Understanding the NMR chemical shifts for 6-halopurines: role of structure, solvent and relativistic effects

A prototypical study of NMR chemical shifts in biologically relevant heteroaromatic compounds containing a heavy halogen atom is presented for two isomers of halogen-substituted purines. Complete sets of 1H-, 13C- and 15N-NMR chemical shifts are determined experimentally in solution. Experimental results are complemented by quantum-chemical calculations that provide understanding of the trends in the chemical shifts for the studied compounds and which show how different physical effects influence the NMR parameters. Chemical shifts for isolated molecules are calculated using density-functional theory methods, the role of solvent effects is studied using polarised continuum models, and relativistic corrections are calculated using the leading-order Breit–Pauli perturbation theory. Calculated values are compared with the experimental data and the effects of structure, solvent and relativity are discussed. Overall, we observe a good agreement of theory and experiment. We find out that relativistic effects cannot be neglected even in the chlorine species when aiming at high precision and a good agreement with the experimental data. Relativity plays a crucial role in the bromine and iodine species. Solvent effects are of smaller importance for 13C shifts but are shown to be substantial for particular 15N shifts. The test of method performance shows that the BLYP and B3LYP functionals provide the most reliable computational results after inclusion of the solvent and relativistic effects while BHandHLYP may—depending on atom in question—slightly improve but mostly deteriorate the data. Ab initio Hartree–Fock suffers from triplet instability in the Breit–Pauli relativistic part while MP2 provides no clear improvement over DFT in the nonrelativistic region. This work represents the first full application of the Breit–Pauli perturbation theory to an organic chemistry problem.