BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 1. STRUCTURE AND REACTIVITY OF BIOORGANIC COMPOUNDS

1.2. Reactions involving bioorganic molecules

The formation of a reaction product from a substrate requires a certain energy input—the activation energy (E_a). Taking into account ΔE_a, the reaction rate constant is determined by the Arrhenius equation:

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where A is the steric factor, ΔE_a is the activation energy change (activation barrier), R is the gas constant, and T is the absolute Temperature. Based on their mechanism, reactions are classified into:

✵ heterolytic (ionic) reactions, which yield a cation and an anion (an electron pair is transferred to a single molecule):

✵ homolytic (radical) reactions involve the Cleavage of a chemical bond (electron pair) to produce free radicals—reaction products that possess an unpaired electron and, consequently, an uncompensated magnetic moment. The reaction scheme is as follows:

Free radicals are highly reactive (and therefore short-lived). Homolytic reactions occur when molecular structures are exposed to radiation, temperature, or redox Enzymes;

✵ molecular (concerted) reactions, resulting in a uniform redistribution of electron density without charge Separation.

According to their direction, reactions include:

✵ addition (A-reactions) According to the scheme

Electrophilic addition (A_E-reactions) is characteristic of unsaturated compounds, such as alkenes and alkadienes. Nucleophilic addition (A_N-reactions) is typical of molecules containing polar double bonds, specifically aldehydes and ketones that feature a carbonyl group;

✵ elimination (E-reactions), for example, the elimination of Water (dehydration) or ammonia (deamination) according to the scheme

Such reactions are typical of halogenated Hydrocarbons, alcohols, hydroxy acids, and Amino Acids;

✵ substitution (S-reactions), which proceed according to the scheme

and are characteristic of Aromatic Compounds, carboxylic acids yielding amides and anhydrides, alcohols, and halogenated saturated hydrocarbons;

✵ rearrangements, an example of which is keto-enol Tautomerism (involving the intramolecular migration of a proton between oxygen and carbon atoms);

✵ redox (oxidation-reduction) reactions, which involve the intermolecular transfer (or migration) of electrons to an oxygen atom that attaches to the molecule undergoing oxidation. The compound accepting the electron acts as the oxidizing agent, while the one donating it acts as the reducing agent. These reactions provide the energy for all vital metabolic processes.

Depending on the number of Molecules Participating in a reaction, they are classified as monomolecular (cleavage and isomerization reactions: A → B + C; A → B) and bimolecular (formation of new compounds via synthesis or rearrangement: A + B → C; A + B → C + D). Trimolecular reactions are rare in biochemistry. Molecules participating in ionic organic reactions are called nucleophiles (Nu^-) and electrophiles (E⁺). The former include anions (OH^-, Cl^-, Br^-, F^-, etc.), neutral molecules with a lone electron pair (R-CO-OH), and unsaturated compounds that donate their π-electrons to an electrophile (alkenes, alkynes, arenes, and their derivatives). Electrophiles tend to attach to a nucleophile.

These include: charged particles (H⁺, NO₃ - nitronium cation, Br⁺, R₃C⁺ - carbocation), free radicals (CH*₃, RO*), and atoms polarized during the reaction within a molecule (Br^δ+ ^ Br^δ-).

Among electrophilic and nucleophilic Reagents, acids and bases are of particular importance. According to the ionic theory, acids are considered to be compounds that, upon electrolytic dissociation in an aqueous solution, yield hydrogen ions H⁺ or, more precisely, hydronium ions (H₃O)⁺:

Bases are compounds that, upon electrolytic dissociation in an aqueous solution, yield hydroxyl ions OH^-:

Depending on the number of atoms capable of being replaced by a metal, acids are classified as monoprotic (HCl, acetic acid - HC₂H₃O₂), diprotic (H₂SO₄, oxalic acid - H₂C₂O₄), triprotic (phosphoric acid - H₃PO₄, citric acid - H₃C₆H₅O₇), and tetraprotic (pyrophosphoric acid - H₄P₂O₇). Depending on the number of OH^- groups capable of being replaced by other atoms, bases are monacidic (NaOH), diacidic (Ca(OH)₂), and triacidic (Fe(OH)₃). Polybasic acids and polyacidic bases dissociate in a stepwise manner. The highest concentration of H⁺ (or OH^-) in solution is provided by the first dissociation step, and the lowest by the last step. The transfer of a proton from an acid to a base is explained by the fact that these two compounds have different proton affinities. Some act in the reaction as proton Donors, re-

leasing it to others that have a higher proton affinity. The same compound in another reaction acts as a proton acceptor, taking it from a compound with a lower proton affinity. Such substances are called amphiphiles. A typical amphiphile is water: H₂O ↔ H⁺ + O^- (donor), H₂O + H⁺ ↔ (H₃O)⁺ (acceptor).

According to the electronic theory, acids are substances capable of accepting an electron pair (acceptors), and bases are substances capable of donating an electron pair (donors). A standard neutralization reaction, from the standpoint of electronic theory, is viewed as The addition of a free electron pair from a hydroxyl ion to a hydrogen ion, which possesses a vacant orbital to accommodate this pair:

According to the ionic theory, the equation for such a reaction has a more convenient form:

Substances with acidic character are called electrophilic, and those with basic character are called nucleophilic. Representatives of electrophilic reagents include metal cations, the proton, and metal halides, which are used as catalysts in many important organic reactions. Nucleophilic reagents include compounds containing heteroatoms (N, O, S) with a lone pair of electrons—such as amines, alcohols, ethers, thiols, and others. Weak bases are substances containing mobile π-electrons within a π-bond or a conjugated π-bond system—such as alkenes, alkadienes, and aromatic compounds.