Physical Chemistry in Biology


Alan Cooper, WestChem Department of Chemistry, Glasgow University, Glasgow, Scotland, United Kingdom

doi: 10.1002/9780470048672.wecb451


Physical chemistry is that area of science that attempts to describe the properties and processes of matter in terms of underlying physical laws. Biology is no exception to these laws. This introductory article briefly sketches the role played by traditional physical chemistry in analyzing and understanding the behavior and control of biologic processes, focusing mostly on the molecular level. Thermodynamics and kinetics place restrictions on the kinds of reactions and processes that can take place as well as on how fast they occur. Electrochemistry, a branch of thermodynamics that deals with charge transfer processes, underpins much of redox biochemistry and membrane phenomena. Spectroscopy gives rise to a wealth of experimental techniques for structural and functional analysis, while quantum chemistry lurks in the background.


Physical chemistry is the area of science that attempts to describe the chemical properties and processes of matter in terms of the underlying physical laws that govern the molecular world. It is a subject of enormous breadth that underpins most areas of science and technology, that lies at the very diffuse interface between physics and chemistry, and that consequently has important ramifications in biology. Throughout history, investigations of physical and biologic phenomena have been closely associated. Scientists, the “natural philosophers” of previous generations, were rightly curious about all aspects of the natural world, with none of the restrictive demarcation issues between “physical” and “biologic” sciences that came later. During the late seventeenth century, working in Edinburgh and Glasgow, Joseph Black was both a practicing medic and one of the founding fathers of thermodynamics and thermochemistry. At the same time, in France, Antoine Lavoisier was applying newly developed calorimetric methods equally to the respiration of mammals and to the combustion of candles. Meanwhile in Italy, Luigi Galvani was famously using frog legs to establish the beginnings of electrochemistry and neurochemistry. And so it is today. Techniques used to probe the fundamental workings of matter at the molecular level and the fundamental laws that emerge are of equal applicability to all materials, whether of biologic origin or otherwise. And the technical challenges posed by biology stimulate new instrumental developments and concepts in physical chemistry.

The objective here is to describe how the traditional field of physical chemistry applies to the study of biology, specifically to provide a broad and relatively nontechnical introduction for nonspecialists. However, a comprehensive description of the role of physical chemistry in biology is a mammoth task that cannot possibly be tackled adequately in a short article such as this. Consequently, I shall simply attempt to give a broad overview from the point of view of a former physicist, now physical chemist, working toward the physical understanding of biomolecular processes. I shall follow the traditional headings, such as might be found in conventional physical chemistry texts (some are listed below in Further Reading, but almost any standard text in any edition will do—like London buses, another one always comes along soon) and shall note particular relevance to biologic systems, with a few specific examples and associated remarks as we proceed. This approach will be entirely unsatisfactory for most readers who require more detail, but it should act as an aide memoir stimulating interest in additional details that may be found elsewhere in this volume.

Thermochemistry and Thermodynamics

Thermodynamics is the area of science that relates to the interplay of heat and other forms of energy. At the molecular level, this science describes the balance between two generally opposing thermodynamic forces: the natural tendency for mechanical systems to move toward lower energies and the equally natural tendency for thermal Brownian motion to perturb this mechanical order. For open systems at constant pressure, this balance is expressed by the classic Gibbs free energy change (∆G):

where ∆H is the change in “enthalpy” or heat content that describes changes in internal kinetic and potential energies of all molecules in the system, corrected for any pressure-volume work done on or by the surroundings during the process; T is the absolute temperature (Kelvin); and ∆S is the change in entropy of the system.

It is convenient (although sometimes confusing) to express the equilibrium constant (K) of a chemical process in terms of the “standard Gibbs free energy change”, ∆G° = -RT∙lnK, where R is the universal gas constant. The standard Gibbs free energy change is the hypothetical free energy change for the process in which the reactants and products are imagined to be present in (arbitrary) “standard states.” In solution, for example, the convention in (most of) chemistry is to adopt a standard-state concentration of 1 M (1 mole per liter) for all reacting species. This convention is clearly a long way from reality for biochemical systems, especially for reactions involving hydrogen (H+) ions, so an alternative convention is frequently adopted here with [H+] = 10-7 M to reflect more closely the near-neutral pH of most biologic processes.

Under any conditions, the actual free energy change depends on concentrations of reactants and products:

where the reaction quotient, Q, is a quantity rather like the equilibrium constant, K, but involves the actual concentrations pertaining to the system rather than concentrations when it has reached equilibrium.

For example, for a hypothetical reaction A + B → C + D

compared with


where [A], [B], [C], and [D] are the actual concentrations, compared with what they would be ([A] Eq, [B] Eq, [C] Eq, and [D] Eq) if the system was at thermodynamic equilibrium, in which case ∆G = 0. (Note that in more rigorous treatments, one should replace concentrations with activities. The activity is related to concentration, but corrected for the nonideality that occurs from interactions not accounted for elsewhere in the analysis. This distinction can be significant for macromolecules in crowded environments inside living cells.)

Such basic thermodynamic considerations are essential to understanding biomolecular energetics. The AG places fundamental constraints on the amount of work (mechanical, chemical, electrical, etc.) that may be done by or on a system under ideal conditions. It follows from the above that any chemical reaction or process away from equilibrium can act as a source of free energy. The prime example here is the way that biology makes use of adenosine triphosphate (ATP) and its hydrolysis to ADP, as a ubiquitous free energy currency. ATP is produced during by a wide range of catabolic (energy-producing) reactions such as glycolysis, and its hydrolysis is coupled to free energy transduction in most molecular machines that drive living processes—muscle contraction, flagellar motion, cell division, membrane pumps, nerve signals, and so forth. Yet perhaps surprisingly, and in contrast to much ill-informed speculation about “high energy phosphate bonds,” the hydrolysis of ATP is not particularly energetic: The standard free energy of hydrolysis (∆G°) of ATP to ADP and inorganic phosphate (about -35 kJ mol-1 at physiologic pH) is relatively small compared with many chemical reactions, and actual free energy values will, in any case, depend on the relative concentrations of all reactants and products and the extent to which they are away from equilibrium. Rather, it would seem that it is the relative ease with which ATP synthesis and hydrolysis can be coupled to the biomolecular energy transduction machinery that has led to its ubiquity. Despite considerable advances in determining the molecular structures of many enzymes and other proteins involved in this machinery, no consensus view yet exists as to how ATP hydrolysis and work are linked at the molecular level. Thermodynamics is a harsh taskmaster here, and proposed mechanisms need to satisfy these fundamental constraints. As the fictional Homer Simpson once said: “In this house we obey the laws of thermodynamics.”

In statistical thermodynamics, the Gibbs free energy (G) is related to the statistical probability (p) of finding the system in a particular state: G = -kBT∙lnp, where kB is the universal Boltzmann constant. Consequently, changes in Gibbs free energy (∆G) tell us about the relative probabilities that processes will occur in the absence of other interventions: Reactions with a positive AG involve transition to a less likely (smaller p) state and, therefore, are unlikely to occur of their own accord; however, reactions with a negative ∆G involve transition to a more probable state (larger p) and may proceed. (Technically, the latter are said to be thermodynamically “spontaneous” processes—a term that can lead to confusion because many such processes, although thermodynamically feasible or spontaneous, will be limited by kinetic barriers and may not take place on a reasonable timescale.)

The Boltzmann statistical definition of entropy, S = kB∙lnW, shows how this quantity, often expressed as a measure of “disorder” in a system, is more rigorously defined in terms of the number of ways (W) in which a system might adopt a particular energy. It follows that in a molecular system, the higher the energy, the greater the number of ways to partition that energy among the various forms of kinetic (translation, rotation, vibration, etc.) and potential energies. As a consequence, systems with high entropy (larger W) tend to be more likely, overall. For closed systems, such as the entire universe for which the total energy is constant, therefore, the total entropy must always be increasing (∆S > 0). However, for regions within such a system that can exchange energy with their surroundings, this mandatory increase is not necessarily the case, and it is the Gibbs free energy described above that determines the way things proceed. Obviously, this occurrence is relevant to living systems that, at first sight, seem to violate the rule of increasing W (or S). However, in the wider context, the flux of energy through such systems contributes to the whole, and thermodynamics remains inviolate. Such concepts of nonequilibrium thermodynamics and dissipative structures have been a major development in twentieth-century physical chemistry (1, 2).

One consequence of this statistical view of thermodynamics has been the appreciation that thermodynamic fluctuations must play a significant role in our understanding of processes that involve biologic macromolecules (3-4—5-6-7). Although normally insignificant for macroscopic objects, thermally induced fluctuations in structural and thermodynamic properties of mesoscopic systems—systems between microscopic and macroscopic, typically relating to objects a few nanometers in size—such as individual proteins or other macromolecules, will be crucial to their function. (Mesoscopic: intermediate between micro - and macroscopic, typically relating to objects a few nanometers in size.) A dramatic illustration of this importance, first highlighted by Max Perutz (8), comes from the structures of the oxygen carrier proteins myoglobin and hemoglobin. Structures for these molecules were among the first to be determined by the emerging techniques of protein crystallography, and they were a major breakthrough in structural biology. Yet these high resolution structures immediately revealed a puzzle. In the (static) X-ray pictures, the oxygen-binding centers are buried deep inside the globular protein structure, with no apparent routes for access or egress of molecular oxygen. However, as we now appreciate in the more dynamic picture, thermodynamic fluctuations allow for transient openings of channels or pathways within the protein structure through which individual oxygens may flow. Incidentally, this discovery also resolves another paradox, because burial of the oxygen-binding iron (heme group) within the fluctuating structure allows binding of O2 to take place with exclusion of water, which would otherwise facilitate irreversible oxidation (“rusting”) of the iron.

At a more basic level, measurements of the energetics of biochemical processes and their couplings to metabolic processes, following the rules of thermodynamics, underpin our understanding of how organisms can function. This understanding operates at all levels, from the “calorific value” of foodstuffs in nutritional biochemistry and food science to the coupling of ATP synthesis/hydrolysis to hydrogen ion gradients [the “proton-motive-force” or “chemiosmotic” principle (9)] at one extreme, to entire ecosystems at the other (10). Experimental physical chemistry has played a role here from the very beginning by supplying the calorimetric tools to measure heat and related thermodynamic quantities in biologic systems and organisms. Indeed, one of the first quantitative applications of calorimetry was the use by Lavoisier of his ice calorimeter in the late eighteenth century to measure metabolic heat from a guinea pig, which established the crucial link between respiration and combustion. More recently, advances in instrumentation have led to the widespread use of microcalorimeters for the determination of biomolecular thermodynamics and, much more generally, as a generic analytic technique. It is now possible to measure directly the heat effects associated with noncovalent processes in quite dilute biomolecular systems (11).


Thermodynamics describes what could possibly happen at equilibrium. Kinetics tells us how fast we are getting there. The world around us, including the subset that we call biology, is never at thermodynamic equilibrium. Living organisms succeed because of the very careful way in which the rates of biochemical processes are controlled. Consequently, the study of kinetics has had a major impact on biologic science.

Catalysis and control is crucial here. For a chemical reaction to take place, it is generally necessary that the molecules collide in the correct orientation and with sufficient energy to overcome the activation energy barrier (EA), which leads to reaction products. This reaction is encapsulated in the classic empirical Arrhenius rate law:

Rate constant

where R is the gas constant and where the pre-exponential factor, A, can be related to the apparent collision frequency and the exponential term reflects the Boltzmann probability that the colliding species will have sufficient energy.

A more rigorous description is given by transition state theory (12, 13):

where h is the Planck constant and AG# is the (notional) Gibbs free energy of activation to the transition state. This equation strictly derives from a quantum statistical mechanical treatment of two-body collisions, so its application to more complex systems (especially those that involve biologic macromolecules in water) needs to be interpreted with due caution.

It follows from this equation that the rates of chemical reactions can, in general, be affected by manipulation of either collision factors or activation parameters or both. And, of course, reaction rates will be very sensitive to temperature change—a key consideration in the evolution of complex pathways of interdependent chemical processes that are necessary for maintenance of biologic organisms.

Absolute reaction rates can be affected by molecular diffusion processes that dictate the rates at which collisional encounter complexes occur before reaction. This affect usually shows up in the way reaction rates depend on the physical form of the reactants (gas, liquid, solid, solution, etc.), particularly on concentrations for reactants in gas or liquid phases. Adsorption of reactants onto surfaces can enhance the effective concentrations of reactive species and/or reduce the dimensionality of the diffusion process. Classic work by Eigen and Richter (14) showed how restricting diffusion to one or two dimensions can dramatically increase potential reaction rates, and this principle has been applied to the kinetics of protein translocation along DNA chains, for example. See References 15 and 16 for more information.

Enzyme catalysis completely exploits all these aspects of the physical chemistry of reaction kinetics. Despite the great enhancement in reaction rates and specificities that can be achieved by biologic catalysts, it is now generally accepted that no new underlying physical principles are involved, just that enzymes are much better at using and optimizing the various factors required for any chemical reaction—particularly ensuring that chemical groups are in the right place, at the right time, with the correct orientation for efficient reaction, in ways that are difficult to achieve with much cruder chemical catalysts. This process is mediated through the evolution of specific protein structures (or other macromolecules) to give binding sites with the correct stereochemistry an environment for reaction, often with the exclusion of water and adjustment of acid/base properties of specific groups, offering alternative reaction pathways that might involve lower activation energy barriers (17-18-19).

Spectroscopy and Photochemistry

The interaction of electromagnetic waves (photons) with matter is crucial to many biologic processes. This interaction is also the basis for a wide range of spectroscopic techniques in physical chemistry that probe the structure and function of molecules, many with applications and implications for biology. Absorption and emission of electromagnetic radiation invariably involves changes in electric or magnetic dipoles, such as relative displacements of electrical charges in atoms or molecules, or reorientation of nuclear magnetic moments, and the frequencies (energies) with which these transitions take place dictates the region of the electromagnetic spectrum involved and the sorts of processes that may occur.

Electromagnetic radiation in the ultraviolet (approximately 180-340 nm) or visible (approximately 340-800 nm) region generally interacts with matter through excitation of electronic transitions in atoms or molecules. This interaction gives rise to the characteristic colors of molecules and materials and is the basis for a multitude of analytical techniques in biochemistry and elsewhere. Life, itself, is dependent on the electronic transitions in chlorophylls, carotenoids, and related molecules in the first stages of photosynthesis, and physico-chemical analyses of these systems have revealed superbly tuned biomolecular structures that exploit fundamental effects in electronic energy transfer and transduction (20). Changes in electronic absorbance properties give rise to color changes that underpin many analytical techniques in biochemistry and medicine, and differences in absorbance of left- or right-circular polarized light by chiral structures is exploited in circular dichroism (CD) techniques to probe macromolecular conformations and their changes in proteins, nucleic acids, and other biomolecules (21).

The electronic excited state is inherently unstable and can decay back to the ground state in various ways, some of which involve (re-)emission of a photon, which leads to luminescence phenomena (fluorescence, phosphorescence, and chemiluminescence) (22). Some biologic molecules are naturally fluorescent, and phosphorescence is a common property of many marine and other organisms. (Fluorescence is photon emission caused by an electronic transition to ground state from an excited singlet state and is usually quite rapid. Phosphorescence is a much longer-lived process that involves formally forbidden transitions from electronic triplet states of a molecule.) Fluorescence measurement techniques can be extremely sensitive, and the use of fluorescent probes or dyes is now widespread in biomolecular analysis. For example, the large increase in fluorescence of a dye molecule (e.g., ethidium bromide) when bound to double-helical DNA is widely used in molecular biology to detect and locate DNA fragments. Chemiluminescence occurs when the electronically excited state develops as a result of chemical reaction. Chemiluminescence is the basis for many biologic light shows, including the flashing lights of firefly tails (using enzyme luciferase-catalyzed hydrolysis of ATP) and many marine organisms.

Vibrational motions of chemical bonds that involve changes in electric dipole moment or polarizability can be detected by IR absorbance or Raman scattering techniques. The strong infrared (IR) absorbance by water makes conventional IR spectroscopy less generally useful in biology, although this disadvantage is overcome by Raman spectroscopy, which relies on the inelastic scattering of high intensity visible (laser) light. Resonance Raman spectroscopy has been particularly useful in picking out the vibrational spectra of biologic chromophores in otherwise complex mixtures, and the differential scattering of circularly polarized light (Raman optical activity) has been developed as a high resolution probe of chiral features, particularly in biologic macromolecules (23).

Phenomena associated with the reorientation of nuclear or molecular magnetic dipoles in applied magnetic fields have led to dramatic advances in molecular spectroscopy and imaging techniques. Nuclear magnetic resonance spectroscopy (NMR) is now routinely applicable to the study of the structure and dynamics of biomolecules, large and small (24), and NMR imaging techniques are used for whole-body diagnostics and related investigations. Electron paramagnetic resonance (EPR) techniques that rely on the reorientation of electronic spins are less generally applicable because of the relative scarcity of appropriate paramagnetic species in biology. However, specific “spin probes” are used in some instances, for example, in the investigation of biologically significant free radical chemistry, and new probes and improved technologies are being developed.

Most spectroscopic processes mentioned so far involve relatively low energy transitions that do not (usually) affect the covalent structure of the sample. However, absorption of higher energy photons (UV, and others) can lead to higher energy-excited electronic states in which chemical transformations can occur. Such photochemistry can be harmful to biologic organisms, particularly at the DNA level (melanomas, etc.), but can also form the basis for useful techniques and therapies. Photochemistry is also, of course, central to crucial biologic processes such as photosynthesis (20) and visual transduction (25). And the speed with which photoprocesses can be initiated is exploited in many biophysical techniques for studying structure and dynamics, for example, flash photolysis and fluorescence recovery after photobleach (FRAP).

Mass spectrometry is one physical technique that does not (at least directly) involve electromagnetic radiation. However, some sample desorption and ionization processes do use high intensity pulses of laser light in techniques such as MALDI (Matrix-Assisted Laser Desorption Ionization) that have proved very useful in mass analysis of proteins and other biologic macromolecules. High resolution mass spectrometry derives from atomic/molecular beam studies in which the trajectories of ionized particles in a vacuum can be manipulated by static magnetic and/or electric fields. This technique has led to very precise mass analysis methods that now form the central core of proteomics for identification and characterization of biologic macromolecules and their interactions (26).

Quantum Theory and Bonding

Quantum mechanics is probably the most successful theory of the twentieth century, if not ever. It explains the structure and spectroscopic properties of atoms and molecules with remarkable precision and is the foundation for our understanding of chemical bonding. It is therefore surprising, perhaps, that it has not yet had any great impact on our understanding of biologic processes. This occurrence is mainly a matter of scale. Quantum theory is remarkably good at describing the electronic structures of atoms and molecules. And, to the extent that biologic (macro)molecules are held together by the same covalent bonds as any other kinds of molecules, the quantum mechanical nature of chemical bonding is inherent to their structure and properties. However, knowing the wave function for the human genome, even if we could calculate it, would be of little use to a molecular biologist. Solving the Schrodinger equation for a polypeptide would not likely tell us how it folds or what its function might be; these problems, for the time being at least, do not need the degree of precision at the atomic and electronic level afforded by quantum theory.

This principle can be illustrated by the wave-particle duality aspects of quantum theory. The de Broglie wavelength (h/mv) for a typical macromolecule (10 kDa) traveling at thermal velocities (> 50 m s-1) is around 0.01 A or less. Consequently, quantum effects deriving from the wave-like behavior of matter and the Heisenberg Uncertainty Principle are unlikely to be of significance at the level of resolution (typically 1 A) currently available for biologic molecules, and classic mechanics is adequate in most cases, which is not to say that quantum effects are entirely absent, however. Quantum mechanical tunneling has been observed in some instances and may be of importance in some enzyme-catalyzed reactions. Tunneling or barrier penetration is a uniquely quantum phenomenon whereby the wave-like nature of particles at the atomic and subatomic level allows them to pass through, rather than over, energy barriers. In some enzyme reactions, this phenomenon is manifest by the deviations from classic Arrhenius kinetic behavior at very low temperatures. Classically, at absolute zero (0 K) all molecular motion stops and chemical reactions should cease, because the molecules no longer have sufficient thermal energy to overcome activation barriers. However, for some reactions, especially those that involve hydride transfer, for example, finite reaction rates have been observed at liquid helium temperatures (27, 28). Room temperature tunneling effects are also significant in electron transfer processes within or between proteins (29, 30). The possible importance of significant quantum effects in wave-like energy transfer processes in the early stages of photosynthesis has recently been reported [31].

More generally, electronic and vibrational spectroscopic properties of biologic molecules will, of course, be subject to the underlying rules of quantum mechanics. However, except in special circumstances, the spectra of biologic molecules in solution rarely show the discrete quantized energy-level structure seen in simpler atomic or small-molecule systems in vacuum. This rare display is because the significant conformational flexibility and dynamic solvent environment gives rise to heterogeneous and homogeneous spectral broadening effects that mask the underlying energy-level structures.

At the theoretical level, full quantum mechanical calculations on biologic macromolecules are not computationally feasible, nor would they be particularly helpful in understanding macromolecular properties without proper inclusion of the solvent water or other biologic matrix on which these properties so intimately depend. However, ab initio quantum mechanical calculations on smaller systems that represent crucial steps in an enzymic reaction, for example, can be helpful in understanding specific processes within macromolecules or in estimating intermolecular forces and stereochemical effects in molecular mechanics simulations that are not experimentally accessible.

Symmetry and Group Theory

Group theory is a very powerful mathematical technique for analyzing molecular structures in terms of their symmetry properties. These properties can be characterized in terms of the various symmetry operations, symmetry elements, and space groups or point groups into which they fall. A symmetry operation is any action (translation, rotation, reflection, etc.) that leaves the object looking the same. A symmetry element is the point, line, or plane about which the symmetry operation is performed. A point group is the list of all possible symmetry operations that leave at least one point in the object unchanged (i.e., without spatial translation). In contrast, a space group is the set of all operations that move a molecule (or object) to another position in space.

Symmetry considerations can be very useful in determining, for example, spectral characteristics of small molecules or functional groups; for instance, the different selection rules regarding IR absorbance or Raman scattering bands in vibrational spectroscopy of small molecules are equally applicable to such group vibrations in larger systems. But most biologic macromolecules and larger complexes lack sufficient symmetry for the full rigor of group theory to be applicable in any generally useful way. Two significant exceptions exist. The classic work of Caspar and Klug on the structures of icosahedral viruses was based on symmetry considerations, many of which derived from the architectural symmetries in the building designs of Buckminster-Fuller (32). And space groups are, of course, central to the analysis of protein crystals, where determination of the space group is the first essential step in crystallographic resolution of protein (and other structures) by X-ray diffraction techniques.


Processes that involve the transfer of charge can be manipulated by electrical potential or, conversely, can generate voltages that can drive other reactions or can be used for analytical purposes. Electron transfer between molecules or chemical groups (i.e., oxidation/reduction or “redox” processes) can be configured as electrochemical cells for numerous purposes, and the thermodynamics of such systems is key to understanding biologic redox processes such as in various intermediate stages of photosynthesis and respiration. Ion transport across membranes or against chemical potential gradients is involved in all aspects of electrolyte balance in biologic systems, both at the microscopic level of individual cells or organelles and at the macroscopic level of whole organisms. It is the basis for the transmission of nerve signals and for the use of membrane potentials for ATP synthesis (9).

The key expression here is the Nernst equation that, under ideal conditions, relates the electrical potential (E) of a system to the standard thermodynamic Gibbs free energy (AG°) of the process and the concentrations (strictly activities) of the participating species:

where E° = -∆G°/nF is the standard electrochemical potential of the process, n is the number of moles of charge transferred per mole of reaction, F is the Faraday (96,500 coulomb/mole), and Q is the “reaction quotient” that involves the relative concentrations (activities) of reactants and products.

This process is the basis for several analytical devices, electrochemical cells, pH- and ion-specific electrodes, and other sensors in which concentrations and electrochemical properties can be measured in terms of the voltage (electrochemical potential) developed across membranes or other partitions separating the two halves of a redox reaction. Various microelectrode technologies employ this approach to study electrochemical potential gradients in single cells, in tissues, and across biologic membranes. Chemical potential gradients across membranes can also drive chemical reactions. This approach is the thermodynamic rationale for chemiosmotic and protonmotive force effects in which H+ or other ion gradients across membranes can provide the driving free energy for synthesis of ATP for example (9). The molecular machinery that involves membrane-associated proton pumps and ATP-synthesizing enzymes must still be worked out in detail, but the basic principles of electrochemistry must apply.

The mobility of ions in an electric field, especially in water, formed the basis of early work in the physical chemistry of solutions. It has now blossomed into the wide range of multipurpose electrophoresis techniques that are the mainstay of most biochemistry and molecular biology laboratories today. Protein gel electrophoresis, in which protein mixtures may be separated on the basis of their size and charge, is a standard analytical and quality assurance methodology. The same is true for DNA and RNA biochemistry. Sequencing the human genome, for example, would not have been possible (or at least greatly hindered) without the development of the high-resolution electrophoresis methods capable of separating strands of DNA that differ in length by just one nucleotide.


Experimental Techniques

Perhaps the greatest contribution of physical chemistry to biology lies not in the theoretical fundamentals, although important, but in the experimental techniques that have developed from physical chemistry. Textbooks are written with the benefit of hindsight, and can give the impression that theory comes first, with experiments playing a subsidiary supporting role. Reality is somewhat different. Most scientific development comes from curiosity-driven observation and experimentation, and experimental techniques developed to study the physics and chemistry of matter are applicable equally to biologic systems. Indeed, the need to study biomolecular processes has acted as a spur to the development and applications of physico-chemical methods, which benefits both sides. Here is a list of just some techniques derived from physical chemistry that have applications in biology:

In no particular order: UV/visible spectroscopy; fluorescence spectroscopy; circular dichroism; Raman spectroscopy; rapid reaction kinetics; stopped-flow and flash photolysis methods; isothermal and scanning (micro)calorimetry; specific electrode technologies; electrophoresis; chromatography; light scattering and diffusion methods; viscosity and rheology; analytical ultracentrifugation; NMR spectroscopy and imaging; X-ray and neutron diffraction; Langmuir-Blodgett films and other surface technologies; mass spectrometry; and EPR spectroscopy...

And the Rest...

A short introductory article such as this cannot possibly cover completely such a wide-ranging subject, and much has been left out. Flick through any physical chemistry textbook and you will find many other topics that we have missed, all of which possess one or more important roles in biology. Here are just a few (with a hint of some biologic significance in parentheses):

Properties of gases (physiology of oxygen uptake); acid-base equilibrium, buffering in aqueous solution (pH control in cells and organisms); colloids, detergents, and micelles (biologic membranes); surface chemistry (bioadhesion and biocatalysis); polymer structure and dynamics (polypeptides, polynucleotides, polysaccharides); crystallography and diffraction techniques (structural biology); noncovalent interactions (hydrogen bonding); and so on.

The list could continue, but it illustrates the key role that physical chemistry has played, and continues to play, in our understanding of biology.


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Further Reading

Atkins P, de Paula J. Physical Chemistry. 8th edition. 2006. Oxford University Press, Oxford, UK.

Cantor CR, Schimmel PR. Biophysical Chemistry. 1980. W.H. Freeman & Co, San Francisco, CA.

Chang R. Physical Chemistry for the Chemical and Biological Sciences. 2000. University Science Books, Sausalito, CA.

Cooper A. Biophysical Chemistry. RSC Tutorial Chemistry Text #16. 2004. Royal Society of Chemistry, Cambridge, UK.

Price NC, Dwek RA, Ratcliffe RG, Wormald MR. Physical Chemistry for Biochemists. 3rd edition. 2001. Oxford University Press, Oxford, UK.

Sheehan D. Physical Biochemistry: Principles and Applications. 2000. John Wiley & Sons, Ltd., Chichester, UK.

See Also

Biology, Chemical Views of

Biology, Computational Chemistry in

Chemical Biology, Technologies and Techniques in

Fluorescence in Living Systems: Overview of Applications in Chemical Biology

Mass Spectrometry: Overview of Applications in Chemical Biology

NMR: Overview of Applications in Chemical Biology

Spectroscopic Techniques: Overview of Applications in Chemical Biology