Midterm 1 Fall 2016.pdf

Name_______________________________ UT EID _______________________________ Score_______________________________...

Name_______________________________ UT EID _______________________________ Score_______________________________ 100 (99+1) points PHM 387M Midterm 1 Carefully read and work through the problems below. It is recommended to bubble answers on the scantron as you go. Only bubble in one choice and choose the best answer. Each question is worth 3 points. !"#$ − !"#!!"#$ + !"#"$%&!! ⇌ !"#$ − !"#"$%&!!!"#$%&' Use table to answer questions 1 and 2 below. Generic Name ΔH (kcal/mol) Nelfinavir 3.1 Indinavir 1.8 Saquinavir 1.2 Lopinavir -3.8 Ritonavir -4.3 1. Which drug is most enthalpically favorable for binding to the receptor target? a. Nelfinavir b. Indinavir c. Saquinavir d. Lopinavir e. Ritonavir 2. For which drug to you have to put the most heat into the system for binding, i.e. drug-receptor complex, to occur? a. Nelfinavir b. Indinavir c. Saquinavir d. Lopinavir e. Ritonavir 1  3. Amorphous drugs are ____________ energetically stable than crystalline drugs. Amorphous drugs are ___________ water soluble than crystalline drugs due __________ entropy. a. Less; more; higher b. Less; less; lower c. Less; more; lower d. More; less; higher e. More; more; higher 4. When albumin is added to a poorly water-soluble, hydrophobic drug in water, the drug binds to albumin, and the entropy of the water molecules _________, breaking up the _________ intermolecular interactions between the water molecules. The albumin interact with the hydrophobic drug via _______ forces. a. increases; ionic; dispersion b. increases; dipole-dipole; dispersion c. increases; dipole-dipole; hydrogen bonding d. decreases; dipole-dipole; dispersion e. decreases; covalent; hydrogen bonding Please use the information provided in table below to answer questions 5 and 6. !"#$ − !"#!!"#$ + !"#"$%&!! ⇌ !"#$ − !"#"$%&!!!"#$%&' Drug name ΔG (kcal/mol) Nelfinavir -12.8 Indinavir -12.4 Ritonavir -13.7 Darunavir -15 Lopinvavir -15.1 5. Which drug binding to the HIV protease is furthest away from equilibrium? a. Nelfinavir b. Indinavir c. Ritonavir d. Darunavir e. Lopinavir 6. Which drug binding process is most spontaneous? a. Nelfinavir b. Indinavir c. Ritonavir d. Darunavir e. Lopinavir ! 2  7. Which of these cocoa butter polymorphs would you predict to have a higher melting temperature? a. Form (I) b. Form (II) c. None of the above d. They have the same melting point-you’re tricking me, Dr. Ghosh! Please use the information provided in table below to answer question 8. Compound Methane Propane Butane Molecular formula CH4 C3 H8 C4H10 Molecular weight 16.04 g/mol 44.1 g/mol 58.12 g/mol 8. Which molecule would be predicted to have the highest boiling point? a. Methane b. Propane c. Butane 9. A scientist is testing the degradation of a pharmaceutical preparation in a chamber where there is no change of volume. Given this information, which of the following First Law equations most accurately describes the change of internal energy associated with this degradation process? a. dE = dQ + PdV b. dE = dQ c. dE = PdV d. dE = 0 ! 3  10. To prepare a glucose solution, a scientist measures the equilibrium constants for dissolution of glucose. The dissolution of glucose is an endothermic reaction. As you increase the temperature of the reaction, which of the following is TRUE: a. the solubility of glucose increases b. the solubility of glucose decreases c. the equilibrium constant increases d. a and c e. b and c 11. Given that the equilibrium constant for amoxicillin dissolution in water at room temperature is 5.24*10-3, calculate the free energy of dissolution of the drug at standard state. a. -0.00310 kcal/mol b. -3.10 kcal/mol c. -0.26 kcal/mol d. +0.26 kcal/mol e. +3.10 kcal/mol Please use the information from the thermogram below to answer question 12. 12. You are formulating an active pharmaceutical ingredient (API) with an inactive excipient and what to confirm its compatibility by DSC. From the above thermogram of an API (bottom), excipient croscarmilose (middle) and the physical mixture of the API with croscamilose (top), would you predict that the excipient is compatible with the API? a. No b. Yes ! 4  13. In a micelle, the polar head interacts with surrounding water molecules via __________ intermolecular interactions while water weakly interacts with the non-polar tail via _________ interactions. a. Dipole-dipole; dipole-induced dipole b. Dipole-dipole; dipole-dipole c. Dipole-induced dipole; ionic bond d. Dipole-induced dipole; covalent bond e. Dipole-dipole; covalent bond 14. Daunorubicin is a water-soluble chemotherapeutic agent to prevents DNA synthesis. At equilibrium, daunorubicin forms dimers. If the enthalpy of formation of dimers at standard state is -7.6 kcal/mol and entropy at standard state is +0.025 kcal/(mol*K), what is the equilibrium constant at 25°C? Are products or reactants favored? a. -1.09*1011; reactants b. +0.78; products c. +1.28; products d. +20.4; products e. +1.09*1011; products 15. A pharmacist prepares a drug Bevotine as a salt, Bevotine-HCl. Bevotine-HCl dissolves into the following: !"#$%&'" − !"#! ↔ !"#$%&'" − !! + !" ! If the equilibrium constant is 6.20*10-2 M, the concentration of Bevotine-HCl is 200 mM and Cl- ion is 120 mM, what is the concentration of ionized form of the drug (Bevotine-H+)? a. +0.00067 M b. +0.0302 M c. +0.103 M d. +9.68 M ! 5  16. The enthalpy of disassociation of Bevotine-HCl into its ionized form is +27 kcal/mol. If you increase the temperature, how would this affect the dissolution? a. No effect on the equilibrium constant b. Products are favored and the equilibrium constant would decrease c. Products are favored and the equilibrium constant would increase d. Reactants are favored and the equilibrium constant would decrease e. Reactants are favored and the equilibrium constant would increase 17. In a chemical reaction, if ΔHreaction and ΔSreaction are both negative, when will the forward reaction be spontaneous? a. The temperature is less than the temperature at equilibrium b. The temperature is greater than the temperature at equilibrium c. It is always spontaneous in the forward direction d. It is never spontaneous in the forward direction Please use the graph below to answer questions 18, 19, and 20. B Heat Flow -> exothermic A C Temperature 18. At which point is the sample most ENDOTHERMIC? a. A b. B c. C 19. At which point is the drug making the transition from crystalline to amorphous form? a. A b. B c. C 20. At which point is the drug most energetically stable (i.e. crystalline)? a. A b. B c. C ! 6  21. Which of the following is TRUE about temperature: a. Measurement of temperature relies on volume b. Temperature is NOT heat c. Achievement of absolute zero has been impossible d. All of the above e. None of the above 22. The Zeroth Law explains which of the following: a. The importance of cold chain to prevent warming and cooling of vaccines b. Thermal equilibrium c. All of the above d. None of the above 23. A drug has a solubility of 50 mg/mL at 250°C. At 50°C, the drug has a solubility of 10 mg/mL. Using this information, what is the heat of solution for this compound? a. -2.70 kcal/mol b. -0.1987 kcal/mol c. +0.1987 kcal/mol d. +2.70 kcal/mol e. +4.54 kcal/mol 24. Trehalose is a good water replacement during quick drying, or lyophilization of therapeutic proteins, because there is ____________ entropy of the system after rehydration, thereby preventing disruption and damaging of the proteins. a. Low b. High ! 7  25. According to Boltzmann’s equation for entropy and the Third Law of Thermodynamics, for the entropy of a pure crystalline drug to be zero, you can only have how many configurations/arrangements? a. 0 b. 1 c. 10 d. infinity 26. Why do heat pads work? a. Feels warm, heat released from system, most likely due to exothermic reaction of forming stronger ionic bonds b. Feels warm, heat absorbed into system, most likely due to exothermic reaction of forming strong ionic bonds c. Feels cold, heat absorbed into system, most likely due to breaking of strong bonds into weaker intermolecular interactions of water d. Feels cold, heat released into system, most likely due to breaking of strong bonds into weaker intermolecular interactions of water 27. How can we explain why crystalline drugs are stable? a. Low number of molecular arrangements, low entropy, energetically stable b. Low number of molecular arrangements, high entropy, energetically unstable c. High number of molecular arrangements, low entropy, energetically stable d. High number of molecular arrangements, high entropy, energetically unstable 28. The 1998 failed batches of Ritonavir had two different polymorphs, one of which was less soluble and led to precipitation at high concentrations. The new batch consisting of Form II failed due to more ______________ intermolecular interactions than Form I. Form II had a _____________ melting temperature than Form I, most likely due to having more of this particular intermolecular interaction. a. Hydrophobic; lower b. Hydrophobic; higher c. Dipole-dipole; higher d. Dipole-dipole; lower e. Covalent; higher ! 8 Please use the schematic of antibody-antigen interactions to answer questions 29-30. A B C 29. Which one of the following interactions involves ion-ion interactions? a. A b. B c. C 30. Which one of the following interactions involves hydrogen bonding? a. A b. B c. C ! 9