BIOC1020 Lecture - Functional Groups - Sem II 2022_23 PDF

Functional Groups & Bonds in Biochemistry BIOC1020: Cellular Biochemistry Lecturer: Dr. S. Stephenson-Clarke E-mail: [email protected]  “You don’t have to be great to start, but you have to start to be great.” –Zig Ziglar Inspirational Quote of the Day: Lecture...

Functional Groups & Bonds in Biochemistry BIOC1020: Cellular Biochemistry Lecturer: Dr. S. Stephenson-Clarke E-mail: [email protected]  “You don’t have to be great to start, but you have to start to be great.” –Zig Ziglar Inspirational Quote of the Day: Lecture 1: Functional Groups and Bonds in Chemistry Learning Outcomes At the end of this lecture, students will be able to: Identify and describe the types of noncovalent, reversible interactions and their importance. Identify the functional groups and bonds for common organic molecules and biomolecules Describe the chemical properties of water and explain how water affects biochemical interactions. Define pH and explain why changes in pH may affect biochemical systems. Cellular Foundations The Unity of Life Biochemistry: Cellular Foundations All cells (prokaryotic and eukaryotic) have some similar structural components: genetic material in the form of chromosomes, a membrane bound lipid bilayer that separates the inside of the cell from the outside of the cell, ribosomes that are responsible for protein synthesis. It explores four classes of biomolecules (and their derivatives) that are also present in all cell types (lipids, proteins, nucleic acids and carbohydrates) Biochemistry: Cellular Foundations Cell - chemical factory that designs, imports, synthesizes, uses, exports and degrades a variety of chemicals (lipids, proteins, nucleic acids and carbohydrates). Must sense the amount of raw and finished chemicals it has available Must respond to its own and external needs by increasing or shutting off production. Biochemistry is the branch of science dedicated to the study of these chemical processes within a cell. Understanding these processes can also lend insight into disease states and the pharmacological effects of toxins, drugs, and other medicines within the body. Biochemistry: Chemistry of Living Matter Chemistry of the cell allows for: a high degree of complexity and organization the extraction, transformation, and systematic use of energy to create and maintain structures and to do work the interactions of individual components to be dynamic and coordinated the ability to sense and respond to changes in surrounding a capacity for fairly precise self-replication while allowing enough change for evolution Biochemistry: Molecular Logic of Life In Biochemistry, we focus on the chemical logics behind the: initiation and acceleration of reactions organization and specificity of metabolism and signaling storage and transfer of information and energy The Molecular Hierarchy of Structure Energy  Living Systems Extract Energy Apart from photosynthesizing organisms (plants, purple and green bacteria, cyanobacteria, algae) which gain energy from electromagnetic radiation, all biochemical needs of the biosphere for life come from: chemical elements salts and molecules These chemicals are usually found in the lower regions of the atmosphere, the hydrosphere (total water on planet) and the upper parts of the lithosphere (outer layer of the Earth). Organisms Can Also Be Classified by Different Energy and Carbon Sources The Chemistry of Living Matter The same biochemistry is used by all living cells that have been studied. Electrons, protons and energy are the fundamental components of biochemistry and bioenergetics. Copyright ©2019, 2016, 2013 Pearson Education Ltd. All Rights Reserved.  Chemistry Fundamentals Chemistry Fundamentals All elements have different nuclei. Atomic nuclei are composed of : protons (+ve charge) neutrons (no charge) electrons (-ve charge) are roughly equal in number to the # of protons in the nucleus. Periodic Table Crucial to Biochemistry Chemical Bonds Cellular functions depend on chemical bonds… How strong are chemical bonds? a) relative to each other? b) relative to other energies? How strong are chemical bonds? Copyright ©2019, 2016, 2013 Pearson Education Ltd. All Rights Reserved. Chemistry Fundamentals: Covalent Bonding Covalent bonds occurs when a pair of electrons is shared between the nuclei of atoms or ions.  Chemistry Fundamentals: Non-Covalent Interactions Weaker and varied electromagnetic inter- and intra-molecular interactions does not involve the sharing of electrons Different categories such as electrostatic, van der Waals forces, and hydrophobic effects Copyright ©2019, 2016, 2013 Pearson Education Ltd. All Rights Reserved. Chemistry Fundamentals: Hydrogen Bonds Hydrogen bonds - the interaction of a hydrogen atom with an electronegative atom such as N, O, F (from another chemical group). Features: H is shared by two electronegative atoms such as nitrogen or oxygen. hydrogen-bond donor is the group that includes an electronegative atom (where the hydrogen atom is more tightly bound to) hydrogen-bond acceptor - electronegative atom that is less tightly bound to the hydrogen atom. Electronegative atom can pull electron density away from the hydrogen atom creating a positive electronegativity charge. H can also interact with an atom that has negative electronegativity charge.  Chemistry Fundamentals: Importance of Hydrogen Bonds Source of unique properties of water Structure and function of proteins Structure and function of DNA Structure and function of polysaccharides Binding of substrates to enzymes Binding of hormones to receptors Matching of mRNA and tRNA Chemistry Fundamentals: Hydrogen Bonds Image by Aleia Kim Chemistry Fundamentals: van der Waals Interactions Weak individually easily broken, reversible Universal occur between any two atoms that are near to each other Biochemical Importance determines steric complementarity stabilizes biological macromolecules (stacking in DNA) facilitates binding of polarizable ligands Chemistry Fundamentals: van der Waals Interactions Hydrophobic Effect & Water Chemistry Fundamentals: Hydrophobic Interactions Refers to the association or interaction of nonpolar molecules or components of molecules in aqueous solution Is one of the main factors behind: protein folding protein-protein association formation of lipid micelles binding of steroid hormones to their receptors Does not arise because of some attractive direct force between two nonpolar molecules Chemistry Fundamentals: Hydrophobic Interactions Hydrophobic molecules such as benzene tend to cluster together in aqueous solutions. This clustering of hydrophobic molecules in water is called the hydrophobic effect. The hydrophobic effect is a powerful organizing force in biological systems. Chemistry Fundamentals: The Hydrophobic Effect Chemistry Fundamentals: The Hydrophobic Effect for Membrane Formation Phospholipids have hydrophilic and hydrophobic properties. Such a molecule, with two distinct chemical personalities, is called an amphipathic or amphiphilic molecule. When exposed to water, phospholipids form membranes. Chemistry Fundamentals: The Hydrophobic Effect Lipid molecules disperse in the solution Nonpolar tails of lipid molecules are caged and surrounded by highly ordered water molecules. Chemistry Fundamentals: The Hydrophobic Effect With high enough concentration of amphipathic molecules, complete aggregation into micelles is possible. Chemistry Fundamentals: The Hydrophobic Effect and Protein Folding  Binding sites in enzymes and receptors Chemistry are often hydrophobic. Fundamentals: The Hydrophobic Such sites can bind hydrophobic Effect for Enzyme- substrates and ligands, such as steroid Substrate hormones, which displace water and Complex increase entropy of the system. Many drugs are designed to take advantage of the hydrophobic effect.  Chemical Foundations: Water Most abundant component of every cell Water influences every reaction that happens in cells, even those deep within enzymes, away from water. The properties of H2O have a powerful effect upon the forces of natural selection at the level of the biomolecule.  Chemical Foundations: Water The molecule has wide ‘V’ shape (the HO-H angle is 104°) with uneven sharing of electrons between O and H atoms. O, with its higher electronegativity, holds electrons closer to itself than H does. H, as a result, has a partial positive charge (typically designated as δ+) while O has a partial negative charge (written as δ- ). Thus, H2O is a polar molecule because charges are distributed around it unevenly, not symmetrically Chemical Foundations: Water The polarity of water allows the formation of hydrogen bonds between water molecules and accounts for the cohesiveness of water. The polarity of water also accounts for its ability to dissolve many important biochemicals. The inability of water to dissolve nonpolar molecules results in an important organizing principle – the hydrophobic effect. Chemical Foundations: Water Structure Water geometry is a distorted tetrahedron. The electronegativity of the oxygen atom induces a net dipole moment. Because of the dipole moment, water can serve as both a hydrogen bond donor and acceptor. Hydrogen Bonding in Water Up to four H-bonds per water molecule gives water its: high boiling point high melting point unusually large surface tension Hydrogen bonding in water is cooperative. Hydrogen bonds between neighboring molecules are weak (20 kJ/mol) relative to the H–O covalent bonds (420 kJ/mol). Hydrogen Bonding in Water  H2O is a solvent; has ability to solvate (dissolve) many molecules Ionic or polar molecules dissolve readily in water, but non-polar substances dissolve poorly in water. E.g. Oil (non-polar and hydrophobic) separates from water when mixed with it while sodium chloride (ionic, hydrophilic) and ethanol (polar, hydrophilic) are able to form hydrogen bonds, so both dissolve in water. Fact: Ethanol’s solubility in water is crucial for brewers, winemakers, Chemical and distillers – otherwise, there would be no wine, beer or spirits. Foundation: Water (Image by Aleia Kim) Water as a Solvent Water is a good solvent for charged and polar substances: amino acids and peptides small alcohols carbohydrates Water is a poor solvent for nonpolar substances: nonpolar gases aromatic moieties aliphatic chains  Chemical Foundations: Water Aliphatic molecules (polar and non-polar regions) such as phospholipids with H2O forms bilayers where non-polar portions interact with each other to exclude water while polar portions arrange themselves on the outside. The interaction of the polar heads with water causes an increase in disorder, or entropy which drives the formation of micelles. Commonly observed with lipid bilayer of membranes, globular proteins in aqueous solutions etc (Image by Aleia Kim) Interactions of amphipathic molecules with water Chemical Foundations: Water (Image by Aleia Kim) Chemical Foundations: Water Dissolving salts involves breaking ionic interactions Chemical Foundations: Water The less water is allowed to interact with aqueous media, the stronger H- bonds can be. This is important in the stability of macromolecules such as DNA However, these bonds are weak enough to be broken by the enzymes of DNA metabolism, thereby allowing access to the genetic information.  Quiz 1. What is a key biochemical advantage of the use of weak bonds in biochemistry? 2. Explain how the following statement applies to biochemistry: “Order can be generated by an increase in randomness.” pH and Buffers  Chemical Foundations: pH pH is the measure of H+ DID YOU KNOW? concentration of a solution. Controlling pH is a crucial function in biological systems. A common example of a pathological modification of environmental pH is Gastric esophageal reflux gastroesophageal reflux disease (GERD). A chronic digestive disease, disease (GERD) is a GERD develops when stomach acid pathological condition that refluxes into the esophagus. results when the esophagus is The backwash of acid, frequently exposed to the acid of the experienced as heartburn, irritates the stomach. lining of the esophagus by exposing the tissue to very acidic conditions (pH 1 to 2). Esophageal ulcers and cancers Effect of pH on Overall Surface Charge of Human Ubiquitin Dependence of protein solubility on pH  Chemical Foundations: pH – Acid vs Base Acids ionize to form a proton and a base. Conjugate base - the chemical formed upon ionization of an acid. Conjugate acid – the acid formed when a base binds a proton. Acid ---> proton donor, whereas base --->proton acceptor Chemical Foundations: pH – Ionization of Acids The ionization equilibrium of a weak acid is given by The equilibrium constant for this reaction is The larger Ka (acid dissociation constant), the stronger the acid.  Chemical Foundations: Weak acids Weak acids are critical for life because their affinity for protons help to keep the H+ concentration (and thus the pH) of the solution they are in relatively constant Consider the bicarbonate/carbonic acid system: Adding hydroxide ions (by adding a strong base like NaOH) to the solution causes the H+ ions to react with OH- ions to make water. It is useful to be able to predict the response of the H2CO3 system to changes in H+ concentration. The Henderson-Hasselbalch equation defines the relationship between pH and the ratio of HCO3 – and H2CO3. pH = pKa + log ([HCO3– ]/ [H2CO3]) This simple equation defines the relationship between the pH of a solution and the ratio of HCO3– and H2CO3 in it. The pKa, is defined and calculated as pKa = -Log Ka The Ka is the acid dissociation constant and is a measure of the strength of an acid. For a general acid, HA, which dissociates as HA ⇄ H+ + A – Diagram Depicting a Variety of Conjugate Acid–Base Pairs  Chemical Foundations: Buffers Buffers - solutions that can resist pH change upon the addition of an acidic or basic components. It can neutralize small amounts of added acid or base. This helps to stabilize the pH of the solution or environment which is critical for processes and/or reactions which require specific and stable pH ranges. The intracellular pH in most living cells is alkaline compared to the pH generated by protons that are transported passively through the plasma membrane by electrochemical forces. Chemical Foundations: Buffers Buffering systems in the body include the bicarbonate- carbonate system, haemoglobin, protein-proton binding, phosphoric acid and several membrane transporters These remove protons from the cytosol and play important roles in maintaining alkalinity in cells. The normal physiological pH of mammalian arterial blood is strictly maintained at 7.40. Clinical Fact: A decrease of more than 0.05 units from the normal pH results in acidosis. Chemical Foundations: pH and Buffer systems of the human body Chemical Foundations: Buffers Many other biomolecules can also exist with or without a dissociable proton or two: acids and bases. H2O can also dissociate into both a weak acid and a weak base. The strength with which a molecule holds onto its dissociable protons (pKa values) are related to the proton concentration (pH value) of its environment. Chemical Foundations: Buffers Water can ionize to a slight extent (10-7 M) to form H+ (proton) and OH– (hydroxide). We measure the proton concentration of a solution with pH, which is the negative log of the proton concentration. pH = -log[H+] If the proton concentration, [H+]= 10-7 M, then the pH is 7. We could just as easily measure the hydroxide concentration with the pOH by the parallel equation, pOH = -log[OH-] In pure water, dissociation of a proton simultaneously creates a hydroxide, so the pOH of pure water is 7, as well. This also means that pH + pOH=14 The pH of the medium will affect the positive and negative charges on many biomolecules, this will in turn affect the ways in which they interact. Functional Groups – Recap Biological Molecules Typically Have Several Functional Groups Functional groups - specific atoms, ions, or groups of atoms having consistent properties, found as part of a larger molecule. The ABCs of Life  Organic Functional Groups… Organic functional groups are made up from specific bonding patterns with the atoms mostly found in organic molecules (C, H, O, N, S, and P). E.g., -OH (hydroxyl group) - characterizes alcohols; oxygen with a hydrogen attached and can be found on a number of different molecules. Organic Functional Groups… All carbon containing molecules have originated from biological, living organisms causing them to be termed organic compounds Organic chemicals consist of a relatively few similar parts, combined in different ways. Structural similarities allow us to predict how a compound may react, if we know how other molecules containing the same types of parts are known to react Common Functional Groups of Biological Molecules R to represent “any substituent.” It may be as simple as a hydrogen atom, but typically it is a carbon- containing group. When two or more substituents are shown in a molecule, we designate them R1, R2, and so forth Can you identify the Functional Groups of this molecule? 85 ? 86 Carboxylic acid ? 87 Carboxylic acid Amino group ? 88 Carboxylic acid Amino group Methylene group ? 89 Carboxylic acid Amino group Methylene group Aryl group 90 dihydroxyphenylalanine Carboxylic acid Amino group Methylene group Aryl group (L-Dopa) L-3,4- Hydroxyl group 91 Functional Groups: Alkanes Characterized by single bonds between carbon and carbon, or between carbon and hydrogen. Methane, CH4, is the natural gas you may burn in your furnace. Octane, C8H18, is a component of gasoline. Functional Groups: Alkenes and Alkynes Alkenes (sometimes called olefins) have carbon- carbon double bonds, and alkynes have carbon- carbon triple bonds Ethene (simplest alkene), is a gas that serves as a cellular signal in fruits to stimulate ripening. Ethyne (or acetylene) is used as a fuel in welding blow torches Functional Groups: Alkenes and Alkynes Many alkenes can take two geometric forms: cis or trans. cis and trans - different isomers with different physical properties because there is a very high energy barrier to rotation about a double bond. Functional Groups: Alkenes and Alkynes Alkanes, alkenes, and alkynes - all classified as hydrocarbons, because they are composed solely of carbon and hydrogen atoms. Alkanes - saturated hydrocarbons, because the carbons are bonded to the maximum possible number of hydrogens Alkenes and Alkynes – unsaturated hydrocarbons as the double and triple-bonded carbons have fewer hydrogen atoms bonded to them Functional Groups: Aromatics Represented by benzene, and naphthalene, a compound with a distinctive ‘mothball’ smell. Aromatic groups are planar (flat) ring structures and are widespread in nature. Fact: Benzene used to be a commonly used solvent on the organic lab, but was shown to be carcinogenic. Functional Groups: Alkyl Halides Alkyl halide or haloalkane - when the carbon of an alkane is bonded to one or more halogens; rare in biomolecules Chloroform - useful solvent in the laboratory; one of the earlier anesthetic drugs used in surgery. Chlorodifluoromethane - was used as a refrigerant and in aerosol sprays until the late twentieth century, but its use was discontinued after it was found to have harmful effects on the ozone layer. Bromoethane - simple alkyl halide often used in organic synthesis. Functional Groups: Alcohols, Phenols and Thiols Alcohols - a carbon is single-bonded to an OH group (the OH group; when it is part of a larger molecule - referred to as hydroxyl group Alcohols react readily with acids to form esters by the elimination of water. Hydrolysis of esters requires little energy. Functional Groups: Alcohols, Phenols and Thiols Except for methanol, all alcohols can be classified as primary, secondary, or tertiary. In a primary alcohol, the carbon bonded to the OH group is also bonded to only one other carbon. In a secondary alcohol and tertiary alcohol, the carbon is bonded to two or three other carbons, respectively. Phenol – formed when hydroxyl group is directly attached to an aromatic ring. Question: Is this Thiol - sulfur analog of an alcohol molecule a Phenol? Functional Groups: Ethers and Sulfides Ether - an oxygen is bonded to two carbons E.g. diethyl ether, a common laboratory solvent and also one of the first compounds to be used as an anesthetic during operations. Thioether or sulfide - the sulfur equivalent of an ether Functional Groups: Organic Phosphates Phosphate ester - phosphate linked to a single organic group Phosphate diester – phosphate has two links to organic groups. A linkage between two phosphates creates a phosphate anhydride. Functional Groups: Aldehydes and Ketones Carbonyl - a number of functional groups that contain a carbon-oxygen double bond. Ketone - the carbon atom of a carbonyl is bonded to two other carbons. Aldehyde - the carbonyl carbon is bonded on one side to a hydrogen, and on the other side to a carbon. Functional Groups: Amines Amines - characterized by N atoms with single bonds to hydrogen and carbon. Just as there are primary, secondary, and tertiary alcohols, there are primary, secondary, and tertiary amines. Ammonia is a special case with no carbon atoms. Amines are basic and are readily protonated to form ammonium cations. Quaternary ammonium ion - where a nitrogen has four bonds to carbon (which is somewhat unusual in biomolecules). Functional Groups: Amines Functional Groups: Amines Functional Groups: Amines Amines are proton acceptors (basic) It is difficult to remove protons: a very high pH (= low [H+]) is needed. If the pH of the surrounding medium is lower ( more acidic) than the pKa of the amine group it will be protonated, and positively charged. This contrasts with the behaviour of acids that are “reluctant” to accept protons unless [H+] is high. Functional Groups: Carboxylic Acids Carboxylic acid - when the carbonyl carbon is bonded to a hydroxyl group. Carboxylate ion - denoted by -COO- when the H+ has been released Functional Groups: Carboxylic Acids Carboxylic acids, like all acids, donate their protons to become carboxylate anions. Such anions can be persuaded to accept protons if the pH is lower (more acidic) than the pKa value of the group. Other derivatives are carboxylic esters (‘esters’), thioesters, amides, acyl phosphates, acid chlorides, and acid anhydrides. With the exception of acid chlorides and acid anhydrides, carboxylic acid derivatives are very common in biological molecules and/or metabolic pathways. Functional Groups of Capsaicin Functional Groups: Other Examples Rxns Forming Major Macro- molecules Recap: Common Organic Functional Groups  Topic Overview Most biochemical interactions take place in aqueous solutions. Water is a polar molecule, with the oxygen atom bearing a partial negative charge and the hydrogen atoms a partial positive charge. The charges on water molecules interact with opposite charges on other water molecules to form hydrogen bonds. Three common types of weak interactions are found in biochemical systems. Electrostatic interactions take place between ions having opposite charges.  Topic Overview The basis of the hydrogen bond is the unequal distribution of charge that results whenever a hydrogen atom is covalently bonded to an electronegative atom, such as oxygen or nitrogen. Hydrogen bonds in biomolecules are weakened in the presence of water because water readily forms hydrogen bonds. Fleeting electrostatic interactions, termed van der Waals interactions, take place when the transient asymmetry of charges on one nonpolar molecule induces complementary asymmetry in nearby nonpolar molecules.  Topic Overview Hydrophobic effect: nonpolar molecules in aqueous solutions cluster together because of the resulting increase in entropy of water molecules. The hydrophobic effect accounts for much of the structure of life, including membrane formation and the specific folding of proteins. Functional groups are groups of atoms found in many different biomolecules that confer specific chemical properties. The pH of a solution is a measure of hydrogen ion concentration and is an important parameter in biochemical systems. Buffers are acid–base conjugate pairs that resist changes in pH. Buffers are crucial in biological systems because changes in can have drastic effects on the structure of biomolecules and can even result in death. Further Reading and Resources 1. Nelson and Cox. (2017). Lehninger: Principles of Biochemistry (7th Ed) – Chapters 1 and 2 2. https://chem.libretexts.org/Courses/Sacramento_City_C ollege/SCC%3A_Chem_309_- _General_Organic_and_Biochemistry_(Bennett)/Text/09. _Organic_Functional_Groups%3A_Structure_and_Nome nclature 3. https://www.khanacademy.org/science/organic- chemistry/bond-line-structures-alkanes- cycloalkanes/functional-groups/v/functional-groups-first 4. https://www.khanacademy.org/science/ap- biology/chemistry-of-life/elements-of-life/v/functional- groups See you next time!!