52nd International Chemistry Olympiad, Istanbul, TURKEY Preparatory problems: THEORETICAL

Problem 25. Spectrophotometric Determination of an

Antihistaminic Drug
Spectrophotometric procedures are simple, rapid, and accurate methods that can be utilized for
the determination of drug molecules. The method is based on formation of a complex between
two reagents. Many complexes are colored and absorb in the visible region; thus they can be
determined spectrophotometrically.

An antihistaminic drug, D, acts as an electron donor group and complexes with a π-acceptor, S.
Absorbance of the resulting complexes recorded at relevant maxima (460 nm) with respect to
drug concentration shows a linear tendency with good correlation coefficients.

𝐷 + 𝑆 ⇌ 𝐷𝑆
[𝐷𝑆]
𝐾=
[𝐷][𝑆]

where [DS], [D], and [S] represent the equilibrium concentrations of the DS complex, D, and S,
respectively.

𝐶𝐷 = [𝐷] + [𝐷𝑆]

where CD is the overall concentration of the drug.

At a wavelength where only the formed DS complex absorbs light, the following expression
holds:

𝐴 = 𝜀𝐷𝑆 𝑙[𝐷𝑆]

where l is the length of the measuring cuvette.

The binding equilibrium constant of the complexation can be calculated using the Benesi–
Hildebrand equation, which depends on the experimental conditions where one of the
component species should be present in large excess so that its concentration is not altered on
formation of complex.

𝐶D 1 1 1
= + ×
𝐴DS DS DS K 𝐶S

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52nd International Chemistry Olympiad, Istanbul, TURKEY Preparatory problems: THEORETICAL

where CS and CD are total concentrations of S and D. ADS is the absorbance of the complex, εDS
is the molar absorptivity of the complex, and K is the equilibrium constant.

7,0E-06
y =6.20E-11 x 2.23E-7
6,0E-06
R² = 0.997

CD/ADS (mol dm-3)

5,0E-06

4,0E-06

3,0E-06

2,0E-06

1,0E-06

0,0E+00
0,0E+00 2,0E+04 4,0E+04 6,0E+04 8,0E+04 1,0E+05
1/ CS (mol-1dm3)

25.1. Considering the Benesi–Hildebrand plot recorded at 25 °C, find the equilibrium constant
for the complex formation and molar absorptivity of the complex.

25.2. The initial equal concentration of D and S is 9 × 10–5 mol dm–3. Calculate the fraction of
the complex formed when equilibrium is reached. Consider there is a 1:1 molar ratio between
D and S in the complexation.

25.3. Calculate the rG° in kJ mol–1 at 25 °C.

The kinetics of complexation of D with S is studied by varying temperature (25, 45, and 60 °C).
The Table gives the rate constant of complexation at different temperatures.

T (°C) k (min–1)
25 0.0200
45 0.0504
60 0.0944

25.4. Calculate the activation energy, Ea.

∆𝐺‡
𝑘𝐵 𝑇
25.5. Given that 𝑘𝑇𝑆𝑇 = 𝑒 − 𝑅𝑇 , calculate the activation enthalpy (H‡), activation entropy
ℎ
(S‡), and free activation enthalpy (G‡) of the reaction for 25 °C.

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