Remarkable Metal Counterion Effect on the Internucleotide J-Couplings and Chemical Shifts of the N−H···N Hydrogen Bonds in the W−C Base Pairs

Abstract

The effects of metal ion binding on the (2h) J(NN)-coupling and delta( (1)H)/Deltadelta( (15)N) chemical shifts of N-H...N H-bond units in internucleotide base pairs were explored by a combination of density functional theory calculations and molecular dynamics (MD) simulations. Results indicate that the NMR parameters vary considerably upon cation binding to the natural GC or AT base pairs, and thus can be used to identify the status of the base pairs, if cation-perturbed. The basic trend is that cation perturbation causes (2h) J(NN) to increase, Deltadelta( (15)N) to decrease, and delta( (1)H) to shift upfield for GC, and in the opposite directions for AT. The magnitudes of variation are closely related to the Lewis acidity of the metal ions. For both base pair series (M(z+)GC and M(z+)AT), these NMR parameters are linearly correlated among themselves. Their values depend strongly on the energy gaps (Delta(ELP-->sigma*)) and the second-order interaction energies ( E(2)) between the donor N lone pair (LP(N)) and the acceptor sigma* N-H localized NBO orbitals. In addition, the (2h) J NN changes are also sensitive to the amount of sigma charge transfer from LP(N) to sigma*(N-H) NBOs or from the purine to the pyrimidine moieties. The different trends are a consequence of the different H-bond patterns combined with the polarization effect of the metal ions in the cationized M(z+)AT series, M(z+) <-- A --> T, and the cationized GC series, M(z+) <-- G <-- C. The predicted cation-induced systematic trends of (2h) J(NN) and delta( (15)N, (1)H) in N-H...N H-bond units may provide a new approach to the determination of H-bond structure and strength in Watson-Crick base pairs, and provide an alternative probe of the heterogeneity of DNA sequences.