Synthesis and acidity constants of (CO2H)-C-13-labelled dicarboxylic acids. pK(a)s from C-13-NMR

Simple dicarboxylic acids: adipic (1), succinic (2) and malonic (3); more complex linear tetrapyrroles with two propionic acid groups: mesobiliverdin-XIII alpha: (4) and mesobilirubin-XIII alpha (5), and a rubin analog with a gem-dimethyl at C-10 (6) were prepared with 99% C-13-enrichment in their CO2H groups. Their pK(a) values were determined from titration curves in water and in H2O-(CD3)(2)SO solutions: plots of carboxyl carbon C-13-NMR chemical shifts with varying PH. Titration curves of diacids 1-3 with known pK(a)'s in H2O served as calibration standards for determination of pK(a)s of tetrapyrrole diacids 4-6: pK(a1) = 3.9, pK(a2) = 5.3 for 4; pK(a1) = 4.2, pK(a2) = 4.9 for 5,and pK(a1) = 4.7, pK(a2) = 5.7 for 6 in H2O. Copyright (C) 1996 Elsevier Science Ltd