Physical Chemistry : Principles and Applications in Biological Sciences

by Tinoco, Ignacio, Jr.; Sauer, Kenneth; Wang, James C.; Puglisi, Joseph D.

• ISBN13: 9780130959430
• ISBN10: 013095943X
• Edition: 4th
• Format: Paperback
• Copyright: 2001-08-06
• Publisher: Prentice Hall

Summary

This best-selling volume presents the principles and applications of physical chemistry as they are used to solve problems in biology and medicine.The First Law; the Second Law; free energy and chemical equilibria; free energy and physical Equilibria; molecular motion and transport properties; kinetics: rates of chemical reactions; enzyme kinetics; the theory and spectroscopy of molecular structures and interactions: molecular distributions and statistical thermodynamics; and macromolecular structure and X-ray diffraction.For anyone interested in physical chemistry as it relates to problems in biology and medicine.

Author Biography

Ignacio Tinoco was an undergraduate at the University of New Mexico, a graduate student at the University of Wisconsin, and a postdoctoral fellow at Yale. He then went to the University of California, Berkeley, where he has remained. His research interest has been on the structures of nucleic acids, particularly RNA. He was chairman of the Department of Energy committee that recommended in 1987 a major initiative to sequence the human genome. His present research is on unfolding single RNA molecules by force.

Kenneth Sauer grew up in Cleveland, Ohio, and received his A.B. in chemistry from Oberlin College. Following his Ph.D. studies in gas-phase physical chemistry at Harvard, he spent three years teaching at the American University of Beirut, Lebanon. A postdoctoral opportunity to learn from Melvin Calvin about photosynthesis in plants led him to the University of California, Berkeley, where he has been since 1960. Teaching general chemistry and biophysical chemistry in the Chemistry Department has complemented research in the Physical Biosciences Division of the Lawrence Berkeley National Lab involving spectroscopic studies of photosynthetic light reactions and their role in water oxidation. His other activities include reading, renaissance and baroque choral music, canoeing, and exploring the Sierra Nevada with his family and friends.

James C. Wang was on the faculty of the University of California, Berkeley, from 1966 to 1977. He then joined the faculty of Harvard University, where he is presently Mallinckrodt Professor of Biochemistry and Molecular Biology. His research focuses on DNA and enzymes that act on DNA, especially a class of enzymes known as DNA topoisomerases. He has taught courses in biophysical chemistry and molecular biology and has published over 200 research articles. He is a member of Academia Sinica, the American Academy of Arts and Sciences, and the U.S. National Academy of Sciences.

Joseph Puglisi was born and raised in New Jersey. He received his B.A. in chemistry from The Johns Hopkins University in 1984 and his Ph.D. from the University of California, Berkeley, in 1989. He has studied and taught in Strasbourg, Boston, and Santa Cruz, and is currently professor of structural biology at Stanford University. His research interests are in the structure and mechanism of the ribosome and the use of NMR spectroscopy to study RNA structure. He has been a Dreyfus Scholar, Sloan Scholar, and Packard Fellow.

Table of Contents

Preface	xvii
About the Authors	xix
Introduction
The Human Genome and Beyond	4	(2)
Transcription and Translation	6	(4)
Ion Channels	10	(1)
References	11	(1)
Suggested Reading	12	(1)
Problem	12	(3)
The First Law: Energy Is Conserved
Concepts	15	(1)
Applications	16	(1)
Energy Conversion and Conservation	16	(13)
Systems and Surroundings	17	(1)
Energy Exchanges	18	(10)
First Law of Thermodynamics	28	(1)
Describing the State of a System	29	(16)
Variables of State	29	(2)
Equations of State	31	(2)
Paths Connecting Different States	33	(3)
Dependence of the Energy and Enthalpy of a Pure Substance on P, V, and T	36	(8)
Relations Between Heat Exchanges and DE and DH	44	(1)
Phase Changes	45	(2)
Chemical Reactions	47	(9)
Heat Effects of Chemical Reactions	47	(3)
Temperature Dependence of ΔH	50	(1)
The Energy Change ΔE for a Reaction	51	(1)
Standard Enthalpies (or Heats) of Formation	51	(2)
Bond Energies	53	(3)
Molecular Interpretations of Energy and Enthalpy	56	(1)
Summary	57	(3)
State Variables	57	(1)
Unit Conversions	57	(1)
General Equations	57	(1)
Pressure-Volume Work Only	58	(1)
Solids and Liquids	58	(1)
Gases	59	(1)
Phase Changes	59	(1)
Chemical Reactions	60	(1)
Mathematics Needed for Chapter 2	60	(1)
References	61	(1)
Suggested Reading	61	(1)
Problems	61	(8)
The Second Law: The Entropy of the Universe Increases
Concepts	69	(1)
Applications	69	(1)
Historical Development of the Second Law: The Carnot Cycle	69	(4)
A New State Function, Entropy	73	(2)
The Second Law of Thermodynamics: Entropy Is Not Conserved	75	(2)
Molecular Interpretation of Entropy	77	(4)
Fluctuations	79	(2)
Measurement of Entropy	81	(1)
Chemical Reactions	81	(1)
Third Law of Thermodynamics	82	(5)
Temperature Dependence of Entropy	82	(1)
Temperature Dependence of the Entropy Change for a Chemical Reaction	83	(1)
Entropy Change for a Phase Transition	84	(1)
Pressure Dependence of Entropy	85	(2)
Spontaneous Chemical Reactions	87	(1)
Gibbs Free Energy	87	(10)
ΔG and a System's Capacity to Do Nonexpansion Work	87	(1)
Spontaneous Reactions at Constant T and P	88	(1)
Calculation of Gibbs Free Energy	89	(2)
Temperature Dependence of Gibbs Free Energy	91	(3)
Pressure Dependence of Gibbs Free Energy	94	(3)
Phase Changes	97	(1)
Helmholtz Free Energy	97	(1)
Noncovalent Reactions	97	(9)
Hydrophobic Interactions	100	(1)
Proteins and Nucleic Acids	101	(5)
Use of Partial Derivatives in Thermodynamics	106	(5)
Relations Among Partial Derivatives	107	(4)
Summary	111	(2)
State Variables	111	(1)
Unit Conversions	111	(1)
General Equations	111	(1)
ΔG and a System's Capacity to Do Nonexpansion Work	111	(1)
Spontaneous Reactions at Constant T and P	111	(1)
Changes in Entropy and Gibbs Free Energy	112	(1)
References	113	(1)
Suggested Reading	113	(1)
Problems	113	(8)
Free Energy and Chemical Equilibria
Concepts	121	(1)
Applications	122	(1)
Chemical Potential (Partial Molar Gibbs Free Energy)	122	(3)
Gibbs Free Energy and the Chemical Potential	122	(1)
The Sum Rule for Partial Molar Quantities	123	(1)
Chemical Potential and Directionality of Chemical Reaction	123	(2)
Reactions of Gases: The Ideal Gas Approximation	125	(5)
Dependence of Chemical Potential on Partial Pressures	125	(2)
Equilibrium Constant	127	(3)
Nonideal Systems	130	(11)
Activity	130	(1)
Standard States	131	(8)
Activity Coefficients of Ions	139	(2)
The Equilibrium Constant and the Standard Gibbs Free Energies of the Reactants and Products	141	(12)
Calculation of Equilibrium Concentrations: Ideal Solutions	144	(6)
Temperature Dependence of the Equilibrium Constant	150	(3)
Galvanic Cells	153	(6)
Standard Electrode Potentials	156	(2)
Concentration Dependence of	158	(1)
Biochemical Applications of Thermodynamics	159	(11)
Thermodynamics of Metabolism	165	(5)
Biological Redox Reactions	170	(6)
NADH-Q Reductase	171	(1)
Cytochrome Reductase	172	(1)
Cytochrome c Oxidase	172	(1)
Double Strand Formation in Nucleic Acids	172	(3)
Ionic Effect on Protein-Nucleic Acid Interactions	175	(1)
Summary	176	(3)
Chemical Potential (Partial Molar Gibbs Free Energy)	176	(1)
Standard States and Activities	177	(1)
Gibbs Free-Energy Change and Equilibrium Constant for a Chemical Reaction	178	(1)
Galvanic Cells	178	(1)
Mathematics Needed for Chapter 4	179	(1)
References	179	(1)
Suggested Reading	179	(1)
Problems	179	(8)
Free Energy and Physical Equilibria
Concepts	187	(1)
Applications	187	(1)
Membranes and Transport	187	(1)
Ligand Binding	188	(1)
Colligative Properties	188	(1)
Phase Equilibria	188	(25)
One-Component Systems	189	(1)
Boiling Point and Freezing Point	189	(4)
Solutions of Two or More Components	193	(4)
Equilibrium Dialysis	197	(1)
The Scatchard Equation	198	(4)
Cooperative Binding and Anticooperative Binding	202	(4)
Free Energy of Transfer Between Phases	206	(4)
Donnan Effect and Donnan Potential	210	(3)
Membranes	213	(14)
Lipid Molecules	213	(1)
Lipid Bilayers	214	(2)
Phase Transitions in Lipids, Bilayers, and Membranes	216	(2)
Surface Tension	218	(4)
Surface Free Energy	222	(2)
Vapor Pressure and Surface Tension	224	(1)
Biological Membranes	225	(2)
Active and Passive Transport	227	(4)
Colligative Properties	231	(8)
Molecular-Weight Determination	239	(2)
Vapor-Pressure Lowering	240	(1)
Summary	241	(3)
Phase Equilibrium	241	(1)
Solutions	242	(2)
References	244	(1)
Suggested Reading	245	(1)
Internet	245	(1)
Problems	245	(8)
Molecular Motion and Transport Properties
Concepts	253	(1)
Applications	254	(1)
Kinetic Theory	255	(10)
Brownian Motion and Random Molecular Motion	255	(1)
Velocities of Molecules, Translational Kinetic Energy, and Temperature	256	(5)
Maxwell-Boltzmann Distribution of Velocities	261	(4)
Molecular Collisions	265	(1)
Mean Free Path	266	(1)
Diffusion	267	(12)
The Random Walk and Diffusion in a Gas	267	(2)
Diffusion Coefficient and Fick's First Law	269	(2)
Fick's Second Law	271	(1)
Determination of the Diffusion Coefficient	272	(1)
Relationship Between the Diffusion Coefficient and the Mean-Square Displacement	273	(1)
Determination of the Diffusion Coefficient by Laser Light Scattering	274	(1)
Diffusion Coefficient and Molecular Parameters	275	(1)
Solvation	276	(1)
Shape Factor	277	(2)
Diffusion Coefficients of Random Coils	279	(1)
Sedimentation	279	(6)
Determination of the Sedimentations Coefficient	281	(2)
Standard Sedimentation Coefficient	283	(2)
Determination of Molecular Weights from Sedimentation and Diffusion	285	(4)
Determination of Molecular Weights from Sedimentation Equilibrium	285	(3)
Density-Gradient Centrifugation	288	(1)
Viscosity	289	(2)
Measurement of Viscosity	290	(1)
Viscosities of Solutions	291	(1)
Electrophoresis	291	(10)
Gel Electrophoresis	292	(1)
DNA Sequencing	293	(1)
Double-Stranded DNA	294	(1)
DNA Fingerprinting	294	(2)
Conformations of Nucleic Acids	296	(1)
Pulsed-Field Gel Electrophoresis	297	(2)
Protein Molecular Weights	299	(1)
Protein Charge	300	(1)
Macromolecular Interactions	301	(1)
Size and Shape of Macromolecules	301	(1)
Summary	302	(5)
Kinetic Theory	302	(2)
Diffusion	304	(1)
Sedimentation	304	(1)
Frictional Coefficient and Molecular Parameters	305	(1)
Combination of Diffusion and Sedimentation	305	(1)
Viscosity	305	(1)
Electrophoresis	306	(1)
Gel Electrophoresis	306	(1)
References	307	(1)
Suggested Reading	307	(1)
Problems	307	(8)
Kinetics: Rates of Chemical Reactions
Concepts	315	(1)
Applications	316	(1)
Kinetics	316	(25)
Rate Law	318	(1)
Order of a Reaction	318	(2)
Experimental Rate Data	320	(1)
Zero-Order Reactions	321	(1)
First-Order Reactions	322	(7)
Second-Order Reactions	329	(5)
Renaturation of DNA as an Example of a Second-Order Reaction	334	(4)
Reactions of Other Orders	338	(1)
Determining the Order and Rate Constant of a Reaction	338	(3)
Reaction Mechanisms and Rate Laws	341	(13)
Parallel Reactions	343	(2)
Series Reactions (First Order)	345	(4)
Equilibrium and Kinetics	349	(2)
Complex Reactions	351	(1)
Deducing a Mechanism from Kinetic Data	352	(2)
Temperature Dependence	354	(3)
Transition-State Theory	357	(3)
Electron Transfer Reactions: Marcus Theory	360	(2)
Ionic Reactions and Salt Effects	362	(1)
Isotopes and Stereochemical Properties	363	(2)
Very Fast Reactions	365	(7)
Relaxation Methods	365	(1)
Relaxation Kinetics	366	(6)
Diffusion-Controlled Reactions	372	(2)
Photochemistry and Photobiology	374	(4)
Vision	377	(1)
Photosynthesis	378	(3)
Summary	381	(6)
Zero-Order Reactions	381	(1)
First-Order Reactions	381	(1)
Second-Order Reactions	382	(1)
Temperature Dependence	383	(2)
Electron Transfer Reactions: Marcus Theory	385	(1)
Relaxation Kinetics	385	(1)
Diffusion-Controlled Reactions	386	(1)
Absorption of Light	386	(1)
Photochemistry	386	(1)
Mathematics Needed for Chapter 7	387	(1)
References	387	(1)
Suggested Reading	388	(1)
Problems	388	(13)
Enzyme Kinetics
Concepts	401	(1)
Applications	401	(2)
Catalytic Antibodies and RNA Enzymes-Ribozymes	401	(2)
Enzyme Kinetics	403	(3)
Michaelis-Menten Kinetics	406	(9)
Kinetic Data Analysis	409	(4)
Two Intermediate Complexes	413	(2)
Competition and Inhibition	415	(8)
Competion	415	(1)
Competitive Inhibition	416	(2)
Noncompetitive Inhibition	418	(1)
Allosteric Effects	419	(3)
Single-Molecule Kinetics	422	(1)
Summary	423	(2)
Typical Enzyme Kinetics	423	(1)
Michaelis--Menten Mechanism	424	(1)
Monod-Wyman-Changeux Mechanism	425	(1)
Mathematics Needed for Chapter 8	425	(1)
References	426	(1)
Suggested Reading	426	(1)
Problems	427	(10)
Molecular Structures and Interactions: Theory
Concepts	437	(1)
Applications	437	(1)
The Process of Vision	438	(3)
Origins of Quantum Theory	441	(5)
Blackbody Radiation	442	(2)
Photoelectric Effect	444	(1)
Electrons as Waves	444	(1)
Heisenberg Uncertainty Principle	445	(1)
Quantum Mechanical Calculations	446	(3)
Wave Mechanics and Wavefunctions	446	(3)
Schrodinger's Equation	449	(6)
Solving Wave Mechanical Problems	451	(1)
Outline of wave Mechanical Procedures	452	(3)
Particle in a Box	455	(8)
Tunneling	463	(2)
Simple Harmonic Oscillator	465	(3)
Rigid Rotator	468	(1)
Hydrogen Atom	469	(1)
Electron Distribution	470	(19)
Electron Distribution in a Hydrogen Atom	471	(5)
Many-Electron Atoms	476	(3)
Molecular Orbitals	479	(5)
Hybridization	484	(2)
Delocalized Orbitals	486	(3)
Molecular Structure and Molecular Orbitals	489	(4)
Geometry and Stereochemistry	489	(2)
Transition Metal Ligation	491	(2)
Charge Distributions and Dipole Moments	493	(1)
Intermolecular and Intramolecular Forces	493	(4)
Bond Stretching and Bond Angle Bending	494	(1)
Rotation Around Bonds	495	(2)
Noncovalent Interactions	497	(17)
Electrostatic Energy and Coulomb's Law	497	(3)
Net Atomic Charges and Dipole Moments	500	(3)
Dipole-Dipole Interactions	503	(2)
London Attraction	505	(1)
van der Waals Repulsion	506	(1)
London-van der Waals Interaction	507	(1)
The Lowest-Energy Conformation	508	(2)
Hydrogen Bonds	510	(2)
Hydrophobic and Hydrophilic Environments	512	(2)
Molecular Dynamics Simulation	514	(2)
Monte Carlo Method	514	(1)
Molecular Dynamics Method	515	(1)
Outlook	516	(1)
Summary	517	(1)
Photoelectric Effect	517	(1)
Wave-Particle Duality	517	(1)
Heisenberg Uncertainty Principle	517	(1)
Schrodinger's Equation	518	(1)
Some Useful Operators	518	(5)
Systems Whose Schrodinger Equation Can Be Solved Exactly	519	(2)
Coulomb's Law	521	(1)
Dipoles and Their Interaction Energy	521	(1)
Intramolecular (Within) and Intermolecular (Between) Interactions	521	(2)
Mathematics Needed for Chapter 9
References	523	(1)
Suggested Reading	523	(1)
Problems	524	(7)
Molecular Structures and Interactions: Spectroscopy
Concepts	531	(1)
Applications	532	(1)
Electromagnetic Spectrum	532	(1)
Color and Refractive Index	533	(2)
Absorption and Emission of Radiation	535	(13)
Radiation-Induced Transitions	536	(2)
Classical Oscillators	538	(1)
Quantum Mechanical Description	538	(2)
Lifetimes and Line Width	540	(1)
Role of Environment in Electronic Absorption Spectra	541	(2)
Beer-Lambert Law	543	(5)
Proteins and Nucleic Acids: Ultraviolet Absorption Spectra	548	(6)
Amino Acid Spectra	549	(1)
Polypeptide Spectra	549	(2)
Secondary Structure	551	(1)
Origin of Spectroscopic Changes	551	(1)
Nucleic Acids	552	(1)
Rhodopsin: A Chromorphic Protein	553	(1)
Fluorescence	554	(13)
Simple Theory	555	(1)
Excited-State Properties	556	(4)
Fluorescence Quenching	560	(1)
Excitation Transfer	561	(2)
Molecular Rulers	563	(1)
Fluorescence Polarization	564	(1)
Phosphorescence	565	(1)
Single-Molecule Fluorescence Spectroscopy	565	(2)
Optical Rotatory Dispersion and Circular Dichroism	567	(6)
Polarized Light	568	(3)
Optical Rotation	571	(2)
Circular Dichroism	573	(1)
Circular Dichroism of Nucleic Acids and Proteins	573	(3)
Vibrational Spectra, Infrared Absorption, and Raman Scattering	576	(3)
Infrared Absorption	576	(1)
Raman Scattering	577	(2)
Nuclear Magnetic Resonance	579	(4)
The Spectrum	581	(2)
Interactions in Nuclear Magnetic Resonance	583	(15)
Chemical Shifts	583	(2)
Spin-Spin Coupling, Scalar Coupling, or J-Coupling	585	(3)
Relaxation Mechanisms	588	(2)
Nuclear Overhauser Effect	590	(1)
Multidimensional NMR Spectroscopy	590	(4)
Determination of Macromolecular Structure by Nuclear Magnetic Resonance	594	(2)
Electron Paramagnetic Resonance	596	(1)
Magnetic Resonance Imaging	597	(1)
Summary	598	(3)
Absorption and Emission	598	(2)
Excitation Transfer	600	(1)
Optical Rotatory Dispersion and Circular Dichroism	600	(1)
Nuclear Magnetic Resonance	600	(1)
References	601	(1)
Suggested Reading	601	(2)
Problems	603	(12)
Molecular Distributions and Statistical Thermodynamics
Concepts	615	(1)
Applications	615	(1)
Binding of Small Molecules by a Polymer	616	(12)
Identical-and-Independent-Sites Model	617	(2)
Langmuir Adsorption Isotherm	619	(1)
Nearest-Neighbor Interactions and Statistical Weights	620	(2)
Cooperative Binding, Anticooperative Binding, and Excluded-Site Binding	622	(3)
N Identical Sites in a Linear Array with Nearest-Neighbor Interactions	625	(1)
Identical Sites in Nonlinear Arrays with Nearest-Neighbor Interactions	626	(2)
The Random Walk	628	(8)
Calculation of Some Mean Values for the Random-Walk Problem	630	(4)
Diffusion	634	(1)
Average Dimension of a Linear Polymer	634	(2)
Helix-Coil Transitions	636	(9)
Helix-Coil Transition in a Polypeptide	636	(5)
Helix-Coil Transition in a Double-Stranded Nucleic Acid	641	(4)
Statistical Thermodynamics	645	(14)
Statistical Mechanic Internal Energy	646	(1)
Work	647	(1)
Heat	648	(1)
Most Probable (Boltzmann) Distribution	649	(4)
Quantum Mechanical Distributions	653	(1)
Statistical Mechanical Entropy	653	(1)
Examples of Entropy and Probability	654	(4)
Partition Function: Applications	658	(1)
Summary	659	(3)
Binding of Small Molecules by a Polymer	659	(1)
Random-Walk and Related Topics	660	(1)
Helix-Coil Transitions	660	(1)
Statistical Thermodynamics	661	(1)
Mathematics Needed for Chapter 11	662	(1)
References	662	(1)
Suggested Reading	663	(1)
Problems	663	(4)
Macromolecular Structure and X-Ray Diffraction
Concepts	667	(1)
Applications	667	(1)
Visible Images	668	(1)
X Rays	668	(16)
Emission of X Rays	669	(1)
Image Formation	669	(1)
Scattering of X Rays	670	(5)
Diffraction of X Rays by a Crystal	675	(3)
Measuring the Diffraction Pattern	678	(1)
Bragg Reflection of X Rays	679	(2)
Intensity of Diffraction	681	(2)
Unit Cell	683	(1)
Determination of Molecular Structure	684	(14)
Calculation of Diffracted Intensities from Atomic Coordinates: The Structure Factor	684	(2)
Calculation of Atomic Coordinates from Diffracted Intensities	686	(2)
The Phase Problem	688	(1)
Direct Methods	688	(1)
Isomorphous Replacement	688	(2)
Multiwavelength Anomalous Diffraction	690	(1)
Determination of a Crystal Structure	691	(3)
Scattering of X Rays by Noncrystalline Materials	694	(1)
Absorption of X Rays	695	(1)
Extended Fine Structure of Edge Absorption	696	(1)
X Rays from Synchrotron Radiation	697	(1)
Electron Diffraction	698	(1)
Neutron Diffraction	699	(1)
Electron Microscopy	700	(4)
Resolution, Contrast, and Radiation Damage	700	(1)
Transmission and Scanning Electron Microscopes	701	(1)
Image Enhancement and Reconstruction	701	(1)
Scanning Tunneling and Atomic Force Microscopy	702	(2)
Summary	704	(3)
X-ray Diffraction	704	(3)
Neutron Diffraction	707	(1)
Electron Microscopy	707	(1)
Mathematics Needed for Chapter 12	707	(1)
References	708	(1)
Suggested Reading	708	(1)
Problems	709	(3)
Appendix	712	(13)
Answers	725	(3)
Index	728

Excerpts

PREFACE There is a deep sense of pleasure to be experienced when the patterns and symmetry of nature are revealed. Physical chemistry provides the methods to discover and understand these patterns. We think that not only is it important to learn and apply physical chemistry to biological problems, it may even be fun. In this book, we have tried to capture some of the excitement of making new discoveries and finding answers to fundamental questions. This is not an encyclopedia of physical chemistry. Rather, we have written this text specifically with the life-science student in mind. We present a streamlined treatment that covers the core aspects of biophysical chemistry (thermodynamics and kinetics as well as quantum mechanics, spectroscopy, and X-ray diffraction), which are of great importance to students of biology and biochemistry. Essentially all applications of the concepts are to systems of interest to life-science students; nearly all the problems apply to life-science examples. For this fourth edition we are joined by Joseph Puglisi, a new, young author who strengthens the structural biology content of the book. We have also tried to make the book more reader-friendly. In particular, we omit fewer steps in the explanations to make the material more understandable, and we have followed the many helpful and specific recommendations of our reviewers to improve the writing throughout. Important new topics, such as single-molecule thermodynamics, kinetics, and spectroscopy, are introduced. Subjects that have become less pertinent to current biophysical chemistry have been deleted or de-emphasized. Reference lists for each chapter have been updated. However, the format and organization of the book is essentially unchanged. Chapter 1 introduces representative areas of active current research in biophysical chemistry and molecular biology: the human genome, the transfer of genetic information from DNA to RNA to protein, ion channels, and cell-to-cell communication. We encourage students to read the current literature to see how the vocabulary and concepts of physical chemistry are used in solving biological problems. Chapters 2 through 5 cover the laws of thermodynamics and their applications to chemical reactions and physical processes. Essentially all of the examples and problems deal with biochemical and biological systems. For example, after defining work as a force multiplied by the distance moved (the displacement), we discuss the experimental measurement of the work necessary to stretch a single DNA molecule from its random-coiled form to an extended rod. Molecular interpretations of energies and entropies are emphasized in each of the chapters. Chapter 4, "Free Energy and Chemical Equilibria," now starts with the application of the chemical potential td chemical reactions. We think that this will make it easier to understand the logic relating activities and equilibrium constants to free energy. Binding of ligands and equilibria between phases are described in chapter 5, "Free Energy and Physical Equilibria." We discuss in detail the allosteric effect and the cooperative binding of oxygen by hemoglobin. We also describe the formation of lipid monolayers, lipid bilayers, and micelles, and their structures are compared to biological membranes. Chapters 6 through 8 cover molecular motion and chemical kinetics. Chapter 6, "Molecular Motion and Transport Properties," starts with the Brownian motion on an aqueous surface of a single lipid molecule labeled with a fluorescent dye. The random motion of the molecule can be followed to test Einstein's equation relating average distance traveled by a single molecule to a bulk diffusion coefficient. Following this direct experimental demonstration of thermal motion of a molecule, we introduce the kinetic theory of gases and discuss transport properties (diffusion, sedimentation, and electrophoresis) of macromolecules. The next two chap