Pharmacy Science: Chemistry of Drugs & Molecules

Fundamentals of Pharmacy Science: Unit 1 - Overview

• This unit explores the fundamental chemistry of drugs and molecules of life.
• Required study materials include a study pack, videos, and web links.
• Recommended resources feature "Chemistry in Context," Marks' "Basic Medical Biochemistry," and "An Introduction to Medicinal Chemistry".

Learning Outcomes

• Identify organic functional groups
• Chemical nomenclature in drug substances
• How atomic hybridization directs bonding
• Importance of 3D shapes and stereochemistry
• Characteristics of 'drug-like' organic molecules
• Drug-receptor interactions involved in the action of medications
• Basic structure/function of amino acids and proteins
• Basic structure/function of nucleic acids
• Basic structure/function of monosaccharides and polysaccharides'
• Basic structure of lipids and explain their functions
• Major classes of vitamins, their roles, and deficiency effects
• Drug discovery process
• Structure-based drug design

Introduction to Chemistry and Biology

• Biology and Chemistry are interconnected, with the former being an extrapolation of the latter.
• Life is a collection of chemical as chemistry underpins biological processes.
• Chemistry is the study of atoms and molecules, their interactions, and their behaviors.
• Biology explores how these substances behave on a larger scale, including cells, tissues, organisms, populations, and ecosystems.
• Reading pack reinforces concepts in depiction, functional groups, nomenclature, bonding, electronics, and stereochemistry.
• The focus is on the application of chemistry to drugs and introduces fundamental macromolecule structures and functions to understand how biological cells and systems work at a molecular level.
• Molecular recognition, drug discovery, and structure-based design are introduced with real design and case studies.

Organic Structures

• Chemical structures can be represented in various ways including molecular, structural, skeletal and models
• Molecular formula indicates atoms in a molecule without connectivity shown.
• Structural and skeletal shows atoms' arrangement and connectivity
• Structural formula displays all atoms
• Skeletal formula focuses on the carbon framework and highlights functional groups.
• In organic chemistry, skeletal formulae simplify structures, where line ends and vertices represent carbon atoms.
• Hydrogen atoms attached to carbon and other atoms are always shown, but carbon atoms must have four bonds.
• Atoms that are not carbon or hydrogen are always labelled

Functional Groups

• Molecules consist of a hydrocarbon skeleton decorated with functional groups.
• The skeleton provides shape, and functional groups determine chemical reactivity.
• Functional groups are atoms or groups of atoms that serve as sites of chemical reactivity and dictate the properties of the molecule.
• Atoms in functional groups are generally more electronegative than carbon, hence contributing to polarity.
• They confer hydrogen bond donor and acceptor properties and may be acidic or basic, especially at physiological pH.
• Molecular interactions determine how a drug molecule behaves and interacts with its receptor.
• Rings, especially heterocycles, are common in drugs
• The numbering of heterocycles starts from a heteroatom.

Nomenclature

• Organic chemical nomenclature facilitates communication but first the naming basics must be understood.
• Chemical names follow a prefix-parent-suffix format.
• The 'parent' refers to the longest carbon chain length.
• The 'suffix' indicates the highest priority functional group with the most oxidized taking precedence
• Carboxylic acid is the most weighted functional grouo
• The 'prefix' describes additional substituents and their positions on the parent chain, with numbering done to give the primary functional group the lowest possible number.

Acids, Bases, and Pharmacy

• Most drugs contain weakly acidic or basic functional groups, while others contain both and are amphoteric.
• Ionisation state of a drug depends on the pH of the medium that can affect solubility, formulation, absorption, distribution and pharmacological activity.
• Pharmaceutical excipients could also contain acidic or basic functional groups.
• Acidic functional groups can donate protons and become negatively charged
• Basic groups accept protons and become positively charged.
• The pKa is the pH at which ionisation is exactly 50%

Bonding and Molecular Shapes

• Molecular shape affects interactions with other molecules, like how drugs work in the body at a molecular level .
• Geometry of an alkyl carbon is tetrahedral
• Carbon has four outer-shell electrons in s (spherical) and p (dumbbell-shaped) orbitals.
• Orbital hybridisation involves mixing atomic orbitals to form new hybrid orbitals for covalent bonds.
• Adding 1 s orbital to 3 p orbitals creates four sp³ hybrid orbitals in a tetrahedral array.
• Overlapping sp³ orbitals form alkane molecules with tetrahedral geometry, and bond angles at 109° 28'.
• In alkenes (carbon-carbon double bond), one p orbital is omitted, resulting hybridization in 3 sp² orbitals, with unused p orbital.
• In alkenes, carbons have bond angles at 120°.
• Two sp² hybridised atoms form a strong sigma (σ) bond via the overlap of an sp² orbital (of each atom)
• Overlap of parallel p-orbitals forms a weaker pi-bond (π) that restricts rotation

Hybridisation and Geometry

• Triple bonds are formed by sp hybridised atoms, with two p-orbitals left out and sp orbitals lying at 180° forming a linear geometry.
• Drug molecules usually contain C, H, N, O, S, F, Cl, P
• The oxygen atom of water has two bonds to H and two lone pairs, adopting a distorted tetrahedral geometry and compressing the bond angle.
• In summary, sigma bonds are formed by sp3 hybrid orbital overlap.
• Pi bonds are formed by p-orbital overlap and restrict rotation unlike single bonds.
• Shapes of individual atoms influence three-dimensionality and flexibility.
• A ring of sp² hybridised atoms, such as benzene results in a planar geometry.
• Chains of sp³ hybridised atoms are flexible while rings of this type of molecule are less so.

Stereochemistry

• Stereochemistry concerns spatial arrangement of atoms in molecules
• Effects impact chemical/physical properties
• In the pharmaceutical industry, stereochemistry affects clinical usage which is dependent on 3D structure.
• Stereochemistry can have impact on toxicity.
• Most drugs contain stereocentres, show stereoisomerism, and exist as enantiomers.
• An sp³ atom with four different attached groups cannot be superimposed onto its mirror image and is chiral/ enantiomer.
• Enantiomers rotate the plane of polarised light and are known as optical isomers. Other points:
• Amino acids have chiral centres while most molecules are natural occurring molecules and therefore also chiral. It is thought that this has an impact as proteins are generated. This impacts drug receptors and enymes and drugs should be optimally administered as single enantiomers.
• The side effects include sideeffect and countering drug effects.
• Thalidomide inhibits blood vessel growth, resulting in abnormalities among developing children of mothers taking the drug as a sedative.
• The (S) enantiomer causes sedation, while the (R) enantiomer causes birth defects.
• The 'chiral centre' of a molecule bears four different substituents
• 'Enatiomers' relate to isomers that are mirror images of each other which can be superimposed
• 'Diastereoisomers' define molecules that are stereoisomers
• 'Racemic Mixture' defines of two enantiomers.

Molecular Interactions Overview

• Every biological event involves molecules interacting in precise orientations.
• Whether it is an enzyme binding its substrate, a drug with an active site etc, it requires time to function properly.
• Bond polarity is the unequal sharing of electrons
• This determines the polarity and charge
• Electronegative atoms like N, O, and halogens have partial negative charges.
• C and H are more neutral or partially positive.
• In polar covalent bonds, most compounds found in medicine is an example of

Hydrogen Bonding

• The difference in electronegativity between atoms causes partial charge separation.
• More electronegative atoms attached to carbon in carbonyl groups, results in dipoles produce dipole interactions between drugs and biological receptors.
• If molecules are close to each other, such as within a micromolecule, this is described as having stringer requirement.
• Hydrogen bonds are a subtype of dipole interactions forming from electronegative atoms.
• Functional groups containing these bonds can be in various biological molecules
• Intermolecular interactions have important biological consequences
• This supports proteins in determing structure and mainaning double-stranded interactions.

Charge-charge Interactions

• Interactions are electrostatic in nature and require a less stringent setup than hydrogen bonds.
• Groups or atoms carrying a charge engage in charge-charge interactions.
• This could either be attractive or repuplsive. Key points:
• Interactions between charged groups are pH-dependent
• Amino acids are linked through peptide bonds
• Therefor carboxyl groups can lead to multiple interactions within or between molecules:
• By meaning water hating' groups hydrophobic interactions do not cause elecrostatic forces.
• Whereby hydrophobic molecules interact differently with water as hydrophilic groups are polar but interect through electrostatic charges
• Methyl groups have no interactions with water as there little tendency to release electrolites.

Complex Molecules: Amino Acids and Proteins

• Proteins consist of amino acids linked by peptide bonds
• Proteins compose of all cells for digestion, neurotransmission and immunity.
• Amino acids have an acidic (carboxylic acid) group while a basic (amine) group also featured.
• All consist of the 20 amino acids.
• They are classed as alpha because they have a carboxyl acid group is a key component to standard bodies.
• Glycine is an exception of general amino acids because it has asymmetric centres.
• For essential bodies, the non essential bodies is an essential part of life.

Amino Acids and Peptide Bonds Continued

• Amino acids have at least two and up to three acid-base groups that are amphoteric.
• This means that if a protein is in the middle of it's solution, it could either react both ways as an amphoteric, i.e. with acids and bases.
• As the amount is increased towards a acidic solution, the amino solution will unionise.
• As solution becomes deprontonated with an active ph, it does not exist.
• Zwitterions have no charge but is formed in between acidic.
• Amino acids can join to become two molecules but is created and know as peptide bonds

Protein Types

• Proteins can further develop to become polyopeptide chains. However over 100 is considered a protein.
• Amino acids are identifiable used a three letter identification. Short chains are named as residues.
• After proteins are formed they are able to adapt by addition from proline for additional function
• There 4 levels of protein structure. This includes the primary, secondary and tertiary, as well as quaternary aspects.
• Some examples of the functions of the proteins include collagen, myosin, and glucose transporters.
• Globular peptides have an irregular rounded shape where they can use alph helices.
• Fibrous proteins have linesr or sheet like structures which can be soluble.
• Structure directly links to the functinality, such as with sickle cell anaemia.

Nucleic Acids

• Nucelic acids form compunounds that encodes proteins through genes.
• Consist of DNA and RNA.
• DNA contains two molecules coiled around each other as a helix with specific bases.
• A pairs with T Key points:
• DNA requires transcription/ tranlation for mRNA to form
• mRNA is translated and transported with ribosomal protein to the 3 based conon.
• Biotechnology defines the uses of molecular methods to form or engineer the genes.
• Molecular diagnostics looks for medical gene changing methods.
• Genetic counselling can be done through different copies of haemooglobin to find which individual was infected.

Optimal Treatment For Medicines

• A person's nucleotides can identify how cuickly their metabolisim wil function
• The liver enzyme CYP2C19 catalyses the function while some possess SNPs, where some patients are effective and some are not.
• Structurally nucliec acid structures allow the change and diagnosis of treatments with diseases.
• Key structures and enzymes are required to maintain function of the body such as in clinical trials.

Sugars and Polysaccharides

• Saccherides are produced from simple molecules
• A good example are monosaccharides which provide enegry Key points:
• Mono saccharides from deoxyribose and ribose is essential for the parts of nucleic acid and DNA.
• Polyosachharide macromolecules cosist of hundreds, or even thousands of saccharides combined togerher via chemical bonds
• Glycogen and starches exist in animals and plants which is stored in the cells and muscle. While cellulose is a component of plants.
• Steriochemistry impacts charateristics such as in lactose. This influences tablets.

Lipid and Cholesterol Introduction

• Oxygen impacts lipids, however their properties influence the saturation and content.
• The bodies have properties from glycerol, with droplets and is an energy source.
• An example of lipids would be cholesterol, which comes with active vitamin D and transport proteins. Key points:
• Bloods such as LDL transports from liver
• While HDL helps in lowering amounts by returning to liver.
• High LDL cholesterols in bodies results in cardiovascular diseases
• Statins reduce LDL levels and is a common treatment
• HMG-CoA leads to increased amount, which decreases if stepped and treated from inflammatory signalling.

Vitamins

• Vitamins act as enzymatic reactions and processes.
• B6 has inter-convertible forms with B molecules which forms most of the molecules.
• Folic acid is a dietary unit for liver green vegetables.

Enzymes and Inhibitors

• Enzymes change substrates and activation energy
• These result in rate of the chemical reactions and consumed without a result Key points:
• Virtually the human body involves enzymes and understanding is important for the bodies health
• Activity works through the quatemary structure
• They require co-enzymes and cofactos, to function properly by being organic molecules.
• How enzymes function and different tests influence the speed.

Drug Design and Descovery

• Popularity in "drugs" lead to substances misused
• The word however defines treatments for medicine which helps. Key points:
• As a part of medical process, it defines molecules which affect bodies both positively and negatively
• There can be negative processes in treatment and effects dependent on dosage.
• Examples include the use of penicilin which assists and supports bacterial growth and the use of sugar for taste
• Types of molecules inclide anti cancer, antibiotics and statins
• There are 3 types of drugs, synethietic, semi-synthetic and other antibiotics