Theoretical insight into [Pd(en)(H2O)2]2+ binding to Guanine form [{Pd(en)(guanine)}4]4+: Kinetic control and thermodynamic control

In the current study, we investigated the detailed reaction mechanism of [Pd(en)(H2O)2]2+ binding to the N1 deprotonated 9-methylguanine formation of various corner adducts and revealed the most viable structure of the tetramer of [{Pd(en)(guanine)}4]4+ by DFT and ab initio calculations. Our calculations indicate that in the first substitution reactions the palladination N7 of guanine is preferred over N1 in kinetics and thermodynamics. The first substituted adducts can further bind to MeG forming corner adducts. There are three possible linkages for corner adducts: N7PdN7, N7PdN1, and N1PdN1. Each product has two conformations, the head to head arrangement (HH) in which the CO6 of two MeG are arranged on the same side of the coordination plane, and head to tail (HT) in which the CO6 of two MeG are located on the opposite side of the plane. Generally, the HT arrangements are more favorable over the HH conformation. The reaction of [Pd(en)(H2O)N(7)MeG]+ binding to the N7 of MeG giving the corner adduct of [Pd(en){N(7)MeG}2] in HT conformation is most favorable in kinetics with activation free energy at 10.1 kcal/mol. However, our calculations for [{Pd(en)(guanine)}4]4+ demonstrate that the tetramer adopts a structure of N1PdN7 linkage. Our NBO analysis clearly illustrates that the NH2⋯OC hydrogen bonds are cooperatively formed among four guanines, which play a pivotal role in stabilizing the tetramer. The analysis of the reaction energies for reactions giving various adducts suggests that the formation of the tetramer adduct is thermodynamically controlled.