Types of intermolecular forces

Basic interactions: Coulomb (electrostatic), van der Waals & steric.

Water-derived: Hydrogen bonding, hydrophobic, hydrophilic (solvation
force).

Wonmuk Hwang, Texas A&M University 1/1

 Electrostatic interaction

Potential energy between charges q1 and q2 separated by a distance r :

1 q1 q2
U(r ) = (1)
40 r r

0 = 8.854 1012 C2 /Jm: Permittivity of vacuum

r : dielectric constant of the medium (80 for water)
Electrostatic potential V : Electrostatic potential energy per unit charge
(1 V=1 J/C).
Potential energy of a charge q at ~r is U(~r ) = qV (~r ).
~ = V
Electric field: E ~ (electrostatic force per unit charge)
Force on a charge q in an E-field E~: F~ = U ~ = q V ~ = qE~.

Wonmuk Hwang, Texas A&M University 2/1

 Ions in solution
Ionic bond between Na+ and Cl (face-centered-cubic lattice) Clickme
qNa = qCl = e = 1.6 1019 C. In a NaCl crystal, r = 2.76 A. Then
1 1
UNaCl = 8.34 1019 J = 120 kcal/mol
r r
air
In air (r ' 1): UNaCl = 120 kcal/mol ( kB T = 0.60 kcal/mol at 300 K).
An ionic bond does not break spontaneously in air.
wat
In water (r ' 80): UNaCl = 1.5 kcal/mol; NaCl dissolves in water.

Solubility: When there are too many ions, it costs free energy to dissolve
additional NaCl pair, so NaCl precipitates. For NaCl, solubility in water is
359 g/l=6.4 M.

Bjerrum length: Length beyond which thermal energy dominates over

electrostatic energy between ions. For monovalent ions in water,
1 e2
kB T = lB = 6.94 1010 m (2)
40 r lB
In addition, due to solvation forces, ions stay separated in water.
Wonmuk Hwang, Texas A&M University 3/1
 Counterion distribution near a flat charged surface
Consider a flat surface with charge density (C/m2 )

Due to counterions, electrostatic potential is screened. Consider 1-dimension. In

general V (x) satisfies the Poisson equation:

2V
P
q(x) zi ei (x)
= = i (3)
x 2  
q(x): charge density at x,  = 0 r .
i: ion index (Na+ , Cl , Mg2+ , Al3+ , CO
3 , etc.)
zi : valence of i-th ion (zNa = +1, zCl = 1, zMg = +2, etc.)
i (x): Number concentration of the i-th ion at x.
Wonmuk Hwang, Texas A&M University 4/1
 Debye-Huckel theory of electrostatic screening

In presence of V (x), i (x) satisfies the Boltzmann distribution:

i (x) =
i e
Ui (x)
=
i e
ezi V (x)
(4)

i : bulk density of the i-th ion.
Then we get the Poisson-Boltzmann equation (PBEQ):

2V e X ezi V (x)
= zi i e (= 2 V (in multi-dim)) (5)
x 2 
i

Wonmuk Hwang, Texas A&M University 5/1

 Debye length
Solve linearized PBEQ in 1-dim: kB T  ezi V (validate below)

2V eX
' zi i (1 ezi V ) (6)
x 2 
i

zi
P
Since the solution far from the surface is neutral, i i = 0.

2V e 2 X 2 V
2
' zi i V = 2
x  lD
i

V (x) ' V0 e x/lD (7)

 1/2
e2
zi2
P
V0 : Surface potential, lD = kB T i i : Debye length.
lD is shorter for: Lower T (counterions stay more easily near the surface),
higher zi ,
i .
Ex) 1 mM NaCl: lD =9.6nm
Ex) Pure water at pH=7: [H3 O+ ]=[OH ]=107 M lD = 960 nm.
When does the linear approximation hold? kB T > eV V < kBeT = 25.9 mV
cf., resting membrane potential: 70 mV action potential: 50 mV
Wonmuk Hwang, Texas A&M University 6/1
 van der Waals interaction - Origin

Both electrostatic and quantum mechanical.

induced dipole-
Dipole-dipole Dipole-induced dipole
induced dipole

+ - + - + - + - + - + -

Dipole-dipole: orientation interaction between polar molecules.

Dipole-induced dipole: induction of polarization on nonpolar molecule by
a polar molecule.
Induced dipole-induced dipole: dispersion force caused by spontaneous
polarization of nonpolar molecules.
CVDW
UVDW (r ) = 6 (8)
r
Coulomb: Depends on electric charges.
VDW: Depends on material properties (dipole moment & polarizability)
Can calculate Cvdw using the Lifshitz theory.

Wonmuk Hwang, Texas A&M University 7/1

 Magnitude of Cvdw

Ne-Ne CH4 -CH4 NH3 -NH3 H2 O-H2 O

79 6
Cvdw (10 Jm ) 4 102 111 139
What about the VDW constant between different materials?
Let C1 and C2 be VDW constants
for material 1 and 2
Between 1 and 2, C12 = C1 C2 (can be used in simulations)

VDW interaction between surfaces: UVDW (r ) = rAn , where n < 6, so that the
interaction can be long-ranged.
Ex) Interaction between a particle and a semi-infinite plane of particle density

CVDW
Uvdw = (D: particle-surface distance) (9)
6D 3

Wonmuk Hwang, Texas A&M University 8/1

 Geometry dependence of VDW interaction

A: Hamaker constant
(A = 2 Cvdw 1 2 1020 J;
1,2 : particle number densi-
ties)
Leckband & Israelachvili, Quater.
Rev. Biophys. 34:105 (2001)

Book: J. Israelachvili, Intermolecu-

lar and Surface Forces

Wonmuk Hwang, Texas A&M University 9/1

 Lennard-Jones potential

Steric interaction (hard-core repulsion):

Quantum mechanical in nature: Due to Pauli exclusion principle (no two
particles can be in the same quantum state).
Strongest & short-ranged.
Use empirical description: UHC r 9 , r 12 , etc.
(
Hard sphere model: 0 r > r0
UH (r ) =
r r0
Lennard-Jones potential: VDW + steric
  
12  6
ULJ (r ) = 4 (10)
r r

(figure by hand)

Wonmuk Hwang, Texas A&M University 10/1

 Structure of water and hydrogen bond

-0.834e

H
0.957
O O 1. 76
H

O
H 104.5o H
0.417e
0.417e H

H
Rg ' 1.4 A.
2 partially charged H
Can form tetrahedral network of hydrogen bonds in 3-dim.
Hydrogen bond:
Shorter than the sum of VDW radii: 1.1 A (H)+1.5 A (O)=2.6 A > 1.7 A.
Strength between covalent & VDW: Ehb = 3 7 kcal/mol,
EVDW 0.24 kcal/mol, Ecov > 100 kcal/mol (kB T = 0.60 kcal/mol)
Directional: Critical for biomolecular structures.

Wonmuk Hwang, Texas A&M University 11/1

 Hydrophobic attraction
Non-polar molecules in water cannot form h-bonds with surrounding water
molecules.
Hydrophobic effect: Tendency of nonpolar molecules in water to attract.
Free energy change G upon aggregation proportional to the change in
solvent-exposed surface area of nonpolar molecules A:
G ' A (: has units of J/m2 =N/m surface tension)
Air-water interface: = 72 mJ/m2 ,
Hydrocarbon-water interface: = 50 mJ/m2
Can be long-ranged (> 100 nm).
Kauzmanns explanation in 1969 for hydrophobic attraction as an entropic
effect driven by liberation of ordered water on surfaces is now accepted to
be wrong (Ball, Chem. Rev. 108:74108 (2008), Fig. 6).
H-phobic effect is not a fundamental interaction with a single origin such as
electrostatic and VDW. Depends on length scale too.
Origin: Composite effect involving hydration shell dynamics, VDW
attraction, and conformational motion of macromolecules and surface
groups (at the scale of biomolecular surfaces; Ravikumar & Hwang, JACS
133:11766 (2011)).
Wonmuk Hwang, Texas A&M University 12/1
 Hydration shell behavior between protein surfaces

H-phobic & H-philic interactions differ in the amplitude and phase of the
weakly oscillating hydration force relative to electrostatic & Lennard-Jones forces.
Ravikumar & Hwang, JACS 133:11766 (2011)

Wonmuk Hwang, Texas A&M University 13/1

 A unified picture for h-phobic/h-philic forces

Ubiquitous hydration shell generates hydration repulsion (solvation force)

between surfaces.
Hydration repulsion is stronger between polar surfaces.
Between nonpolar surfaces, weaker hydration repulsion does not prevent
VDW attraction (cannot be screened): appears as hydrophobic attraction.
Formation of local contacts due to conformational motion may contribute
to the apparent long-ranged nature of h-phobic interaction.
Hydrophobic/hydrophilic represent two idealized limits of water-mediated
interactions, and interactions between real surfaces lie between these limits.

Wonmuk Hwang, Texas A&M University 14/1

 Rules of Thumb

Strong forces
Steric repulsion: Strongest of all, but very short-ranged.
Covalent: 100300 kB T (60180 kcal/mol). Can break by an enzyme.
Ionic: a few hundred kB T (comparable to covalent) in vac, but weak in
water.
Modest/weak forces
Electrostatic: Can be strong and long-ranged, but screened in presence of
electrolytes.
VDW: Can be significant between macromolecular surfaces. Not screened.
Hydrogen bond: 712 kB T (47 kcal/mol). 1.62.4 A range, directional.
Ideal for specific interaction.
Hydration repulsion: Strength depends on surface properties. > 3 A range.
Hydrophobic attraction: Apparently long-ranged (> 100 nm). G = A.

Wonmuk Hwang, Texas A&M University 15/1

 Driving forces for macromolecular self-assembly

Balance between attraction (VDW, h-phobic, electrostatic, solvation etc.) and

repulsion (electrostatic, solvation, etc.) required.
Attraction  repulsion: Disordered aggregation.
Attraction < repulsion: No assembly.
Attraction & repulsion: Ordered assembly
Protein folding:
1. Polypeptide synthesis
2. Rapid formation of non-polar groups to form molten globule (h-phobic
collapse). Due to lack of orientation dependence in h-phobic contacts, the
protein performs conformational searching.
3. Hydrogen bond formation (directional) determines specific structure.

Wonmuk Hwang, Texas A&M University 16/1