In this article, you will learn the basics of hydrolysis, including its background chemistry and mechanics. You will also learn the step-by-step mechanisms of some of the most important mechanisms, as well as examples using biomolecules.
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Reactivity of Water
We often like to think of water (H2O) as boring, simple, and underwhelming; after all, it doesn’t even have a taste! Save for the occasional flood, tsunami, or riptide, water appears like some inert, unthreatening liquid, despite being so fundamental for biology and geology.
With an understanding of chemistry, however, the exciting power of water becomes unleashed. When in contact with certain compounds, water can form acidic or basic solutions that can corrode metal and chemically burns flesh. When in contact with certain metal cations, water can serve as a ligand and produce brilliantly colored salt complexes. More relevant to today’s topic, water can also fundamentally alter the structure of salts and organic compounds, making it an important reagent in organic synthesis and biochemical systems.
The utility of water comes from its most basic characteristic: its polar structure. With this polarity, water can serve as a nucleophile, and secondarily as an electrophile, in organic reactions. The most important class of organic reactions using water as a nucleophile goes by the name “hydrolysis”. The definition of hydrolysis is the breaking of a chemical bond through a reaction with water. Importantly, only ionic bonds and highly polar bonds can “hydrolyze,” meaning break down with water.
Let’s take a close look at the mechanism for hydrolysis.
What is Hydrolysis?
The most basic mechanism for hydrolysis only involves hydrogen bonds. Typically, this mechanism only breaks ionic bonds, such as those of salts. Importantly, it is this mechanism that occurs when table salt, NaCl, is dumped into liquid water. A salt’s ionic bond may break if its positive and negative ions have a higher electrostatic attraction to the polar regions of water than they do to themselves. Salts with weaker ionic bonds tend to thus be more “soluble,” or more easily broken down in a solvent of water.
The mechanisms for hydrolysis of organic compounds are a bit more complex. Hydrolysis can occur under conditions of acid catalysis or base catalysis, but the mechanism is a bit different for each. Generally, hydrolysis only occurs on amides and esters, as only these function groups have sufficient polar character. The amino and carboxy groups, respectively, serve as the electronegative leaving groups.
Organic hydrolysis follows this basic reaction equation:
CE + H2O → COH + HE
E: Electronegative leaving group, often an amino or carboxy
C: Electropositive group, often a carbonyl
In the acid-catalyzed mechanism, the first step involves water or some generic acid protonating the carbonyl and the leaving group, making both positive.
Second, water attacks the carbon, acting as a nucleophile. This pushes the pi bond electrons involved in the carbonyl onto the adjacent oxygen, neutralizing the positive charge. Third, the attacking water group becomes deprotonated, either by water or some generic base, generating a diol (two-alcohol) species.
Fourth, one of the diols converts into a carbonyl. This involves a free electron pair on the oxygen forming a double bond with the carbon, pushing out the leaving group. Fifth, the newly formed carbonyl becomes deprotonated, resulting in a neutrally-charged carboxylic acid.
In the base-catalyzed mechanism, the first step involves water or some hydroxide attacking the carbon, pushing an electron pair onto the carbonyl oxygen. If water serves as the attacking species, it quickly becomes deprotonated. Second, the oxide group reforms into a carbonyl, pushing out the leaving group, resulting in a neutrally-charged carboxylic acid.
Hydrolysis in Biomolecules
In organisms, biomolecules generally follow the mechanisms for acid- and base-catalyzed hydrolysis. In organisms, important enzymes called hydrolases catalyze these hydrolysis reactions. Importantly, hydrolysis serves as the primary means of breaking down large polymer molecules. In this way, many think of hydrolysis as the opposite of dehydration synthesis, which involves building polymers through condensation reactions. Let’s take a look at the most important examples of hydrolysis in biomolecules.
To separate two monosaccharide monomers, a hydrolysis reaction must occur to break the glycosidic bond. Importantly, these bonds do not involve carbonyl groups, so a modified version of the previous mechanism instead takes place.
Both acid- and base-catalyzed hydrolysis can take place. In acid-catalyzed carbohydrate hydrolysis, the oxygen of the glycosidic bond is protonated. Then, water acts as a nucleophile and attacks one of the carbons, breaking the bond between the carbohydrates. The attacking water is then deprotonated, completing the acid catalysis.
The base-catalyzed mechanism is somewhat similar; hydroxide attacks a carbon, breaking the glycosidic bond. The remaining oxide then becomes protonated.
To break down triglycerides or phospholipids, organisms perform hydrolysis reactions to break the bonds between the fatty acids and the glycerol. Since these bonds involve ester groups, the acid- and base-catalyzed mechanisms we covered before fully explain how these hydrolyses take place.
To break down proteins, hydrolysis reactions must occur to break the peptide bonds between amino acids. As with lipids, the previous mechanisms work well to explain these reactions, as peptide bonds involve amide groups.
The hydrolysis of the phosphates of ATP serves a crucial role in providing energy for unfavorable biochemical reactions. Unlike the other hydrolysis examples, ATP involves a mechanism that doesn’t involve carbon. Instead, the polar bonds being broken are phosphodiester bonds, between oxygen and phosphorus. The acid- and base-catalyzed mechanisms still broadly take place, but the phosphorus fully takes the place of carbon.