Mass spectrometric and ab initio study of the interaction between 9-methylguanine and amino acid amide group

Abstract

The temperature dependent field ionization mass spectrometry method combined with ab initio calculations was used to determine the interaction energies and the structures of 9-methylguanine-acrylamide dimers. Acrylamide mimics the side chain amide group of the natural amino acids asparagine and glutamine. The experimental enthalpy of the dimer formation derived from the van't Hoff plot is −59.5 ± 3.8 kJ mol−1. The value is higher than interaction energies between acrylamide and other nucleic acid bases which were determined to be −57.0 for 1-methylcytosine, −52.0 for 9-methyladenine, and −40.6 kJ mol−1 for 1-methyl-uracil. In total, eight hydrogen bonded dimers formed by the three lowest energy 9-methylguanine tautomers and acrylamide were found in the quantum chemical calculations performed at the DFT/B3LYP/6-31++G** and MP2/6-31++G** levels of theory. The relative stability and the interaction energies of the dimers were calculated accounting for the basis set superposition error and the zero-point vibrational energy correction. The lowest energy dimer found in the calculations is formed by acrylamide (Ac) with the keto tautomer of 9-methylguanine (Gk). It is stabilized by two intermolecular H bonds, C6=O(Gk) · · · H—N(Ac) and Nl—H(Gk) · · ·O(Ac), and it is more stable than the second lowest energy dimer by ≈ 25 kJ mol−1. The calculated interaction energies of the lowest energy 9-methylguanine-acrylamide dimer are −65.0 kJ mol−1 and −67.7 kJ mol−1 at the MP2 and DFT levels of theory, respectively. The experimental enthalpy of the dimer formation is in good agreement with both the calculated interaction energies of the GkAc dimer and much higher than the interaction energies calculated for all other 9-methylguanine-acrylamide dimers. This proved that only one dimer was present in the experimental samples. To verify whether acrylamide is a good model of the amino acid-amide group, we performed direct calculations of the 9-methylguanine-glutamine dimers at the same levels of theory as used for the complexes involving acrylamide. The interaction energies found for the lowest energy 9-methylguanine-glutamine dimer are −65.1 kJ mon−1 (MP2/6-31++G**) and −66.2 kJ mol−1 (DFT/B3LYP/6-31++G**) and these values are very close (within 0.5 kJ mol−1) to the interaction energies obtained for the 9-methylguanine-acrylamide dimers.