What is acid-base chemistry? |

Structure and Functions

The existence of acids and bases is critical to the functioning of the human body. An acid is a compound that contains hydrogen, can accept unshared electron pairs, has a pH that is less than 7, and is water-soluble. A base is a compound that contains a hydroxyl (OH) group, can give up unshared pairs of electrons, can accept protons, has a pH that is greater than 7, and is water-soluble. An acid and a base can react together to form a salt.

Both acids and bases can be classified further as either “hard” or “soft.” Bases are classified as soft if they have high polarizability and low electronegativity, are easily oxidized, or have low-energy, empty orbitals. Opposite properties tend to classify them as hard bases. Hard acids are those that have low polarizability, small size, and a high oxidation state (valence) and that do not have easily removed outer electrons. Soft acids possess reversed properties. Generally, a hard acid always reacts with a hard base and a soft acid always reacts with a soft base. The reaction of a hard acid (or base) with a soft base (or acid) is always unfavorable (absorbs energy). The hard-and-soft concept of acids and bases is used only as a way to classify and predict reactions. In the acid-base reactions of a living being, however, one must consider acids as proton donors and bases as proton acceptors.

A neutral solution is defined as one whose proton (hydrogen ion) and hydroxyl concentrations are equal. A solution that has more protons than hydroxyl groups is acidic, while a solution with more hydroxyl ions than protons is basic. Expressing the hydrogen ion concentration in moles per liter is rather complex. Instead, the pH of a solution is used. The pH is the negative logarithm of the hydrogen ion concentration. Neutral solutions have a pH of 7, acidic solutions have a pH that is less than 7, and basic solutions have a pH that is higher than 7. Thus, a pH of zero is strongly acidic and a pH of 14 is strongly basic.

Buffers are solutions whose contents allow very small changes in pH upon the addition of small quantities of acids and bases. Usually, buffers are solutions of a weak acid and one of its salts, or they are solutions of a weak base and one of its salts. A buffer becomes ineffective when there are no more anions (if a weak acid is part of the buffer) or cations (if a weak base is involved). At this point, the buffer capacity of the solution is said to be exceeded.

General acid catalysis is a process in which partial proton transfer from an acid lowers the free energy of a reaction’s transition state. A reaction can also be accomplished by a general base catalysis, in which a base enhances the rate by partially stealing a proton. Such reactions often have such a high activation energy that they cannot take place unless the specific catalysis is involved.

Many well-known substances encountered in everyday life are weak acids or bases. Aspirin (acetylsalicylic acid, a headache remedy), phenobarbital (a sedative), niacin (nicotinic acid, vitamin B), and saccharin (an artificial sweetener) are weak acids. The majority of drugs and narcotics (such as heroin, cocaine, and morphine) in their free-base states are weak bases. Among the components of deoxyribonucleic acid (DNA), which is a polymer of deoxyribonucleotide units, are nitrogenous bases, the purines and pyrimidines. An amino acid is either neutral, acidic, or basic, depending on the chemical group found in its side chain.

The normal metabolic processes of the body result in the continuous production of acids, such as carbonic acid (H2CO3), phosphoric acid (H3PO4), lactic acid, and pyruvic acid. In cellular oxidations, the main acid end product is carbonic acid, with 10 to 20 moles formed per day. In terms of acidity, this amount is equivalent to 1 to 2 liters of concentrated hydrochloric acid. Although some alkaline end products are also formed, the acid type predominates, and the body is faced with the necessity of continually removing the large quantities of acids that are formed within cells. The greatest restriction is that these products should be transported to the organs of excretion (via the extracellular fluids) with a minimal change in the hydrogen ion concentration.

Most biochemical processes are extremely sensitive to the level of hydrogen ions. The enzymes and other proteins involved in biological reactions, as well as many of the smaller molecules, are weak electrolytes whose state of ionization is a function of the hydrogen ion concentration. Most enzymes are active only within a narrow pH range, usually from 5 to 9. At a pH other than the optimum one, the binding of substrates to enzymes, the catalytic activity of enzymes, and changes in protein structure are seriously affected. Since the catalytic properties of enzymes are dependent on their state of ionization, it is not surprising that living cells cannot tolerate more than very minor changes in hydrogen ion levels. As a result, biological fluids are in general strongly buffered, so that their pH is maintained within narrow limits under physiological conditions.

Blood is buffered by plasma proteins and by hemoglobin, which can either accept or donate protons. The role of buffers can be understood by the following example. The addition of 0.01 mole hydrochloric acid in 1 liter of blood lowers the pH only from 7.4 to 7.2. When added to an isotonic saline (sodium chloride) solution, the same amount of hydrochloric acid lowers the pH from 7.0 to 2.0, since the saline solution has no buffering capacity. Another example of the effectiveness of the blood plasma indicates that 1.3 liters of concentrated hydrochloric acid are needed to drop the pH of the whole 5.5 liters of blood of an average human being from 7.4 to 7.0.

Metabolism in tissues leads to the production of carbon dioxide (CO2), which, when dissolved in water, forms carbonic acid and the following equilibrium:

Carbon dioxide
enters the bloodstream from tissues and is exchanged in the lungs for oxygen, which is then transported throughout the body by the hemoglobin in the blood. The fact that the ratio of bicarbonate to carbonic acid is relatively high (10:1) seems to put this buffer well outside its maximum capacity. Nevertheless, the system is appropriate because the need to neutralize excess acid (such as lactic acid, which is produced during exercise) is much greater than the need to neutralize excess base. The excess bicarbonate serves this purpose. Strenuous exercise also leads to an increased formation of carbon dioxide by body tissues, which is accumulated in the air spaces of the lungs. Under normal circumstances, the bicarbonate in the blood buffer will lead to a shifting in the equilibrium toward the optimum 7.4 value. Should excess alkalinity take place, carbon dioxide from the lungs can be reabsorbed to form carbonic acid, which will help the neutralization process.

Many biochemically important reactions take place because of either acid or base catalysis, including the hydrolysis of peptides and esters, the reactions of phosphate groups, tautomerizations (keto-enol equilibria), and condensations of carbonyl groups. Sometimes, the side chains of several amino acid residues in aspartic acid, glutamic acid, histidine, cysteine, tyrosine, and lysine act in the enzymatic capacity of general acid and/or base catalysis.

The kidneys, which are usually seen as the organs of excretion, also act as regulators in water, electrolyte, and acid-base balance. Acid-base balance takes place in the tubules of the kidneys through the exchange of sodium ions and hydrogen ions. It is regulated by the pH of blood plasma and the ability of the tubular cells to acidify the urine through proton and ammonia formation. The glomerular filtrate contains the electrolytes, acids, and bases present in the blood plasma. The cations are mostly sodium ions, while the anions are either chloride, phosphate, or bicarbonate. At a pH of 7.4, 95 percent of the carbon dioxide is in the form of sodium bicarbonate, while 83 percent of the phosphate is disodium hydrogen phosphate. Normally, most of the sodium ions are taken up by the tubular cells in exchange for the protons formed there. The sodium ions are then returned to the plasma after associating with the bicarbonate anions. The role of the kidneys is to stabilize the bicarbonate concentration and to neutralize the nonvolatile sulfuric and phosphoric acids. Base conservation by the kidneys takes place with the aid of ammonia formed by the
decomposition of glutamine (via the enzyme glutaminase) and the amino acids (via amino acid oxidase).

Disorders and Diseases

Acids and bases are among the most important chemicals of the living being. Life depends on pH and acid-base reactions. The presence of buffers is also important for the optimum function of enzymes. Thus, in metabolic reactions enzymes have pH optima that allow the maximum catalysis of the substrate reactions. The means of maintaining a steady pH of 7.4 in the blood involve a mechanism for the regulation of acid-base balance, which includes water and electrolyte balance, hemoglobin, and blood buffers, as well as the action of lungs and kidneys.

The pH of different body fluids in human beings varies greatly. For example, the pH range of gastric juices is 1 to 2, while that of intestinal juices is 8 to 9. If the blood plasma pH of 7.4 for a healthy individual varies by 0.2 or more units, then serious medical conditions arise; if not corrected, they may lead to death. Such reactions occur primarily because the functioning of enzymes is sharply pH-dependent.

Life can be described as a continuous fight against pH change. Nature has equipped the body with the buffers and the various mechanisms that keep organs functioning. The kidneys, lungs, and skin all share the common role of controlling the ionic balance of the organism and thus controlling the bicarbonate concentration and pH. Cell pH regulation is complicated, however, because of the heterogeneous nature of the cell contents. For example, mitochondrial fluid is more alkaline than that of the cytoplasm, which allows the establishing of a hydrogen ion gradient between these two compartments of the cell. Basic functions such as oxidative phosphorylation, which is the transfer of metabolic energy to adenosine triphosphate (ATP), are believed to depend on this hydrogen ion gradient.

When the blood pH is lower than 7.4, acidosis results. Most forms of acidosis are metabolic or respiratory in origin. Metabolic acidosis is caused by a decrease in bicarbonate and occurs with uncontrolled diabetes mellitus (as a result of ketosis, the excessive production of ketone bodies such as acetone), with certain kidney diseases, with poisoning by an acid salt, and in cases of vomiting when nonacid fluids are lost. Respiratory acidosis may occur with diseases that impair respiration, such as emphysema, asthma, and pneumonia. Under these conditions, carbon dioxide is not properly expired and, as a result, carbonic acid levels increase relative to those of bicarbonate.

Alkalosis results when bicarbonate becomes favored in the buffer ratio. Metabolic alkalosis is observed when excessive vomiting (loss of acid, in the form of hydrochloric acid) takes place, while respiratory alkalosis occurs with hyperventilation (such as that brought on by a high altitude). Mountain climbers reaching the summit of Mount Everest without supplemental oxygen were found to have pH increases to 7.7 or 7.8.

The chief cause of dental decay is lactic acid, which is formed in the mouth by the action of specific bacteria, such as Streptococcus mutans, on the carbohydrates (and their by-products) that are attached to tooth surfaces in a sticky plaque. The normal pH of plaque is 6.8, but lactic acid lowers it to 5.5 or less, which speeds up the corrosion of enamel and leads to tooth decay. The application of fluoride-containing substances directly to the teeth or the drinking of fluoride-containing water changes the composition of teeth and forms a new substance called fluorapatite, which forms a new enamel that is much more resistant to acidity.

Perspective and Prospects

Acids and bases have been known to human beings since ancient times. The word acid is derived from the Latin acidus (sour) and has been redefined several times over the centuries. Alchemists have considered an acid as a substance with a sour taste, that dissolves many metals, and that reacts with alkalies to form salts. The French scientist Antoine-Laurent Lavoisier (1743–94) insisted that an acid should involve the presence of oxygen. In 1810, the English chemist Sir Humphry Davy (1778–1829) showed that hydrogen is the element that all acids have in common. In 1840, German Justus von Liebig (1803–73) redefined an acid as a compound that contains hydrogen and produces hydrogen gas upon reaction with metals. His definition coincided with the theories postulated separately by the Swedish chemist Svante A. Arrhenius (1859–1927) and the German chemist Carl W. Ostwald (1883–1943), who also pointed out that bases were substances that carried a hydroxyl group.

In 1909, the Danish chemist Søren Peter Lauritz Sørensen (1868–1939) proposed the pH system, which has become the standard measure of acidity. In separate works announced in 1923, Johannes N. Brønsted (1879–1947) and Thomas M. Lowry supported the Arrhenius-Ostwald theory and went further to postulate that the hydrogen ion is never found in the free state but instead exists in combination with another base (for example with water when the hydrogen is in an aqueous solution). As a result, their work broadened the definition of a base, which according to them would include any compound that was a proton (hydrogen ion) acceptor. In 1938, American Gilbert N. Lewis (1875–1946) broadened the acid-base concept even further: An acid is an electron pair acceptor, while a base is an electron pair donor. In 1963, Ralph Gottfrid Pearson proposed the simple and effective way of classifying acids and bases as hard or soft.

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