Energetics and possible mechanisms of ion-beam protein tritiation based on AB initio potential surfaces

Ab initio self-consistent field potential energy surfaces for the approach of T, T2, T+, T3+ and HeT+ to glycine in the gas phase have been determined and this data used to obtain insight into mechanisms of experimental ion-beam protein tritiation processes. Results of these calculations show that the ionic species T+, T3+ and HeT+ can form stable adducts with glycine (Gly) and that each functions as a tritiation agent forming the complex GlyT+. Neutral T and T2 experience a purely repulsive interaction with Gly and do not form an intermediate complex. These neutral species are expected to be less effective tritiation agents than the respective ions, in agreement with experimental observations. The fate of the stable GlyT+ complex is discussed and it is proposed that this species is neutralized by electron capture to give GlyT which spontaneously dissociates to either Gly+T or tritiated glycine (Gly*)+H, with the latter reaction product channel favored statistically. The most likely site of exchange is predicted to be at the amine nitrogen although significance exchange is expected to occur at the alpha-carbon site by a somewhat more complex reaction mechanism.