MECHANISM OF REACTION OF AN ARENEDIAZONIUM ION IN AQUEOUS-SOLUTIONS OF ACETAMIDE, N-METHYLACETAMIDE, AND N,N-DIMETHYLACETAMIDE - A POTENTIAL METHOD FOR CHEMICALLY TAGGING PEPTIDE-BONDS AT AGGREGATE INTERFACES

The mechanism of dediazoniation of 2,4,6-trimethylbenzenediazonium ion , 1-ArN2+, in concentrated aqueous solutions of acetamide, N-methylace tamide, and N,N-dimethylacetamide (peptide bond models) was probed by a combination of techniques including HPLC, GC/MS, and (H2O)-O-18 isot opic labeling. The kinetics and product distributions are completely c onsistent with the heterolytic dediazoniation mechanism, i.e., rate-de termining loss of N-2 followed by trapping of the aryl cation intermed iate, 1-Ar+, by H2O and the oxygens and nitrogens of the amides. Aryl imidates formed from trapping by amide O hydrolyze rapidly into aryl e ster/amine and amide/phenol product pairs. The results were used to es timate the selectivity of 1-Ar+ toward the amide oxygens and nitrogens versus H2O. 1-Ar+ is only 10-40% more selective toward H2O than amide O, but it is more than 10 times mon selective toward H2O than the ami de N. 1-Ar+ is slightly more selective toward the N of acetamide than N-methylacetamide. However, within the HPLC detection limit, 1-Ar+ doe s not give a product from reaction with the N,N-dimethylacetamide nitr ogen. The selectivities are interpreted by using a preassociation mode l, i.e., selective solvation by the different nucleophiles of the reac tive diazonio group in the ground state. These results indicate that c hemical tagging (trapping by N) and cleaving (trapping by O) of the pe ptide bonds and the weakly basic side chains of polypeptides and prote ins bound to association colloids, vesicles and biomembranes, and emul sions may provide new information on their topologies and orientations at the aggregates' interfaces.