Molecular Framework Modification in Mass Spectrometry: Atom Exchange, Insertion, and Deletion.

Area of Science:

• Analytical Chemistry
• Organic Chemistry
• Mass Spectrometry

Background:

• Mass spectrometry (MS) is known to induce molecular rearrangements in gas-phase ions.
• Electrospray ionization (ESI) is a common ionization technique used in MS.
• Skeletal rearrangements involve changes in the carbon framework of molecules.

Purpose of the Study:

• To explore skeletal rearrangements occurring during the electrospray ionization (ESI) process.
• To investigate atom exchange, insertion, and deletion reactions within ring systems.
• To demonstrate the intrinsic reactivity of ESI-MS for molecular transformations.

Main Methods:

• Electrospray ionization mass spectrometry (ESI-MS).
• MSⁿ and high-resolution MS (HRMS) for detailed analysis.
• Exact-mass measurements and isotopic distribution analysis for product identification.
• MS/MS fragmentation analysis and comparison with authentic standards.

Main Results:

• Observed skeletal rearrangements including atom exchange, insertion, and deletion in pre-existing ring systems.
• Demonstrated ESI-MS reactivity through reactions like Baeyer-Villiger oxidation, Beckmann rearrangement, Favorskii rearrangement, and a novel sulfur-for-oxygen exchange.
• Confirmed product identities using HRMS, isotopic patterns, and MS/MS fragmentation.

Conclusions:

• ESI-MS is an intrinsically reactive technique capable of inducing significant molecular framework modifications.
• These findings expand the scope of reactive MS derivatization.
• The study opens avenues for novel strategies in late-stage functionalization of molecules.