Exam I: EWG, EDG, Acid-Base Chem Flashcards
What effects do functional groups have on drugs activity in the body?
- Drug transport through the body
- Mechanism to bind to receptors
- How it causes a biological response
- How it undergoes metabolism
- How it is excreted
- Drug stability during storage
Tautomerization is the equilibrium reaction between a ____ their less stable ____ .
Tautomerization is the equilibrium reaction between a Keto their less stable Enol.
What is the field effect?
Polarization experience through space rather than bonds
ex. An oxygen atom on a carbonyl can pull electron density from a nitrogen a few carbons away
What is the inductive effect?
Polarization due to the electronegativity difference between bonded atoms
How can an alkyl group contribute to delocalizing a neighboring positive charge? What is this process called?
An alkyl can break a hydrogen bond so that the newly freed electrons can stabilize a cation
This is called hyperconjugation.
Alkyl groups are EWG or EDG? Why?
Alkyl groups are electron donating groups through induction.
There is a partial negative charge on the carbon due to its pull on electron density from bonded hydrogen atoms.
-CH3, -CH2, CH, C-R. Which group would be the best electron donating group?
-CH3 because it has the greatest number of hydrogen bonded to it
-NO2, -F, CO2H. Put in order from most to least EWG.
-NO2 > CO2H > F
Would a ketone or a carboxylic acid have greater electron withdrawing potential? Why?
A ketone would have greater electron withdrawing potential.
Carbonyls attached to electronegative heteroatoms have weaker withdrawing power due to resonance which decreases the positive charge that builds on the carbonyl carbon.
Put the halogens in order of withdrawing power (-I, -Br, -F, -Cl). Explain this order.
-F > -Cl > -Br > -I
Larger atoms have lower electronegativity due to less shielding of the positive charge of the nucleus.
What type of environment do drugs exert their biological activity?
Aqueous
Bronsted and Lowry acid and base
Acid - Donates proton (hydrogen)
Base - Accepts proton (hydrogen)
Do strong or weak hydrogen bonds make strong acids? What heteroatoms typically form the weakest bonds with hydrogen?
Weak hydrogen bonds make stronger acids
Oxygen, sulfur, nitrogen and phosphorus tend to form the weakest bonds to hydrogen
If a compound (not an atom) is not an acid nor a base then it is considered positive, negative or neutral?
Neutral
Lewis acids and bases
Lewis acid - electron acceptor (electrophile)
Lewis base - electron donor (nucleophile) - must have a lone pair
What is the equation for Ka?
Ka = [H+][A-]/[HA]
What is the equation for pKa?
pKa = -log(Ka)
Highest possible Ka value? Lowest possible pKa value?
Ka = 1 for the dissociation of hydronium ion (H3O+)
pKa = 0
High Ka –> Strong or weak acid?
High Ka = strong acid
Low pKa –> Strong or weak acid?
Low pKa = strong acid
What is the Kw of autoionization of water forming H3O+ and OH-?
1 x 10^-14
What are the three equations for gibbs free energy discussed? Two are ΔG = and one is pKa =.
ΔG = -RTlogKa
ΔG = Total energy of products - Total energy of reactants
pKa = ΔG/RT
Value for R gas constant. Include units.
1.987 cal/mol⋅K
Unit for temperature in gibbs free energy equations. Conversion to this unit.
Kelvin (K)
T(°C) + 273.15 = T(K)
Gibbs free energy and pKa are _____ related?
Gibbs free energy and pKa are proportionally related
↑ ΔG = ↑ pka
F3CO2H vs H3CO2H. Which is a stronger acid?
F3CO2H is a stronger acid
In water what are the ranges for pka and pkb?
0 - 14
High kb = Strong or weak base?
Strong base
Low pkb = Strong or weak base?
Strong base
pH can be compared to pka and pkb. (True/False)
False
pH can only be compared to pKa
If pkb (base) = 4, what is the pka of the conjugate acid?
pka + pkb = 14 therefore, pka = 10
In a molecule there are two substituents. Group 1 (pka = 9) - Group 2 (pka 4). Which group would donate a proton first?
Group 2 because it is more acidic
In a molecule there are two substituents. Group 1 (pkb = 5) - Group 2 (pkb = 10). Which group would gain a proton first?
Group 1 because it is more basic
What is a salt?
A salt forms when an acid reacts with a base
Ionized form
Why are a vast majority of drugs in the salt form?
Charged compounds typically have good water solubility
Usually have a crystalline structure
Good bioavailability
What is the henderson-hasselbalch equation?
pka = pH + log[HA]/[A-}
What is the percent ionization equation? Define what an ionized molecule is.
%ionization = [ionized]/[ionized+nonionized]
The ionized molecule has a charge does not matter if it is the acid or base form
NH4+ (Ionized acid) - OH- (ionized base)
What equation is used to find the concentrations of the ionized and nonionized molecules?
Henderson-hasselbalch equation
pka = pH + log[HA]/[A-}
What are the steps to find the percent of acetic acid ionized at pH 5? Given acetic acid pka = 4.
- Write down the equation to visual the ionized form
AcOH –> AcO- + H+ - Use pka = pH + log[HA]/[A-} to find the concentrations
AcOH/AcOH- = 1/10 - Calculate the percent ionization
10/1+10 x 100% = 90.9%
What are the pH within the following body compartments: stomach, intestine (duodenum), intestine (lower ileum), circulating fluids (i.e. plasma, CSF)?
Stomach - pH 1
Intestine (duodenum) - pH 5
Intestine (lower ileum) - pH 8
Circulating fluids - pH 7
pka of water H-OH without any added groups?
pka 14
pkb of ammonia H-NH2 without any added groups?
pkb 5
How do electron withdrawing groups affect acid-bases?
EWG can stabilize conjugate bases of an acid so the acid becomes stronger (lower pKa)
Put these EWG in order from strongest. Carbonyl, sulfonyl, aryl.
- Sulfonyl SO2
- Carbonyl CO
- Aryl = phenyl group
Why is aniline (benzene with -NH2) a weaker base than ammonia (NH3)?
EWG delocalize lone pairs weakening the basicity of aniline
Why does acetamide behave as an acid?
Acetamide H3C C=O NH2
Carbonyl delocalizes the lone pair on the nitrogen giving it a positive charge through resonance
Use the pka-pka scale to determine the pka or pkb of ph-o-ph.
This compound is neither an acid nor a base because there is no hydrogen to donate or any available lone pairs to accept a hydrogen.
Reference notes on how to determine pka of a compound that must be converted to conjugate acid or base to solve.
Beneath “how could you predict the pka for this compound?”
Note: to predict pka/pkb the compound must be neutral (no charge)
Why are imines (H3C C=NH CH3) less basic than amines (-NH2)?
Sp2 orbitals are smaller than sp3 orbitals
Sp2 orbitals have greater shielding of the positive charge of the nucleus
Imines have a greater hold on their electrons than amines
Is N(CH3)3 an acid or a base? Compare to ph-o-ph
This is a base.
Note that nitrogen is not a highly electronegative atom so a hydrogen atom can be added to nitrogen and acquire a positive charge
ph-o-ph is a neutral compound because oxygen is too electronegative to donate electrons to a hydrogen and acquire a positive charge
Effect of H or Alkyl (-CH3) to pka? As first and second group.
H or Alkyl (-CH3) groups do not have an affect on pka
H2O and Ethanol have the same pka
Effect of aryl, C=C (double bond), C=N, N=N, C (triple bond)? As first and second group.
First group - 5
Second group - 2
(toward pka end) = more acidic
Effect of C=O or Ar C=O? As first or second group.
First group - 10
Second group - 5
(toward pka end) = more acidic
Effect of SO2 or ArSO2? As first or second group.
First group - 15
Second group - 7
(toward pka end) = more acidic
pka/pkb of aniline
pkb 10
pka/pkb of MeSo2-NH2
pka 9
In amidine, which nitrogen is more basic (imine or amine)?
The imine nitrogen is the stronger base because resonance stabilizes the conjugate acid
See note for a visual or write down the reaction
If an EWG like a carbonyl is added to the imine nitrogen in amidine, what would happen to the pkb? Increase or decrease?
The nitrogen would become less basic so the pkb would increase
