ACID AND BASE

Q.1 What is an acid?

An acid is a substance that yields an excess of hydrogen ions when dissolved in water.

There are three important points to understand about hydrogen in acids:

•Although all Arrhenius acids contain hydrogen, not all hydrogen atoms in a substance are capable of dissociating; thus the -CH3 hydrogens of acetic acid are “non-acidic”. An important part of knowing chemistry is being able to predict which hydrogen atoms in a substance will be able to dissociate.

•Those hydrogens that do dissociate can do so to different degrees. The strong acids such as HCl and HNO3 are effectively 100% dissociated in solution. Most organic acids, such as acetic acid, are weak; only a small fraction of the acid is dissociated in most solutions. HF and HCN are examples of weak inorganic acids.

•Acids that possess more than one dissociable hydrogen atom are known as polyprotic acids; H2SO4 and H3PO4 are well-known examples. Intermediate forms such as HPO4

-2 , being capable of both accepting and losing protons, are called ampholytes.

Just as an acid is a substance that liberates hydrogen ions into solution, a base yields hydroxide ions when dissolved in water.

Sodium hydroxide is an Arrhenius base because it contains hydroxide ions. However, other substances which do not contain hydroxide ions can nevertheless produce them by reaction with water, and are therefore classified as bases.

Neutralization

Acids and bases react with one another to yield two products: water, and an ionic compound known as a salt. This kind of reaction is called a neutralization reaction.

The product of the hydrogen ion and hydroxide ion concentrations in any aqueous solution will always be 1 x 1014 at 250 ±C.

In other words,

This expression is known as the ion product of water, and it applies to all aqueous solutions, not just to pure water.

It implies that if the concentration of H+ is large, that of OH- will be

small, and vice versa. This means that H+ ions are present in allaqueous solutions, not just acidic ones.

The proton donor-acceptor concept of acids and bases

Arrhenius viewed acids and bases as substances which produce hydrogen ions or hydroxide ions on dissociation.

J.N. Bronsted proposed - An acid is a proton donor; a base is a proton acceptor.

These definitions carry a very important implication: a substance cannot act as an acid without the presence of a base to accept the proton, and vice versa.

A reaction of an acid with a base is thus a proton exchange reaction; if the acid is denoted by AH and the base by B, then we can write a generalized acid-base reaction as-

But the product BH+ is now capable of losing its newly-acquired proton to another acceptor, and is therefore potentially another acid:

Conjugate Acids & Bases

– Conjugate baseConjugate base: The species formed from an acid when it donates a proton to a base.

– Conjugate acid:Conjugate acid: The species formed from a base

when it accepts a proton from an acid.

NH4+CH3COOH CH3COO-NH3+ +

Acetic acidAmmonia

(acid)

conjugate acid-base pair

Acetate ion

Ammoniumion

(base) (conjugate baseacetic acid)

(conjugate acidof ammonia)

conjugate acid-base pair

– We can use curved arrows to show the flow of electrons in an acid-base reaction.

CH3-C-O

O

H N HH

H CH3-C-O -

O

H-N-HH

H+ +

Acetic acid(proton donor)

Acetate ion

:

:: ::

:: :: :

Ammonia(proton acceptor)

Ammoniumion

• Many organic molecules have two or more sites that can act as proton acceptors. The favored site of protonation is the one in which

the charge is more delocalized.

CH3-C-O-H

O

+ H2SO4 CH3-C-O-HH

O+

+ HSO4-orCH3-C-O-H

HO+

A(protonated

on thecarbonyl oxygen)

B(protonated

on thehydroxyl oxygen)

Q.1 Which oxygen of a carboxylic acid is protonated?

Q. 2 Q. 2 Does proton transfer to an amide group occur preferentially on the amide oxygen or the amide nitrogen?

CH3-C-N-H

H

+HCl

+

CH3-C-N-H

OH

H

CH3-C-N-H

H

H+

+ Cl -or

A(protonation

on theamide oxygen)

B(protonation

on theamide nitrogen)

Acetamide(an amide)

OO

An important part of understanding chemistry is being able to recognize what substances will exhibit acidic and basic properties in aqueous solution

Acid-Base Behavior and the Henderson-Acid-Base Behavior and the Henderson-Hasselbach EquationHasselbach Equation

Henderson-Hasselbalch EquationAccording to the Brønsted-Lowry theory of acids and bases, an acid (HA) is capable of donating a proton (H+) and a base (B) is capable of accepting a proton. After the acid (HA) has lost its proton, it is said to exist as the conjugate base (A-). Similarly, a protonated base is said to exist as the conjugate acid (BH+).The dissociation of an acid can be described by an equilibrium expression:

We can describe this relationship with an equilibrium constant:

we will use KA for the acid dissociation constant. Taking the negative log of both sides of the

equation gives:

This can be rearranged:

By definition, pKA = -logKA and pH = -log[H+], so

This equation can then be rearranged to give the Henderson-Hasselbalch equation:

Application of Acid Base Concept and Handerson Haselbach Equation In Field or Practice

Histamine is a fairly straight forward example of a base with several protonation sites. Typically, primary, secondary and tertiary alkyl amines are strong bases and their protonated forms are thus weak acids.

Which Ring is this

The imidazole ring has one nitrogen that has a double bond to it (it’s an imine). These sp2 hybridized nitrogens are weak bases so their protonated form (i.e. their conjugate acid) is usually a strong organic acid with pKa’s in the 3-4 range. In the case of imidazole itself, however, the pKa is ~6.9 due to the influence of the other double bond. Adding the electron withdrawing alkyl ammonium 2 carbon side chain drops this to the 5.8 observed for histamine.

Q. 4. Tell the Significance of Acid Base and Handerson Hasselbach eqn-

Check with simple example of HISTAMINE

The second nitrogen in the imidazole ring is protonated (but neutral) and is a very weak acid with a pKa in the 14-15 range..

So now let’s examine the solution behavior of histamine. We’ll start at pH = 1 and gradually raise the pH by adding hydroxide, i.e we’ll do a titration. At this very low starting pH the imine nitrogen on the imidazole ring:

As we start to raise the pH with hydroxide, at pH = 5.8 the concentrations of acid and conjugate base areequal and the pH equals the pKa. As we continue to raise the pH to physiologic pH of 7.4 more andmore of the acid is converted into the conjugate base. At pH = 1 :

That means that at physiologic pH, the concentration of the protonated primary amine form of histamine (i.e. the conjugate base) is the predominant species in solution.

Raising the pH still further will eventually result in removing the final proton from the imidazole nitrogen and at pH 15.7 the predominant form in solution is the conjugate base of that acid

A pharmaceutical molecule with antifungal properties is only active when deprotonated and negatively charged (A-). The protonated state (HA) is inactive. If the pKa of this drug is 10.0, (a) calculate the ratio of protonated to deprotonated compound at physiological pH (7.4). (b) Is this drug likely to be a useful pharmaceutical agent?

APPLICATION 2

(a) calculate the ratio of protonated to deprotonated compound at physiological pH (7.4). Since we are given both the pH and pKa of the compound, we can use the Henderson-Hasselbalch equation to solve for the ratio of [HA] to [A-].

pH = pKa - log([HA] / [A-]) log([HA] / [A-]) = pKa – pH log([HA] / [A-]) = 10.0 – 7.4 log([HA] / [A-]) = 2.6 ([HA] / [A-]) = 398.11 ([HA] / [A-]) = 400

The ratio of protonated (inactive) compound to deprotonated (active) compound is 400 to 1 at physiological pH.

(b) Is this drug likely to be a useful pharmaceutical agent? Since the vast majority of the compound is in the inactive form at physiological pH, it is unlikely to be a useful pharmaceutical agent.

However, if the active compound is highly potent, it is possible that a small fraction of active compound is sufficient for useful antifungal activity.

Absorption of aspirin (acetylsalicylic acid, C9H8O4,) into the bloodstream occurs only when the molecule is in its conjugate base form.

(a) If a patient takes two tablets of aspirin (325 mg each), how many grams of aspirin are available for immediate absorption in the stomach? The pH of the stomach is 1.6, and the pKa of aspirin is 3.5.

APPLICATION 3

Henderson-Hasselbalch equation to solve for the ratio of [HA] to [A-]

The ratio of protonated aspirin to its conjugate base is 79 to 1. So one-eightieth (1/80) of the total aspirin taken will be in the conjugate base form and available for immediate absorption in the stomach: 2 x 325 mg x (1/80) = 8.75 mg 9 mg

It will be more in small Intestine.

57-year-old male executive, arrives at the pharmacy for his blood pressure medications (enalapril and amlopidine) and a new prescription for famotidine. He wants to know if he can take all three medications at the same time.

APPLICATION 4

HOME WORKDO YOU WANT ANY GUESS…..

Complete the table below considering all three of the drug molecules

• Famotidine (pKa = 10.5) is sold as the hydrochloride salt. Is the molecule as drawn acidic, basic or neutral? Given that famotidine decreases the secretion of acid into the lumen of the stomach (stomach pH = 3.5 in presence of famotidine), will famotidine be ionized or unionized in the stomach?

• Considering the structural features of enalapril (pKa’s of 3.0 and 5.5) and amlopidine (pKa = 9.0), determine the ionization state of each of these agents in the stomach (pH = 1) in the absence of famotidine and in its presence (stomach pH = 3.5).

Thank God

Finished