MEDICINAL CHEMISTRY Flashcards

1
Q

medicinal plants

A

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

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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
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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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
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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
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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.