The science that describes the structure, interactions, and reactions of organic compounds of biological significance at the molecular level. It represents the meeting of biochemistry, as attempts are made to describe the structure and physiology of organisms on an ever smaller scale, with organic chemistry, as attempts are made to synthesize and understand the behavior of molecules of ever-increasing size and complexity. Areas of research include enzymatic catalysis, the structure and folding of proteins, the structure and function of biological membranes, the chemistry of poly(ribonucleic acids) and poly(deoxyribonucleic acids), biosynthetic pathways, immunology, and mechanisms of drug action.
Being at the interface of two disciplines, bioorganic chemistry utilizes experimental techniques and theoretical concepts drawn from both. Important experimental techniques include organic synthesis, kinetics, structure-activity relationships, the use of model systems, methods of protein purification and manipulation, genetic mutation, cloning and overexpression (engineered enhancement of gene transcription), and the elicitation of monoclonal antibodies. Theoretical concepts important to bioorganic chemistry include thermodynamics, transition-state theory, acid-base theory, concepts of hydrophobicity and hydrophilicity, theories of stereocontrol, and theories of adaptation of organisms to selective pressures.
Historically, a major focus of bioorganic research has been the study of catalysis by enzymes. Enzymes have a dramatic ability to increase the rates at which reactions occur. One of the ways that enzymes increase the rates of bimolecular reactions is to overcome the entropic barrier associated with bringing two particles together to form one. See also Enzyme.
Enzymes also catalyze reactions by facilitating proton transfers. Many of the reactions catalyzed by enzymes, such as the formation and hydrolysis of esters and amides, require the deprotonation of a nucleophile (base catalysis) or the protonation of an electrophile (acid catalysis).
Enzymes may act as preorganized solvation shells for transition states. If the active site of an enzyme has just the right size, shape, and arrangement of functional groups to bind a transition state, it will automatically bind the reactants less well. Selective binding of the transition state lowers the energy of the transition state relative to that of the reactants. Because the energy barrier between reactants and transition state is reduced, the reaction proceeds more rapidly.
The selectivity of enzymes makes them useful as catalysts for organic synthesis. Surprisingly, enzymes are able to catalyze not only the reactions that they mediate in living systems but also similar, selective transformations of unnatural substrates. Because of their selectivity, several enzyme-catalyzed reactions may run simultaneously in the same vessel. Thus, a reactant can undergo several reactions in series without the need for isolation of intermediates. Enzymes can be combined so as to reconstitute within a reaction vessel naturally occurring metabolic pathways or to create new, artificial metabolic pathways. Sequences of up to 12 serial reactions have been executed successfully in a single reaction vessel. See also
The biological activity of a protein, whether binding, catalytic, or structural, depends on its full three-dimensional or conformational structure. The linear sequence of amino acids that make up a protein constitutes its primary structure. Local regions of highly organized conformation (α-helices, β-pleats, β-turns, and so on) are called secondary structure. Further folding of the protein causes regions of secondary structure to associate or come into correct alignment. This action establishes the tertiary structure of the native (active) protein. A goal of bioorganic chemistry is to achieve an understanding of the process of protein folding. See also Amino acids; Biochemistry; Organic chemistry; Protein.
