Iodine isotope exchanges between O-Iodohippuric acid and radioiodide

Even though a lately reported method of high temperature exchange labelling of o-iodohippuric acid (Hippuran) in the absence of oxidizing agent was considered to be an attractive one, the exchanges mechanism unclear. In this study iodine isotope exchange betwen o-iodohippuric acid (OIH) and radioiodide (125I-) or between OIH and molecular radioiodine (125I2) were carried out at two different temperatures. Rate constants and activation parameters were measured by applying a radio-paper chromatography technique. Since o-iodobenzoic acid is known as a by-product in the exchange labelling of OIH, data were also obtained for the OIB-iodide systems for comparison. The rate constant was increased in order of OIB...125I->OIB...125I2>OIH...125I-> OIH...125I2 and the activation parameters for OIH were generally larger than those for OIB; ΔH unequal to sub(OIH)>ΔH unequal to sub(OIB), ΔS unqueal to sub(OIH)>ΔS unequal to sub(OIB). These results suggest that the mechanism of the high temperature exchange is predominantly nucleophilic even though some electrophilic character can also be involved depending upon reaction conditions. Such a fact may well be caused by a feasible formation of hydrogen bonding type transition state due probably to the ortho substituent effect of-CONHCH2COOH. Thus, the high temperature exchange method is estimated to be quite effective for labelling Hippuran especially at a small research center where reducing agent-free 131I is unavailable. (author)