Do d(GCGAAGC) Cations Retain the Hairpin Structure in the Gas Phase? A Cyclic Ion Mobility Mass Spectrometry and Density Functional Theory Computational Study

0577006 - MBÚ 2024 RIV US eng J - Journal Article
Wan, J. - Nytka, M. - Qian, H. - Lemr, Karel - Tureček, F.
Do d(GCGAAGC) Cations Retain the Hairpin Structure in the Gas Phase? A Cyclic Ion Mobility Mass Spectrometry and Density Functional Theory Computational Study.
Journal of the American Society for Mass Spectrometry. Roč. 34, č. 10 (2023), s. 2323-2340. ISSN 1044-0305. E-ISSN 1879-1123
Institutional support: RVO:61388971
Keywords : Computation theory * Density functional theory * Dissociation * Electrospray ionization * Gases * Hydrogen bonds * Ion mobility spectrometers * Mass spectrometry * Oligonucleotides
OECD category: Microbiology
Impact factor: 3.2, year: 2022
Method of publishing: Limited access
https://pubs.acs.org/doi/10.1021/jasms.3c00228

d(GCGAAGC) is the smallest oligonucleotide with a well-defined hairpin structure in solution. We report a study of multiply protonated d(GCGAAGC) and its sequence-scrambled isomers, d(CGAAGCG), d(GCGAACG), and d(CGGAAGC), that were produced by electrospray ionization with the goal of investigating their gas-phase structures and dissociations. Cyclic ion mobility measurements revealed that dications of d(GCGAAGC) as well as the scrambled-sequence ions were mixtures of protomers and/or conformers that had collision cross sections (CCS) within a 439-481 & Aring,(2) range. Multiple ion conformers were obtained by electrospray under native conditions as well as from aqueous methanol. Arrival time distribution profiles were characteristic of individual isomeric heptanucleotides. Extensive Born-Oppenheimer molecular dynamics (BOMD) and density functional theory (DFT) calculations of d(GCGAAGC)(2+) isomers indicated that hairpin structures were high-energy isomers of more compact distorted conformers. Protonation caused a break up of the C2<middle dot><middle dot><middle dot>G6 pair that was associated with the formation of strong hydrogen bonds in zwitterionic phosphate anion-nucleobase cation motifs that predominated in low energy ions. Multiple components were also obtained for d(GCGAAGC)(3+) trications under native and denaturing electrospray conditions. The calculated trication structures showed disruption of the G<middle dot><middle dot><middle dot>C pairs in low energy zwitterions. A hairpin trication was calculated to be a high energy isomer. d(GCGAAGC)(4+) tetracations were produced and separated by c-IMS as two major isomers. All low energy d(GCGAAGC)(4+) ions obtained by DFT geometry optimizations were zwitterions in which all five purine bases were protonated, and the ion charge was balanced by a phosphate anion. Tetracations of the scrambled sequences were each formed as one dominant isomer. The CCS calculated with the MobCal-MPI method were found to closely match experimental values. Collision-induced dissociation (CID) spectra of multiply charged heptanucleotides showed nucleobase loss and backbone cleavages occurring chiefly at the terminal nucleosides. Electron-transfer-CID tandem mass spectra were used to investigate dissociations of different charge and spin states of charge-reduced heptanucleotide cation radicals.
Permanent Link: https://hdl.handle.net/11104/0347825