Spectroscopic Evidence for Lactam Formation in Terminal Ornithine b2+ and b3+ Fragment Ions

Zachary M Smith; Xiye Wang; Jonathan R Scheerer; Jonathan Martens; Giel Berden; Jos Oomens; Vincent Steinmetz; Arpad Somogyi; Vicki Wysocki; John C Poutsma

doi:10.1007/s13361-019-02244-0

Spectroscopic Evidence for Lactam Formation in Terminal Ornithine b₂⁺ and b₃⁺ Fragment Ions

J Am Soc Mass Spectrom. 2019 Sep;30(9):1565-1577. doi: 10.1007/s13361-019-02244-0. Epub 2019 Jun 10.

Authors

Affiliations

¹ Department of Chemistry, The College of William & Mary, Williamsburg, VA, 23187-8795, USA.
² Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Nijmegen, The Netherlands.
³ Laboratorie de Chimie Physique, CNRS UMR 8000, Université Paris, 91405, Orsay, France.
⁴ Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, 43210-1173, USA.
⁵ Department of Chemistry, The College of William & Mary, Williamsburg, VA, 23187-8795, USA. jcpout@wm.edu.

Abstract

Infrared multiple photon dissociation action spectroscopy was performed on the AlaOrn b₂⁺ and AlaAlaOrn b₃⁺ fragment ions from ornithine-containing tetrapeptides. Infrared spectra were obtained in the fingerprint region (1000-2000 cm^-1) using the infrared free electron lasers at the Centre Laser Infrarouge d'Orsay (CLIO) facility in Orsay, France, and the free electron lasers for infrared experiments (FELIX) facility in Nijmegen, the Netherlands. A novel terminal ornithine lactam AO⁺ b₂⁺ structure was synthesized for experimental comparison and spectroscopy confirms that the b₂⁺ fragment ion from AOAA forms a lactam structure. Comparison of experimental spectra with scaled harmonic frequencies at the B3LYP/6-31+G(d,p) level of theory shows that AO⁺ b₂⁺ forms a terminal lactam protonated either on the lactam carbonyl oxygen or the N-terminal nitrogen atom. Several low-lying conformers of these isomers are likely populated following IRMPD dissociation. Similarly, a comparison of the experimental IRMPD spectrum with calculated spectra shows that AAO⁺ b₃⁺-ions also adopt a lactam structure, again with multiple different protonation sites, during fragmentation. This study provides spectroscopic confirmation for the lactam cyclization proposed for the "ornithine effect" and represents an alternative b_n⁺ structure to the oxazolone and diketopiperazine/macrocycle structures most often formed.

Keywords: IRMPD spectroscopy; Peptide fragmentation; b2+ ions.

Abstract

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