Stereospecific collision-induced dissociation and vibrational spectroscopy of protonated cyclo (Tyr-Pro)

The protonated cyclo (LTyr-LPro) and cyclo (LTyr-DPro) dipeptides based on a diketopiperazine (DKP) ring are studied by tandem mass spectrometry in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Collision-induced dissociation (CID) and infrared multiple-photon dissociation (IRMPD) spectroscopy results are interpreted with the aid of quantum chemical calculations and chemical dynamics simulations. All the conformers identified for each diastereomer, denoted c-LLH+ and c-LDH+, respectively, are protonated on the carbonyl group of the tyrosine. The most stable form has an extended structure with the aromatic ring oriented outside the DKP ring; it is stabilized by an OH+…π interaction. Distinct IR signatures are obtained for the extended conformers of c-LLH+ and c-LDH+, which differ by the strength of the OH+…π interaction, much stronger in c-LLH+. Less stable species with the aromatic ring folded over the DKP ring are kinetically trapped in our experimental conditions, but their IR spectrum is identical for c-LLH+ and c-LDH+. The main collision-induced dissociation products of the protonated dipeptides are analyzed using chemical dynamics simulations. More efficient CID is observed for c-LDH+, in particular for the formation of the iminium ion of tyrosine. In contrast to the monomers, the protonated dimers of c-LLH+ and c-LDH+ show identical IR spectra. This is explained in terms of a structure involving a single strong OH+…O interaction between subunits not sensitive to the absolute configuration of the residues, i.e., from a folded protonated monomer to an extended neutral monomer. [Display omitted] •The two diastereomers of the protonated cyclo (tyrosyl-prolyl) dipeptide are studied in an ICR ion trap.•Vibrational spectra are obtained by Infra-Red Multiple Photon Dissociation.•The nature of the collision-induced dissociation (CID) products is interpreted by chemical molecular dynamics.•Both structures and CID efficiencies depend on the absolute configuration of the residues.•A stronger OH+…π interaction in the natural LL protonated dipeptide explains its larger stability.