MEDICINAL CHEMISTRY

Question 1

medicinal plants

Answer 1

medicinal plants: plant extracts that have a biological impact on the body

Question 2

extraction and purification of active ingredients

Answer 2

• extract the molecules of interest from the plant
• separate the molecules from each other
• determine the structure of each component

Question 3

solvent extraction

Answer 3

• transfer all the molecules of interest from plant into a solvent
• extract- molecules of interest in a solvent
• solvent extraction is a separation process that involves a liquid and solid
• plant - solid is placed into contact with the solvent - liquid → allow extract to go into solvent
• plant is often ground or blended to break up plant structure
• solvent is selected to ensure that the polarity of the solvent matches the polarity of the molecules of interest
  
  • water for extracting polar molecules
• temp may be adjusted to help w extraction

Question 4

steam distillation

Answer 4

• used when active ingredients are volatile and thermally stable
  
  • doesn’t break down or easily degrade when heat is applied
• boiler is used to porduce a flow of steam - passes through the leaves
• the hot steam breaks down the plant cells and carries plant oils with it
• steam and oils are then condensed
• oils - non-polar form a layer on top and can be separated from water layer at the bottom
• plant oils produced this way are not pure substances and are a mixture of many components

Question 5

separating the molecules in plant extract and determining their structure

Answer 5

• using chromatographic techniques
• extracts obtained often contain many diff compounds
• chromatographic techniques such as HPLC can be used to separate these mixtures into individual components
• can be determined using mass spectroscopy, NMR, and infrared spectroscopy

Question 6

structure of protein

Answer 6

• function of protein depends on the 3d shape of the protein
• proteins are directional molecules
  
  • order - sequence of amino acids guides how a protein bends and folds
• the amino acid side chain within the sequence bond with another to hold a length of a protein in a certain shape or conformation - determines its unique 3d shape
• shape of protein: primary, secondary, tertiary and quaternary structures
• using higher order structure phrase may be beneficial

Question 7

primary structure of proteins

Answer 7

• the linear sequence of amino acids that make up a protein
• tells us the number, type and sequence of the amino acid units in a protein
• entire shape pf protein is determined by the precise orderin which the amino acids are joined together

Question 8

secondary structure of proteins

Answer 8

• describes the coiling or pleating of sections of the chain
• hydrogen bonds can occur between the -NH group in one peptide link and the C=O group in another peptide link
• these hydrogen bonds can form at regular intervals creating coils (alpha helices) or parallel sections (beta pleated sheets)
• highly ordered segments and stabilised by hydrogen bonds
• most proteins contain multiple helices and sheet

Question 9

alpha helices

Answer 9

• hydrogen bonds make the long molecule coil around into a shape called an alpha helic
• hydrogen bonds link four amino acid units along the chain

Question 10

beta pleated sheets

Answer 10

• can form between peptide links when two or more parts of the chain line up parallel to each other
• the repeating structure of the backbone of the protein chain (N-C-C-N-C-C-N) ALLOWS HYDROGEN BONDS to form at regular intervals which stabilises the protein structure
• silk - protein with Beta pleated sheets
  
  • every second R group is a H atom
  • small side chains enable section of the protein molecule in silk to line up closely
  • enable hydrogen bonds to form between these adjacent sections to produce beta pleated sheets
  • form a regular pattern giving silk its strength and texture

Question 11

tertiary structure of proteins

Answer 11

• overall 3d shape of a protein
• produced by further folding of its secondary structures (α-helices or β-pleated sheets).
• overall 3d shape is influenced by side chains - R group of the amino acid units
• some side chains
  
  • very large/small
  • polar
  • hydrophobic (non-polar)
  • charged (dependent on pH)

Question 12

5 type of attractions in tertiary structures

Answer 12

• hydrogen bonds
• dipole-dipole interactions
• ionic interactions -> between NH3+ AND COO-
• covalent crosslinks -> disulfide bridges - cysteins R-groups
• dispersion forces
• note - although ionic bonds are very strong in ionic solids - in a protein structure they are disrupted before the covalent primary structure
  
  • covalent bonds are stronger than ionic in proteins

Question 13

quaternary structure of proteins

Answer 13

• made up of more than one polypeptide chain
• some proteins may even interact with non-protein molecules to produce large, complex functional units

Question 14

denaturation of proteins

Answer 14

• protein is highly dependent on 3d structure - when denatured, proteins loses its function
• denaturation is a process in which proteins lose their quaternary, tertiary and secondary structures
  
  • bonds that give the proteins specific 3d shape are disrupted or broken
  • protein become unfolded
  • can be reversible or non-reversible
• proteins can be denatured when it is subjected to any treatment that breaks its hydrogen bonds, ionic bonds or hydrophobic bondsby changing temperature, pH, or adding a reductant
• when a protein is denatures, the tertiary and quaternary structures are disrupted first, then the secondary structure
• in tertiary structures, dispersion forces are the weakest
  
  • hydrogen bonds are stronger than normal dipole bonds and covalent bonds are stronger than ionic bonds

Question 15

enzymes

Answer 15

• biological catalysts that accelerate the rate of chemical reactions in cells
• only needed in small amounts
• not used up or changed
• provide an alternative pathway - lower activation energy
• increase rate of reaction
• doesn’t change equilibrium constant
• compared to inorganic catalysts - enzymes are more sensitive to changes in reaction conditions
• catalysts only work under a narrow temp range and are sensitive to changes in the pH
• enzymes are very specific for a single reaction or type of reaction

Question 16

structure and function of enzymes - lock and key model

Answer 16

• an enzymes 3d shape is dependent on the tertiary and quaternary structure
• enzymes specificity depends on overall 3d structure
• the active site is usually uniquely shaped flexible hollow or cavity within the protein where the reaction occurs
• the reactant molecule binds with the active site - substrate
• enzyme and substrate together → enzyme-substrate complex
• lock and key model
  
  • substrates are specific to enzyme’ active site

Question 17

effect of temp on enzyme activity

Answer 17

• the temp at which enzyme activity is the greatest - optimum temperature
• diff enzymes have diff optimum temp
• enzymes in human have optimum temp of 37

when temp are above optimum

• increased kintetic energy disrupts the 3d structure of the enzyme
• increased movement causes breaks in some intermoelcular forces (hydrogen bonds) that hold the tertiary and quarternary structure in place
• change in the 3d shape of the enzyme means the active site can no longer effectively catalyse the reaction
  
  • reaction rate decrease rapidly

when temperatures are below optimum

• enzyme and substrate molecules have lower kinetic energy - less frequent and less energetic collisions
• enzymes are deactivated

Question 18

denaturation vs hydrolysis

Answer 18

• when temp is too high or pH changes are too large→ kinetic energy of the polypeptide chains cause the bonds between side chains R groups to break - denaturation
• destroys 3d structure of enzyme - often irreversible
• enzyme is denatured - and has lost its catalytic activity

denaturation vs hydrolysis

• denaturation
  
  • 3d structure - tertiary and/or quaternary structure is destroyed
  • polypeptide chain is still intact
• hydrolysis
  
  • polypeptide chain is broken
  • amide (peptide) bonds are broken

Question 19

effect of pH on enzyme activity

Answer 19

• most effective within a narrow pH range
• all proteins are affected by pH
• eg. lysine and glutamic acid forms ionic bonds called salt bridges at intermediate pH values
• when a strong acid or base is added, salt bridge is disrupted and leads to denaturation of the protein
• causes the enzymes active site to change shape - enzyme loses its ability to function effectively - loss in enzyme activity
• pH affects the protonation of R groups changing its interaction with side chains
• a change in pH could add or remove H+ ions, resulting in the loss of an ionic interaction
• a reducing environment could add H atoms to the S atoms in a disulfide bridge, thus breaking the S–S covalent bond

Question 20

stereoisomers

Answer 20

• atoms are connected in the same order but they are oriented differently in space
• have the same molecular and semi-structural formula but have diff chmical properties
• optical isomers - chiral moelcules which do not contain a plane of symmetry
• chiral molecules - has a chiral centre (carbon bonded to four different group of atoms)
  
  • cannot be superimposed on its mirror image
  • marked with an asterisk
  • a molecule must have one chiral centre to be considred chrial
  • some molecules with more than one chiral centre are not always chrial
• dashed line represents a bond facing away from you
• wedge line represents a bond facing towards you

Question 21

enantiomers

Answer 21

• cannot be superimposed on each other
• are mirror images
• do not contain a plane of symmetry
• enantiomers have identical physical properties - same boiling/melting point, solubility EXCEPT for the rotation of polarised light
• chiral molcules interact differently with other chiral molecules

Question 22

distinguishing between enantiomers

Answer 22

• if polarised light rotated clockwise → it is the + enantiomer (D/R- enantiomer)
• if it is rotated anticlockwise, it is the - enantiomer (L/S enantiomer)
• when optically active substances are synthesised, a 50/50 mixture of two enantiomers are often produced

Question 23

chiral drugs

Answer 23

• human body contains mainly chiral molecules
• optical isomrs hav diff effects on human body
• many pharmaceutical drugs exist as enantiomers - only one has th desired pharmeceutical effect
• outcomes when pharmecutical activity of enantiomers are compared
  
  • one is more effective than the other
  • each enantiomer has a diff effect on the body
  • one enantiomer is effective while the other is harmful

Question 24

competitive enzyme inhibitors

Answer 24

• bind to the active site of an enzyme in place of its substrate
• the inhibitor and the substrate tend to have similar shapes - competition between two molecules to bind to the active site
• the inhibitor can bind to the active site - prevent reaction from proceeding
• substrate can also bind to active site and reaction proceeds
• extent of inhibition depends on the concentration of the substrate, concentration of the inhibitor and the relative binding affinity to the active site**
• small structural differences between inhibitor and substrate may increase binding affinity of the inhibitor to the active site**

Question 25

non-competitive enzyme inhibitors

Answer 25

• works by binding to a different part of an enzyme than the active site
• this causes the shape of the active site to change such that it no longer matches the shape of the substrate
• as the inhibitor is not directly competing for the active site of the enzyme - concentration of substrate doesn’t impact the effectiveness of the inhibitor

Question 26

enzyme action and chirality

Answer 26

• Enantiomers of a chiral compound have the same molecular and structural formula, but different spatial arrangements of the atoms (mirror images)
• Active site often can only be accessed by one enantiomer of a chiral compound
• A chiral compound has a carbon atom with four different groups bonded to it
• When determining if a compound is chiral, discount any Cs with more than one H
• Most amino acids are chiral – exception is glycine

Question 27

why has chirality become a strong focus in drug development

Answer 27

• Chiral molecules are optical isomers, whose mirror images cannot be superimposed on top of each other.
• Chiral molecules are identified through chiral centres; usually a carbon atom with four different atom groups bonded to it.
• The two enantiomers of a drug can have different biological effects. Sometimes the two enantiomers have different therapeutic effects and sometimes one enantiomer could have
  a detrimental effect.

The challenges faced by manufacturers could include
* Increased testing of enantiomer drugs is required to check for biological effects and safety.
* Separation and purification of the enantiomers can be difficult and costly.
* Increased length of time between development and availability to the public.
* Working within government regulations that require single enantiomer drugs due to possible negative side effects.
* New technologies may need to be developed to allow for greater separation and purification of enantiomers, increasing the cost and time required.