Chemistry XXI The central goal of this unit is to help you identify the environmental and structural...
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Transcript of Chemistry XXI The central goal of this unit is to help you identify the environmental and structural...
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I
The central goal of this unit is to help you identify the environmental and structural factors that can
be used to control chemical reactions.
Unit 6How do we control chemical change?
In order to control chemical processes, we
need to consider two important factors:
STRUCTURE
ReactantsProducts
CONDITIONS
T and PSolvent
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IUnit 6
How 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.
FOUR MAIN MODULES
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Context
To illustrate the power of chemical ideas and models in controlling chemical change, we will focus our
attention in understanding the synthesis and properties of drugs and the way they interact inside
our body.
Why do you think drug designers and pharmacists may be interested in learning how to control chemical
reactions ?Why do
we care?
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The Problem
Drugs are chemical compounds that interact with a biological system to produce a biological response.
It is thus of central importance to know how to control their synthesis as well as their chemical
behavior inside our body.
Drugs should be able to resist decomposition inside our body and target specific
organs or sites without affecting others.
Tetracycline
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IUnit 6
How do we control chemical change?
Module 1: Characterizing Interactions
Central goal:
To characterize the nature and effect of
interactions between polar molecules and
water.
-
+
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The Challenge
Drugs interact with a variety of systems in our body: in the stomach, in the bloodstream,
inside cells. Drug action and delivery depends on the nature and effect of these interactions.
TransformationHow do I change it?
How can we predict the types of interactions
that drugs will have with their surroundings?
Recognizing potential interactions between substances is crucial in controlling chemical reactions.
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The Setting
The structure that drugs adopt inside our body depends on their interactions with substances such
as water, lipids, proteins, and nucleic acids.
How do drugs react with water?
How can we predict the outcome?
In most cases, the interaction of drugs with water produces a chemical reaction that alters the charge
distribution in these molecules. This in turn affects the way drugs interact
with other substances.
-
+
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Water molecules are polar and many chemical reactions in which these molecules participate are
driven by interactions with their positive and negative charge centers.
Polar Water
-
+
H2O - +
Proton (H+) transfer is common in water. This is a FAST process (equilibrium is reached quickly)
that leads to redistribution of charge.
H3O+
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Liquid Water
Proton transfer even occurs between two water molecules :
H2O (l) + H2O(l) H3O+(aq) + OH-(aq)
22
3
][
]][[
OH
OHOHKc
Auto-ionization is not thermodynamically favored, though. In pure liquid water:
[H3O+] = [OH-] = 1.0 x 10-7 M at 25 oC
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]][[][ 32
2 OHOHOHKK cw
Given that [H2O] does not change much by auto-ionization, we can take it as a constant and include it as part of the auto-ionization equilibrium constant:
Water’s Auto-Ionization
H2O (l) + H2O(l) H3O+(aq) + OH-(aq)
Kw = [H3O+][OH-] = (1.0 x 10-7)2 = 1 x 10-14
The value of the auto-ionization constant Kw for water at 25 oC is then:
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pH and pOH
It is common to express and monitor the concentrations of H3O+ and OH- in water solutions
using pH or pOH values:
pH = -log [H3O+]
pOH = -log[OH-]
Given that Kw = [H3O+][OH-] = 1 x 10-14
ALWAYS in water solutions:
pH + pOH = 14 in water solutions.
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Water as a ReactantMany substances react with water via proton transfer
and alter the concentration of H3O+ and OH- ions in solution (change the pH).
pH scale
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ILet’s Think
The pH of Milk of Magnesia is close to 10.5; that of our stomach is close to 2.0.
How many times larger is [H3O+] in our stomach compared to [OH-] in Milk of Magnesia?
6.311016.3
1000.1
10
10
10
10
][
][4
2
145.10
23
x
x
OH
OHpOH
pH
H3O+(aq) + OH-(aq) 2 H2O (l)Given that the reaction:
is pretty favored.
What would you expect to happen when equal amounts of these two solutions are mixed?
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Those substances that react with water via proton transfer are classified as
Brønsted-Lowry acids or bases:
Acid-Base Reactions
B-L AcidsProton Donors(Increase H3O+)
HCl(g) + H2O(l)
-
+
B-L BasesProton Acceptors
(Increase OH-)NH3(g) + H2O(l)
-
+
Cl (aq) + H3O+(aq)
Hydronium Ion
NH4+(aq) + OH (aq)
Hydroxide ion
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ILet’s Think
Predict the outcome of the reaction of these drugs with water. Determine whether they behave as
acids or bases in this solvent.
B-L AcidProton Donor
+ H3O+(aq) -+ H2O(l)
Aspirin
+ H2O(l)
Ephedrine
+ OH-(aq)
B-L BaseProton Acceptor
2+
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Conjugate Species
HCl(g) + H2O(l) Cl (aq) + H3O+(aq)
Conjugate AcidBaseConjugate BaseAcid
In these reactions, new acids and bases are formed:
Acid
Conjugate AcidBase
Cl-(aq) + H2O HCl(aq) + OH-(aq)
Conjugate BaseBase Conjugate Acid
NH3(g) + H2O(l) NH4+(aq) + OH-(aq)
What happens
in this case?
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ILet’s Think
The solubility and activity of most drugs strongly depends on their acid-base properties.
Identify all of the conjugate pairs in these acid-base equilibria involving common drugs?
C4H4N2O3(aq) + H2O(l) C4H3N2O3 (aq) + H3O+(aq)
C17H19NO3(aq) + C6H8O6(aq) C17H20NO3+(aq) + C6H7O6(aq)
Barbituric Acid Barbiturate Ion (Base)
Morphine
(Base)
Morphine Ion
(Acid)
C9H8O4(aq) + C6H7O7+(aq) C9H7O4
(aq) + C6H8O7(aq) Acetylsalicylic
AcidAcetylsalicylate Ion
(Base)
Ascorbic Acid
Ascorbate Ion (Base)
Citrate Ion (Base)
Citric Acid
Base Acid
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StrengthThe extent to which an acid or base reacts with water
determines its strength.
HCl(g) + H2O(l) Cl (aq) + H3O+(aq)
HCl is a strong acid.
1][
]][[ 3
HA
AOHKa
For a strong acid HA:
HA(aq) + H2O(l) A-(aq) + H3O+(aq)
HCl, HNO3, H2SO4
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Weak acids are much less than 100% ionized in water.
1][
]][[ 3
HA
AOHKa
Strength
Similar ideas can be applied to evaluate the strength of basic substances.
HA(aq) + H2O(l) A (aq) + H3O+(aq)
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HA(aq) + H2O(l) A (aq) + H3O+(aq)
In general, we can use the value of these dissociation constants to judge acid/base strength.
Strength
If we take, Ka x Kb for a conjugate pair, we see that:
The larger the value of Ka (the stronger the acid), the smaller Kb (the weaker the conjugate base).
][
]][[ 3
HA
AOHKa
][
]][[
A
OHHAKb
wba KOHOHA
OHHAx
HA
AOHKK
]][[][
]][[
][
]][[ x 3
3
A (aq) + H2O(l) HA(aq) + OH-(aq)
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ILet’s Think
C4H4N2O3/C4H3N2O3
Identify the “strongest” species
in each pair.
C17H20NO3+/C17H19NO3
C9H8O4/C9H7O4
Barbituric/Barbiturate
Morphine Ion/Morphine
Acetylsalicylic/Acetylsalicylate
Ka = 9.77 x 10-5
Kb = 7.4 x 10-7
Ka = 3.16 x 10-4
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IpKa and pKb
It is common to express the strength of an acid or a base using these quantities:
pKa = - log (Ka)
pKb = - log (Kb)
The larger the value of pKa, the weaker the acid.The larger the value of pKb, the weaker the base.
For a conjugate acid/base pair:
pKa + pKb = 14
Let’s Think
pKa = 7.4pKa = 8.1
Pentobarbital Phenobarbital
Which is a stronger acid?
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Let′s apply!
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Drugs, Drugs, Drugs
Over 70% of the drugs in the market have acid-base properties. Of these, close to 60% are bases, around
25% are acids, and the rest are amphoteric.
The strongest acids tend to be carboxylic acids (pka ~ 4) ; the weakest tend to be
barbiturates.
pKa ~ 8
Most of the basic drugs contain amine groups.
pKa ~ 9
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The analysis of the acid-base properties of drugs is crucial to understand and control their
behavior in our body.
For example, in the stomach, drugs such
as morphine and aspirin mainly exist in their “acid” form.
MorphineC17H20NO3
+
AspirinC9H8O4This determines which
will be absorbed faster.
Drugs’ Behavior
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MorphineC17H20NO3
+
AspirinC9H8O4
Let′s apply! Predict
Which of these two drugs will be absorbed at a faster rate through stomach cell membranes
(made of lipids)?
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Drugs’ Behavior
Ionic forms are more likely to be soluble in water and insoluble in cell membranes, made of non-polar lipids. Thus, charged species tend to be
absorbed at a slower rate.
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Let′s apply! Infer
OH
CHCH
C
CH CH
C NH
C
CH3
O
CH
CH CH
CH
CC
C
O
OH O C
CH3
O
CH
C
CH CH
C
CH
CH
CH3
C OH
O
CH2
CHCH3
CH3
Tylenol
Aspirin
Ibuprofen
Which proton are these drugs likely to transfer
to water? Write the chemical equation of
their reaction with water.
All of these analgesics are acidic.
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Let′s apply! Identify
OH
CHCH
C
CH CH
C NH
C
CH3
O
CH
CH CH
CH
CC
C
O
OH O C
CH3
O
CH
C
CH CH
C
CH
CH
CH3
C OH
O
CH2
CHCH3
CH3
Tylenol
Aspirin
Ibuprofen
Which is stronger, the acid form of each analgesic or its
conjugate base?
pKa = 3.5pKa = 4.5
pKa = 9.1
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Discuss with a partner what are the main differences between a weak
acid and a strong base.
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Characterizing Interactions
Summary
Many substances react with water via proton transfer and alter the concentration of H3O+ and OH- ions in
solution (change the pH).
These reactions are driven by the interactions between + and – charge centers.
-
+
Brønsted-Lowry AcidsProton Donors(Increase H3O+)
Brønsted-Lowry BasesProton Acceptors
(Increase OH-)
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Dissociation
Although acids and bases change [H3O+] and [OH-] in water, the concentration of these ions is related by:
Kw = [H3O+][OH-] = 1 x 10-14 in water at 25 oC.
We can use the value of equilibrium dissociation constants to judge acid and base strength:
HA(aq) + H2O(l) A (aq) + H3O+(aq)][
]][[ 3
HA
AOHKa
][
]][[
B
OHBHKb
B(aq) + H2O(l) BH+(aq) + OH-(aq)
Acid Conjugate Base
Base Conjugate Acid
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For next class,
Investigate how changes in concentration and temperature affect acid-base reactions.
How does chemical equilibrium shift in an acid-base reaction when the concentration of
reactants or products are changed?