Table of Contents... XI

Transcription

1 Table of Contents Table of Contents... XI 1 Introduction...1 Learning Objectives Aims and Scope Filling the Black Box What Is Mass Spectrometry? Mass Spectrometry Mass Spectrometer Mass Scale Mass Spectrum Ion Chromatograms Performance of Mass Spectrometers Sensitivity Detection Limit Signal-to-Noise Ratio Terminology General Aspects Basic Terminology in Describing Mass Spectra Units, Physical Quantities, and Physical Constants...17 References Principles of Ionization and Ion Dissociation...21 Learning Objectives Gas Phase Ionization by Energetic Electrons Formation of Ions Processes Accompanying Electron Ionization Ions Generated by Penning Ionization Ionization Energy Ionization Energy and Charge-Localization Vertical Transitions Ionization Efficiency and Ionization Cross Section...29

2 XII Table of Contents 2.4 Internal Energy and the Further Fate of Ions Degrees of Freedom Appearance Energy Bond Dissociation Energies and Heats of Formation Randomization of Energy Quasi-Equilibrium Theory QET s Basic Premises Basic QET Rate Constants and Their Meaning k (E) Functions Typical Examples Reacting Ions Described by k (E) Functions Direct Cleavages and Rearrangement Fragmentations Time Scale of Events Stable, Metastable, and Unstable Ions Time Scale of Ion Storage Devices Internal Energy Practical Implications Reverse Reactions and Kinetic Energy Release Activation Energy of the Reverse Reaction Kinetic Energy Release Energy Partitioning Isotope Effects Primary Kinetic Isotope Effects Measurement of Isotope Effects Secondary Kinetic Isotope Effects Determination of Ionization Energies Conventional Determination of Ionization Energies Improved IE Accuracy from Data Post-Processing IE Accuracy Experimental Improvements Photoionization Processes Determining the Appearance Energies Kinetic Shift Breakdown Graphs Gas Phase Basicity and Proton Affinity References Isotopic Composition and Accurate Mass Learning Objectives Isotopic Classification of the Elements Monoisotopic Elements Di-isotopic Elements Polyisotopic Elements Representation of Isotopic Abundances Calculation of Atomic, Molecular, and Ionic Mass Natural Variations in Relative Atomic Mass Calculation of Isotopic Distributions Carbon: An X+1 Element... 74

3 Table of Contents XIII Terms Related to Isotopic Composition Binomial Approach Halogens Combinations of Carbon and Halogens Polynomial Approach Oxygen, Silicon, and Sulfur Polyisotopic Elements Practical Aspects of Isotopic Patterns Bookkeeping with Isotopic Patterns in Mass Spectra Information from Complex Isotopic Patterns Isotopic Enrichment and Isotopic Labeling Isotopic Enrichment Isotopic Labeling Resolution and Resolving Power Definitions Resolution and its Experimental Determination Resolving Power and its Effect on Relative Peak Intensity Accurate Mass Exact Mass and Molecular Formulas Mass Defect Mass Accuracy Accuracy and Precision Mass Accuracy and the Determination of Molecular Formulas Extreme Mass Accuracy Special Considerations Applied High-Resolution Mass Spectrometry External Mass Calibration Internal Mass Calibration Compiling Mass Reference Lists Specification of Mass Accuracy Deltamass Kendrick Mass Scale Van Krevelen Diagrams Resolution Interacting with Isotopic Patterns Multiple Isotopic Compositions at Very High Resolution Isotopologs and Accurate Mass Large Molecules Isotopic Patterns at Sufficient Resolution Large Molecules Isotopic Patterns at Low Resolution Charge State and Interaction with Isotopic Patterns References Instrumentation Learning Objectives How to Create a Beam of Ions Time-of-Flight Instruments Time-of-Flight Basic Principles TOF Instruments Velocity of Ions and Time-of-Flight Linear Time-of-Flight Analyzer...123

4 XIV Table of Contents Reflector Time-of-Flight Analyzer Higher Vacuum Improves Resolving Power Delay Before Extraction to Improve Resolving Power Analog-to-Digital Conversion Orthogonal Acceleration TOF Analyzers Operation of the oatof Analyzer Duty Cycle Time-to-Digital Conversion Magnetic Sector Instruments Evolution of Magnetic Sector Instruments Principle of the Magnetic Sector Focusing Action of the Magnetic Field Double-Focusing Sector Instruments Geometries of Double-Focusing Sector Instruments Adjusting the Resolving Power of a Sector Instrument Innovations in Sector Instruments Linear Quadrupole Instruments Introduction The Linear Quadrupole Resolving Power of Linear Quadrupoles RF-Only Quadrupoles, Hexapoles, and Octopoles Linear Quadrupole Ion Traps Linear RF-Only Multipole Ion Traps Mass-Analyzing Linear Quadrupole Ion Trap with Axial Ejection Mass-Analyzing Linear Ion Trap with Radial Ejection Three-Dimensional Quadrupole Ion Trap Introduction The Quadrupole Ion Trap Visualization of Ion Motion in the Ion Trap Mass-Selective Stability Mode Mass-Selective Instability Mode Resonant Ejection Axial Modulation and Automatic Gain Control Nonlinear Resonances Digital Waveform Quadrupole Ion Trap External Ion Sources for the Quadrupole Ion Trap Fourier Transform Ion Cyclotron Resonance Ion Cyclotron Resonance Ion Cyclotron Motion Cyclotron Motion Excitation and Detection Cyclotron Frequency Bandwidth and Energy-Time Uncertainty Fourier Transform Basic Properties Nyquist Criterion Excitation Modes in FT-ICR-MS Axial Trapping and Design of ICR Cells Magnetron Motion and Reduced Cyclotron Frequency

5 Table of Contents XV Detection and Accuracy in FT-ICR-MS FT-ICR Instruments Orbitrap Analyzer Orbitrap Principle of Operation Ion Detection and Resolving Power of the Orbitrap Ion Injection into the Orbitrap Hybridization with a Linear Quadrupole Ion Trap Hybrid Instruments Evolution of Hybrid Mass Spectrometers Ion Mobility-Mass Spectrometry Systems Detectors Discrete Dynode Electron Multipliers Channel Electron Multipliers Microchannel Plates Post-Acceleration and Conversion Dynode Focal Plane Detectors Vacuum Technology Basic Mass Spectrometer Vacuum System High Vacuum Pumps Purchasing an Instrument References Practical Aspects of Electron Ionization Learning Objectives Electron Ionization Ion Sources Layout of an Electron Ionization Ion Source Generation of Primary Electrons Overall Efficiency and Sensitivity of an El Ion Source Optimization of Ion Beam Geometry Sample Introduction Reservoir or Reference Inlet System Direct Insertion Probe Sample Vials for Use with Direct Insertion Probes Fractionation When Using Direct Insertion Probes Direct Exposure Probe Pyrolysis Mass Spectrometry Gas Chromatograph Liquid Chromatograph Low-Energy Electron Ionization Mass Spectra Analytes for EI Mass Analyzers for EI Mass Spectral Databases for EI NIST/EPA/NIH Mass Spectral Database Wiley Registry of Mass Spectral Data Mass Spectral Databases General Aspects References...245

6 XVI Table of Contents 6 Fragmentation of Organic Ions and Interpretation of EI Mass Spectra Learning Objectives Cleavage of a Sigma-Bond Writing Conventions for Molecular Ions σ-bond Cleavage in Small Nonfunctionalized Molecules Even-Electron Rule σ-bond Cleavage in Small Functionalized Molecules Alpha-Cleavage α-cleavage of Acetone Molecular Ion Stevenson's Rule α-cleavage of Nonsymmetrical Aliphatic Ketones Acylium Ions and Carbenium Ions α-cleavage When Heteroatoms Belong to the Aliphatic Chain α-cleavage of Aliphatic Amines Nitrogen Rule α-cleavage of Aliphatic Ethers and Alcohols Charge Retention at the Heteroatom α-cleavage of Thioethers α-cleavage of Halogenated Hydrocarbons Double α-cleavage Double α-cleavage for the Identification of Regioisomers Distonic Ions Definition of Distonic Ions Formation and Properties of Distonic Ions Distonic Ions as Intermediates Benzylic Bond Cleavage Cleavage of the Benzylic Bond in Phenylalkanes The Further Fate of [C 6 H 5 ] + and [C 7 H 7 ] Isomerization of [C 7 H 8 ] + and [C 8 H 8 ] + Ions Rings Plus Double Bonds Allylic Bond Cleavage Cleavage of the Allylic Bond in Aliphatic Alkenes Methods for the Localization of the Double Bond Cleavage of Non-Activated Bonds Saturated Hydrocarbons Carbenium Ions Very Large Hydrocarbons Recognition of the Molecular Ion Peak McLafferty Rearrangement McL of Aldehydes and Ketones Fragmentation of Carboxylic Acids and Their Derivatives McL of Aromatic Hydrocarbons McL with Double Hydrogen Transfer Retro-Diels-Alder Reaction Properties of the Retro-Diels-Alder Reaction

7 Table of Contents XVII Influence of Positional Isomerism on the RDA Reaction RDA Reaction in Natural Products Widespread Occurrence of the RDA Reaction Elimination of Carbon Monoxide CO Loss from Phenols CO and C 2 H 2 Loss from Quinones Fragmentation of Arylalkylethers CO Loss from Transition Metal Carbonyl Complexes CO Loss from Carbonyl Compounds Differentiation Between Loss of CO, N 2, and C 2 H Thermal Degradation vs. Ion Fragmentation Decarbonylation and Decarboxylation Retro-Diels-Alder Reaction Loss of H 2 O from Alkanols EI Mass Spectra of Organic Salts Alkene Loss from Onium Ions McL of Onium Ions Onium Reaction Ion-Neutral Complexes Evidence for the Existence of Ion-Neutral Complexes Attractive Forces in Ion-Neutral Complexes Criteria for Ion-Neutral Complexes Ion-Neutral Complexes of Radical Ions Ortho Elimination (Ortho Effect) Ortho Elimination from Molecular Ions Ortho Elimination from Even-Electron Ions Ortho Elimination in the Fragmentation of Nitroarenes Heterocyclic Compounds Saturated Heterocyclic Compounds Aromatic Heterocyclic Compounds Guide to the Interpretation of Mass Spectra Summary of Rules Systematic Approach to Mass Spectra References Chemical Ionization Learning Objectives Basics of Chemical Ionization Formation of Ions in Positive-Ion Chemical Ionization Chemical Ionization Ion Sources Sensitivity of Chemical Ionization Chemical Ionization Techniques and Terms Protonation in Chemical Ionization Source of Protons Methane Reagent Gas Plasma CH 5 + and Related Ions...356

8 XVIII Table of Contents Energetics of Protonation Impurities of Higher PA than the Reagent Gas Methane Reagent Gas PICI Spectra Other Reagent Gases in PICI Proton Transfer Reaction Mass Spectrometry Reactant Ion Formation in PTR-MS Analyte Ion Formation in PTR-MS Charge Exchange Chemical Ionization Energetics of CE Reagent Gases for CE-CI Compound Class-Selective CE-CI Regio- and Stereoselectivity in CE-CI Negative-Ion Chemical Ionization Electron Capture Ion Formation by Electron Capture Energetics of EC Creating Thermal Electrons Appearance of EC Spectra Applications of EC Desorption Chemical Ionization Analytes for CI References Field Ionization and Field Desorption Learning Objectives Field Ionization Process FI and FD Ion Sources Field Emitters Blank Metal Wires as Emitters Activated Emitters Emitter Temperature Handling of Activated Emitters Field Ionization Mass Spectrometry Origin of [M+H] + Ions in FI-MS Multiply-Charged Ions in FI-MS Field-Induced Dissociation Accurate Mass FI Spectra Coupling Gas Chromatography to FI-MS FD Spectra Ion Formation by Field Ionization in FD-MS Desorption of Preformed Ions in FD-MS Cluster Ion Formation in FD-MS FD-MS of Ionic Analytes Best Anode Temperature and Thermal Decomposition FD-MS of Polymers Types of Ions in FD-MS

9 Table of Contents XIX 8.6 Liquid Injection Field Desorption Ionization General Properties of FI-MS and FD-MS Sensitivity of FI-MS and FD-MS Analytes and Practical Considerations for FI, FD, and LIFDI Mass Analyzers for FI and FD References Tandem Mass Spectrometry Learning Objectives Concepts of Tandem Mass Spectrometry Tandem-in-Space and Tandem-in-Time Pictograms for MS/MS Experiments Metastable Ion Dissociation Collision-Induced Dissociation Effecting Collisions in a Mass Spectrometer Energy Transfer During Collisions Single and Multiple Collisions in CID Time Scale of Ion Activating Processes Surface-Induced Dissociation Tandem MS on TOF Instruments Utilizing a ReTOF for Tandem MS Curved-Field Reflectron Tandem MS on True Tandem TOF Instruments Tandem MS with Magnetic Sector Instruments Dissociations in the FFR Preceding the Magnetic Sector Mass-Analyzed Ion Kinetic Energy Spectra Determination of Kinetic Energy Release B/E = Const. Linked Scan Additional Linked Scan Functions Multi-Sector Instruments Tandem MS with Linear Quadrupole Analyzers Triple Quadrupole Mass Spectrometers Scan Modes for Tandem MS with Triple Quadrupole Instruments Penta Quadrupole Instruments Tandem MS with the Quadrupole Ion Trap Tandem MS with Linear Quadrupole Ion Traps Tandem MS on QqLIT Instruments Tandem MS on LITs with Radial Ejection Tandem MS with Orbitrap Instruments Higher-Energy C-Trap Dissociation Extended LIT-Orbitrap Hybrid Instruments Tandem MS with FT-ICR Instruments Part I Sustained Off-Resonance Irradiation-CID in ICR Cells Infrared Multiphoton Dissociation IRMPD in QITs and LITs Electron Capture Dissociation...452

10 XX Table of Contents Principles of Electron Capture Dissociation Peptide Ion Cleavages Upon ECD Tandem MS with FT-ICR Instruments Part II IRMPD for Tandem FT-ICR-MS Infrared Photodissociation Spectroscopy Blackbody Infrared Radiative Dissociation ECD for Tandem FT-ICR-MS Electron Transfer Dissociation Electron Detachment Dissociation Summary of Ion Activation Techniques Special Applications of Tandem MS Ion Molecule Reactions in Catalytic Studies Gas Phase Hydrogen Deuterium Exchange Determination of Gas Phase Basicities and Proton Affinities Neutralization-Reionization Mass Spectrometry References Fast Atom Bombardment Learning Objectives Ion Sources for FAB and LSIMS FAB Ion Sources LSIMS Ion Sources FAB Probes Ion Formation in FAB and LSIMS Ion Formation from Inorganic Samples Ion Formation from Organic Samples Liquid Matrices for FAB and LSIMS The Role of the Liquid Matrix FAB Matrix Spectra General Characteristics Unwanted Reactions in FAB-MS Applications of FAB-MS FAB-MS of Analytes of Low to Medium Polarity FAB-MS of Ionic Analytes High-Mass Analytes in FAB-MS Accurate Mass Measurements in FAB Mode Continuous-Flow FAB Low-Temperature FAB FAB-MS and Peptide Sequencing FAB and LSIMS General Characteristics Sensitivity of FAB-MS Types of Ions in FAB-MS Analytes for FAB-MS Mass Analyzers for FAB-MS Massive Cluster Impact Californium Plasma Desorption References

11 Table of Contents XXI 11 Matrix-Assisted Laser Desorption/Ionization Learning Objectives Ion Sources for LDI and MALDI Ion Formation Ion Yield and Laser Fluence Effect of Laser Irradiation on the Surface Temporal Evolution of a Laser Desorption Plume Processes of Ion Formation in MALDI Lucky Survivor Model of Ion Formation MALDI Matrices Role of the Solid Matrix Matrices in UV-MALDI Characteristics of MALDI Matrix Spectra Sample Preparation MALDI Target Standard Sample Preparation Cationization Cation Removal Solvent-Free Sample Preparation Additional Methods of Sample Supply Applications of LDI Applications of MALDI Protein Analysis by MALDI-MS Peptide Sequencing and Proteomics Carbohydrate Analysis by MALDI-MS Oligonucleotide Analysis by MALDI-MS MALDI-MS of Synthetic Polymers Special Surfaces to Mimic the Matrix Desorption/Ionization on Silicon Nano-Assisted Laser Desorption/Ionization Further Variations of the MALDI Theme MALDI Imaging Atmospheric Pressure MALDI General Characteristics of MALDI Sample Consumption and Detection Limit Analytes for MALDI Types of Ions in LDI and MALDI-MS Mass Analyzers for MALDI-MS References Electrospray Ionization Learning Objectives Development of ESI and Related Methods Atmospheric Pressure Ionization Thermospray Electrohydrodynamic Ionization...565

12 XXII Table of Contents Electrospray Ionization Ion Sources for ESI Basic Design Considerations Adaptation to Different Flow Rates Improved Electrospray Configurations Advanced Electrospray Interface Designs Nozzle-Skimmer Dissociation Nanoelectrospray Practical Considerations for NanoESI Spray Modes of NanoESI Nanoelectrospray from a Chip Ion Formation in ESI Formation of the Electrospray Plume Disintegration of Charged Droplets Formation of Ions from Charged Droplets Multiply Charged Ions and Charge Deconvolution Dealing with Multiply Charged Ions Mathematical Charge Deconvolution Computerized Charge Deconvolution Hardware Charge Deconvolution Controlled Charge Reduction in ESI Applications of ESI-MS ESI-MS of Small Molecules ESI of Metal Complexes ESI of Surfactants Oligonucleotides, DNA, and RNA ESI-MS of Oligosaccharides High-Mass Proteins and Protein Complexes Summary of ESI Characteristics Sample Consumption Types of Ions in ESI Mass Analyzers for ESI Atmospheric Pressure Chemical Ionization Ion Sources for APCI Ion Formation in APCI APCI Spectra Atmospheric Pressure Photoionization Ion Formation in APPI APPI Spectra References Ambient Mass Spectrometry Learning Objectives Desorption Electrospray Ionization Experimental Setup for DESI Mechanisms of Ion Formation in DESI

13 Table of Contents XXIII Analytical Features of DESI Desorption Atmospheric Pressure Chemical Ionization Desorption Atmospheric Pressure Photoionization Other Methods Related to DESI Desorption Sonic Spray Ionization Extractive Electrospray Ionization Electrospray-Assisted Laser Desorption/Ionization (ELDI) Laser Ablation Electrospray Ionization Atmospheric Pressure Solids Analysis Probe Direct Analysis in Real Time Experimental Setup for DART Ion Formation in DART Analytical Applications of DART Overview of Ambient Mass Spectrometry References Hyphenated Methods Learning Objectives Concept of Chromatography-Mass Spectrometry Ion Chromatograms Repetitive Acquisition of Mass Spectra During Elution Selected Ion Monitoring Selected Reaction Monitoring Quantitation Quantitation by External Standardization Quantitation by Internal Standardization Quantitation by Isotope Dilution Retention Times of Isotopologs Gas Chromatography-Mass Spectrometry GC-MS Interfaces Volatility and Derivatization Column Bleed Fast GC-MS Multiplexing for Increased Throughput Liquid Chromatography-Mass Spectrometry Multiplexed LC-ESI-MS Ion Mobility Spectrometry-Mass Spectrometry Tandem MS as a Complement to LC-MS Ultrahigh-Resolution Mass Spectrometry References Inorganic Mass Spectrometry Learning Objectives Thermal Ionization Mass Spectrometry Spark Source Mass Spectrometry Glow Discharge Mass Spectrometry...694

14 XXIV Table of Contents 15.4 Inductively Coupled Plasma Mass Spectrometry Laser Ablation ICP-MS Secondary Ion Mass Spectrometry Atomic SIMS Instrumentation for Atomic SIMS Molecular SIMS Polyatomic Primary Ion Beams Accelerator Mass Spectrometry Conclusion References Appendix A.1 Units, Physical Quantities, and Physical Constants A.2 Isotopic Composition of the Elements A.3 Carbon Isotopic Patterns A.4 Chlorine and Bromine Isotopic Patterns A.5 Silicon and Sulfur Isotopic Patterns A.6 Isotopologs and Accurate Mass A.7 Characteristic Ions A.8 Common Impurities A.9 Amino Acids A.10 Method Selection Guide A.11 How to Recognize Cationization A.12 Systematic Approach to Mass Spectra A.13 Rules for the Interpretation of Mass Spectra A.14 Nobel Prizes for Mass Spectrometry Subject Index