2009. "Effect of the Surface on Charge Reduction and Desorption Kinetics of Soft Landed Peptide Ions." Journal of the American Society for Mass Spectrometry 20(6):901-906. Abstract Charge reduction and desorption kinetics of ions and neutral molecules produced by soft-landing of mass-selected singly and doubly protonated Gramicidin S (GS) on different surfaces was studied using time dependant in situ secondary ion mass spectrometry (SIMS) integrated in a specially designed Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) research instrument. Soft-landing targets utilized in this study included inert self-assembled monolayers (SAMs) of 1-dodecane thiol (HSAM) and its fluorinated analog (FSAM) on gold and hydrophilic carboxyl-terminated (COOH-SAM) and amine-terminated (NH2-SAM) SAM surfaces. We observed efficient neutralization of soft-landed ions on the COOH-SAM surface, partial retention of only one proton on the HSAM surface and efficient retention of two protons on the FSAM surface. Slow desorption rates measured experimentally indicate fairly strong binding between peptide molecules and SAM surfaces with the binding energy of 20-25 kcal/mol.
2007. "Is Dissociation of Peptide Radical Cations an Ergodic Process?" Journal of the American Chemical Society 129(31):9598-9599. Abstract Achieving a fundamental understanding of the mechanism of unimolecular dissociation of internally excited complex molecules is one of the most important challenges in modern mass spectrometry. One of the central questions is whether the dissociation of large molecules is properly described by statistical theories—RRKM/QET or Phase Space Theories —that have proved to be remarkably successful both for small molecules and a number of small and medium size peptides. The concept question is whether the ergodic assumption that the internal excitation of the ion is randomly redistributed among the vibrational degrees of freedom prior to fragmentation is satisfied for large molecules. The validity of the ergodic hypothesis for dissociation of gas-phase biomolecules has been recently reviewed and will be only briefly discussed here.
2007. "Charge Retention by Peptide Ions Soft-Landed onto Self-Assembled Monolayer Surfaces." International Journal of Mass Spectrometry 265(1):237-243. Abstract Soft-landing of singly and doubly protonated peptide ions onto three self-assembled monolayer surfaces (SAMs) was performed using a novel ion deposition instrument constructed in our laboratory and a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially designed for studying collisions of large ions with surfaces.. Modified surfaces were analyzed using in situ 2 keV Cs+ secondary ion mass spectrometry or ex situ 15 keV Ga+ time-of-flight secondary ion mass spectrometry (ToF-SIMS). The results demonstrate that a fraction of multiply protonated peptide ions retain more than one proton following soft-landing on the FSAM surface. [M+2H]2+ ions observed in FT-ICR SIMS spectra are produced by desorption of multiply charged ions from the surface, while re-ionization of singly protonated ions or neutral peptides is a source of [M+2H]2+ ions in Tof-SIMS spectra. Differences in neutralization efficiency of soft-landed ions following exposure of surfaces to laboratory air has a measurable effect on the results of ex situ ToF-SIMS analysis of soft-landed ions on SAM surfaces.
2007. "First Observation of Charge Reduction and Desorption Kinetics of Multiply Protonated Peptides Soft Landed onto Self-Assembled Monolayer Surfaces." Journal of Physical Chemistry C 111(49):18220-18225. doi:10.1021/jp075293y Abstract The kinetics of charge reduction and desorption of different species produced by soft-landing of mass-selected ions was studied using in situ secondary ion mass spectrometry (SIMS) in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS). The improved SIMS capability described in this work utilizes an in-line 8 keV Cs+ ion gun and allows us to interrogate the surface both during the ion deposition and after the deposition is terminated. As a model system doubly protonated ions of Gramicidin S were deposited onto a fluorinated self-assembled monolayer (FSAM) surface. Our results demonstrate for the first time that various peptide-related peaks in FT-ICR SIMS spectra follow very different kinetics. We obtained unique kinetics signatures for doubly protonated, singly protonated and neutral peptides retained on the surface and followed their evolution as a function of time. The experimental results are in excellent agreement with a kinetic model that takes into account charge reduction and thermal desorption of different species from the surface.
2007. "Design and Performance of a Novel Instrument for Soft-Landing of Biomolecular Ions on Surfaces." Analytical Chemistry 79(17):6566-6574. doi:10.1021/ac070600h Abstract A new ion deposition apparatus was designed and constructed in our laboratory. Our research objectives were to investigate interactions of biomolecules with hydrophilic and hydrophobic surfaces and to carry out exploratory experiments aimed at highly-selective deposition of spatially defined and uniquely selected biological molecules on surfaces. The apparatus includes a high-transmission electrospray ion source, quadrupole mass filter, bending quadrupole that deflects the ion beam and prevents neutral molecules originating in the ion source from impacting the surface, an ultrahigh vacuum (UHV) chamber for ion deposition by soft landing, and a vacuum-lock system for introducing surfaces into the UHV chamber without breaking vacuum. Ex situ analysis of surfaces following soft-landing of mass-selected peptide ions was performed using 15 keV Ga+ time-of-flight secondary ion mass spectrometry (TOF-SIMS) and grazing incidence infrared reflection-absorption spectroscopy (IRRAS). It will be shown that these two techniques are highly complementary methods for characterization of surfaces prepared with a range of doses of mass-selected biomolecular ions.
2006. "Mechanisms of Peptide Fragmentation from Time-and Energy-Resolved Surface-Induced Dissociation Studies: Dissociation of Angiotensin Analogs." International Journal of Mass Spectrometry 249-250:462-472. Abstract Energetics and mechanism of dissociation of singly protonated angiotensin III (RVYIHPF) and its analogs RVYIFPF, RVYIYPF, RVYIHAF, and RVYIHDF was studied using surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for studying ion activation by collisions with surfaces. The energetics and dynamics of peptide fragmentation were deduced by modeling the time- and energy-resolved survival curves for each precursor ion using an RRKM based approach developed in our laboratory. Fragmentation mechanisms were inferred from comparison of time- and energy-resolved fragmentation efficiency curves (TFECs) of different fragment ions followed by RRKM modeling of dissociation of angiotensin III into six major families of fragment ions. Detailed modeling demonstrated that dissociation of these peptides is dominated by loss of ammonia from the precursor ion and characterized by a high energy barrier of 1.6 eV. Loss of NH3 and subsequent rearrangement of the MH-NH3 ion results in proton mobilization and release of ca. 30 kcal/mol into internal excitation of the MH-NH3 ion. The resulting highly excited ion accesses a variety of non-specific dissociation pathways with very high rate constants. Fast fragmentation of excited MH-NH3 ion forms a variety of abundant bn-NH3 and an-NH3 fragment ions. Abundant XH and HX internal fragments are also formed, reflecting the stability of histidine-containing diketopiperazine structures.
2006. "Protein Identification Via Surface-Induced Dissociation in an FT-ICR Mass Spectrometer and a Patchwork Sequencing Approach." Journal of the American Society for Mass Spectrometry 17(5):700-709. Abstract Surface-induced dissociation (SID) and collision-induced dissociation (CID) are ion activation techniques based on energetic collisions with a surface or gas molecules, respectively. One noticeable difference between CID and SID is that SID does not require a collision gas for ion activation and is therefore directly compatible with the high vacuum requirement of Fourier Transform Ion Cyclotron Resonance mass spectrometers (FT-ICR MS). Eliminating the introduction of collision gas into the ICR cell for collisional activation dramatically shortens the acquisition time for MS/MS experiments, suggesting that SID could be utilized for high-throughput MS/MS studies in FT-ICR MS. We demonstrate for the first time the utility of SID combined with FT-ICR MS for protein identification. Tryptic digests of standard proteins were analyzed using a hybrid 6-Tesla FT-ICR MS with SID and CID capabilities. SID spectra of mass-selected singly and doubly charged peptides were obtained using a diamond-coated target mounted at the rear trapping plate of the ICR cell. The broad internal energy distribution deposited into the precursor ion following collision with the diamond surface allowed a variety of fragmentation channels to be accessed by SID. Composition and sequence qualifiers produced by SID of tryptic peptides were used to improve the statistical significance of database searches. Protein identification MASCOT scores obtained using SID were comparable or better than scores obtained using sustained off-resonance irradiation collision-induced dissociation (SORI-CID) –the conventional ion activation technique in FT-ICR MS.
2006. "Soft-Landing of Peptides onto Self-Assembled Monolayer Surfaces." Journal of Physical Chemistry A 110(4):1678-1687. doi:10.1021/jp0555044 Abstract Mass-selected peptide ions produced by electrospray ionization were deposited as ions by soft-landing onto fluorinated and hydrogenated self-assembled monolayer surfaces (FSAM and HSAM) surfaces using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially designed for studying interactions of large ions with surfaces. Analysis of the modified surface was performed in situ by combining 2 keV Cs+ secondary ion mass spectrometry with FT-ICR detection of the sputtered ions (FT-ICR-SIMS). Collision energy dependent data indicated that peptide fragmentation observed in Cs+ SIMS analysis of surfaces modified by soft landing occurred in the analysis step (SIMS) rather than during ion deposition. The peptide ion deposition efficiency showed a gradual decrease with increase in collision energy which parallels the decrease in the Langevin cross section with ion velocity at impact. Peptide ion soft-landing on FSAM surfaces gave twice the sputtered ion signal seen for hydrocarbon self-assembled monolayer (HSAM) surfaces. This indicates stronger interaction of peptide ions with the FSAM surface, in good agreement with larger polarizability of fluorinated hydrocarbons. The efficiency of soft landing of different peptides on the FSAM surface increases with the charge state of the ion, consistent with an ion-polarizable molecule model for the initial stage of soft landing on SAM surfaces.
2005. "Activation of Large Ions in FT-ICR Mass Spectrometry." Mass Spectrometry Reviews 24(2):135-167. Abstract The advent of soft ionization techniques, notably electrospray and laser desorption ionization methods, has enabled the extension of mass spectrometric methods to large molecules and molecular complexes. This both greatly extends the applications of mass spectrometry and makes the activation and dissociation of complex ions an integral part of these applications. This review emphasizes the most promising methods for activation and dissociation of complex ions and presents this discussion in the context of general knowledge of reaction kinetics and dynamics largely established for small ions. We then introduce the characteristic differences associated with the higher number of internal degrees of freedom and high density of states associated with molecular complexity. This is reflected primarily in the kinetics of unimolecular dissociation of complex ions, particularly their slow decay and the higher energy content required to induce decomposition-the kinetic shift (KS). The longer trapping time for Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) significantly reduces the KS, which presents several advantages over other methods for the investigation of dissociation of complex molecules.
2005. "Preparation and in situ Characterization of Surfaces Using Soft-Landing in a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer." Analytical Chemistry 77(11):3452-3460. Abstract Mass-selected peptide ions produced by electrospray ionization were deposited onto fluorinated self-assembled monolayer surfaces (FSAM) surfaces by soft-landing using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially designed for studying interactions of large ions with surfaces. Analysis of the modified surface was performed in situ by combining 2 keV Cs+ secondary ion mass spectrometry with FT-ICR detection of the sputtered ions (FT-ICR-SIMS). Regardless of the initial charge state of the precursor ion, the SIMS mass spectra included singly-protonated peptide fragment ions and peaks characteristic of the surfaces in all cases. In some experiments multiply-protonated peptide ions and [M+Au]+ ions were also observed upon SIMS analysis of modified surfaces. For comparison with the in situ analysis of the modified surfaces, ex situ analysis of some of the modified surfaces was performed by 25 kV Ga+ time of flight – secondary ion mass spectrometry (ToF-SIMS). The ex situ analysis demonstrated that a significant number of soft-landed peptide ions remain charged on the surface even when exposed to air for several hours after deposition. Charge retention of soft-landed ions dramatically increases the ion yields obtained during SIMS analysis very sensitive detection of deposited material at less than 1% of monolayer coverage. Accumulation of charged species on the surface undergoes saturation due to Coulomb repulsion between charges at close to 30% coverage. We estimated that close to 1 ng of peptide could be deposited on the spot area of 4 mm2 of the FSAM surface without reaching saturation.
2004. "Surface-Induced Dissociation of Ions Produced by Matrix-Assisted Laser Desorption Ionization in a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer." Analytical Chemistry 76(2):351-356. Abstract Intermediate pressure matrix assisted laser ionizaton (MALDI) source was constructed and interfaced with a 6T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for surface-induced dissociation (SID) studies.
2004. "Fragmentation Energetics for Angiotensin II and its Analogs from Time-and Energy-Resolved Surface-Induced Dissociation Studies." International Journal of Mass Spectrometry 234(1-3):89-99. Abstract Surface-induced dissociation (SID) of four model peptides: DRVYIHPF, RVYIHPF, RVYIHAF, and RVYIHDF was studied using a novel Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for SID experiments.
2004. "Relative Proton Affinities from Kinetic Energy Release Distributions for Dissociation of Proton-Bound Dimers: 2. Diamines as a Test Case." International Journal of Mass Spectrometry 233:223-231. Abstract Dissociation of proton-bound dimers containing diamines is often characterized by a substantial entropy difference between the two competing reaction channels. Kinetic energy release distributions (KERDs) upon dissociation of diamine-containing dimers are utilized along with Finite Heat Bath theory analysis to obtain relative proton affinities of monomeric species composing the dimer. When dissociation of a proton-bound dimer is not associated with reverse activation barrier our method provides reliable relative energetics and dynamics.
2003. "Dynamics of the Dissociative and Non-dissociative Scattering of Hyperthermal CS2+ from a Self-Assembled Fluoroalkyl Monolayer Surface on Gold Substrate." Journal of Chemical Physics 118(24):11217-11225. doi:DOI:10.1063/1.1574311 Abstract Dissociative and inelastic scattering of low energy CS2+ ions colliding with a self assembled monolayer surface of fluorinated alkylthiol [CF3 (CF2)9 CH2 CH2SH ] on gold at 45o with respect to the surface normal has been studied using a modified crossed-beam instrument. Dissociation of CS2+ ions begins at about 30 eV collision energy, much higher than the thermochemical threshold of 4.7 eV for the lowest energy dissociation channel forming S+. This product channel is dominant up to ion energy of ~ 50 eV, the highest energy accessible with the present apparatus. Both inelastically scattered parent ions and product ions leave the surface with modest kinetic energies, demonstrating that most of the ions? kinetic energy is taken up by the surface rather than transferred into internal modes of recoiling ions. The scattered ion intensity maximum is found between the specular angle and the surface parallel, consistent with kinematics of an ion-surface collision process that absorbs so much of the kinetic energy of the projectile ion. At all energies studied, projectile ion intensity remains higher than that of fragment ions. Further, the intensity of S+ is higher than that of CS+ fragment ions, suggesting that the distribution of internal excitation of the recoiling CS2+ ions extends only slightly above the thresholds for the two product channels. A comparison of relative intensities with those found for earlier collision-induced dissociation study of the CS2+ ions with xenon suggests that only ~ 6.5 eV and ~7.5 eV are transferred into internal modes for 30.6 eV and 49.8 eV energy collisions, respectively.
2003. "Dynamics of Hyperthermal Energy Ion-Surface Collisions: Dissociative and non-dissociative Scattering of Ethanol cations from a Self-Assembled Monolayer Surface of Fluorinated Alkyl Thiol on Au (111)." International Journal of Mass Spectrometry 223(1-3):783-801. Abstract Dissociation and inelastic scattering of ethanol molecular ions from self-assembled monolayers (SAM) surface of fluorinated alkyl thiol on an Au (111) monocrystal have been studied at 28.9 and 52.9 eV collision energies. A single dynamics mechanism for quasi0inelastic scattering was found at both energies. Ions recoil nearly parallel to the surface with very small kinetic energy losses of the order of <2 eV. Dissociation dynamics featuers for the main dissociation channel, loss of methyl radical, are dramatically different from that of inelastically scattered primary ions and are different at the two collision energies studies. At 28.9 eV two energetically and angularly resolved features are observed, one corresponding to the loss of very large amounts (nearly all) of ion’s translational energy and the other appearing to gain energy (superelastic scattering). This implies a lifetime of such excited ions of more than 5µs. The same dynamics features are observed at 52.9 eV ion energy except that a second inelastic process begins to compete with the nearly fully inelastic process. Moreover, at this energy the delayed ion dissociation mechanism is the dominant mechanism. The hypothesis that collision of ethanol cations useful rationale for the observed dynamics. Support for this hypotheses is provided by Newton diagrams, which summarize momentum conservation relationships in terms of a common center-of-mass, cmeff, which provides a bisis for describing different ion-surface interactions contributing to surface-induced dissociation of ethanol ions. Preliminary experiments with Ar+ scattered from the same surface exhibit very similar dynamics features to the observed for ethanol cations. Finally, we note that intensities of scattered primary or fragment ions never approach the specular angle at the energies investigated here.
2003. "A Beam Scattering Instrument for the Dynamics Studies of Surface-Induced Dissociation Processes." Review of Scientific Instruments 74(1):168-175. Abstract A new beam scattering instrument has been constructed to study the dynamics of ion-surface collisions, especially surface-induced dissociation of polyatomic ions. The instrument uses a bench top double focusing mass spectrometer as the source of a well-defined ion beam for transmission into a collision chamber. The primary ions are decelerated to desired ion energy (as low as 5 eV) by a series of tube lenses and collide the surface at 45 degrees. Thus, the ion energy for surface-induced dissociations can be varied from ~5 cV to >1 keV. The secondary ions are energy and mass analyzed by a cylindrical energy analyzer and quadrupole mass filter, respectively, and detected by a channel electron multiplier operating in pulse counting mode. The detector assembly can be rotated with respect to the collision center between the specular angle and surface parallel to measure intensity and energy distributions of scattered primary and fragment ions as a function of scattering angle. The newly constructed instrument has been tested for its performance and used to study the dissociation of ethanol molecular ions colliding with a self-assembled monolayer surface of fluorinated thiol on gold (111) crystal and first results are presented here.
2003. ""Surface-Induced Dissociation of Acetone Cations from Self-Assembled Monolayer Surface of Flourinated Alkyl Thiol on Au (111) Substrate at Low Collision Energies"." International Journal of Mass Spectrometry 228(2-3):563-576. Abstract We have studied the dissociation of acetone molecular cations to acetyl cations following collision with a monolayer surface of fluorinated alkyl thiol (FC12) self-assembled on Au (111) substrate at 13, 25.2 and 49.6 eV kinetic energies. Three energetically distinct dissociation processes contribute to total dissociation in this energy range. At all energies there is a common dissociation pathway involving loss of nearly all of the parent ion’s kinetic energy in the collision process. Fragment ions resulting from this dissociation mechanism are scattered over a wide range of angles. The second pathway, observed at 25.2 and 49.6 eV kinetic energy is delayed dissociation of collisionally excited acetone cations after only a small fraction of the ion’s kinetic energy is lost in the collision process. Fragment ions resulting from this unique dynamics feature are scattered close to the surface parallel. These dissociations take place after the excited ions have passed through the collision region and the energy analyzer and prior to their entering the mass analyzer. At 49.6 eV kinetic energy, a small intensity fragment ion peak appears at intermediate kinetic energy spectra between the low energy loss and the highly inelastic scattering peaks.
2003. "Surface-Induced Dissociation of Peptide Ions: Kinetics and Dynamics." Journal of the American Society for Mass Spectrometry 14(12):1340-1347. doi:10.1016/j.jasms.2003.08.004 Abstract Kinetics and dynamics studies have been carried out for the surface-induced dissociation (SID) of a set of model peptides utilizing a specially designed electro spray ionization Fourier Transform Ion cyclotron resonance mass spectrometer in which mass-selected and vibrationally relaxed ions are collided on an orthogonally-mounted fluorinated self-assembled monolayer on Au {111} crystal. The sampling time in this apparatus can be varied from hundreds of microseconds to tens of seconds, enabling the investigation of kinetics of ion decomposition over an extended range of decomposition rates. RRKM-based modeling of these reactions for a set of polyalanines demonstrates that kinetics of these simple peptides is very similar to slow, multiple-collision activation and that the distribution of internal energies following collisional activation is indistinguishable from a thermal distribution. For more complex peptides comprised of several amino acids and with internal degrees of freedom (DOF) of the order of 350 there is a dramatic change in kinetics in which RRKM kinetics is no longer capable of describing the decomposition of these complex ions. A combination of RRKM kinetics and the “sudden death” approximation, according to which decomposition occurs instantaneously, is a satisfactory description. This implies that a population of ions – which is dependant on the nature of the peptide, kinetic energy and sampling time – decomposes on or very near the surface. The shattering transition is described quantitatively for the limited set of molecules examined to date.
2003. "Shattering of Peptide Ions on Self-Assembled Monolayer Surfaces. ." Journal of the American Chemical Society 125(6):1625-1632. Abstract ABSTRACT Time- and energy-resolved surface-induced dissociation (SID) of des-Arg1- and des-Arg9-bradykinin on a fluorinated self-assembled monolayer (SAM) surface was studied using a novel Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially equipped to perform SID experiments. Time-resolved data was modeled using an RRKM-based approach developed in our laboratory. Both experimental observations and modeling establish a very sharp transition in the dynamics of ion-surface interaction: the shattering transition. Shattering opens a variety of dissociation pathways that are not accessible to slow collisional and thermal ion activation. This results in a much better sequence coverage for the singly protonated peptides than dissociation patterns obtained with any of the slow activation methods. Modeling demonstrated that for short reaction delays dissociation of these peptides is solely determined by shattering. Internal energies required for shattering transition are approximately the same for des-Arg1 and des-Arg9-bradykinin, resulting in the overlap of fragmentation efficiency curves obtained at short reaction delays. At longer delay times parent ions depletion is mainly determined by a slow decay rate and fragmentation efficiency curves for des-Arg1 and des-Arg9-bradykinin diverge. Dissociation thresholds of 1.17 and 1.09 eV and activation entropies of -22.2 and -23.3 cal/mol K were obtained for des-Arg1 and des-Arg9-bradykinin from RRKM modeling of time-resolved data. Dissociation parameters for des-Arg1-bradykinin are in good agreement with parameters derived from thermal experiments. However, there is a significant discrepancy between the thermal data and dissociation parameters for des-Arg9-bradykinin obtained in this study. The difference is attributed to the differences in conformations that undergo thermal activation and activation by ion-surface collisions prior to dissociation.
2003. "Shattering of Peptide Ions on Self-Assembled Monolayer Surfaces." Journal of the American Chemical Society 125(6):1625-1632. Abstract Time- and energy-resolved surface-induced dissociation (SID) of des-Arg1- and des-Arg9-bradykinin on a fluorinated self-assembled monolayer (SAM) surface was studied using a novel Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially equipped to perform SID experiments. Time-resolved data was modeled using an RRKM-based approach developed in our laboratory. Both experimental observations and modeling establish a very sharp transition in the dynamics of ion-surface interaction: the shattering transition. Shattering opens a variety of dissociation pathways that are not accessible to slow collisional and thermal ion activation. This results in a much better sequence coverage for the singly protonated peptides than dissociation patterns obtained with any of the slow activation methods. Modeling demonstrated that for short reaction delays dissociation of these peptides is solely determined by shattering. Internal energies required for shattering transition are approximately the same for des-Arg1 and des-Arg9-bradykinin, resulting in the overlap of fragmentation efficiency curves obtained at short reaction delays. At longer delay times parent ions depletion is mainly determined by a slow decay rate and fragmentation efficiency curves for des-Arg1 and des-Arg9-bradykinin diverge. Dissociation thresholds of 1.17 and 1.09 eV and activation entropies of ?22.2 and -23.3 cal/mol K were obtained for des-Arg1 and des-Arg9-bradykinin from RRKM modeling of time-resolved data. Dissociation parameters for des-Arg1-bradykinin are in good agreement with parameters derived from thermal experiments. However, there is a significant discrepancy between the thermal data and dissociation parameters for des-Arg9-bradykinin obtained in this study. The difference is attributed to the differences in conformations that undergo thermal activation and activation by ion-surface collisions prior to dissociation.
2003. "Entropy is the Major Driving Force for Fragmentation of Proteins and Protein-Ligand Complexes in the Gas-Phase." Journal of Physical Chemistry A 107:5836-5839. Abstract This paper presents a critical analysis of Arrhenius parameters for gas-phase fragmentation of proteins and protein-ligand complexes reported in the literature. We demonstrate that there is a surprisingly strong correlation between the Arrhenius activation energy (Ea) and the pre-exponential factor (A). This correlation becomes extremely important for reactions characterized by very high or very low values of A. This correlation is a direct consequence of the relative change in the spacing between vibrational levels of the reactant and the transition state for reaction. Converting the Arrhenius activation energy into the threshold energy for the reaction using Tolman’s theorem reveals the true magnitude of the correlation between molecular complexity and stability. Tolman’s correction factor (Ecorr) increases linearly with Log(A) from 3 kcal/mol for Log(A) of 16.2 to 36.4 kcal/mol for Log(A) of 39.2. Threshold energies extracted from the Arrhenius activation parameters for 56 different reactions are the same within the experimental error bars, while the pre-exponential factors differ by many orders of magnitude. This indicates that activation entropy is the major driving force for dissociation of proteins and protein-ligand complexes in the gas phase.
2003. "Energy Transfer in Collisions of Peptide Ions with Surfaces." Journal of Chemical Physics 119(6):3413-3420. Abstract Time- and energy-resolved surface induced (SID) dissociation of a singly protonated octapeptide des-Arg1-bradykinin (PPGFSPFR) was used to study the effect of physical properties of the SID target on the efficiency of translational to vibrational energy transfer (T -> V) in collisions of peptide ions with surfaces. Four SID targets of varying chemical composition and stiffness were examined in this work: self-assembled monolayers of 1-dodecane thiol (HSAM) and its fluorinated analog (CF3(CF2)9C2H4SH - FSAM) on gold, a 300 nm thick layer of lithium fluoride (LiF) on a polished titanium surface, and a 2 µm carbon vapor deposited diamond layer on a titanium surface. An RRKM-based modeling approach was utilized to extract internal energy distributions deposited into the precursor ion upon collisions with different surfaces. We found that the percent of T -> V transfer increases in the order: HSAM (10.1%), LiF (12.0 %), diamond (19.2 %), FSAM (20.5 %). Furthermore, the width of the energy deposition function (EDF) is affected by the properties of the SID target. Collisions of peptide ions with the HSAM surface results in deposition of relatively narrow internal energy distributions with the width of the EDF increasing in the order: HSAM < FSAM < LiF < Diamond. The results demonstrate that surface stiffness has a major effect on the width of the EDF, while the average energy deposited into the ion is mainly affected by the mass of the chemical moiety representing an immediate collision partner for the ion impacting the surface.
2003. "Collisional Activation of Peptide Ions in FT-ICR Mass Spectrometry." Mass Spectrometry Review 22:158-181. Abstract In the last decade characterization of complex molecules, particularly biomolecules became a focus of both fundamental and applied research in mass spectrometry. Most of these studies utilize tandem mass spectrometry (MS/MS) for obtaining structural information for complex molecules. . Tandem mass spectrometry (MS/MS) typically involves the mass selection of a primary ion, its activation by collision or photon excitation, unimolecular decay into fragment ions characteristic of the ion structure and its internal excitation, and mass analysis of the fragment ions. Although the fundamental principles of tandem mass spectrometry of relatively small molecules are fairly well understood, our understanding of the activation and fragmentation of large molecules is much more primitive. For small ions a single energetic collision is sufficient to dissociate the ion but this is not the case for complex molecules. For large ions two fundamental limits severely constrain fragmentation in tandem mass spectrometry. First the center-of-mass collision energy?the absolute upper limit of energy transfer in a collision process?decreases with increasing mass of the projectile ion for fixed ion kinetic energy and neutral mass. Secondly, the dramatic increase in density of states with increasing internal degrees of freedom of the ion decreases the rate of dissociation by many orders of magnitude at a given internal energy. Consequently most practical MS/MS experiments with complex ions involve multiple collision activation (MCA-CID), multi-photon activation or surface-induced dissociation (SID). This review is focused on what has been learned in recent research studies concerned with fundamental aspects of MCA-CID and SID of model peptides with emphasis on experiments carried out using Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS). These studies provide the first quantitative comparison of gas-phase multiple-collision activation and SID of peptide ions. Combining collisional energy-resolved data with RRKM-based modeling revealed the effect of peptide size and identity on energy transfer in collisions ? very important characteristics of ion activation from both fundamental and the analytical perspectives. Finally, the combination of FT-ICR with SID was utilized to carry out the first time-resolved experiments, which examine the kinetics of peptide fragmentation. This has lead to the discovery that the time dependence of ion dissociation varies smoothly up to certain collision energy and then shifts dramatically to a time independent, extensive dissociation. This near instantaneous ?shattering? of the ion generates a large number of relatively small fragment ions. Shattering of ions on surfaces opens up a variety of dissociation pathways that are not accessible using multiple-collision and multiphoton excitation.
2003. "Energetics of Selective Cleavage at Acidic Residues Studied by Time-and Energy-Resolved Surface-Induced Dissociation in FT-ICR-MS." International Journal of Mass Spectrometry 222(1-3):313-327. Abstract Surface-induced dissociation (SID) of four model peptides: LDIFSDF, LDIFSDFR, RLDIFSDF, and LEIFSEFR, was studied using a novel Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially equipped to perform SID experiments. The energetics and dynamics of selective cleavages at acidic residues were deduced by modeling the time- and energy-resolved fragmentation efficiency curves (TFECs) using an RRKM based approach developed in our laboratory. RRKM modeling revealed that addition of a basic residue to the C-terminus of a peptide has a very small effect on the dissociation threshold. However, the dynamics of dissociation is dramatically affected by the presence of the arginine. The Arrhenius pre-exponential factorfor dissociation of LDIFSDF is two orders of magnitude higher than the pre-exponential factor for dissociation of arginine-containing peptides. The difference in the pre-exponential factors is indicative of a complex rearrangement process associated with selective fragmentation. Molecular mechanics modeling of the four parent ions gives some qualitative insight into the differences in fragmentation mechanisms.
2002. "Surface-induced dissociation in a Fourier transform ion cyclotron resonance mass spectrometer: Instrument design and evaluation." Analytical Chemistry 74:3255-3261. Abstract A new Fourier Transform Ion Cyclotron Resonance mass spectrometer (FT-ICR MS) has been constructed in our laboratory. The instrument employs surface-induced dissociation (SID) as an activation method for obtaining structural information on biomolecules in the gas phase. Tandem SID mass spectra can be acquired using either a continuous or a pulsed mode of operation. Collision energy of precursor ion is controlled by a dc offset of the ICR cell. This approach eliminates defocusing of the ion beam by the ion transfer optics as a function of ion kinetic energy and constitutes a significant improvement over our previous experimental setup. Furthermore, it can be easily implemented on any FT-ICR mass spectrometer. Very high signal-to-noise ratios of 200-500 were obtained in single-scan SID mass spectra of model peptides with acquisition time less than 1.1 s. Reasonable SID signal was detected in single-scan spectra with total acquisition time of only 0.3 s. The high signal-to-noise ratio and the fast acquisition time point on a potential application of SID for high-throughput studies in FT-ICR MS.
2002. "On the Relative Stability of Singly Protonated des-Arg1 and des-Arg9 Bradykinins. ." Journal of Physical Chemistry A (106):9832-9836. Abstract Normal-incidence surface-induced dissociation of singly protonated des-Arg1-bradykinin (PPGFSPFR) and des-Arg9-bradykinin (RPPGFSPF) has been studied using a specially designed Fourier Transform Ion Cyclotron Resonance mass spectrometer (FT-ICR MS). We found that with a reaction time of 1 s the collision energy-resolved fragmentation efficiency curve (FEC) for des-Arg9-bradykinin is shifted to lower energies by about 4 eV relative to the FEC for des-Arg1-bradykinin. Because the Arrhenius activation energies found by Williams and co-workers in BIRD experiments are 0.82 eV and 1.2 eV for des-Arg1 and des-Arg9 bradykinin, respectively, we expected to find the reverse order in our long reaction time FTICR-SID experiments. We rationalize the difference between our data and the thermal kinetics using Tolman?s theorem to calculate threshold energies from the Arrhenius activation parameters. The threshold energies are 1.15 eV and 1.24 eV for des-Arg1 and des-Arg9 bradykinin, respectively. However, des-Arg1-bradykinin dissociates via a very tight transition state. Consequently, microcanonical rate-energy dependencies for these two peptides cross at low internal energies. Rate constants of 1 s-1 are reached at internal energies of 7.9 eV for des-Arg1-bradykinin and 6.9 eV for des-Arg9 bradykinin, in excellent agreement with the energy shift in our FECs.
2002. "On the Efficiency of Energy Transfer in Collisional Activation of Small Peptides." Journal of Chemical Physics 116(10):4302-4310. Abstract We present a study of the efficiency of internal excitation of small peptide ions upon multiple-collision activation with Ar and ion-surface interaction with self-assembled monolayers of fluorinated alkylthiol on gold. Internal energy distributions are extracted from RRKM modeling of collision energy-resolved fragmentation efficiency curves for protonated tri-, tetra-, penta-alanine, and prolyltetra-alanine. The efficiency of T?V transfer in surface collisional activation decreases for larger peptides. This is readily rationalized by the corresponding decrease in the center-of-mass collision energy. For all peptides except protonated dialanine, energy transfer upon multiple-collision activation is rather insensitive to the peptide size and composition. The average energy deposited into protonated dialanine is substantially lower than the excitation level achieved for other peptides. Master equation modeling revealed that energy-transfer efficiency in peptide collisions with Ar is the same for all peptides excluding (AA)H+. The results suggest that protonated dialanine has a more extended structure than larger peptides studied in this work.
2002. "Fragmentation Energetics of Small Peptides from Multiple-Collision Activation and Surface-Induced Dissociation in FT-ICR MS." International Journal of Mass Spectrometry 219:189-201. Abstract Collision-induced and surface-induced dissociation of protonated tri- and tetraalanine ((AAA)H+ and (AAAA)H+) were studied using a 7 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS). Energy-resolved fragmentation efficiency curves obtained using both techniques were modeled using RRKM/QET formalism. The stability of small polyalanines decreases with increasing peptide size. The major reaction channels of protonated di- tri-and tetraalanine have dissociation thresholds of 2.11 eV, 1.46 eV and 1.23 eV, respectively. The rates of formation of C-terminal and N-terminal fragments from protonated tetraalanine are the same, while C-terminal fragmentation of trialanine is energetically more demanding than N-terminal fragmentation.
2002. "Relative Proton Affinities from Kinetic Energy Release Distributions for Dissociation of Proton-Bound Dimers." Journal of Physical Chemistry A 106(50):12051-12057. Abstract Kinetic energy release distributions (KERDs) upon dissociation of proton-bound dimers are utilized along with Finite Heat Bath theory analysis to obtain relative proton affinities of monomeric species composing the dimer. The proposed approach allows accurate measurement of relative proton affinities based on KERD measurements for the compound with unknown thermochemical properties versus a single reference base. It also allows distinguishing the cases when dissociation of proton-bound dimers is associated with reverse activation barrier, for which both our approach and the kinetic method become inapplicable. Results are reported for the n-butanol-n-propanol dimer, for which there is no significant difference in entropy effects for two reactions and for the pyrrolidine-1,2-ethylenediamine dimer, which is characterized by a significant difference in entropy effects for the two competing reactions. Relative protonation affinities of -1.0?0.3 kcal/mol for the n-butanol-n-propanol pair and 0.27?0.10 kcal/mol for the pyrrolidine-1,2-ethylenediamine pair are in good agreement with literature values. Relative reaction entropies were extracted from the branching ratio and KERD measurements. Good correspondence was found between the relative reaction entropies for the n-butanol-n-propanol dimer (D(DS?) =-0.3?1.5 cal/mol K) and the relative protonation entropy for the two monomers (D(DSp)=0). However, the relative reaction entropy for the pyrrolidine-1,2-ethylenediamine dimer is higher than the difference in protonation entropies (D(DS?) =8.2?0.5 cal/mol K vs. D(DSp)=5 cal/mol K).
2001. "A Comparative Study of Collision-Induced and Surface-Induced Dissociation. II. Fragmentation of Small Alanine-Containing Peptides in FT-ICR MS. ." Journal of Physical Chemistry B 105(9):1895-1900. Abstract Multiple collision activation (MCA-CID) and surface-induced dissociation (SID) of protonated trialanine, (AAA)H+; tetraalanine, (AAAA)H+; pentaalanine, (AAAAA)H+; and prolyltetraalanine, (PAAAA)H+ were studied using a 7 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS). Fragmentation efficiency curves obtained using both techniques were compared by converting the SID collision energy into an "effective" center-of-mass frame using an arbitrary neutral encounter of mass, MN. The best overlap between the SID and MCA-CID fragmentation efficiency curves was obtained using very similar values of MN for all the peptides, indicating that all the protonated precursor ions were undergoing similar interaction with terminal chemical groups on the fluorinated self-assembled monolayer (SAM) surface. Collision energy-resolved fragmentation efficiency curves obtained using both methods are very similar and both methods of collisional activation result in a quasi-thermal population of ion internal energies. We suggest that ion-surface collisions involve multiple interactions of the projectile ion with chemical groups on the surface with efficient transfer of impact energy into the surface and into the internal energy of the ion. This mechanism, except for time frame for the activation process, is analogous to the sequential gas phase collisional activation of these model peptides.
2000. "Simulation-Based Optimization of the Electrodynamic Ion Funnel for High Sensitivity Electrospray Ionization-Mass Spectrometry." International Journal of Mass Spectrometry 203(1-3):31-47. Abstract High sensitivity is one of the most important requirements for applications of electrospray ionization mass spectrometry (ESI MS). Recent work with the electrodynamic ion funnel has demonstrated that it can provide significantly improved ion transmission through the ESI interface. Here we summarize the results of the simulations for several ion funnel configurations and their comparison with experimental measurements. We also report an alternative treatment of the ion funnel operation based on the effective potential approximation. The analytical relationships derived are used to generalize the results oc computer simulations and develop an optimized ion funnel design. The new configuration reduces the spacing between ring electrodes to 1 mm and provides an optimized profile of the ring electrodes radii. It can also generate a deeper effective potential well, resulting in transmission of higher input ion currents over an extended mass range and increased operating pressure range (up to ~20 Torr). Furthermore, light m/z ion transmission is improved due to suppression of the effective potential wells near the ion funnel exit. Simulations for an optimized ion funnel configuration indicate unit transmission efficiency in the m/z range of interest for most biomolecular research using ESI (approximately m/z 100-5000), for 1-5 Torr pressure and ion currents >~1 nA, typical for low flow rate charge-constrained electrosprays (i.e. nanospray). Experimental results obtained with an improved electrodynamic funnel validate the model and demonstrate its general utility for designing rf-damped focusing elements.
2000. "Tandem Mass Spectrometry: Dissociation of Ions by Collisional Activation." Journal of Mass Spectrometry 35(9):1069-1090. Abstract This Review presents a brief historical introduction to the development of tandem mass spectrometry and its principal applications. It is placed in the context of the general principles underlying mass spectrometry, particularly the relationships between internal energy and fragmentation kinetics. The center-of-mass framework is presented as a convenient means of applying conservation of momentum to the energy transfer problem in tandem mass spectrometry as a means of deducing energy transfer in the collisional activation step and kinetic energy release as activated ions dissociate into fragment ions and neutrals. The principles of molecular beam methods are summarized and illustrative examples are given for which definitive information on reaction dynamics is available. The importance of scattering-very little appreciated in early discussions of tandem mass spectrometry-is shown to be the natural consequence of impulsive collisions, which appears to be a quite general mechanism for energy exchange in collisional activation. It is shown that the average energy transferred in single collisions is much less than the theoretical maximum given by the center-of-mass collision energy. The issues of energy transfer in collisions of large molecular ions with low mass neutrals are reviewed and a general description of energy transfer in multiple collisions is presented. It is shown that the center-of-mass and Massey criterion limitations are pragmatically overcome by multiple collision activation in ion traps. Surface-induced dissociation is presented as a viable alternative to multiple collision activation which is especially attractive for activation of large molecular ions. Finally a few of the emerging dynamics principles governing energy transfer and dissociation of peptides are summarized.
2000. "The Theoretical Basis of the Kinetic Method from the point of View of Finite Heat Bath Theory." Journal of Physical Chemistry A 104(38):8829-8837. Abstract We present a rigorous theoretical basis of the kinetic method based on Finite Heat Bath Theory (FHBT) developed by Klots. A simple analytical expression for the branching ratio is derived from FHBT formalism. This expression simplifies to the expression given by the absolute reaction rate theory 1) for very large clusters or 2) for reactions having a negligible kinetic shift. The reacting population is described by two different temperatures rather than by the "effective" temperature as suggested previously. Simulations performed using both RRKM and FHBT revealed that the kinetic plots are slightly non-linear. The observed curvature is related to the changes in the transition state temperature as a function of the critical energy for fragmentation. The curvature of the plots decreases for larger clusters. We show that the "effective" temperature closely resembles the average value of the transition state temperature. This allows us to assign a new definition of the effective temperature and predict its properties. The results of simulations confirm that the extended version of the kinetic method introduced by Fenselau and co-workers provides accurate relative energetics for competitive reactions for both small and large ions. However, accurate thermochemical information can be obtained from the kinetic method only if reactions under investigation have negligible reverse activation energies. A new approach for extracting relative fragmentation energetics and entropy differences for two competing reactions is proposed. This approach requires a measurement of kinetic energy release distributions (KERDs) for the two fragmentation channels; the relative energetics and dynamics can be extracted from a single measurement.
2000. "Internal Energy Distributions Resulting from Sustained Off-Resonance Excitation in Fourier Transform Ion Syclotron Resonance Mass Spectrometry.II. Fragmentation of the 1-Bromonaphthalene Radical Cation ." Journal of Physical Chemistry A 104(23):5484-5494. Abstract The collision energy dependence of the fragmentaiton of C10H7Br+? was studied using sustained off-rsonance excitation (SORI) in a 7 T Fourier Trnasform Mass Spectrometer (FTMS). Fragmentation efficiency curves were obtained as a function of collision energy at four different pressures of Ar bath gas corresponding to collision numbers of 3, 5, 15 and 20. The results were modeled using RRKM/QET formalism. A refined analytical form for the collisional energy deposition function is prposed. The ability to obtain accurate framentation energetics of a complex system using the present approach is demonstrated. The "effective temperatures" deduced from the average internal energies for C6H5Br+? and C10H7Br+? were found to be the same for both ions provided the bath gas pressure and the maximum value of center-of-mass collision energy were the same.
2000. "A Comparative Study of Collision-Induced and Surface-Induced Dissociation. I Fragmentation of Protonated Dialanine." Journal of the American Chemical Society 122(40):9703-9714. Abstract Collision-induced and surface-induced dissociation of protonated dialanine (Ala-AlaH+) was studied using a 7 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS). Energy-resolved fragmentation efficiency curves were obtained using both techniques. The results were modeled using RRKM/QET formalism. The energetics and dynamics of the four primary and some secondary fragmentation pathways were determined from the RRKM modeling. Both multiple-collision CID and SID results could be reproduced within the same model. The strong correspondence of fragmentation efficiency curves obtained in the high-pressure CID and SID experiments indicates that the internal energy distributions of Ala-AlaH+ activated by multiple collisions and by surface impact are remarkably similar.
2000. "Design and Implementation of a New Electrodynamic Ion Funnel." Analytical Chemistry 72:2247-2255. Abstract A new electrodynamic (rf) ion funnel has been developed and evaluated for use in the interface regions (at ~1-10 Torr) of atmospheric pressure ion sources (e.g., electrospray ionization (ESI) for mass spectrometry). The ion funnel consists of a ring electrode ion guide with decreasing i.d. and with a superimposed dc potential gradient along the ring stack. The thicknesses of the ring electrodes and the spacings between them were reduced to 0.5 mm from 1.59 mm compared to those used for previous designs. The new ion funnel displays a significant improvement in low-mass transmission (m/z >200) and sensitivity compared to previous designs. The transmission efficiencies for electrosprayed peptides and proteins (ranging in mass from 200 to 17000 Da) were typically 50-60% of total incoming currents from a heated capillary inlet. The transmitted ion currents were a factor of 30-56 greater than those of the standard interface for peptide samples and a factor of 18-22 greater than those for protein samples. The sensitivity gains realized at the MS detector were somewhat lower, possibly due to space charge effects in the octapole ion beam guide following the ion funnel. The improved ion transmission properties result primarily from the use of reduced spacings between ring electrodes. We also show that the ion funnel can be operated in two different modes, one using low-rf-amplitude scans, allowing fragile noncovalent complexes (as well as generally undesired adducts) to be transmitted, and the other using high-rf-amplitude scans, providing greater collisional activation and more effective adduct removal (or the dissociation of lower m/z species).
2000. "Development of tandem mass spectrometry: one perspective." International Journal of Mass Spectrometry 200(1-3):495-508. Abstract Tandem mass spectrometry is the branch of mass spectrometry concerned with selection of a particular ion (a component of the normal mass spectrum) formed from a molecule or a mixture of molecules and its activation - usually by one or more collisions - to generate characteristic secondary fragment ions. The motivation may be analytical, determination of ion structure(s), fundamental studies of properties of ions or any combination thereof.