What is the overall order of reaction when the hydrolysis occurs in basic solutions? (1 mark) 2. What is the order of reaction with respect to aspirin hydrolysis under acidic conditions? (1 mark) 3. Explain how the reaction has been manipulated such that the change in reaction rate is dependent on temperature and the aspirin concentration and not the hydroxide concentration? (2 mark) 4. Given the following reaction mechanisms (k = rate constants) draw a reaction coordinate diagram for the hydrolysis of aspirin. The following information may be used to determine the relative energy levels for the reactants, intermediates and products: Keq1 (equilibrium constant for step 1) is small; Keq2 (step 2) and Keq3 (step 3) are large; and, 1 / Keq1 ≈ Keq2. Label all reactants, intermediates and products on your diagram. (4 marks) O H3C OR + OH - k1 k-1 H3C OR HO O k2 k-2 O H3C OH + -OR k3 k-3 O O - H3C + HORStudent Name:_____________________________ Laboratory Group:____ Date:_____ 2 | Mark ___ / ___ 5. A standard calibration curve of ____________ (Figure 1) was used to determine the concentration of ____________ at five times, 0, 15, 30, 45 and 60 minutes from four aspirin decomposition reactions at 55° C, 60° C, 65° C and 70° C (table 1 and 2). Table 2 lists the aspirin concentrations ([A]t), inferred using equation 7, and the transformed values, ln [A]t for each decomposition reaction. t t [A] [A] [SA] 0 Eq. 7 (2 marks) Figure 1. Calibration curve of absorbance versus concentration of salicylic acid at 295 nm. (2 marks) Table 1. Absorbance values of salicylic acid (SA) Temperature (°C) Absorbance and [SA] at 295 nm after t minutes 15 min 30 min 45 min 60 min Abs [SA] Abs [SA] Abs [SA] Abs [SA] 55 60 65 70 (4 marks)Student Name:_____________________________ Laboratory Group:____ Date:_____ 3 | Mark ___ / ___ Table 2. Concentrations values of aspirin ([A]t) calculated using equation 7, and ln [A]t . Temperature (°C) Concentration of aspirin (mol. dm -3 ) k' (_____) 15 min 30 min 45 min 60 min [A] ln [A] [A] ln [A] [A] ln [A] [A] ln [A] 55 60 65 70 (5 marks) 6. The plots in figure 2 illustrate the relationship between ln [A]t . and t at each temperature. From these plots it is clear that the rate of aspirin decomposition ____________ with increased temperature. From these plots the pseudo-first order rate constant (k') for each temperature was estimated. The pseudo-first order rate constants (k') were observed to ____________ with increasing temperature. Figure 2. Overlayed plots of ln [A]t and t at 55, 60, 65, and 70 °C. (4 marks) 7. The k' values estimated for the four different temperature regimes allowed the application of Arrhenius' law to estimate the activation energy (Ea) of the aspirin decomposition process. Figure 3 indicates that this reaction is ____________ with Arrhenius law giving a Student Name:_____________________________ Laboratory Group:____ Date:_____ 4 | Mark ___ / ___ __________ relationship between ln k' and 1/T. The activation energy was calculated to be_______________, indicating that this reaction is __________ temperature dependent. (4 marks) 8. Using the pseudo-first order rate constant (k') obtained from the decomposition of aspirin at 55 °C calculate the half-life of aspirin under the conditions employed in this experiment. Hint: equation 4 may be a useful starting point. (4 marks) 9. What is a prodrug and why are these important in drug design? With this in mind discuss the significance of the design features of aspirin? (5 marks) 10. With respect to your responses to questions 8 and 9 comment on the storage conditions required to maximise the shelf-life of aspirin. (