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Over the course of the COVID-19 pandemic, mRNA-based vaccines have gained tremendous importance. The development and analysis of modified RNA molecules benefit from advanced mass spectrometry and require sufficient understanding of fragmentation processes. Analogous to the degradation of RNA in solution by autohydrolysis, backbone cleavage of RNA strands was equally observed in the gas phase; however, the fragmentation mechanism remained elusive. In this work, autohydrolysis-like intermediates were generated from isolated RNA dinucleotides in the gas phase and investigated using cryogenic infrared spectroscopy in helium nanodroplets. Data from both experiment and density functional theory provide evidence for the formation of a five-membered cyclic phosphate intermediate and rule out linear or six-membered structures. Furthermore, the experiments show that another prominent condensed-phase reaction of RNA nucleotides can be induced in the gas phase: the tautomerization of cytosine. Both observed reactions are therefore highly universal and intrinsic properties of the investigated molecules., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Im Laufe der COVID‐19 Pandemie haben mRNA‐basierte Impfstoffe an immenser Bedeutung gewonnen. Massenspektrometrie ist für die Entwicklung und Analyse von modifizierten RNA Molekülen unerlässlich, setzt jedoch ein grundlegendes Verständnis über Fragmentierungsprozesse voraus. Analog zu der Zersetzung von RNA in Lösung durch Autohydrolyse, kann die Spaltung des RNA Rückgrats ebenso in der Gasphase stattfinden. Bislang sind die Fragmentierungsmechanismen jedoch unzureichend untersucht. In dieser Arbeit wurden Intermediate aus isolierten RNA Dinukleotiden in der Gasphase generiert und mittels kryogener Infrarotspektroskopie in Helium‐Nanotröpfchen untersucht. Die experimentellen Daten, unterstützt durch Dichtefunktionaltheorie, liefern Hinweise dafür, dass die Bildung eines fünfgliedrigen zyklischen Phosphat‐Intermediats begünstigt ist, während lineare oder sechsgliedrige Strukturen ausgeschlossen werden können. Weiterhin zeigen die Experimente, dass eine zusätzliche, bekannte Reaktion von RNA Nukleotiden in Lösung auch in der Gasphase induziert werden kann: die Tautomerisierung von Cytosin. Die beiden beobachteten Reaktionen spiegeln daher universelle und intrinsische Eigenschaften der untersuchten Moleküle wider. [ABSTRACT FROM AUTHOR]

Over the course of the COVID‐19 pandemic, mRNA‐based vaccines have gained tremendous importance. The development and analysis of modified RNA molecules benefit from advanced mass spectrometry and require sufficient understanding of fragmentation processes. Analogous to the degradation of RNA in solution by autohydrolysis, backbone cleavage of RNA strands was equally observed in the gas phase; however, the fragmentation mechanism remained elusive. In this work, autohydrolysis‐like intermediates were generated from isolated RNA dinucleotides in the gas phase and investigated using cryogenic infrared spectroscopy in helium nanodroplets. Data from both experiment and density functional theory provide evidence for the formation of a five‐membered cyclic phosphate intermediate and rule out linear or six‐membered structures. Furthermore, the experiments show that another prominent condensed‐phase reaction of RNA nucleotides can be induced in the gas phase: the tautomerization of cytosine. Both observed reactions are therefore highly universal and intrinsic properties of the investigated molecules. [ABSTRACT FROM AUTHOR]

Autohydrolysis, Fragmentation, Infrared Spectroscopy, Mass Spectrometry, RNA Keywords: Autohydrolysis; Fragmentation; Infrared Spectroscopy; Mass Spectrometry; RNA EN Autohydrolysis Fragmentation Infrared Spectroscopy Mass Spectrometry RNA 1 1 1 04/27/22 20220502 NES 220502 B RNA b In their Communication (e202115481), Kevin Pagel et al. use cryogenic gas-phase infrared spectroscopy to study the key intermediate of RNA autohydrolysis. Frontispiece: Studying the Key Intermediate of RNA Autohydrolysis by Cryogenic Gas-Phase Infrared Spectroscopy. [Extracted from the article]

Keywords: Autohydrolyse; Fragmentierung; Infrarotspektroskopie; Massenspektrometrie; RNA DE Autohydrolyse Fragmentierung Infrarotspektroskopie Massenspektrometrie RNA 1 1 1 04/27/22 20220502 NES 220502 B RNA b In ihrer Zuschrift (e202115481) verwenden Kevin Pagel et al. kryogene Gasphasen-Infrarotspektroskopie zur Untersuchung der Schlüsselzwischenstufe der RNA-Autohydrolyse. [Extracted from the article]