Isotope effects in chemistry and biology /

Table Of Contents:
Chapter 1 Theoretical Basis of Isotope Effects from an Autobiographical Perspective 1(40)

Jacob Bigeleisen

I. From Soddy鈥擣ajans through Urey鈥擥reiff 1(2)

II. Equilibrium Systems 鈥?General 3(1)

III. Equilibrium in Ideal Gases 4(8)

A. Classical and Quantum Mechanical Systems 4(1)

B. The Reduced Partition Function Ratio of an Ideal Gas 5(3)

1. Numerical Calculation of the Reduced Partition Function Ratio 7(1)

C. Corrections to the Bigeleisen鈥擬ayer Equation 8(4)

IV. Isotope Chemistry and Molecular Structure 12(6)

A. The First Order Rules of Isotope Chemistry 12(1)

B. Statistical Mechanical Perturbation Theory 13(1)

C. Polynomial Expansions of the Reduced Partition Function Ratio 14(4)

V. Kinetic Isotope Effects 18(7)

VI. Condensed Matter Isotope Effects 25(7)

Acknowledgments 32(1)

References 33(8)
Chapter 2 Enrichment of Isotopes 41(48)

Takanobu Ishida and Yasuhiko Fujii

I. Overview 42(2)

A. Separation Factor, Material Balance, and Cascade of Separation Stages 42(2)

II. Enrichment Processes 44(12)

A. Enrichment Processes Based on Steady State Phenomena of Reversible Processes 44(9)

1. Distillation 50(1)

2. Chemical Exchange 50(3)

3. Gas Centrifugation 53(1)

B. Enrichment Processes Based on Nonsteady State Phenomena of Reversible Processes 53(1)

C. Enrichment Based on Irreversible Processes 53(3)

1. Laser Isotope Separation 53(1)

2. Gaseous Diffusion 54(1)

3. Thermal Diffusion 55(1)

4. Electrolysis 55(1)

5. Electromagnetic Method: Calutron 56(1)

III. Separation Cascade 56(10)

A. Ideal Cascade: Thermodynamic Efficiency and No-Mixing 56(2)

B. Product-End Refluxer 58(3)

C. McCabe-Thiele Diagram for Square Cascade 61(3)

1. Case of Total Reflux 63(1)

2. Case of Minimum Reflux Ratio 63(1)

D. Separative Capacity for Close-Separation, Ideal Cascade 64(1)

E. HETP (Height Equivalent of Theoretical Plate) 65(1)

IV. Startup of Isotope Enrichment Cascade 66(1)

A. Time-Dependence of Enrichment Profile along the Length of Cascade during Startup 66(1)

B. Rate of Attainment of Steady-State Profile vs. Holdups 67(1)

V. Empirical Determination of HETP and Separation Factor a 67(2)

A. By Use of Analytic Solution of Material Balance Equation under Transient Condition 67(2)

B. From Graphical Solution of Material Balance Equation under the Condition of Zero Time-Dependence at All Stages 69(1)

VI. Miscellaneous Other Considerations 69(3)

A. Possible Needs of Chemical Waste Disposal 70(1)

B. Possibility of Failure to Achieve a High Target Enrichment 70(1)

C. Possible Explosion of Working Material 71(1)

D. Consideration of Supply for the Feed 72(1)

VII. Enrichment by Nonsteady State Phenomena Involving Reversible Process 72(10)

A. Ion Exchange Isotope Separation 72(2)

B. Chromatographic Isotope Separation 74(1)

C. Nonsteady-State Enrichment 75(3)

1. Enrichment Profile 75(2)

2. HETP 77(1)

D. Isotope Separation by Ion Exchange 78(12)

1. Boron Isotope Separation 78(1)

2. Nitrogen Isotope Separation 79(2)

3. Uranium Isotope Separation 81(1)

VIII. Concluding Remarks 82(1)

Acknowledgments 83(1)

References 83(6)
Chapter 3 Comments on Selected Topics in Isotope Theoretical Chemistry 89(30)

Max Wolfsberg

I. Introduction 89(1)

II. Born鈥擮ppenheimer Approximation and Molecular Vibrations/Potential Energy Surfaces 90(10)

A. Born 鈥擮ppenheimer Oppenheimer Approximation 90(1)

B. The Adiabatic Correction to the Born鈥擮ppenheimer Approximation 91(5)

C. Molecular Vibrations/Potential Energy Surfaces 96(3)

1. General 96(1)

2. The Determination of Harmonic Force Constants in Valence Coordinates 97(1)

3. The Determination of Harmonic Force Constants in Cartesian Displacement Coordinates 98(1)

D. Two Important Equalities for Harmonic Frequencies of Isotopomers 99(1)

III. The Statistical Mechanics of Equilibrium Isotope Effects in the Gas Phase 100(9)

A. Equilibrium Constants 100(2)

B. Rate Constants 102(2)

C. The Symmetry Number in Isotope Chemistry 104(5)

IV. Numerical Calculations of Isotope Effects 109(6)

A. "Early" Calculations 109(1)

B. Isotope Effect Calculations Coupled with A Priori Calculation of Electronic Structures 110(10)

1. Some General Considerations of Electronic Structure Calculations 110(2)

2. The Program THERMISTP 112(3)

References 115(4)
Chapter 4 Condensed Matter Isotope Effects 119(34)

W. Alexander Van Hook

I. Introduction 120(1)

II. The Vapor Pressure Isotope Effect in Liquids and Solutions 120(11)

A. Measurements on Separated Isotopes 120(3)

1. The Vapor Phase 121(1)

2. The Condensed Phase 122(1)

3. The VPIE 123(1)

B. Fractionation Factors 123(1)

C. Relation of VPIE to Condensed Phase Molecular Properties and Vibrational Dynamics 124(10)

1. Application to Polyatomics 125(1)

2. What Happens When Molecules Condense? A Simplified Physical Picture 125(2)

3. VPIEs in Monatomic and Polyatomic Systems. Approximate Vibrational Analysis 127(1)

4. Monatomic Systems Continued. Accurate Calculations of VPIE 128(1)

5. Polyatomic Systems in First Approximation: The Cell Model 129(1)

6. Spectroscopic vs. Thermodynamic Precision 130(1)

7. A Further Approximation. The AB Equation 130(1)

III. Illustrations. Representative Effects, Especially H/D Effects 131(3)

IV. Further Remarks on Connections with Spectroscopy 134(2)

A. Anharmonicity 134(1)

B. The Dielectric Effect 134(6)

1. Example, VPIE of Carbon Disulfide 134(2)

V. The Molar Volume Isotope Effect 136(2)

VI. Excess Free Energies in Solutions of Isotopes. The Relation between VPIE, the Liquid Vapor Fractionation Factor, a, and RPFR 138(1)

VII. Anharmonicity 139(1)

VIII. Some Examples 140(5)

A. Ethylene 140(1)

B. Benzene 141(1)

C. Water 142(3)

IX. Solute and Solvent IEs in Polymer鈥擯olymer and Polymer Solvent Mixtures 145(3)

A. Demixing of Polymer鈥擯olymer Isotopomer Solutions 145(1)

B. Demixing in Polymer鈥擲olvent Systems 145(3)

X. Conclusion 148(1)

References 148(5)
Chapter 5 Anharmonicities, Isotopes, and IR and NMR Properties of Hydrogen-Bonded Complexes 153(22)

Janet E. Del Bene

I. Introduction 153(1)

II. Hydrogen Bond Types 154(1)

A. Traditional 154(1)

B. Ion-Pair 154(1)

C. Proton-Shared 154(1)

III. X鈥揌 Stretching Bands in the IR Spectra of Complexes with X鈥揌鈥揧 Hydrogen Bonds 154(11)

A. Anharmonicity Effects 154(4)

B. Matrix Effects 158(4)

C. Deuterium Substitution Effects on Proton-Stretching Frequencies 162(3)

IV. Two-Bond Spin鈥揝pin Coupling Constants across Hydrogen Bonds 165(6)

A. Anharmonicity and Field Effects 166(4)

B. Isotopic Substitution Effects on Zero-Point Motion and Thermal Vibrational Averaging of Coupling Constants 170(1)

V. Concluding Remarks 171(1)

References 172(3)
Chapter 6 Isotope Effects on Hydrogen-Bond Symmetrization in Ice and Strong Acids at High Pressure 175(18)

Katsutoshi Aoki

I. Introduction 175(2)

A. Hydrogen-Bond Symmetrization 175(1)

B. Candidate Compounds and Promising Probe 176(1)

II. Hydrogen-Bond Symmetrization in Ice 177(6)

A. Crystal Structure 177(1)

B. Infrared Absorption Study 178(5)

1. Symmetrization in Ice VIII 179(2)

2. Symmetrization in Ice VII 181(1)

3. Phase Diagram and Isotope Effect 182(1)

III. Hydrogen-Bond Symmetrization in Hydrogen Chloride 183(7)

A. Crystal Structure 183(2)

B. Raman Scattering Study 185(9)

1. Symmetrization in HCl 185(2)

2. Symmetrization in DCl 187(2)

3. Isotope Effect on Stretching Vibration and Symmetrization 189(1)

IV. Summary 190(1)

References 191(2)
Chapter 7 Hydrogen Bond Isotope Effects Studied by NMR 193(38)

Hans-Heinrich Limbach, Gleb S. Denisov, and Nikolai S. Golubev

I. Introduction 193(1)

II. Theoretical Section 194(11)

A. The Crystallographic View of Hydrogen Bonded Systems 194(2)

B. Origin of Hydrogen Bond Isotope Effects 196(2)

1. Influence of the Hydron Potential 196(1)

2. Effects of the Environment 197(1)

C. Inclusion of Quantum Corrections in Hydrogen Bond Correlations 198(4)

D. H/D Isotope Effects on NMR Parameters and Hydrogen Bond Geometries: The Point Approximation 202(2)

E. H/D Isotopic Fractionation, Hydrogen Bond Geometries and NMR Parameters 204(1)

III. Applications 205(21)

A. H/D Isotope Effects in Strong NHN Hydrogen Bonds 205(5)

B. H/D Isotope Effects in OHN Hydrogen Bonded Pyridine鈥揂cid and Collidine鈥揂cid Complexes 210(7)

1. Low-Temperature NMR Spectroscopy of Pyridine鈥揂cid Complexes Dissolved in Liquefied Freon Mixtures 210(1)

2. Geometric Hydrogen Bond Correlations of OHN Hydrogen Bonded Complexes 211(2)

3. H/D Isotope Effects on the NMR Parameters of Pyridine鈥揂cid and Collidine鈥揂cid Complexes 213(4)

4. H/D Isotopic Fractionation and NMR Parameters of Pyridine鈥揂cid Complexes 217(1)

C. Temperature-Induced Solvent H/D Isotope Effects on NMR Chemical Shifts of FHN Hydrogen Bonds 217(5)

D. H/D Isotope Effects on the NMR Parameters and Geometries of Coupled Hydrogen Bonds 222(4)

IV. Conclusions 226(1)

Acknowledgments 227(1)

References 227(4)
Chapter 8 Isotope Effects and Symmetry of Hydrogen Bonds in Solution: Single- and Double-Well Potential 231(22)

Jonathan S. Lau and Charles L. Perrin

I. Introduction 232(2)

A. Single- and Double-Well H-Bonds 232(1)

B. Low-Barrier H-Bonds, Short, Strong H-Bonds, "Symmetric" H-Bonds 232(2)

1. Resonance-Assisted H-Bonds, Charge-Assisted H-Bonds 233(1)

2. Sterically Enforced H-Bonds 233(1)

II. Computational Work 234(2)

A. Energetic and Geometric Descriptions 234(1)

B. Accounting for Solvation 235(1)

III. Methods of Observation 236(5)

A. Measurement of pKa 237(1)

B. Fractionation Factors 237(1)

C. NMR Chemical Shifts 238(1)

D. NMR Coupling Constants 239(1)

E. Infrared (IR) 240(1)

F. X-Ray and Neutron Diffraction 240(1)

IV. Current Work 241(6)

A. Intramolecular Systems 241(4)

1. Enol Tautomers of β-Dicarbonyls and Related Molecules 241(1)

2. Proton Sponge 242(1)

3. Dicarboxylic Acids 243(1)

4. Schiff Bases 244(1)

B. Intermolecular Systems 245(14)

1. Pyridine-Acid Complexes 245(1)

2. Enzymes 246(1)

V. Conclusion 247(1)

Acknowledgments 247(1)

References 247(6)
Chapter 9 NMR Studies of Isotope Effects of Compounds with Intramolecular Hydrogen Bonds 253(28)

Poul Erik Hansen

I. Introduction and Outline 253(2)

II. Definitions 255(1)

III. Theory 255(3)

IV. Experimental Conditions 258(1)

V. Static Systems 259(10)

A. Resonance-Assisted Hydrogen Bonded Systems 259(3)

1. Transmission of Isotope Effects across Hydrogen Bonds 261(1)

B. Non-RAHB Cases 262(2)

C. Medium- and Long-Range Isotope Effects 264(1)

D. Isotope Effects through Space 264(1)

E. nΔ15N(D) 265(1)

1. 鹿Δ15N(D) 265(1)

2. 5A.15N(D) 266(1)

F. nΔ17O(D) 266(1)

G. nΔYH(XH) (X,Y = O or N) 266(1)

H. nΔ19F(XD) 267(1)

I. nΔ鹿鲁C(18O) 267(1)

J. Primary Isotope Effects 267(1)

K. Summary for Intrinsic Isotope Effects 268(1)

1. RAHB Systems 268(1)

2. Non-RAHB Systems 269(1)

VI. Equilibrium Isotope Effects 269(6)

A. General Findings 269(4)

B. Long-Range Effects in Equilibrium Systems 273(1)

C. Identifying Equilibrium Systems 274(1)

VII. Calculations 275(1)

References 275(6)
Chapter 10 Vibrational Isotope Effects in Hydrogen Bonds 281(24)

Zofia Mielke and Lucjan Sobczyk

I. Introduction 281(4)

A. Classical and Quantum Mechanical Calculations of Force Field and Vibrational Spectra in the Harmonic Approximation 282(2)

B. The Effect of Deuterium Substitution on the Vibrations Involving Hydrogen Motion 284(1)

C. The Isotopic Substitution, the Potential Energy Distribution, and the Frequency Isotopic Ratio (ISR) 284(1)

II. Sources of Anomalous H/D Isotope Effects in Hydrogen-Bonded Systems 285(2)

III. The Hydrogen Bond Effect on Anharmonicity of Protonic Vibrations 287(3)

IV. Potential Energy Functions for the Proton-Stretching Vibrations 290(2)

V. The Shape of the Potential and Evolution of IR Spectra of Hydrogen-Bonded Systems 292(2)

VI. Frequency Isotopic Ratio (ISR) and Its Correlation with Other Parameters of Hydrogen Bonds 294(2)

VII. The Isotope Effect upon Other Spectroscopic Parameters of Hydrogen-Bonded Systems 296(2)

VIII. Low-Barrier Hydrogen Bonds 298(3)

References 301(4)
Chapter 11 Isotope Selective Infrared Spectroscopy and Intramolecular Dynamics 305(56)

Michael Hippler and Martin Quack

I. Introduction 306(5)

A. Principles of Isotope Effects in Infrared Spectroscopy and Molecular Dynamics 306(2)

B. Intramolecular Dynamics and Isotope Selective Spectroscopic Techniques: An Overview 308(3)

II. Intramolecular Redistribution Processes: From High-Resolution Spectroscopy to Ultrafast Intramolecular Dynamics 311(6)

A. Intramolecular Quantum Dynamics and Molecular Spectroscopy 311(2)

B. Spectroscopic States and Intramolecular Dynamics: An Intuitive Perspective 313(7)

1. General Aspects 313(1)

2. An Example of Two-Level Dynamics 314(2)

3. Coupling Many Levels in a Multistate Dynamics 316(1)

III. The Experimental Approach to Infrared Spectroscopy with Mass and Isotope Selection (IRSIMS) 317(3)

IV. Mass Selective Overtone Spectroscopy by Vibrationally Assisted Dissociation and Photofragment Ionization: OSVADPI 320(9)

A. Mechanism of Vibrationally Assisted Dissociation and Photofragment Ionization 320(3)

B. Isotopomer Selective Overtone Spectroscopy of the Nj = 42 CH Chromophore Absorption of CHCl3 323(2)

C. Isotopomer Selective Overtone Spectroscopy of the Nj = 41 CH Chromophore Absorption of CHCl3: A Hierarchy of Time Scales and Isotope Effects in Intramolecular Vibrational Energy Redistribution (IVR) 325(4)

V. Isotope Selective Overtone Spectroscopy by Resonantly Enhanced Two-Photon Ionization of Vibrationally Excited Molecules 329(17)

A. Overview 330(1)

B. Mechanism of Resonantly Enhanced Two-Photon Ionization of Vibrationally Excited Molecules 331(3)

C. The N = 2 NH Chromophore Absorption of Aniline Isotopomers Near 6750 cm-鹿: Isotope Effects and Vibrational Mode Specificity in IVR and Tunneling Processes 334(4)

D. 鹿鲁C Isotope Effects in the IVR of Vibrationally Excited Benzene 338(8)

VI. Conclusions and Outlook 346(2)

Acknowledgments 348(1)

References 348(13)
Chapter 12 Nonmass-Dependent Isotope Effects 361(26)

Ralph E. Weston, Jr.

I. Introduction 361(3)

II. Ozone Isotopologues 364(8)

A. Laboratory Experiments 364(3)

B. Atmospheric Ozone 367(1)

C. Theoretical Explanations of the NMD Isotopic Fractionation in Ozone 368(4)

III. Carbon Monoxide Isotopologues 372(2)

A. Laboratory Experiments 372(2)

B. Atmospheric Carbon Monoxide 374(1)

IV. Carbon Dioxide Isotopologues 374(2)

A. Laboratory Experiments 374(1)

B. Atmospheric Carbon Dioxide 375(1)

C. Theoretical Models for NMD Isotopic Fractionation in Carbon Dioxide 375(1)

V. Nitrous Oxide Isotopologues 376(1)

A. Laboratory Experiments 376(1)

B. Atmospheric Nitrous Oxide 376(1)

C. Theoretical Explanations and Modeling Calculations 376(1)

VI. Oxygen and Sulfur Isotopic Fractionation in Terrestrial and Extraterrestrial Solids 377(3)

A. Carbonates 377(1)

B. Sulfates 378(2)

1. Laboratory Experiments 378(1)

2. Terrestrial Sulfates 379(1)

3. Extraterrestrial Sulfur Compounds 379(1)

C. Nitrate Aerosols 380(1)

VII. Other Molecules 380(1)

A. Hydrogen Peroxide Isotopologues 380(1)

B. Atmospheric Oxygen Isotopologues 381(1)

Acknowledgments 381(1)

References 382(5)
Chapter 13 Isotope Effects in the Atmosphere 387(30)

Etienne Roth, Ren茅 L茅tolle, C.M. Stevens, and Fran莽ois Robert

I. Introduction 388(1)

II. Isotopes in Geochemical Cycles 389(1)

III. Isotope Effects in the Water Cycle 390(6)

A. The Reservoir Model 390(1)

B. Exchange between Different Phases of Water 390(1)

C. Vapor鈥擫iquid Isotope Fractionation and the Study of Reservoirs 391(1)

D. Water in Precipitation 392(6)

1. The Isotope Composition of Rain 392(1)

2. Migration Effects, Altitude Effects, Seasonal Effects, Reevaporation Effects 392(1)

3. The Case of Hailstorms 393(1)

a. Early Tenets of the Method 393(1)

i. Experiments 393(1)

ii. Results, Further Models, and Discussion 393(2)

4. The δH-δ18O Relation in Precipitations 395(1)

IV. Archives of Atmospheric Isotopic Effects Retained by Ice Caps 396(2)

V. Isotopic Effects on Atmospheric Carbon in the Carbon Cycle 398(4)

A. Isotopes of Atmospheric Methane 398(2)

1. Sources 399(1)

2. Discussion 399(1)

3. Removal Processes 399(1)

4. Atmospheric 14CH4 400(1)

5. Atmospheric δD 400(1)

B. Isotopes of Atmospheric Carbon Monoxide 400(2)

1. Sources and Sinks 400(1)

2. Atmospheric Concentration and Isotopic Composition 401(1)

3. Summary 401(1)

C. Isotopes of Atmospheric Carbon Dioxide 402(1)

VI. Isotope Effects of Atmospheric Nitrogen 402(1)

VII. Isotope Effects of Atmospheric Oxygen 403(1)

A. Air Oxygen 403(1)

B. Ozone 403(1)

C. Nitrous Oxide 403(1)

D. Atmospheric Sulfates 403(1)

VIII. Isotope Effects of Atmospheric Sulfur 403(4)

A. Introduction 404(1)

B. Turnover and Inventory 405(1)

C. Nature, Isotopic Composition, and Atmospheric Chemistry of Sulfur 405(2)

D. Effects during Removal of Sulfur from the Atmosphere 407(3)

1. Archean Isotope Atmospheric Chemistry of Sulphur and Nonmass-Dependent Isotope Effect 407(1)

IX. Isotope Effects on Zinc and Lead in the Atmosphere 407(1)

X. Deuterium Enrichments in the Organic Molecules of the Interstellar Medium 407(3)

XI. Constraints in Using Deltas, Capital Deltas, and Reference Samples 410(1)

A. Possible Evolution of Measurements of Isotope Effects 411(1)

Acknowledgments 411(1)

References 411(6)
Chapter 14 Isotope Effects for Exotic Nuclei 417(16)

Olle Matsson

I. Introduction 417(1)

II. Isotope Effects with Short-Lived Radionuclides 418(1)

A. Fluorine Kinetic Isotope Effects 418(1)

B. Carbon Kinetic Isotope Effects 418(1)

III. Synthesis of Compounds Labelled with Short-Lived Radionuclides 419(1)

A. Labelling with 鹿鹿C 419(1)

B. Labelling with 18F 419(1)

IV. Kinetic Methods 鈥?A Combination of Liquid Chromatography and Liquid Scintillation 420(1)

V. Determination of Rate-Limiting Steps 421(2)

A. Using Leaving Group F KIEs 鈥?Nucleophilic Aromatic Substitution 421(1)

1. The Effect of Solvent on the Rate-Limiting Step 422(1)

2. The Effect of Steric Hindrance on the Rate-Limiting Step 422(1)

B. Concerted or Stepwise Reaction? The Use of F KIEs and Double Labelling for a Base-Promoted Elimination 422(1)

VI. Probing Transition-State Structure 鈥?Nucleophilic Aliphatic Substitution 423(3)

A. Relative Carbon KIEs 423(1)

B. Labelled Central atom: Probing Steric Effects 424(1)

C. Labelled Nucleophile 425(10)

1. The Effect of Substitution in the Substrate 425(1)

2. The Effect of Substitution in the Leaving Group 426(1)

VII. The Determination of Secondary Deuterium KIEs by the Aid of Radioactive Carbon 426(1)

VIII. Secondary Carbon KIE in a Proton-Transfer Reaction 427(1)

IX. Carbon Isotope Effects for Enzyme-Catalysed Reactions 428(1)

Acknowledgments 428(1)

References 428(5)
Chapter 15 Muonium 鈥?An Ultra-Light Isotope of Hydrogen 433(18)

Emil Roduner

I. Physical Properties and the Chemical Nature of Mu in Comparison with H and D 434(1)

II. Chemically Bound Mu States: Structural Isotope Effects of Vibrating Species 435(6)

A. Zero-Point Energy and Anharmonicity Effects 435(1)

B. Isotope Effects in Vibrationally Averaged Bond Lengths and Bond Angles 436(1)

C. Isotope Effects in Equilibrium Conformations 437(2)

D. Isotope Effects in Hyperfine Interactions of Free Radicals 439(1)

E. The Validity of the Born鈥揙ppenheimer Approximation 439(2)

III. Kinetic Isotope Effects: The Competing Effects of Zero-Point Energy and Tunneling 441(5)

A. The Mu Reaction with Molecular Hydrogen: The Dominance of Zero-Point Energy 441(1)

B. Mu Addition to Benzene: Evidence of Tunneling 442(1)

C. Mu Addition to Dioxygen: Cross-Over of Isotope Effects 443(1)

D. Mu Transfer: A World Record of a Kinetic Isotope Effect 444(1)

E. A Reaction Proceeding over a Solvent-Induced Barrier: A Dynamic Solvent Effect 445(1)

IV. Mass Effect on Diffusion 446(1)

A. Coherent and Incoherent Tunneling of Mu Diffusion in Crystals 446(1)

B. Diffusion of Mu in Liquid Water 447(1)

V. Concluding Remarks 447(1)

References 448(3)
Chapter 16 The Kinetic Isotope Effect in the Photo-Dissociation Reaction of Excited-State Acids in Aqueous Solutions 451(14)

Ehud Pines

I. Introduction 451(1)

II. General Kinetic Models for Acid鈥揃ase Reactions in Solutions 452(4)

A. The Two-State Proton-Transfer Reaction Model (The Eigen鈥揥eller Model) 452(2)

B. Free-Energy Correlations of the Proton (Deuteron) Transfer Rates 454(1)

C. The Isotope Effect in a Series of Similar Reactions 455(1)

III. The Isotope Effect in the Equilibrium Constant of Photoacids 456(3)

IV. The KIE in Photoacid Dissociation 459(3)

V. Concluding Remarks on the KIE in Photoacid (Phenol-Type) Dissociation 462(1)

References 462(3)
Chapter 17 The Role of an Internal-Return Mechanism on Measured Isotope Effects 465(10)

Heinz F. Koch

I. The Internal-Return Mechanism for Hydron-Transfer Reactions 466(2)

II. The Internal-Return Mechanism for Alkoxide-Promoted E2 Dehydrohalogenations 468(2)

III. Chlorine Isotope Effects vs. the Element Effect 470(1)

IV. Hydron Transfer from Alcohols to Carbanions 471(1)

V. Conclusions 472(1)

References 472(3)
Chapter 18 Vibrationally Enhanced Tunneling and Kinetic Isotope Effects in Enzymatic Reactions 475(24)

Steven D. Schwartz

I. Introduction 475(1)

II. Theoretical Approaches to the Study of Chemical Dynamics in Complex Systems 476(3)

III. Promoting Vibrations and the Dynamics of Hydrogen Transfer 479(3)

A. Promoting Vibrations and the Symmetry of Coupling 479(1)

B. Promoting Vibrations 鈥?Corner Cutting and the Masking of KIEs 480(2)

IV. Enzymatic Hydrogen Transfer and KIEs 482(9)

A. Alcohol Dehydrogenase 482(5)

B. Lactate Dehydrogenase 487(4)

V. Hydrogen Transfer Coupled to Electron Transfer 鈥?Kinetic Trends in the Presence of a Promoting Vibration 491(4)

VI. Conclusions 495(1)

Acknowledgments 495(1)

References 495(4)
Chapter 19 Kinetic Isotope Effects for Proton-Coupled Electron Transfer Reactions 499(22)

Sharon Hammes-Schiffer

I. Introduction 499(1)

II. Theory and Methods 500(6)

A. Electron Transfer Theory 500(1)

B. Proton Transfer Theory 501(1)

C. Proton-Coupled Electron Transfer Theory 502(3)

D. Methodological Developments 505(1)

III. Applications to Chemical and Biological Systems 506(8)

A. PCET in Solution 506(2)

B. Enzyme Reactions 508(4)

C. Role of Motion in Enzyme Reactions 512(2)

IV. Summary and Conclusions 514(1)

Acknowledgments 515(1)

References 515(6)
Chapter 20 Kinetic Isotope Effects in Multiple Proton Transfer 521(28)

Zorka Smedarchina, Willem Siebrand, and Antonio Fern谩ndez-Ramos

I. Introduction 521(2)

II. Theoretical Methods 523(6)

A. Transition State Theory 523(1)

B. Tunneling Preliminaries 524(2)

C. Approximate Instanton Method 526(2)

D. Isotope Effects 528(1)

E. Comparison of AIM with Other Methods 528(1)

III. Stepwise Transfer 529(6)

A. Example: Porphine 529(1)

B. Isotope Effects 530(2)

C. Temperature Effects 532(1)

D. Applications 533(2)

IV. Concerted Transfer 535(8)

A. Example: Acetic Acid鈥擬ethanol Complex 535(2)

B. Hydrogen Bonded Dimers and Complexes 537(1)

C. Water Wires 537(5)

D. The Proton Inventory Problem 542(1)

V. Conclusions 543(1)

Acknowledgments 544(1)

References 544(5)
Chapter 21 Interpretation of Primary Kinetic Isotope Effects for Adiabatic and Nonadiabatic Proton-Transfer Reactions in a Polar Environment 549(30)

Philip M. Kiefer and James T. Hynes

I. Introduction 549(4)

II. Adiabatic Proton Transfer 553(9)

A. Adiabatic Proton-Transfer Free-Energy Relationship 553(5)

1. General Adiabatic Proton-Transfer Picture 553(2)

2. Adiabatic Proton-Transfer Free-Energy Relationship 555(2)

3. Further Analysis of the Intrinsic Barrier. Mass Scaling 557(1)

B. Adiabatic Proton-Transfer KIEs 558(3)

1. KIE Arrhenius Behavior 559(1)

2. KIE Magnitude and Variation with Reaction Asymmetry 559(1)

3. Swain鈥揝chaad Relationship 560(1)

C. Further Discussion of Nontunneling KIEs 561(1)

III. Nonadiabatic 'Tunneling' Proton Transfer 562(10)

A. General Nonadiabatic Proton-Transfer Perspective and Rate Constant 562(5)

B. Nonadiabatic Proton-Transfer KIEs 567(17)

1. KIE Magnitude and Variation with Reaction Asymmetry 567(1)

2. Temperature Behavior 568(3)

3. Swain鈥揝chaad Relationship 571(1)

IV. Concluding Remarks 572(1)

Acknowledgments 573(1)

References 573(6)
Chapter 22 Variational Transition-State Theory and Multidimensional Tunneling for Simple and Complex Reactions in the Gas Phase, Solids, Liquids, and Enzymes 579(42)

Donald G. Truhlar

I. Introduction 580(3)

II. Previous Reviews 583(1)

III. Validation Against Accurate Quantum Mechanical Dynamics 583(1)

IV. Theory 584(16)

A. Gas Phase 584(6)

B. Reactions in the Solid State and at Solid Surfaces 590(1)

C. Reaction in Liquids 591(8)

1. Solute鈥揝olvent Separation 591(1)

2. Reaction Coordinates and Nonequilibrium Solvation 592(2)

3. VTST/MT Methods for Condensed-Phase Reactions 594(1)

a. Implicit Bath 594(1)

b. Reduced-Dimensionality Bath 595(1)

c. Explicit Bath 596(3)

D. Reactions in Enzymes 599(1)

V. Applications to KIEs 600(5)

A. Gas Phase 600(3)

B. KIEs in Liquid Phase 603(1)

C. Enzymes 603(2)

VI. Software 605(1)

VII. Concluding Remarks 605(1)

Acknowledgments 606(1)

Glossary 606(1)

References 607(14)
Chapter 23 Computer Simulations of Isotope Effects in Enzyme Catalysis 621(24)

Arieh Warshel, Mats H.M. Olsson, and Jordi Vill脿-Freixa

I. Introduction 621(2)

II. Methods for Simulations of Chemical Processes in Enzymes 623(3)

A. QM/MM Molecular Orbital Methods 624(1)

B. EVB as a Reliable QM/MM Method 625(1)

III. Simulating Nuclear Quantum Mechanical Effects in Condensed Phase 626(4)

A. The Dispersed Polaron (Spin Boson) Model 626(1)

B. Quantized Classical Path Simulations 627(3)

IV. Simulations of the KIE and Nuclear Quantum Mechanical Effects in Enzymatic Reactions 630(5)

A. Systematic Studies of Hydride Transfer in Solutions 630(1)

B. Simulating NQM Effects in LDH by a Microscopically Based Quasiharmonic Model and a QCP Treatment 630(1)

C. Nuclear Quantum Mechanical Effects in Carbonic Anhydrase 631(1)

D. Nuclear Quantum Mechanical Effects in Alcohol Dehydrogenase 632(2)

E. Lipoxygenase and the Large Tunneling Limit 634(1)

V. What is the Catalytic Contribution from Nuclear Quantum Mechanical Effects? 635(1)

VI. What Can and What Cannot be Learned from Simulations of Isotope Effects? 636(3)

A. The Use of Vibronic Models in Studies of Isotope Effects 636(1)

B. Using Calculated and Observed Isotope Effects as a Tool for Validating Single Only Simulations of NQM and Determining the Catalytic Contributions of NQM Effects 637(1)

C. Determining the Concertedness of Enzymatic Reactions by the KIE 638(1)

D. Dynamical Effects and Promoting Modes 638(1)

VII. Concluding Remarks 639(1)

Acknowledgments 640(1)

References 640(5)
Chapter 24 Oxygen-18 Isotope Effects as a Probe of Enzymatic Activation of Molecular Oxygen 645(26)

Justine P. Roth and Judith P. Klinman

I. Introduction 645(1)

II. Instrumentation 646(2)

III. Equilibrium Isotope Effects 648(2)

IV. Applications 650(15)

A. Glucose Oxidase 650(3)

B. Tyrosine Hydroxylase 653(2)

C. Soybean Lipoxygenase 655(2)

D. Methane Monooxygenase 657(1)

E. Cytochrome P-450 658(2)

F. Dopamine β-Monooxygenase and Peptidylglycine α-Hydroxylating Monooxygenase 660(2)

G. Copper Amine Oxidases 662(3)

V. Overview and Perspectives for the Future 665(1)

References 666(5)
Chapter 25 Solution and Computational Studies of Kinetic Isotope Effects in Flavoprotein and Quinoprotein Catalyzed Substrate Oxidations as Probes of Enzymic Hydrogen Tunneling and Mechanism 671(20)

Jaswir Basran, Laura Masgrau, Michael J. Sutcliffe, and Nigel S. Scrutton

I. Enzymic H-Tunneling and Kinetic Isotope Effects 671(2)

A. Stopped-Flow Methods to Access the Half-Reactions of Flavoenzymes and Quinoproteins 672(1)

II. Interpreting Temperature Dependence of Isotope Effects in Terms of H-Tunneling 673(2)

III. H-Tunneling in Flavoenzymes PETN Reductase and MR 675(3)

IV. H-Tunneling in TTQ-Dependent MADH and AADH 678(1)

V. Computational Studies of Substrate Oxidation in TTQ-Dependent Amine Dehydrogenases 679(3)

VI. H-Tunneling in Flavoprotein Amine Dehydrogenases: TSOX and Engineering Gated Motion in TMADH 682(3)

VII. Concluding Remarks 685(1)

Acknowledgments 685(1)

References 685(6)
Chapter 26 Proton Transfer and Proton Conductivity in Condensed Matter Environment 691(34)

Alexander M. Kuznetsov and Jens Ulstrup

I. Introduction 691(2)

II. Mechanisms of Elementary Proton Transfer between Molecular Fragments 693(9)

A. Basic PT Model at Fixed Donor/Acceptor Distance 693(2)

B. The Born鈥揙ppenheimer Approximation and Potential Free-Energy Surfaces 695(1)

C. Totally Diabatic Proton Transfer 696(1)

D. Partially Adiabatic Proton Transfer 697(1)

E. Totally Adiabatic Proton Transfer 698(1)

F. General Expressions for the Tunnel Transmission Coefficient and Transition Probability. The Environmental Medium Dynamics 698(2)

G. Fluctuations of the Interreactant Distance and Gated Proton Transfer 700(1)

H. Free Energy Relations and Kinetic Isotope Effects 701(1)

III. Proton Transfer in Hydrogen-Bonded Systems 702(8)

A. Hydrogen Bonds with Double-Well Proton Potentials 703(2)

B. Excess Aqueous Proton Conductivity and Proton Transfer 705(4)

1. Proton Hops between Two Water Molecules 706(1)

2. Short-Range Proton Transfer via Adjacent Zundel Complexes 706(1)

3. Long-Range Proton Transfer via Remote Zundel Complexes 707(2)

B. Proton Transfer in Single-Well Proton Potentials 709(1)

IV. Electron-Coupled Proton Transfer 710(10)

A. Mechanisms of Dynamic and Step-Wise Coupling 711(3)

B. A View on Coherent Two-Proton Transfer in Zundel Complexes 714(1)

C. Models and Mechanisms of Electron-Coupled Proton Transfer (ECPT) 715(5)

1. Diabatic States 716(2)

2. Mechanisms of Transitions and Rate Constants 718(2)

D. Synchronous Electron and Proton Transfer 720(1)

V. Concluding Remarks 720(2)

Acknowledgments 722(1)

References 722(3)
Chapter 27 Mechanisms of CH-Bond Cleavage Catalyzed by Enzymes 725(18)

Willem Siebrand and Zorka Smedarchina

I. Introduction 725(2)

II. Observations 727(3)

A. Rate Constants 727(1)

B. kinetic Isotope Effects 728(1)

C. Temperature Dependence 728(1)

D. Systems without Proteins 729(1)

III. Theoretical Models 730(5)

A. Two-Oscillator Models 730(1)

B. Golden Rule Treatment 731(3)

C. Semiclassical Instanton Approach 734(1)

D. Model Parameters 734(1)

IV. Applications 735(3)

A. Coenzyme B12 735(1)

B. Lipoxygenase 736(1)

C. Primary Amine Dehydrogenases 737(1)

D. Dicopper Complexes 738(1)

V. Discussion 738(1)

Acknowledgments 739(1)

References 739(4)
Chapter 28 Kinetic Isotope Effects as Probes for Hydrogen Tunneling in Enzyme Catalysis 743(22)

Amnon Kohen

I. Introduction 744(1)

A. Enzyme Catalysis 744(1)

B. The Chemical Step: Contributions of Quantum Mechanical Tunneling, Equilibrium Fluctuations, and Dynamics 744(1)

II. Kinetic Isotope Effects as Probes of the Chemical Step 745(8)

A. Semiclassical Relationship of Reaction Rates of H, D, and T 746(1)

B. Primary (1掳) Swain鈥擲chaad Relationship 746(2)

1. Intrinsic 1掳 KIE 746(2)

2. Experimental Examples Using Intrinsic 1掳 KIE 748(1)

a. Peptidylglycine α-Hydroxylating Monooxygenase 748(1)

b. Thymidylate Synthase 748(1)

c. Dihydrofolate Reductase 748(1)

C. Secondary (2掳) Swain鈥擲chaad Relationship 748(5)

1. Mixed Labeling Experiments as Probes for Tunneling and 1掳-2掳 Coupled Motion 749(1)

2. Upper Semiclassical Limit for 2掳 Swain鈥擲chaad Relationship 750(1)

a. Zero-Point Energy and Reduced Mass Considerations 750(1)

b. Vibrational Analysis 751(1)

c. Effect of Kinetic Complexity 751(1)

d. The New Effective Upper Limit 752(1)

3. Experimental Examples Using 2掳 Swain鈥擲chaad Exponents 753(1)

a. Horse Liver Alcohol Dehydrogenase 753(1)

b. Thermophilic ADH from Bacillus stearothermophilus (ADH-hT) 753(1)

III. Temperature Dependence of KIEs 753(4)

A. Temperature Dependence of Reaction Rates and KIEs 753(1)

B. KIEs on Arrhenius Activation Factors 754(1)

C. Experimental Examples Using Isotope Effects on Arrhenius Activation Factors 755(2)

1. Soybean Lipoxygenase-1 755(1)

2. Thermophilic ADH (ADH-hT) 756(1)

IV. Theoretical Approaches 757(2)

A. Phenomenological "Marcus-Like" Models 757(1)

B. QM/MM Models and Simulations 758(1)

V. Comparison to Studies of Nonenzymatic Reactions 759(1)

VI. Conclusions 760(1)

References 760(5)
Chapter 29 Hydrogen Bonds, Transition-State Stabilization, and Enzyme Catalysis 765(28)

Richard L. Schowen

I. The Problem of Enzyme Catalysis 766(5)

A. Magnitudes of Catalytic Accelerations by Enzymes 766(1)

B. Transition-State Stabilization and Catalysis 767(1)

C. H-Bonds as a Means of Transition-State Stabilization 768(2)

D. Beyond the Transition-State Theory of Catalysis 770(1)

II. Structure and Strength of H-Bonds 771(4)

A. The Concept of H-Bond Strength 771(1)

B. Categorization of H-Bonds 772(1)

C. Some Probes of Hydrogen Bonds 772(3)

1. NMR Approaches 773(1)

2. Theoretical Studies of H-Bonds 773(1)

3. Thermochemical, Spectroscopic, and Structural Approaches 774(1)

III. Isotope Effects in Hydrogen Bonding 775(2)

A. Simple H-Bonds 775(1)

B. Unusual H-Bonds 776(1)

C. Primary Catalytic H-Bonds 776(1)

D. Secondary Catalytic H-Bonds 777(1)

IV. Issues in H-Bonding and Enzyme Catalysis 777(11)

A. Cautionary Notes on Mutations at H-Bonding Sites in Enzymes 777(4)

1. H-Bonds in the Orientation of Ligands for Optimal Catalysis 777(2)

2. The Catalytic Triad of Serine Hydrolases 779(2)

B. Primary Catalytic H-Bonds 781(1)

C. Secondary Catalytic H-Bonds 781(6)

1. The Catalytic Triad of Serine Hydrolases 781(4)

2. The Oxyanion Hole of Serine Hydrolases 785(2)

D. Conformational Changes Signaled by Proton Inventories 787(1)

V. Summary 788(1)

References 789(4)
Chapter 30 Substrate and pH Dependence of Isotope Effects in Enzyme Catalyzed Reactions 793(18)

William E. Karsten and Paul F. Cook

I. Introduction 794(1)

A. Nomenclature 794(1)

B. Types of Isotope Effects 794(1)

II. Enzyme-Catalyzed vs. Nonenzymatic Reactions 794(2)

A. Physical vs. Chemical Steps 794(1)

B. Commitment Factors 795(1)

C. Substrate Stickiness 795(1)

III. Substrate Dependence of Isotope Effects 796(6)

A. Sequential Mechanisms 796(4)

1. Ordered Mechanisms (k5, k6, k7, and k8 = 0) 797(1)

a. Formate Dehydrogenase 797(1)

b. Mannitol Dehydrogenase 798(1)

2. Random Mechanisms (All Rate Constants of Mechanism 3 Apply) 798(1)

a. NAD-Malic Enzyme 799(1)

b. Ketopantoate Reductase 799(1)

B. Ping Pong Kinetic Mechanisms 800(1)

1. Dihydroorotate Dehydrogenase 801(1)

2. p-Cresol Methylhydroxylase 801(1)

C. Substrate Dependence of Isotope Effects in Terreactant and Higher Order Mechanisms 801(1)

1. NAD-Malic Enzyme 802(1)

2. Alanine Dehydrogenase 802(1)

IV. pH Dependence of Isotope Effects 802(5)

A. Proton Transfer and Chemistry are Concerted 802(4)

1. Random Addition of Proton and Substrate to Enzyme 803(1)

a. NADP-Malic Enzyme 804(1)

b. Nitroalkane Oxidase 804(1)

2. Dead-End Protonation of Enzyme 804(1)

a. NAD-Malic Enzyme 805(1)

3. Dead-End Protonation of Enzyme and the Enzyme-Reactant Complex 805(1)

a. Ketpantoate Reductase 805(1)

4. Dead-End Formation of a Protonated Enzyme-Reactant Complex 806(1)

B. Proton Transfer and Chemistry not Concerted 806(6)

1. Equine Liver Alcohol Dehydrogenase 807(1)

V. Closing Remarks 807(1)

References 808(3)
Chapter 31 Catalysis by Alcohol Dehydrogenases 811(26)

Bryce V. Plapp

I. Introduction 811(1)

II. Mechanism and Structure of Alcohol Dehydrogenases 812(2)

A. Kinetic Mechanism from Isotope Effects 812(1)

B. Structural Studies of Ternary Complexes 813(1)

III. Transient Kinetics and Simulation of Complete Mechanisms 814(2)

IV. Unmasking Chemistry for Mechanistic Studies 816(6)

A. Poor Substrates and Chemical Modification 816(1)

B. Site-Directed Mutagenesis 816(2)

C. Isotope Effects and Altered Rate Constants 818(4)

V. Dynamics of Hydrogen Transfer 822(5)

A. Tunneling Detected by Comparison of H/D/T Isotope Effects 822(1)

B. Temperature Dependence and Isotope Effects 822(3)

C. Pressure and Isotope Effects 825(1)

D. Protein Motions and Computational Studies 826(1)

VI. Solvent (D2O) Isotope Effects and Proton Transfer 827(1)

A. Steady-State Kinetic Studies 827(1)

B. Transient Kinetic Studies and a Low-Barrier Hydrogen Bond 827(1)

VII. Future Studies 828(2)

Acknowledgments 830(1)

References 830(7)
Chapter 32 Effects of High Hydrostatic Pressure on Isotope Effects 837(10)

Dexter B. Northrop

I. Introduction 837(1)

II. Theory 837(4)

III. Experimental Examples 841(3)

A. Hydrogen Tunneling 841(1)

B. Yeast Alcohol Dehydrogenase 842(2)

C. Yeast Formate Dehydrogenase 844(1)

IV. Conclusion 844(1)

References 844(3)
Chapter 33 Solvent Hydrogen Isotope Effects in Catalysis by Carbonic Anhydrase: Proton Transfer through Intervening Water Molecules 847(14)

David N. Silverman and Ileana Elder

I. Introduction 847(3)

A. Catalytic Mechanism 848(1)

B. Structure 849(1)

C. Relevance of Ordered Water in Crystal Structures of Carbonic Anhydrase 850(1)

II. Isotope Effects on First Stage of Catalysis 鈥?The Hydration of CO2 850(1)

III. Solvent Hydrogen Isotope Effects on the Proton Transfer Steps 850(7)

A. Intramolecular Proton Transfer in Catalysis by Carbonic Anhydrase 850(6)

1. Proton inventory 850(1)

2. Interpreting the Isotope Effects 851(1)

3. Theorists View of Isotope Effects in Catalysis by Carbonic Anhydrase 851(1)

4. Use of 18O Exchange 852(1)

5. Marcus Rate Theory Allows Enhanced Interpretation of Proton-Transfer Rates 853(1)

6. Marcus Plot for Intramolecular Proton Transfer 854(1)

7. Marcus Plot for Solvent Hydrogen Isotope Effects 855(1)

B. Intermolecular Proton Transfer in Catalysis by Carbonic Anhydrase 856(10)

1. Marcus Plot for Solvent Hydrogen Isotope Effects 856(1)

2. The Marcus Formalism Extended to the β and γ Classes 857(1)

VI. Conclusions 857(1)

References 857(4)
Chapter 34 Isotope Effects from Partitioning of Intermediates in Enzyme-Catalyzed Hydroxylation Reactions 861(14)

Paul F. Fitzpatrick

I. Introduction 861(1)

II. Theory 862(4)

III. Examples 866(5)

A. Cytochrome P450 866(2)

B. The Aromatic Amino Acid Hydroxylases 868(2)

C. Dopamine β-Monooxygenase 870(1)

IV. Conclusion 871(1)

References 871(4)
Chapter 35 Chlorine Kinetic Isotope Effects on Biological Systems 875(18)

Piotr Paneth

I. Introduction 875(3)

A. Dehalogenation 鈥?Environmental Perspective 875(1)

B. Chlorine Kinetic Isotope Effects 876(1)

C. Calculations of Chlorine KIEs 876(1)

D. Chlorine Isotopic Ratio Measurements 877(1)

II. Chlorine Isotopic Fractionation in Microbial Processes 878(10)

A. Chlorine KIEs on Microbial Degradation of Chlorinated Compounds 878(1)

1. Reduction of Perchlorate 878(1)

2. Reduction of Chlorinated Aliphatic Hydrocarbons 879(1)

B. Chlorine KIEs on Reactions Catalyzed by Dehalogenases 879(7)

1. Haloalkane Dehalogenases 880(3)

2. DL-2-Haloacid Dehalogenase 883(2)

3. Fluoroacetate Dehalogenase 885(1)

4. 4-Chlorobenzoil-CoA Dehalogenase 885(1)

C. Chlorine KIEs on Enzymatic Halogenation 886(2)

III. Future Perspectives 888(1)

Acknowledgments 888(1)

References 888(5)
Chapter 36 Nucleophile Isotope Effects 893(22)

Vernon E. Anderson, Adam G. Cassano, and Michael E. Harris

I. Nucleophilic Activation and Reaction Mechanisms 893(2)

II. 18O Isotope Effects 895(13)

A. Activation of Water and Associated Equilibrium Isotope Effects 895(4)

1. Desolvation and H-Bonding 895(3)

2. Equilibrium Isotope Effects on Hydroxide Formation 898(1)

3. Isotope Effects on Coordination of Water by Metal Ions 898(1)

B. Kinetic Effects on Reactions 899(9)

1. Experimental and Theoretical Considerations 899(2)

2. Nucleophilic Attack on Electrophilic sp2 Carbon 901(2)

3. Attack on Carbon鈥揙xygen Double Bonds, Addition to Carbonyl Compounds 903(1)

a. Hydrolysis of Formic Acid Derivatives 903(1)

b. Carboxypeptidase Catalyzed Amide and Ester Hydrolysis 905(1)

4. Hydrolysis of Phosphate Esters 905(2)

5. 18knuc Effect on Hexokinase 907(1)

III. 15N Isotope Effects 908(2)

A. Equilibrium Isotope Effects on Protonation and N鈥揅 Bond Formation 908(1)

B. Kinetic Isotope Effects on Nucleophilic Attack at sp鲁 Carbon 908(1)

C. Kinetic Isotope Effects on Enzyme Catalyzed Nucleophilic Attack at sp虏 Carbons 909(1)

IV. Prospectus 910(1)

Acknowledgments 911(1)

References 911(4)
Chapter 37 Enzyme Mechanisms from Isotope Effects 915(16)

W. Wallace Cleland

I. Isotope Effect Theory 915(10)

A. Notation 916(1)

B. Measurement of Isotope Effects 916(5)

1. Direct Comparison 916(1)

2. Internal Competition 917(1)

a. The Remote Label Method 鈥?Stable Isotopes 918(1)

b. The Remote Label Method 鈥?Radioactive Isotopes 920(1)

3. Equilibrium Perturbation 920(1)

C. Equation for the Isotope Effect 921(2)

D. Determination of Intrinsic Isotope Effects 923(2)

1. Northrop's Method 923(1)

2. Multiple Isotope Effect Method 924(1)

II. Examples of Mechanistic Analysis 925(3)

A. Aspartate Transcarbamoylase 925(1)

B. Malic Enzyme 926(1)

C. Oxalate Decarboxylase 927(1)

D. Chorismate Mutase 927(1)

E. L-Ribulose-5-P 4-Epimerase 928(1)

F. Other Enzymes 928(1)

References 928(3)
Chapter 38 Catalysis and Regulation in the Soluble Methane Monooxygenase System: Applications of Isotopes and Isotope Effects 931(24)

John D. Lipscomb

I. Introduction 931(1)

II. sMMO Components 932(1)

III. sMMO Catalytic Cycle 933(3)

IV. Kinetic Solvent Isotope Effect used to Probe Proton Donors 936(2)

V. The Mechanism of Q Reaction with Substrates 938(4)

VI. Arrhenius Plots for the Reactions of Reaction Cycle Intermediates 942(1)

VII. The Effects of MMOB 943(2)

VIII. A Test of the Molecular-Sieve Model using KIE Studies 945(1)

IX. A Tunneling Reaction 946(1)

X. New Insight into the Mechanism of C鈥揌 Bond Cleavage 947(2)

Acknowledgments 949(1)

References 949(6)
Chapter 39 Secondary Isotope Effects 955(20)

Alvan C. Hengge

I. Theory and Nomenclature 955(1)

II. Origins of Secondary Isotope Effects 956(5)

A. Secondary Isotope Effects Resulting from Hybridization Changes 956(3)

B. Secondary Isotope Effects on Acidities 959(1)

C. Steric Secondary Isotope Effects 960(1)

III. Secondary Isotope Effects in Particular Reactions 961(14)

A. Acyl Transfer 961(3)

B. Glycosyl Transfer 964(1)

C. N-Ribosyl Hydrolases and Transferases 965(1)

D. Phosphoryl Transfer 966(2)

E. Methyl Transfer 968(1)

F. Hydride Transfer 969(1)

G. Peptidyl Prolyl Cis鈥揟rans Isomerase 969(6)

References 975(1)
Chapter 40 Isotope Effects in the Characterization of Low Barrier Hydrogen Bonds 975(20)

Perry A. Frey

I. Introduction 975(2)

II. Zero-Point Energy Effects and Hydrogen Bonds 977(5)

A. Classification of Hydrogen Bond Types 977(1)

B. NMR Chemical Shifts of Strong Hydrogen Bonds 978(1)

C. Isotope Effects on Physical Parameters 979(2)

1. Isotope Effects on Vibrational Frequencies 979(1)

2. Isotope Effects on Chemical Shifts of LBHBs 980(1)

3. D/H Fractionation Factors 981(1)

D. Strengths of Hydrogen Bonds 981(1)

III. Low-Barrier Hydrogen Bonds in Enzymes 982(5)

A. Serine Proteases 982(3)

B. Cholinesterases 985(1)

C. Δ5-3-Ketosteroid Isomerase 986(1)

IV. Role of Low-Barrier Hydrogen Bonds in the Actions of Enzymes 987(3)

A. Serine Proteases and Esterases 987(3)

B. Δ5-3-Ketosteroid Isomerase 990(1)

C. Other Enzymes 990(1)

Acknowledgments 990(1)

References 990(5)
Chapter 41 Theory and Practice of Solvent Isotope Effects 995(24)

Daniel M. Quinn

I. Introduction 995(1)

II. Origins of Solvent Isotope Effects 996(2)

A. Equilibrium Solvent Isotope Effects 996(1)

B. Kinetic Isotope Effects 997(1)

III. The Kresge鈥擥ross鈥擝utler Equation 998(6)

A. Derivation 998(2)

B. The Proton Inventory Technique 1000(4)

1. Proton Inventories of Elementary Steps 1000(1)

2. Effects of Reactant State Fractionation 1001(1)

3. Proton Inventories of Multistep Enzyme Reactions 1002(2)

IV. Fractionation Factors 1004(2)

A. Reactant State Fractionation Factors of Common Functional Groups 1004(1)

B. Transition State Fractionation Factors 1005(1)

V. Practical Considerations 1006(2)

VI. Examples 1008(8)

A. Nonenzymic Reactions 1008(1)

B. Enzymatic Reactions 1009(12)

1. Serine Proteases 1009(3)

2. Acetylcholinesterase 1012(2)

3. Carbonic Anhydrase 1014(1)

4. Tyrosine Hydroxylase 1015(1)

VII. Conclusions 1016(1)

References 1016(3)
Chapter 42 Enzymatic Binding Isotope Effects and the Interaction of Glucose with Hexokinase 1019(36)

Brett E. Lewis and Vern L. Schramm

I. Introduction 1020(1)

II. History of Enzymatic Binding Isotope Effects 1020(1)

III. Contributions of Binding and Prebinding Steps to Isotope Effects in Enzymology 1021(11)

A. BIE and ME 1022(4)

1. Expressions of D(kcat/Km) and T(kcat/Km) 1022(2)

2. Expressions of Dkcat 1024(2)

B. Prebinding Isomeric Isotope Effects and KIE 1026(4)

1. Effect on Competitive (kcat/Km) KIE Measurements 1026(1)

a. Regimes I鈥擨II 1027(1)

b. Regimes IV鈥擵I 1027(1)

c. Regimes VII鈥擨X 1028(1)

2. Effect on Noncompetitive Dkcat Measurements 1029(1)

3. Curtin鈥擧ammet Principle 1029(1)

C. Prebinding Isotope Effects and BIE 1030(2)

D. Conclusions 1032(1)

1. Transition State Studies 1032(1)

2. Determination of Rate-Limiting Steps and Tunneling 1032(1)

IV. Physical Basis for Binding and Kinetic Isotope Effects 1032(14)

A. Frequency Changes due to Reaction and Heavy-Atom Labeling 1033(4)

1. Heavy Atom Labeling 1033(1)

2. High-Frequency CH Bond Stretch: Equilibrium Isotope Effects 1034(1)

3. Lower-Frequency CN Bond Stretch: Equilibrium Isotope Effects 1035(1)

4. When Does MMI Count? 1036(1)

5. When Does EXC Count? 1036(1)

B. Alteration in Force Constants 1037(8)

1. How Many Modes Actually Matter? 1038(1)

2. Isotope Effects from Altering Mode Coupling Partners 1039(3)

3. Sterics and Hyperconjugation 1042(3)

C. Summary 1045(1)

V. Example: Glucose and Brain Hexokinase 1046(3)

A. Methods 1046(1)

B. The Binary Complex 1047(1)

C. The Ternary Complex 1048(1)

VI. Applications for BIE 1049(1)

VII. Conclusion 1049(1)

Acknowledgments 1050(1)

References 1050(5)
Index 1055