTIC CONSTANTS OF NIZATIDINE, RANITIDINE AND N,N'-DIMETHYL-2-NITRO-1,1-ETHENEDIAMINE - SPECTROPHOTOMETRIC AND THEORETICAL INVESTIGATION

The prototropic exchange equilibria of two drugs, nizatidine (I) and r anitidine (II); and also of structurally related the N,N'-dimethyl-2-n itro-1,1-ethenediamine molecule (III) were investigated. From the chan ges in electronic spectra in media of various acidity several protonat ion constants were determined. For nizatidine pK values were -0.82, 1. 95, and 6.67; for ranitidine pK values were 1.95 and 8.13; and for III was 2.60. The hydroxylation equilibrium constant in strongly alkaline media was determined too. Corresponding pK(a) values were 13.23 for I , 13.26 for II and 13.76 for III. Molecular orbital calculations of el ectronic spectra confirmed that pK 1.95 for I and II, and pK 2.60 for III, are associated with C-protonation of nitroethenediamine fragment, while all pK(a) values correspond to the addition of HO- anion at the same double bond. (C) 1997 Elsevier Science B.V.