Unidad 2
Interacciones Moleculares
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“The Greeks were the first to consider forces in a nonreligious way.
They found that they needed only two fundamental forces to account
for all natural phenomena: Love and Hate. The first brought things
together, while the second caused them to part. The idea was first
proposed by Empedocles around 450 B.C., was much “improved” by
Aristotle, and formed the basis of chemical theory for 2000 years”
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 1). Copyright © 2011 Elsevier.
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 1). Copyright © 2011 Elsevier.
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The Forces of Nature
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 1). Copyright © 2011 Elsevier.
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Four Kinds of Forces
There are just four basic forces known (presently) to physics: In the order of
decreasing strength:
1. Strong
2. Electromagnetic
3. Weak
4. Gravitational
The strong forces, which hold protons and neutrons together in the atomic
nucleus, have extremely short range, so we do not "feel" them, in spite of the fact
that they are a hundred times more powerful than electrical forces. The weak
forces, which account for certain kinds of radioactive decay, are not only of short
range; they are far weaker than electromagnetic ones to begin with. As for gravity,
it is so pitifully feeble (compared to all of the others) that it is only by virtue of huge
mass concentrations (like the earth and the sun) that we ever notice it at all.
From Griffiths D.J., Introduction to Electrodynamics 3rd ed. Copyright © 1999 Prentice Hall.
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Molecular interactions
• Biological matter is comprised of small molecules (e.g., water), macromolecules
(biopolymers), supramolecular assemblies or macromolecular complexes, which
assemble into subcellular particles and cells, which in their turn form supracellular
systems such as tissues and organs.
• One of the key ingredients of biological systems is represented by the complex,
specific or non-specific, intra- and inter-molecular interactions, which determine the
structure and, further, the biological functions associated to structure.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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Molecular interactions
There exists a wide variety of physical interactions relevant to the structure and
function of biological systems:
• Attractive or repulsive electrostatic interactions (e.g., charge-charge, charge-dipole,
charge-multipole, dipole-multipole, etc.).
• Attractive electrodynamic interactions, hydrogen bonds, and hydrophobic
“interactions.”
From a quantitative point of view, physical interactions can be described either as forces
or as energies of interaction
The strength of intermolecular interactions determines the physical properties of a
substance (e.g., melting and boiling temperatures, surface tension, etc.).
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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Charge-Charge Interactions
The electrostatic energy of interaction, WES, between two point charges, q1 and q2, separated by a
distance, r, and embedded in a homogenous medium of relative permittivity, εr, is given (in IS units)
by:
Represents the dielectric constant of free space.
Used for the description of the following type of interactions:
• Ion-ion interactions
• Interactions between ions and charged chemical groups attached to a macromolecule
• Interactions between two (or more) charged chemical groups belonging either to different
macromolecules or to the same macromolecule.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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In the case of the electric field around a charge q, the electric potential is a radial function of the
distance r from this point. According to this definition, the potential ψi at distance ri from charge q is
given by:
Equipotential lines and field
vectors around a positively
charged point
From Glaser, R., Biophysics: An Introduction, 2nd ed. (Chapter 2). Copyright © 2012 Springer-Verlag Berlin Heidelberg.
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 3). Copyright © 2011 Elsevier.
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Lines of force of the electric field of an electric dipole
From Griffiths D.J., Introduction to Electrodynamics 3rd ed. Copyright © 1999 Prentice Hall.
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Electron density isosurfaces overlaid with the molecular electrostatic surface potential
(MESP) in accordance with the color-code legend to the right.
Methanol, CH3OH Water, H2O
From Gurav et al. J. Chem. Phys. 142, 214309 (2015)
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 4). Copyright © 2011 Elsevier.
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 4). Copyright © 2011 Elsevier.
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Interaction Between a Charge and a Permanent Dipole
with s << r
Electrical potential, φdipole, created by the dipole at the location of the charge q:
Charge-dipole interactions may occur, e.g., between water molecules (i.e., permanent dipoles), which have a very
high dipole moment of about 1.8D [1D (Debye) = 3.336×10−30Cm], and the charges attached to the
macromolecule chains, or between water molecules and ions from the cytosol.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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Charge-dipole interaction energy
in vacuum (ε = 1) between a unit
charge e and a dipole of moment
u = ql = 1 D (1 Debye) oriented at
different angles θ to the charge.
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 4). Copyright © 2011 Elsevier.
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van der Waals Interactions
The term van der Waals interactions represents three classes of interactions:
(a) Orientation or Keesom interactions (first described by Keesom in 1912) between
permanent electric multipoles (i.e., dipoles, quadrupoles, octopoles, etc.).
(b) Debye induction interactions (Debye, 1920) between permanent multipoles and
induced multipoles.
(c) London dispersion interactions (London, 1930) between instantaneous dipoles/
multipoles and instantaneous induced dipoles/multipoles.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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Mutual interaction between two aligned dipoles (EDD)
Using the approach r > l:
From Glaser, R., Biophysics: An Introduction, 2nd ed. (Chapter 2). Copyright © 2012 Springer-Verlag Berlin Heidelberg.
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Potential energy functions for
dipole-dipole interactions.
From van Holde, K.E., Johnson, C., and Ho, P.S. Principles of Physical Biochemistry 2nd (Chapter 3). Copyright © 2005 Prentice Hall.
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 4). Copyright © 2011 Elsevier.
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Keesom Interactions
Two electrical charge distributions with their
“centers” situated distance R apart.
Electrostatic energy of interaction:
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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Keesom interactions (instantaneous interaction between two dipoles) are
represented by the last term:
The instantaneous positions and orientations of the two dipoles (multipoles) are usually unknown
and may also rapidly change due to the thermal motion. Therefore, a time average of the Keesom
energy of interaction is sometimes more meaningful:
Average Keesom interaction energy:
kB = 1.38×10−23 J/K is the Boltzmann constant and T is the absolute temperature.
Keesom interactions are attractive interactions, as their average energy is always negative; they are
also short-range interactions, since the energy decreases abruptly with the distance R.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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Note: Strictly speaking, the former expression represents the total internal energy of interaction,
which is twice the free energy of interaction. Thus, for Keesom interaction:
The reason why the interaction free energy (the energy available for doing work or the energy that
gives the force) is less than the total internal energy of two interacting dipoles is because some of
the energy is taken up in aligning the dipoles as they approach each other. This unavailable part of
the energy is associated with the entropic contribution to the interaction.
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 4). Copyright © 2011 Elsevier.
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The angle-averaged free energy for the charge-dipole interaction is therefore:
which is attractive and temperature dependent.
kB = 1.38×10−23 J/K is the Boltzmann constant and T is the absolute temperature.
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 4). Copyright © 2011 Elsevier.
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On the Polarizability of Atoms and Molecules
This involves the dipole moments induced in molecules by the electric fields emanating from
nearby molecules.
All atoms and molecules are polarizable. Their (dipole) polarizability α is defined according to the
strength of the induced dipole moment uind they acquire in a field E that is
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 5). Copyright © 2011 Elsevier.
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Electronic polarizability
Induced dipole in a one-electron atom. (a)
No external field, uind=0. (b) In an external
field E the electron’s orbit is shifted by a
distance l from the positive nucleus so
that the induced dipole moment is uind = el
= α0E.
The polarizability (α0) of atoms and
molecules that arises from such electronic
displacements is known as the electronic
polarizability.
The unit of polarizability is 4πε0 x (volume) or C2 m2 J-1.
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 5). Copyright © 2011 Elsevier.
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 5). Copyright © 2011 Elsevier.
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Orientational polarizability
A freely rotating dipolar molecule (whose time-averaged dipole moment is zero) also has an
orientational or a dipolar polarizability, arising from the effect of an external field on the Boltzmann-
averaged orientations of the rotating dipole.
In the presence of an electric field E, these orientations will no longer time-average to zero but will
be weighted along the field.
If at any instant the permanent dipole u is at an angle θ to the field E, its resolved dipole moment
along the field is u cos θ, and its energy in the field is u
︎ E cos θ, so the angle-averaged induced
dipole moment is given by
An additional contribution to the molecular polarizability is the dipolar or orientational polarizability,
defined by
The total polarizability of a polar molecule is therefore given by the Debye-Langevin equation:
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 5). Copyright © 2011 Elsevier.
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Interaction Between a Charge and an Induced Dipole
An induced dipole gives rise to a “reaction” dipole field Er
A neutral (nonpolar) molecule in a field E will acquire an induced dipole of moment uind = ql = αE.
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 5). Copyright © 2011 Elsevier.
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When a molecule of polarizability α is at a distance r from an ion of charge ze, the electric field of
the ion will induce in the molecule a dipole moment of
The induced dipole will point away from the ion if it is a cation and toward the ion if it is an anion. In
either case this will lead to an attractive force between the ion and the polarized molecule.
The attractive energy will be
(Using the polarizability α in C2 m2 J-1)
From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 5). Copyright © 2011 Elsevier.
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Debye Interactions
The electrical field produced by a dipole, locally characterized by the intensity E, induces in a
neighboring molecule an electric dipole pi, given by the expression:
! !
pi = α E α is the polarizability of the molecule in C2 m2 J-1.
Each dipole induces an instantaneous dipole into the other charge distribution.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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These charge distributions will
generate electrostatic fields:
The total induction interaction energy is therefore given by:
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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The instantaneous energy of interaction:
It is dependent upon the instantaneous orientations of the dipole moments. The interaction is
attractive, for any orientation of the permanent dipoles.
Average energy of interaction:
Note: In the former expressions a modified polarizability is used. This polarizability corresponds to
α/ε0ε, where α is used in C2 m2 J-1.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 2). Copyright © 2011 Elsevier.
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From Israelachvili, J.N. Intermolecular and Surface Forces 3rd ed (Chapter 2). Copyright © 2011 Elsevier.
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Graphene
Graphite
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Trans. Faraday Soc., 1937,33, 8b-26
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London (Dispersion) Interactions
They are attributed to charge fluctuations in a molecule. Dispersion interactions seem to be the
most important van der Waals forces, because they are always present even in the absence of net
charges or permanent dipoles.
Even in nonpolar molecules, such as benzene, charge fluctuations may cause the center of positive charges to be
shifted away from the center of the negative charges, the molecule becoming, for a very short time, a dipole. This
instantaneous (transient) dipole will induce an instantaneous dipole into a neighboring molecule, and the two
dipoles will exert attractive electrostatic forces upon one another. These forces are not directional, because the
transient dipole induces a dipole in a neighboring molecule irrespective of its spatial orientation.
The dispersion interaction energy
between two molecules:
ħ=h/2π is the reduced Planck constant (h = 6.626 x 10-34 Js),ω and ω’ are the absorption angular frequencies (ω
= 2πν, ν being the electronic absorption frequency) of the molecules, while α and α’ are their corresponding
polarizabilities.
London interactions are attractive, independent of temperature (being instantaneous), and, again, short-range
(i.e., dependent upon R−6).
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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F. London, The general theory of molecular forces. Trans. Faraday Soc., 1937,33, 8b-26
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Comparison of the Contributions to the Interaction Energy
From: Castellan, G.W., Physical Chemistry 3rd (Chapter 26). Copyright © 1983 Addison Wesley Publishing Company.
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From: Castellan, G.W., Physical Chemistry 3rd (Chapter 26). Copyright © 1983 Addison Wesley Publishing Company.
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Sometimes the expression of energy associated to London dispersive interactions is given in terms of the
ionization energy, Ik =hνk (k =1, 2):
The Lenard-Jones Potential
By superimposing the attractive van der Waals interactions and repulsive quantum interactions we obtain the so
called Lenard-Jones potential energy,WLJ(r):
(A and B are positive constants)
The Lenard-Jones potential energy provides to the interacting
molecules an “energetic landscape” that presents a minimum,
Wmin, for a certain distance, rmin, between the two molecules.
For r >> rmin, the molecules attract each other, while for r << rmin,
they repel each other.
From Raicu, V. and Popescu, A., Integrated Molecular and Cellular Biophysics (Chapter 1). Copyright © 2008 Springer Science.
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Proceedings of the Royal Society of London. Series A
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The Lennard-Jones potential is normally written in the form
The two parameters are:
-ε (epsilon), the depth of the well
-σ, the separation at which V = 0
The well minimum occurs at r = 21/6σ.
From Atkins, P. and De Paula, J. Physical Chemistry for the Life Sciences, 2nd ed. (Chapter 11). Copyright © 2010 Oxford University
Press.
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From van Holde, K.E., Johnson, C., and Ho, P.S. Principles of Physical Biochemistry 2nd (Chapter 3). Copyright © 2005 Prentice Hall.
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Relationship of Noncovalent Interactions to the
Distance Separating the Interacting Molecules, r
From van Holde, K.E., Johnson, C., and Ho, P.S. Principles of Physical Biochemistry 2nd (Chapter 1). Copyright © 2005 Prentice
Hall.
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A DNA dodecamer in aqueous
environment has been studied
by means of molecular
dynamics simulation, with a
modified force field accounting
for the hypothetical absence of
London dispersion forces. Under
these conditions, the double-
helical DNA oligomer passes via
an extended, ladder-like
intermediate to a collapsed
structure.
From Kolář M, Kubař T, Hobza P. J. Phys. Chem. B. 115(24):8038-46 (2011).
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Functions: y = r-n to illustrate the character of short- and long-distance interactions.
From Glaser, R., Biophysics: An Introduction, 2nd ed. (Chapter 2). Copyright © 2012 Springer-Verlag Berlin Heidelberg.
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