Funchem 8 Intermolecular Forces - RCSI - 2024

Fundamentals of Medicinal and Pharmaceutical Chemistry FUNCHEM.8 Intermolecular interactions: The medical importance of water in the body Professor Celine J. Marmion DAT E : 1 4 t h O c t o b e r 2 0 2 4 Breaking News – Nobel Prize in Chemistry 2024! “One of the discoveries being recognised this...

Fundamentals of Medicinal and Pharmaceutical Chemistry FUNCHEM.8 Intermolecular interactions: The medical importance of water in the body Professor Celine J. Marmion DAT E : 1 4 t h O c t o b e r 2 0 2 4 Breaking News – Nobel Prize in Chemistry 2024! “One of the discoveries being recognised this year concerns the construction of spectacular proteins. The other is about fulfilling a 50-year-old dream: predicting protein structures from their amino acid sequences. Both of these discoveries open up vast possibilities” Heiner Linke, Chair of the Nobel Committee for Chemistry Proteins generally consist of 20 different amino acids, which can be described as life’s building blocks. In 2003, David Baker succeeded in using these blocks to design a new protein that was unlike any other protein. Since then, his research group has produced one imaginative protein creation after another, including proteins that can be used as pharmaceuticals, vaccines, nanomaterials and tiny sensors In 2020, Demis Hassabis and John Jumper presented an AI model called AlphaFold2. With its help, they have been able to predict the structure of virtually all the 200 million proteins that researchers have identified. Since their breakthrough, AlphaFold2 has been used by more than two million people from 190 countries. Among a myriad of scientific applications, researchers can now better understand antibiotic resistance and create images of enzymes that can decompose plastic. Learning outcomes At the end of this lecture, the learner will be able to Recall ‘electronegativity’ and explain how dipoles arise in molecules. Predict whether a molecule has a net dipole moment taking into account both polarity and shape. Recall and explain ion-dipole, dipole-dipole, dipole-induced dipole and instantaneous dipole-induced dipole forces of attraction. Recall and explain hydrogen bonding and how it can account for physical properties such as melting and boiling points. Differentiate, in terms of strength of interaction, between different types of intermolecular forces of attraction. Discuss medical, biochemical and pharmacological implications associated with intermolecular forces of attraction. Intermolecular forces Intermolecular forces are: attractive forces between molecules. primarily responsible for the bulk properties of matter (for example, melting point and boiling point). are much weaker than intramolecular forces which hold atoms together in a molecule. e.g. 41 kJ will evaporate 1 mole of water at its boiling point. 930 kJ is required to break the two O-H bonds in one mole of water molecules. Intermolecular forces Boiling points and melting points of substances often reflect the strength of intermolecular interactions. The state of matter is determined by the strength of the intermolecular interactions  Solid, Liquid and Gas Solid Liquid Gas  The basis of intermolecular interactions A magnet demonstrates the fundamental requirements for intermolecular interactions. Attraction occurs between oppositely charged regions. Magnets Molecules Dipole H-F is a covalent compound with a polar bond. δ+ H – F δ- The shift of electron density is When a molecule has a δ+ and a δ- end symbolized by placing a then the molecule is said to be polarised or crossed arrow above the possess a dipole. structure to indicate the direction of the e- shift Dipoles arise from the unequal sharing of electrons in a covalent bond. δ+ δ- H–F Electronegativity of atoms determine the δ+ δ- H – Cl sharing of electrons in bonds. δ+ H – Br δ- The greater the electronegativity the δ+ H–I δ- greater the dipole. δ (delta) denotes a partial charge  A guide to dipole moments The quantitative measure of the degree of polarity in a bond or molecule.  It is measured in Debye units denoted by 'D' Diatomic molecules containing the same atoms have no dipole moment e.g. H2, Cl2, O2= 0D i.e. NON POLAR Diatomic molecules containing different atoms may have dipole moment e.g. HCl, CO, NO > 0D i.e. POLAR The Dipole moment of polyatomic molecules depends on: Polarity of the bonds. Shape of the molecule. Shape and polarity In CO2 the two dipole moments are equal. If CO2 is a linear molecule, the dipoles are opposite in direction = 0 D If CO2 is a bent the moments are not No dipole moment completely opposite > 0 D Would have dipole moment Molecule and Dipole moment H2 0 D CO2 0 D H2O 1.94 D NH3 1.16 D CH4 0 D Different types of intermolecular forces 1. DIPOLE – DIPOLE FORCES 2. ION – DIPOLE FORCES 3. ION – INDUCED DIPOLE FORCES 4. DIPOLE – INDUCED DIPOLE FORCES 5. INSTANTANEOUS DIPOLE – INDUCED DIPOLE FORCES 6. HYDROGEN BONDS 7. ION – ION FORCES 1. Dipole – dipole forces Dipole-dipole interactions occur between polar molecules (i.e. molecules that possess a dipole moment). The larger the dipole moment the larger the force. To the right is an illustration of alignment of polar molecules in a solid. Alignment of polar molecules in a liquid is not a rigid but similar. 2. Ion – dipole forces The attractive forces between an ion and a polar molecule. The strength of the interaction depends on the charge and size of the ion and the magnitude of the dipole moment and size of the molecule. Hydration of ions is an example of ion – dipole forces. 2. Ion – dipole forces ION – DIPOLE FORCES – VARIABLE MAGNITUDE Mg2+ ion has a higher charge and a smaller ionic radius (78 pm) than that of the Na+ ion (98 pm), it interacts more strongly with water molecules 2. Ion – dipole forces Ion - Dipole Ion - Dipole 3. Ion – induced dipole forces When an ion is placed next to an atom or non-polar molecule, the e- distribution of the atom (or molecule) is distorted by the force of the ion or dipole moment. The dipole in the atom or molecule is said to be an induced dipole. Polarizability is the ease with which the electron distribution in the atom (or molecule) can be distorted. Generally more e- 4. Dipole – induced dipole forces When a polar molecule is placed next to an atom or non-polar molecule, the e- distribution of the atom (or molecule) is distorted by the force of the ion or dipole moment. The dipole in the atom or molecule is said to be an induced dipole. The extent to which a dipole is induced depends on: – Charge on ion or size of dipole moment – Polarizability of atom or non-polar molecule Polarizability is the ease with which the electron distribution in the atom (or molecule) can be distorted. Generally more e- 5. Instantaneous dipole – induced dipole forces Polarizability enables the creation of instantaneous dipole moments. At any instant it is likely that an atom or non- polar molecule will have a dipole moment (instantaneous dipole) An instantaneous dipole can induce a dipole in Instantaneou Induced s dipole each of its nearest neighbors. dipole The magnitude of this attractive interaction is directly proportional to the polarizability of the atom or molecule 5. Instantaneous dipole – induced dipole forces- also known as dispersion forces Usually increase with molar mass as Melting Point dispersion forces increase in strength (°C) with the number of electrons present. CH4 −182.5 In many cases, dispersion forces are CF4 −150.0 comparable to or even greater than CCl4 −23.0 the dipole-dipole forces between CBr4 90.0 polar molecules. CI4 171.0 6. Hydrogen bonds Particularly strong type of intermolecular force A special type of dipole-dipole interaction between the hydrogen atom in a polar bond, such as N—H, O—H, or F—H, and an electronegative O, N, or F atom The H atom involved in the bond is known as the H bond donor. The atom whose lone pair is involved in the bond is the H bond acceptor. H bond H bond acceptor donor H bond H bond acceptor donor 6. Hydrogen bonds To be considered a hydrogen bond the H must be attached directly to the electronegative atom (N, O, F) H bond Not a H bond 7. Ion – ion forces A form of electrostatic force Effectively ionic bonding – E.g. NaCl, MgSO4. Form ionic lattice structures using the electrostatic forces of the fully charged ions. – Ionic interactions take place between many neighbouring ions. Strong interactions Relative strength of intermolecular forces 10000 Intermolecular force energy 1000 100 range kJ/mol 10 1 0.1 0.01 Dispersion forces can vary to a great degree. they can be the weakest form of intermolecular interaction they can also be quite strong and exceed the strength of other forces such as dipole – dipole forces. Properties of water The properties of water and in general other liquids are dictated by the nature of their intermolecular interactions. Water has a high boiling point because its molecules are bound together by hydrogen bonding, It takes more kinetic energy, or a higher temperature, to break the hydrogen bonding between water molecules, thus allowing them to escape as steam. Heat capacity of water Unusually high heat capacity due to the presence of H bonding. Specific heat capacity: Energy required to heat 1g of a liquid by 1oC. – Specific Heat capacity of water = 4.184 J/g. – Specific heat capacity of ethanol = 2.46 J/g. The adult body: 60% water. – Our bodies can absorb or lose a lot of heat without resulting in the body temp changing by 1oC. Medical and biological relevance of intermolecular forces. Sickle cell anaemia The symptoms of Sickle Cell Anaemia – Narrow capillaries become blocked. – The body recognises the sickled cells as abnormal and destroys them faster than they are replace. – Anaemia results Sickle cell anaemia – explained Sickle cell anemia results from a single amino acid substitution (out of 287 amino acids) in the beta-chain of HbA. The only difference between HbA and sickle cell hemoglobin (HbS) is the substitution of a negatively charged glutamic acid for a hydrophobic valine. GLUTAMIC ACID VERSUS VALINE Valine which is a non-polar a.a. residue replaces polar glutamic acid. Valine is exposed in low [O2] and forms a hydrophobic region. The HbS molecules aggregate and precipitate. Glutamic acid Valine Red blood cells become distorted by precipitate and begin to block capiliaries. Structure of DNA The double helix structure of DNA is only stable due to the extensive hydrogen bonding holding each strand together. Drug design Drugs are now designed to target specific sites or receptors. Very often the structure of the drugs are designed to compliment the site. –Often this means creating strong intermolecular interactions between drug and target. In conclusion - For people as for molecules… NO2 The greatest thing you’ll ever learn is just to love… O 2N NO2 NH 2 O …and to be loved in return! HO O H Thank you F O R M O R E I N F O R M AT I O N P L E A S E C O N TA C T Professor Celine J. Marmion EMAIL: [email protected] 32