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.
But the product BH+ is now capable of losing its newly-acquired proton to another acceptor, and is therefore potentially another acid:
conjugate acid-base pair conjugate acid-base pair CH3 COOH + N H3 Acetic acid Ammonia (acid) (base) CH3 COO- + N H4 + Acetate Ammonium ion ion (c onjugate bas e (c onjugate acid ac etic acid) of ammonia)
We can use curved arrows to show the flow of electrons in an acid-base reaction.
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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.
+ HSO4 -
Q. 2 Does proton transfer to an amide group occur preferentially on the amide oxygen or the amide nitrogen?
An important part of understanding chemistry is being able to recognize what substances will exhibit acidic and basic properties in aqueous solution
Henderson-Hasselbalch Equation
According to the Brnsted-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 will use KA for the acid dissociation constant. Taking the negative log of both sides of the equation gives:
Application of Acid Base Concept and Handerson Haselbach Equation In Field or Practice
The imidazole ring has one nitrogen that has a double bond to it (its 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 pKas 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. 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 lets examine the solution behavior of histamine. Well start at pH = 1 and gradually raise the pH by adding hydroxide, i.e well 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 are equal and the pH equals the pKa. As we continue to raise the pH to physiologic pH of 7.4 more and more 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
APPLICATION
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?
(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.
APPLICATION 3
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. 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.
APPLICATION
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.
HOME WORK
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 (pKas 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