CHEM 150 Chemistry Primaquine Molecule Worksheet

Chem 150/160, Fall 2019
Name: _______________________________
Final Assignment
In this assignment, you will be exploring a single drug from the World Health Organization (WHO) list of
essential medicines. These molecules are important to the establishment of a medical system that can serve
the needs of a majority of its population. You should have picked a molecule in class on Monday, Dec 9. If you
do not have a molecule, contact your instructor immediately.
This project is taking the place of a traditional exam, and will hopefully give many of you the opportunity to
showcase what you’ve learned this semester without the constraints of an exam setting. You are allowed to
use any resources you see fit throughout the project. I ask, though, that you be sure to cite your sources for
each answer, and credit anyone you worked with. You must also show your work for all calculations you do.
1. Introduction
What is the name of your molecule? Does it have any other generic or trade names? (2 points)
Briefly, what is it used for? (3 points)
Draw a full bond-line structure of your molecule. (2 points)
Draw a full Lewis structure of your molecule, showing all atoms, bonds, and lone pairs. If formal charges are
present (and they may or may not be), show these as well. (5 points)
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For each non-terminal atom above, identify the hybridization and geometry. For example, the oxygen in water
has sp3 hybridization and a bent geometry. (You may use the space below for this task, or you may annotate
the structure you drew above. Just be sure that your intentions are clearly communicated.) (5 points)
Identify the most polar bond or bonds in the above structure. (2 points)
Identify which atom in the above structure is the most electronegative. (2 points)
Identify which atom in the above structure has the largest atomic radius. (2 points)
How many s bonds are there in the above structure? (3 points)
___________
How many p bonds are there in the above structure? (3 points)
___________
How many
sp3
non-terminal atoms are there in the above structure? (3 points)
___________
How many sp2 non-terminal atoms are there in the above structure? (3 points)
___________
How many sp non-terminal atoms are there in the above structure? (3 points)
___________
Are there any atoms that do not conform to the octet rule in the above structure? If so, which? (2 points)
___________
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2. Physical Properties
Look up the average atomic weight of each element in your compound and list them below. Use as many
significant figures are you can. A good source for this data is ptable.com. (3 points)
Element
Mass
Element
Mass
Calculate the total average molecular mass of your compound using the above values. Pay special attention to
significant figures here and show your work. (5 points)
Which element is limiting the precision of your calculation? (2 points)
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The “Rules of 5” is a set of criteria that describe what most orally available drugs tend to have in common.
Does your molecule follow each of the following criteria?
A mass below 500 g/mol. You just determined the molar mass of your drug. Restate it and also state whether it
fits this criterion. (1 point)
5 or fewer hydrogen bond donors. How many does it have? (3 points)
10 or fewer hydrogen bond acceptors. How many does it have? (3 points)
The last of the rules of 5 is called “logP”, and relates to the relative solubility in water versus octanol. What
intermolecular forces will be present between your molecule and water? Drawings may help. (5 points)
Look up octanol. How do you think the intermolecular forces will be different? Drawings may help. (5 points)
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3. Dose
One of the most common routes of administration for a drug is in the form of a pill. For the sake of this
assignment, let’s assume that the active dose of your drug molecule is 0.050 millimoles of drug per kilogram of
patient.
How many milligrams of drug should a 62 kg human take? (Incidentally, this is the global average for human
mass) (5 points)
Most pills come in fixed sizes and have a fair amount of mass that isn’t drug – a standard pill is only about 33%
active ingredient by mass. If you wanted to only take 2 pills per dose, how big would each pill need to be? Do
you think this is a reasonable size? (3 points)
The fasting stomach contains about 35 mL of water. What would be the molarity of drug in the patient’s
stomach if the pills dissolved completely? (5 points)
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The volume of human blood is about 4.7 L. As the drug moves from the stomach to the blood, it will become
more dilute. What will be its final molarity in the blood? (5 points)
4. Metabolism
In addition to removal by the kidneys, many drugs are processed in the liver by a type of enzyme called
cytochrome P450. The general equation for this metabolism is as follows:
Drug–H(aq) + O2(g) + NADPH(aq) + H3O+(aq)
Drug–OH(aq) + 2 H2O(l) + NADP+(aq)
To think about this oxidation reaction, draw the molecular orbital diagram for molecular oxygen. Identify its
bond order, and indicate which orbital(s) are the HOMO and which are the LUMO. (3 points)
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Look up the molecular orbital diagram for water. Is the HOMO of water higher or lower in energy than that of
O2? How do you know? (5 points)
Showing your reasoning, provide the oxidation state of oxygen in O2 and in H2O based on the discussion in
chapter 13.6. Was oxygen oxidized or reduced in the conversion to water? (5 points)
The reaction above is favored at body temperature. What is the sign of ∆S in this reaction? How do you know?
(3 points)
What is the sign of ∆H in this reaction? How do you know? Does this mean the reaction is endothermic or
exothermic? (3 points)
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You’re worried that a fever might interfere with drug metabolism. Would increasing temperature make this
reaction more or less favorable? How do you know? (3 points)
Body temperature is 37°C, and a dangerously high fever is 42°C. Based on these temperatures, do you think
the metabolism reaction above will be significantly affected by a fever? Why or why not? (Hint: It may help to
remember that it is best to use absolute temperature in scientific arguments.) (2 points)
5. Formulation
Many pharmaceutical compounds are formulated as salts to improve shelf-stability,
water solubility, and the dynamics of the molecule within the body. You’ve decided to
reformulate your molecule as a diglycine salt. The structure of diglycine is shown to
the right.
O
HO
H
N
NH2
O
The oxygen end of diglycine has a pKa of 2.3, and the nitrogen end has a conjugate acid pKa of 9.6. Draw the
two reactions described by these pKa values, placing each pKa value over the relevant reaction arrow. (6
points)
O
HO
H
N
NH2
O
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Diglycine also has the potential to self-react in water. Which side of the equilibrium below will be favored?
Justify your choice. (3 points)
O
HO
O
H
N
NH2
O
O
H
N
NH3
O
That deprotonated carboxylic acid is interesting. Using resonance structures and drawings of p orbitals,
describe the bonding and distribution of charge on a deprotonated carboxylic acid. (3 points)
O
O
It turns out that there is an energetic barrier between two conformations of diglycine:
O
HO
O
H
N
NH2
O
HO
H
N
O
NH2
This is usually justified by saying that nitrogen atoms next to carbonyls can rehybridize to partially π bond with
the C=O. Why would this justification explain the barrier to rotation around the C–N bond? Drawings may be
helpful to make your case. (3 points)
THE END.
Thanks for a great semester! I hope you all have a wonderful break.
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