Electron transfer dissociation versus collisionally activated dissociation of cationized biodegradable polyesters

Abstract

Biodegradable polyesters were ionized by electrospray ionization and characterized by tandem mass spectrometry using collisionally activated dissociation (CAD) and electron transfer dissociation (ETD) as activation methods. The compounds studied include one homopolymer, polylactide and two copolymers, poly(ethylene adipate) and poly(butylene adipate). CAD of [M+2Na](2+) ions from these polyesters proceeds via charge-remote 1,5-H rearrangements over the ester groups, leading to cleavages at the (CO)O-alkyl bonds. ETD of the same precursor ions creates a radical anion at the site of electron attachment, which fragments by radical-induced cleavage of the (CO)O-alkyl bonds and by intramolecular nucleophilic substitution at the (CO)-O bonds. In contrast to CAD, ETD produces fragments in one charge state only and does not cause consecutive fragmentations, which simplifies spectral interpretation and permits conclusive identification of the correct end groups. The radical-site reactions occurring during ETD are very similar with those reported for ETD of protonated peptides. Unlike multiply protonated species, multiply sodiated precursors form ion pairs (salt bridges) after electron transfer, thereby promoting dissociations via nucleophilic displacement in addition to the radical-site dissociations typical in ETD.

Electron transfer dissociation of sodium cationized polyesters: Reaction time effects and combination with collisional activation and ion mobility separation

“…ETD employs ion-ion reactions between a negatively charged reagent anion and a multiply charged precursor cation to energetically excite the precursor so that it decomposes into structurally indicative fragments [5][6][7][8][9]. Our study, conducted on a quadrupole ion trap (QIT) mass spectrometer, showed that ETD of metal-cationized polyesters results in both radical-induced reactions that cleave the COO alkyl bonds as well as charge-induced reactions that cleave the CO O bonds [4], ultimately leading to more types of fragments than CAD, which mainly proceeds via charge-remote 1,5-H rearrangements that cleave the COO alkyl bonds [4,[10][11][12]. Meanwhile, the extent of consecutive fragmentations, which may compromise end group determination, was negligible in ETD, but significant in CAD [4].…”

“…Meanwhile, the extent of consecutive fragmentations, which may compromise end group determination, was negligible in ETD, but significant in CAD [4]. These features indicate that ETD could develop into a promising MS 2 method, complementary to CAD, for the determination of polyester structures [4,13], as is true for many types of biopolymers [14][15][16][17][18].…”

“…The QIT was a Bruker HCT Ultra II ion trap (Bruker Daltronics, Billerica, MA) [4,29]. With this instrument, the samples were infused into the ESI source at a flow rate of 3 L/min.…”

“…Our study, conducted on a quadrupole ion trap (QIT) mass spectrometer, showed that ETD of metal-cationized polyesters results in both radical-induced reactions that cleave the COO alkyl bonds as well as charge-induced reactions that cleave the CO O bonds [4], ultimately leading to more types of fragments than CAD, which mainly proceeds via charge-remote 1,5-H rearrangements that cleave the COO alkyl bonds [4,[10][11][12]. Meanwhile, the extent of consecutive fragmentations, which may compromise end group determination, was negligible in ETD, but significant in CAD [4]. These features indicate that ETD could develop into a promising MS 2 method, complementary to CAD, for the determination of polyester structures [4,13], as is true for many types of biopolymers [14][15][16][17][18].…”

“…The most widely used technique in synthetic polymer analyses has undoubtedly been collisionally activated dissociation (CAD) [2,3]. We recently reported the first MS 2 study using electron transfer dissociation (ETD), which was applied to the characterization of biodegradable polyesters [4]. ETD employs ion-ion reactions between a negatively charged reagent anion and a multiply charged precursor cation to energetically excite the precursor so that it decomposes into structurally indicative fragments [5][6][7][8][9].…”