Structure of Indole···Imidazole Heterodimer in a Supersonic Jet: A Gas Phase Study on the Interaction between the Aromatic Side Chains of Tryptophan and Histidine Residues in Proteins

Abstract

In this study, we have investigated the binding motifs between the aromatic side chains of tryptophan and histidine residues in proteins by studying the indole···imidazole heterodimer in a supersonic jet. Different spectroscopic techniques including resonant two-photon ionization (R2PI), UV–UV hole-burning, and resonant ion dip infrared (RIDIR) spectroscopy merged with quantum chemistry calculations have been used for this work. UV–UV hole-burning spectroscopy has been used to confirm the presence of only one structure of the dimer in the experiment. From the comparison of the RIDIR spectrum of the observed dimer with the theoretical IR spectra of different structures of the dimer, it is found that the dimer present in the experiment has a V-shaped structure held by N–H···N hydrogen bond, C–H···π, and weakly present π···π stacking interactions. The most important finding of the present study is that the noncovalent interactions present in the observed dimer have a close resemblance with those present between tryptophan and histidine residues in a nonfluorescent flavoprotein. The present spectroscopic investigation on the indole···imidazole dimer has also immense pharmaceutical significance as this imparts molecular level understanding about the binding motifs of the imidazole drugs with the indole chromophore present in proteins.