2.

1 What is the main difference at the molecular level between a soft material, such as a gel or a
liquid crystal and a hard material such as a metal, concrete or glass?

The difference is in the strength and the outreach of secondary interactions that hold the molecules
(chemical entities) together. Hard materials are held together by strong and long-range
intermolecular interactions (perfect example for that is the ionic bond or the H-bond network in ice),
while soft materials are heled together by medium-range weak interactions.

2. The following question refers to the equilibrium:

a) Suppose that the concentrations of free A and B and the complex AB are all equal, i.e.
[A]free = [B]free = [AB]. Show that the total concentration of A that needs to be dissolved to
achieve this, [A]total, equals 2/K.
b) A binds to B with an equilibrium constant of 1.0 × 103 M-1 and A is dissolved to a
concentration of 1mM. Calculate what the concentration of B needs to be for 90% of A to be
complexed to B.
c) A is dissolved to a concentration of 1mM, but now A binds to B with a binding constant of
1.0 × 106 M-1. Calculate what the concentration of B needs to be for 90% of A to be
complexed to B.
d) The Figures below show plots of the percentage of A ([A]t = 1 mM) that is complexed to B as
a function of the total concentration of B in the solution when K = 1.0 × 103 M-1 and when K
= 1.0 × 106 M-1. Sketch the curve that corresponds to K = 1.0 × 109 M-1.
e) Equilibrium constants are routinely measured through titration of a concentrated solution of
B into a solution of A and feeding the data into curve-fitting software. Discuss whether or
not the curves in d) would be suitable for such analysis.

[𝐴𝐵] 1 1 2
a) 𝐾 = = , thus [𝐴] = and [𝐴]𝑡𝑜𝑡 = [𝐴] + [𝐴𝐵] = 2[𝐴] = .
[𝐴][𝐵] [𝐴] 𝐾 𝐾

b) A + B = AB

Initial cA cB -

Consumed/formed -x -x x

Remained cA-x cB-x x

The equations to be solved:

𝑐𝐴 = 0.001𝑀

𝑥 = 0.9𝑐𝐴
𝑥
103 = (1)
(𝑐𝐴 − 𝑥)(𝑐𝐵 − 𝑥)

From here 𝑐𝐵 = 9.9 × 10−3M.

c) The equations to be solved:

 𝑐𝐴 = 0.001𝑀

𝑥 = 0.9𝑐𝐴
𝑥
106 =
(𝑐𝐴 − 𝑥)(𝑐𝐵 − 𝑥)

From here 𝑐𝐵 = 9.09 × 10−4M. The larger K is, the lower excess of the ligand is needed to complex A
to an equal extent.

d) From the equation (1) one gets

𝐾𝑐𝐴 + 𝐾𝑐𝐵 + 1 − �(𝐾𝑐𝐴 + 𝐾𝑐𝐵 + 1)2 − 4𝐾 2 𝑐𝐴 𝑐𝐵

𝑥= (2)
2𝐾

and thus

𝐾𝑐𝐴 + 𝐾𝑐𝐵 + 1 − �(𝐾𝑐𝐴 + 𝐾𝑐𝐵 + 1)2 − 4𝐾 2 𝑐𝐴 𝑐𝐵

𝑐𝐴𝐵 % = 100 × (3).
2𝐾𝑐𝐴
𝐶𝐵
Taking cA= 0.001 M and defining 𝐸𝑞𝑢𝑖𝑣𝑎𝑙𝑒𝑛𝑡𝑠 𝐵 = 𝐶𝐴
, one gets the following curve:

e) The K= 109 M-1 and K= 106 M-1cases are not suited for titrations, because small errors (e.g. in the
concentration measurements) cause large changes in the measured values so that the overall error
of the measurement is considerably high.

3. Consider the binding equilibrium shown in Question 2. Describe qualitatively what happens
upon 1000-fold dilution of a solution of [A]t = [B]t = 10 mM and K = 105 M-1. And what happens
when the resulting solution is diluted by another 1000-fold?
Le Chatelier-Brown principle: When a system at equilibrium is subjected to change
in concentration, temperature, volume, or pressure, then the system readjusts itself to (partially)
counteract the effect of the applied change and a new equilibrium is established.

In the reaction A + B = AB, the concentration decreases (2 molecules bind to each other to give 1
molecule). Upon dilution, the concentration of all species decrease, let”s say, to p-fold (p>1). If the
equilibrium was not shifted, the product of the concentrations after dilution would be (if the
equilibrium is:
𝑐𝐴𝐵
𝑝 𝑐𝐴𝐵
𝑐𝐴 𝑐𝐵 = 𝑐 𝑐 𝑝 = 𝐾𝑝 > 𝐾
𝐴 𝐵
𝑝 𝑝

Which means that the numerator of the fraction should decrease so that the overall expression is
again equal to K. This means that cAB should decrease, thus dissociation should occur to some extent.

From a quantitative point of view , let´s say 𝑐𝐵 = 𝑐𝐴 = 𝑐 and thus from equation (1):

𝑥
105 =
(𝑐 − 𝑥)2

In the original case c= 10-2M and x=9.68×10-3M, thus 97% is complexed.

Upon 1000-fold dilution c= 10-5M and x=3.82×10-6M, thus 38% is complexed.

Upon further 1000-fold dilution c= 10-8M and x=10-11M, thus practically 0 % is complexed.

Take-home message: the higher the dilution is, the more dissociated the complex is.

4. Binding constants are typically determined through titrations. Why are these best performed at
[A]t of approximately 2/K? Hint: think of what titration curves will look like if [A]t is much lower
or much higher than 2/K.

Let us consider equation (2) and construct graphs showing 𝑐𝐴𝐵 % as a function of log(K×cB) at various
K×cA values. (the logarithmic scale shows the concentration changes more sharply throughout the
whole ligand concentration range). For the normal case K×cA=2, for the two extremes let us choose
values which are 3 orders of magnitude higher and lower, respectively.

It can be seen that at too high cA, the amount of complexed A barely changes compared to its initial
value even upon addition of a few equivalents of the ligand, while at too low cA, complexation
happens too early, when the amount of the ligand is still low, thus the amount of usable data points
is not enough, moreover, as in 2.d, small experimental errors can lead to considerable overall errors
in the determination of K.
5. Consider the dimerization equilibrium below. Assume that _Go is in the order of -44 kJ/mol (at
298 K).

a) Assuming that the rate of self-association of 1 is diffusion controlled (i.e. in the order of 109
M-1s-1). Would you expect the complexation to be slow or fast on the NMR time scale?
Motivate your answer.
b) Which experimental technique would be most suitable to determine the equilibrium
constant for formation of this complex in chloroform as a solvent? Motivate your answer.
Reference: F. H. Beijer, R. P. Sijbesma, H. Kooijman, A. L. Spek, E. W. Meijer, J.Am.Chem.Soc., 1998, 120, 6761.

a) Diffusion-controlled reactions are the fastest among all chemical reactions ( K= 109-1010 M-
1s-1), whereas proton NMR relaxation times are in the range of 104-10-1 s 1, which means that
the reaction is fast on the NMR scale.
b) From ∆𝐺 = −𝑅𝑇𝑙𝑛𝐾 one gets 𝐾 = 5.2 × 107 𝑀−1 , which renders it suitable for ITC and
fluorescence spectroscopy as analytical methods (although the latter is not well-suited as
neither the substrate nor the product shows fluorescence).

1
R.G. Bryant, J. Chem. Educ., 1983, 60 (11), p 933