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M3. Analyzing the Products. Unit 6 How do we control chemical change?. The central goal of this unit is to help you identify the structural and environmental factors that can be used to control chemical reactions. Recognizing interactions between reacting molecules. - PowerPoint PPT Presentation
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The central goal of this unit is to help you identify the structural and environmental factors that can
be used to control chemical reactions.
Unit 6How do we control chemical change?
M4. Selecting the Reactants
M2. Changing the Environment .
M3. Analyzing the ProductsAnalyzing the effect of charge
stability.
Exploring the influence of external factors.
Evaluating the impact of electronic and steric effects.
M1. Characterizing InteractionsRecognizing interactions
between reacting molecules.
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IUnit 6
How do we control chemical change?
Module 2: Changing the Environment
Central goal:
To analyze the effect concentration,
temperature, and nature of the solvent on reaction extent.
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The Challenge
Drugs must travel through different part of our body before
reaching their final target.
TransformationHow do I change it?
How can we predict the effect of different
environmental conditions on their structure and
properties?
How can we take advantage of this knowledge to control their behavior?
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The extent (Thermodynamics) and rate (Kinetics) to which a substance, like an drug, reacts with
another, like water, depends on the environmental conditions.
Reaction Control
We can affect and control chemical reactions by
changing the concentration of reactants and products, the temperature and pressure of
the surroundings, or the nature of the solvent in which
the process takes place.
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Fast Processes
Proton (H+) transfer in water is a fast process. Thus, we are more interested in controlling the thermodynamics than the kinetics of acid-base
reactions in liquid water.
Thus, we will focus our attention on how
to control reaction extent
in this case.
CONCENTRATION
TEMPERATURE
SOLVENT
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HA(aq) + H2O(l) A (aq) + H3O+(aq)
Let us consider an acidic drug HA that undergoes this type of reaction when dissolved in water:
Concentration Effects
For example, phenobarbital, the most
widely used anticonvulsant worldwide.
pKa = 7.4
][
]][[ 3
HA
AOHKa
What factors will determine the values of [H3O+], [A-], and [HA] at equilibrium?
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Concentration Effects
HA(aq) + H2O(l) A (aq) + H3O+(aq)
The actual concentration of each species at equilibrium depends on the values of Ka and the
initial concentrations [HA]o, [A-]o, and [H3O+]o.
][
]][[ 3
HA
AOHKa
Let us now analyze the case in which the initial values of [A-]o and [H3O+]o are negligible
compared to the value of [HA]o.
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HA(aq) + H2O(l) A (aq) + H3O+(aq)
Equilibrium Values (Acids)
If the initial concentration of HA in water is Co(mol/L) and we assume that x amount reacts with water:
Initial Co 0 1 x 10-7
Final Co- x x x + 1 x 10-7
If we assume that x << Co but x >> 1x10-7,
and we know that:
][
]][[ 3
HA
AOHKa
][
]][[
oa C
xxK
2/1)( aoao KCKCx
Higher Co Higher x
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ILet’s Think pKa = 7.4
Phenobarbital (HA) has poor solubility in water ~ 1.0 g/L.
Estimate the pH of a saturated solution of this drug.
2/1)( aoao KCKCx
M(C12H12N2O3) = 232.2 g/mol
M 103.42.232
mol 10.1 3 x
gx
L
gCo
2/14.73 )10103.4( xxx M 103.1 5 xx
Are our assumptions (x >> 1.0 x 10-7) valid?
pH = -log (x) = 4.9
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Equilibrium Values (Bases)
A similar procedure can be followed to determine the equilibrium concentrations when a base reacts
with water:
B(aq) + H2O(l) BH+(aq) + OH-(aq)
Initial Co 0 1 x 10-7
Final Co- x x x + 1 x 10-7
][
]][[
B
OHBHKb
][
]][[
ob C
xxK
2/1)/( awobo KKCKCx wba KKK
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ILet’s Think
Due to the poor solubility of its acid form (HA),
phenobarbital is often administered as an ionic salt of its basic form (A-) (100 times more soluble).
][
]][[
A
OHHAKbA (aq) + H2O(l) HA(aq) + OH-(aq)
If we know that this reaction will take place in water:
pKa = 7.4
Estimate the pH of a a saturated solution of sodium phenobarbital (100. g/L).
M(NaC12H11N2O3) = 254.2 g/mol
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A (aq) + H2O(l) HA(aq) + OH-(aq)
Initial Co 0 1 x 10-7
Final Co- x x x + 1 x 10-7
)10/101093.3()/( 4.71412/1 xxKKCKCx awobo
][
]][[
A
OHHAKbM(NaC12H11N2O3) = 254.2 g/mol
M 1093.32.254
mol 1.100 1 x
gx
L
gCo
Let’s Think
][
]][[
ob C
xxK wba KKK
41014.3][ xOHxpOH = 3.5 pH = 10.5
Higher Co Higher x
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Imagine now that you have an acid in equilibrium in aqueous solution and you decide to add more
acid. What would you expect to happen to the concentration of the other species?
HA(aq) + H2O(l) A (aq) + H3O+(aq)
Concentration Effects
]][[ 2OHHAkRate ff
]][[ 3 OHAkRate bb
Increasing [HA] increases Ratef compared to Rateb.
Kinetic ArgumentMore A- and H3O+ will be produced until the rates
become equal again.
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eq
eqeqa HA
AOHK
][
][][ 3
nHA
AOHQ
][
]][[ 3
<Actual Value
Equilibrium Value
Thermodynamic Argument
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CH
CH CH
CH
CC
C
O
OH O C
CH3
O
Imagine you have a 0.125 M aqueous solution of
aspirin, an acid drug with pKa = 3.5, in equilibrium.
Let’s Think
a) Estimate the pH of the solution.
b) Predict what would happen to the pH when:
you add more A-; you add more HA; you add OH-
you add more H2O;
Use both, kinetic and thermodynamic arguments.
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Use the simulation at
http://www.chem./arizona.edu/chemt/C21/sim
Acid
to verify your estimates and predictions.
Let’s Think
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Let’s Think
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Understanding how the concentration of one species affects the concentrations of the others is crucial to predict and control the form that a drug
will take in different parts of our body.
Drugs go through various parts of our body that
have relatively fixed but different values of pH.
How do the drugs change? Where are they
more likely to be absorbed?
Concentration Effects
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Equilibrium Ratios
The ratio of the conjugate forms of and acid-base pair is determined by the equilibrium constant:
][
]][[ 3
HA
AOHKa
][][
][
3
OH
K
HA
A a
By taking logarithms, this relationship can be transformed into:
pKapHOHKHA
Aa
]log[log][
][log 3
][
][log
HA
ApKapH
Henderson-HasselbalchEquation
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Henderson-Hasselbalch
pKapHHA
A
][
][log
For example, [HA] = [A-] when pH = pKa
How much of a an acid is in A- or HA form depends on the pH of the medium
where we put it.
When analyzing drugs, it is useful to calculate the percentage of the drug that exist in acid or basic form
in different parts of the body:
100][][
][% x
HAA
AA
pHpKa
AHA
101
100
][][
1
100
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% Ionization = % A-
if pH > pKa
[A-] > [HA]
[A-][A-] < [HA]
if pH < pKa
[HA]
pHpKaA
101
100%
Consider a drug with a pKa = 4.0.
AHA %100%
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Let’s Think
Determine the dominant form of each of these drugs in different parts of the body.
What % of the drug is ionized at each point?Where is the drug more likely to be absorbed?
Drug Stomach
(pH = 2.0)
Duodenum
(pH = 6.0)
Jejunum
(pH = 7.5)
Aspirin
(Acid, pKa = 3.5)
Phenobarbital
(Acid, pKa = 7.4)
Ephedrine
(Base, pKa = 9.6)
3.1% A- 99.7% A- 99.99% A-
4x10-4% A- 3.8% A- 55.7% A-
3x10-6% A- 3x10-1% A- 0.8% A-
pHpKaA
101
100%
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Temperature Effects
The extent of a chemical reaction can also be controlled by changing the temperature of the system.
As we have seen before, the higher T the greater
the fraction of molecules with enough energy to
react.
RT
Ea
Aek
k
T
Reaction rate increases with T.
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Temperature Effects
The effect of temperature on reaction rate depends on the activation energy Ea of the reaction.
RT
Ea
Aek
The effect is more pronounced
the higher the value of Ea.
P
R
Ep
Reaction Coordinate
Eaf
Eab
Thus, for a system in equilibrium, the forward and backward rates are not affected in the same proportion and there is a shift in the equilibrium.
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P
R
Ep
Reaction Coordinate
Eaf
Eab
Use a kinetic argument to make a prediction
about the effect on the equilibrium for these two
types of reactions.
P
R
Ep
Reaction Coordinate
Eaf Ea
b
Let’s Think
Endothermic/Exothermic processes
(Ho > 0/Ho < 0) shift towards
products/reactants at higher T.
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Thermodynamic Argument
The same conclusion can be derived by analyzing the
effect of T on the equilibrium constant:
)(RT
Gorxn
eK
Gorxn= Ho
rxn–TSorxn
)(R
S
RT
H orxn
orxn
eK
This approach allows us to see that it is actually the
sign of Horxn which
determines the effect of T.
Exothermic T K
Endothermic T K
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Use the simulation at
http://www.chem./arizona.edu/chemt/C21/sim
Acid
to determine whether the reaction is exothermic or endothermic.
Let’s Think
H2O molecules not shown
in the simulation
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Let’s Think
How does the temperature affect the pH of this solution?
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Solvent Effects
The rate and extent of a reaction can also be controlled by changing the solvent in which the
process takes place.
A given solvent can stabilize or destabilize
the reactants or products of a reaction, or the
transition state.
Thus, they may affect both reaction rate and extent.
PR
G
Reaction Coordinate
Sol1
Sol2
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Solvent Effects
In acid-base reactions, the effect of the solvent is crucial because it is actually one of the reactants:
HA + SH A + SH2+
Let′s think!Many drugs are insoluble in water. Thus, to measure their acid-base it is common to use other solvents,
such as methanol (CH3OH).
The Ka of most carboxylic drugs in CH3OH decreases by a factor of 105
compared to that in water. How do you explain it?
Formation of ions is
less likely in less polar solvents.
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Our analysis reveals the central role that environmental factors play in the extent and rate of
chemical processes:
We can control the extent and rate of chemical reactions by altering the concentration of reactants and products, modifying the temperature and pressure of the system, or changing the solvent in which the reaction takes place.
The effect of these factors is better understood by considering both kinetic and thermodynamic arguments.
Reaction Control
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I Assess what you know
Let′s apply!
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Amino Acids and ProteinsAs we know, proteins are natural polymers made of
amino acid chains.
Amine Carboxyl
Peptidebond
Amino Acid
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The average pH inside cells is close to 7.4 (similar to blood plasma). Calculate the % ionization of these amino acid residues and predict which of them will
mostly be in their ionized forms.
Let′s apply! Predict
Neutral
AcidpKa = 3.9
AcidpKa = 8.3
BasepKa = 10.8
AcidpKa = 10.1
99.96% 0.2% 11.2% 99.97%
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The presence of charged groups helps the protein to fold due to ion-ion interactions and
ion-dipole interactions between residues.
Protein folding can be represented as a chemical process:
Unfold Fold
Protein Folding
This process is affected by temperature.
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Let′s apply! Predict
The unfolded form of a protein is favored a higher temperatures.
The unfolded species does not have
catalytic properties.
How do you explain the effect of temperature on folding from the kinetic and the thermodynamic perspectives?
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Imagine someone gives you the pKa of a drug. Work with a partner making a list of the things you could tell that person about the properties of the drug outside and inside your body.
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Changing the Environment
Summary
We can control the extent of a reaction by altering the concentration of reactants and products, modifying the temperature, or changing the solvent in which the reactions takes place.
Given the expression and value of the dissociation constant for and acid or base in water (pKa, pKb), we
can evaluate things such as:
pH of solution;Degree of dissociation as function of pH;
Effect on pH of changes in C and T.
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For next class,
Investigate what structural features of substances can be used to predict their relative
acid strength.
How can we predict whether one substance will be a stronger acid than another by analyzing
their molecular structure?