Combined Mass Spectrometric and ab Initio Study of the Point Contacts between 9-Methyladenine and the Amide Group

Abstract

We applied the temperature-dependent field ionization mass spectrometry method to determine the interaction energy between 9-methyladenine and acrylamide. Acrylamide mimics the side chain amide group of the natural amino acids asparagine and glutamine. The experimental enthalpy of the dimer formation derived from van't Hoff's plot is −52.0 ± 5.0 kJ mol-1. This value is close to the interaction energy between acrylamide and 1-methylcytosine (−57.0 kJ mol-1) and much higher than the interaction energy between acrylamide and 1-methyluracil (−40.6 kJ mol-1). The DFT/B3LYP/6-31++G** and MP2/6-31++G** quantum-chemical methods were used to determine the structures and the interaction energies of the 9-methyladenine−acrylamide dimers. In the calculations, two energetically almost equivalent equilibrium structures were found. They are stabilized by intermolecular H-bonds formed between the acrylamide amide group and the Watson−Crick and Hoogsteen sites of 9-methyladenine, respectively. The calculated interaction energies of the dimers are −41.4 and −39.2 kJ mol-1, respectively, at the DFT level of theory and −40.9 and −38.8 kJ mol-1, respectively, at the MP2 level. We also performed calculations for 9-methyladenine−glutamine dimers at the DFT/B3LYP/6-31++G** level of theory. The interaction energy differences between the corresponding 9-methyladenine−acrylamide and 9-methyladenine−glutamine dimers of less than 1 kJ mol-1 were obtained in the calculations. This result demonstrates that acrylamide is a good model for the amino acid amide group. The experimantal and the calculated data indicate that the amino acid amide group can interact with the adenine residue in the single-stranded DNA, as well as in the major groove of double-stranded DNA. The influence of the interaction with the amide group on the stability of the adenine−uracil base pair is discussed.