First Direct Evidence of Interpartner Hydride/Deuteride Exchanges for Stored Sodiated Arginine/Fructose-6-phosphate Complex Anions within Salt-Solvated Structures

Abstract

Mass spectrometric investigations of non-covalent binding between low molecular weight compounds revealed the existence of gas phase (GP) noncovalent complex (NCC) ions involving zwitterionic structures. ESI MS is used to prove the formation of stable sodiated NCC anions between fructose (F6P) and arginine (R) moieties.Theoretical calculations indicate a folded solvated salt (i.e., sodiated carboxylate interacting with phosphate) rather than a charge-solvated form. Under standard CID conditions, [(F6P+R-H+Na)-H]competitively forms two major product ions (PIs) through partner splitting [(R-H+Na) loss] and charge-induced cross-ring cleavage while preserving the noncovalent interactions (noncovalent product ions (NCPIs)).MS/MS experiments combined with in-solution proton/deuteron exchanges (HDXs) demonstrated an unexpected labeling of PIs i.e., a correlated D-enrichment/D-depletion. Increase in activation time up to 3000 ms favors such processes when limited to two H/D exchanges. These results are rationalized by inter-partner hydride/deuteride exchanges (<HDX>) through stepwise isomerization/dissociation of sodiated NCC-d11 anions.In addition, the D-enrichment/D-depletion discrepancy is further explained by back HDX with residual water in LTQ (selective for the isotopologue NCPIs as shown by PI relaxation experiments). Each isotopologue leads to only one back HDX unlike multiple HDXs generally observed in GP. This behavior shows that NCPIs are zwitterions with charges solvated by a single water molecule, thus generating a back HDX through a relay mechanism, which quenches the charges and prevents further back HDX. By estimating back HDX impact on Ddepletion, the inter-partner <HDX> complementarity was thus illustrated. This is the first description of interpartner <HDX>and selective back HDX validating salt solvated structures.

Discovery and quantification of lipoamino acids in bacteria

“…Main displayed fragmentations in product ion spectra of the deprotonated C13-Asn. General interpretations of even-electron molecular ionic species are based on the following considerations: (i) deprotonation can occur competitively at carboxylic acid, amide and enolizable ester sites resulting in a mixture of various [LpAA-H] deprotomers [32], (ii) the negative (or positive) charge exclusively promotes fragmentations under low collision energy conditions and (iii) dissociations may yield simple cleavages as well as rearrangements. The latter can occur directly or through stepwise processes (e.g.…”

Energy-Resolved Ion Mobility Spectrometry: Composite Breakdown Curves for Distinguishing Isomeric Product Ions

“…Alternatively, [(C16Glu-H)-H 2 O] − , m / z 366 (or [(C12Glu-H)-H 2 O] − , m / z 310) formed from molecular deprotomer (nomenclature introduced in ref ) with amidate structure yields consecutively [ y- H 2 O] − ( m / z 128, Figure c) rather than from the carboxylate deprotomer (competitive m / z 255 ( m / z 199) and m / z 128 formation, Figure a). The nitrogen atom of amidate (Figure c) may also yield nucleophilic attack at the γ-carboxylic acid, resulting in the five-membered tetrahedral intermediate.…”

“…The former mode allows exclusive activation of the selected precursor ion (essentially yielding competitive dissociations), while the latter leads to activation of the precursor ion followed by that of the product ions which can decompose consecutively and competitively (Figure S1). ERMS profiles allow (i) distinction of isomeric precursor ions, 10 (ii) a contribution to a better understanding of dissociations, even those taking place along complex pathways such as via an ion−dipole intermediate, 11 and (iii) estimation of E Threshold for selected ion dissociations. 12 Formation of a product ion with isomeric forms generated by different pathways from a precursor ion with one unique structure had not previously been described by ERMS using commercial tandem MS.…”

Hydrogen/deuterium exchange mass spectrometry in the world of small molecules

“…Finally, a recent study on the sodiated d11‐noncovalent complex (d11‐NCC) anion constituted by d7‐arginine (R d7 ) and d6‐fructose‐6‐phosphate (F6P d6 ) partners (all mobile protons being exchanged: [(F6P d6 + R d7 −D + Na)‐D] − ) submitted to resonant excitation in an ion trap cell such as LTQ (linear ion trap quadrupole) shows two main competitive dissociations (Darii et al, 2021): (i) one involves the sodiated d11‐NCC anion splitting into the [F6P d6 −D] − anion and (ii) the second yields the [(F6P d6 + R d7 −D + Na)‐C 3 H 3 D 3 O 3 ] − product anion resulting from cross‐ring covalent bond cleavage without weakening the noncovalent interaction. Interestingly, the latter is characterized by a d ‐depletion resulting by an one and two D/H exchanges related to the C 3 H 2 D 4 O 3 and C 3 HD 5 O 3 releases rather than the expected C 3 H 3 D 3 O 3 neutral.…”