MEDICINAL CHEMISTRY Flashcards
1
Q
medicinal plants
A
medicinal plants: plant extracts that have a biological impact on the body
2
Q
extraction and purification of active ingredients
A
- extract the molecules of interest from the plant
- separate the molecules from each other
- determine the structure of each component
3
Q
solvent extraction
A
- 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
4
Q
steam distillation
A
- 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
5
Q
separating the molecules in plant extract and determining their structure
A
- 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
6
Q
structure of protein
A
- 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
7
Q
primary structure of proteins
A
- 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
8
Q
secondary structure of proteins
A
- 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
9
Q
alpha helices
A
- 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
10
Q
beta pleated sheets
A
- 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
11
Q
tertiary structure of proteins
A
- 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)
12
Q
5 type of attractions in tertiary structures
A
- 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
13
Q
quaternary structure of proteins
A
- made up of more than one polypeptide chain
- some proteins may even interact with non-protein molecules to produce large, complex functional units
14
Q
denaturation of proteins
A
- 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
15
Q
enzymes
A
- 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
16
Q
structure and function of enzymes - lock and key model
A
- 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
17
Q
effect of temp on enzyme activity
A
- 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
18
Q
denaturation vs hydrolysis
A
- 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
19
Q
effect of pH on enzyme activity
A
- 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
20
Q
stereoisomers
A
- 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
21
Q
enantiomers
A
- 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
22
Q
distinguishing between enantiomers
A
- 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
23
Q
chiral drugs
A
- 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
24
Q
competitive enzyme inhibitors
A
- 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**
25
Q
non-competitive enzyme inhibitors
A
- 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
26
Q
enzyme action and chirality
A
- 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
27
Q
why has chirality become a strong focus in drug development
A
- 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.
