Collision Cross-Section Measurements of Collision-Induced Dissociation Precursor and Product Ions in an FTICR-MS and an IM-MS: A Comparative Study

Abstract

Sustained off-resonance irradiation-cross-sectional areas by Fourier transform ion cyclotron resonance mass spectrometry (SORI-CRAFTI) is an FTICR-MS strategy to collisionally activate precursor ions and then measure their ion-neutral collision cross sections, as well as those of selected products, at the same time. We benchmarked SORI-CRAFTI using protonated leucine-enkephalin, to excellent agreement (typically within 1–2%) with previous studies performed via collision-induced dissociation-ion mobility (CID-IMS). SORI-CRAFTI was then applied to alkali metal-cationized leucine-enkephalin and compared with CID-IMS via precursor/product cross-section ratios. Qualitative agreement between SORI-CRAFTI and CID-IMS was excellent (again, usually within 1–2%); however, neither SORI-CRAFTI nor CID-IMS could determine if metalated leucine-enkephalin was present in its canonical or zwitterionic form. When SORI-CRAFTI was used on [2.2.2]-cryptand+Cs+, SORI activation resulted in a 5% decrease in collision cross section, consistent with migration of the externally bound Cs+ into the cryptand’s cavity and similar to the cross section observed when electrospraying from an isopropanol-rich solvent. Thus, SORI-CRAFTI is useful for studying gas-phase ion chemistry of small- to medium-sized molecules and host–guest systems.

Advancing Orbitrap Measurements of Collision Cross Sections to Multiple Species for Broad Applications

“…16 This method has been employed for determination of CCSs of a wide array of analytes ranging from small molecules 14,15,25 to proteins 16 and more recently has been used to study structural changes upon binding of alkali metal ions to the peptide leucine enkephalin and a macrocyclic cryptand as well as measure CCSs of product ions generated from collisional activated dissociation of the complexes. 26 The possibility of measuring CCS by using an Orbitrap mass spectrometer was first proposed in 2009, in which it was surmised that relative CCSs could be determined by the rate of transient signal decay in the time domain (eq 2), where c represents the decay constant and N o represents the number of ions at time zero. 27 This decay constant along with the ion's path length (l) and frequency (f 0 ) may be used to calculate CCS as shown in eq 3.…”

“…CCS measurements were first reported using FT-ICR mass spectrometers several decades ago, − and a more recent strategy adapted for FT-ICR instruments developed a relationship between the full width half-maximum (FWHM) of the frequency domain peak (Δω) and CCS (σ) (eq ) derived from the hard-sphere collision model description of ion-neutral collisions. − , σ = normalΔ ω N v To establish this relationship, the ion’s speed ( v ) and the pressure within the ICR cell must also be defined, the latter of which was used to calculate the density of neutral gas molecules ( N ) . This method has been employed for determination of CCSs of a wide array of analytes ranging from small molecules ,, to proteins and more recently has been used to study structural changes upon binding of alkali metal ions to the peptide leucine enkephalin and a macrocyclic cryptand as well as measure CCSs of product ions generated from collisional activated dissociation of the complexes . The possibility of measuring CCS by using an Orbitrap mass spectrometer was first proposed in 2009, in which it was surmised that relative CCSs could be determined by the rate of transient signal decay in the time domain (eq ), where c represents the decay constant and N o represents the number of ions at time zero .…”