Medicinal Chem SAC 5

What is a qualitative test

Where you test for the presence or absence of some component

What is a quantitive test

Where we seek to measure the amount present

What reaction will be used for a carbon double bond to determine its presence

A reaction with a reactive addition reagent

What is an example test that can be used on a Alkene to determine its presence

Bromine water - if a double bond is present then the brown bromine water becomes decolorised, while if no double bonds are present then the brown colour will persist

Why is a water solubility test useless to determine the presence of a carboxylic acid group?

• other functional groups such as hydroxy and amino groups also confer solubility

• Carboxylic aids with large non-polar, hydrophobic regions will have low solubility

What are the tests we can do to determine the presence of a carboxylic acid?

• use an indicator such as litmus paper or universal indicator - only works if soluble in water

• Reacting it with carbonate or hydrogen carbonate base, which produces a fizz due to formation of carbon dioxide - Acid + NaHCO3 → salt + water + carbon dioxide

What is the test you should do to test for an alcohol

Oxidation, as the oxidants will undergo a characteristic color change when they react

Which alcohol does oxidation not work for to determine its presence

A tertiary alcohol

What is the better way of determining alcohol presence

React it with a carboxylic acid to form a ester, after the reaction, if alcohol was present the ester will sit on the top

How do you assess purity in a lab

• in modern labs you use a high pressure liquid chromatography machine

• The melting a boiling point provide a simple lab method for assessing purity

To measure melting point, what should you do to the substance

Crush it up to increase surface area

What will impurities do to melting point

• lower the melting point - never increase it

• Broaden the range over which the melting point occurs

What should be done to assess purity if coincidently different compounds share similar melting temperatures and why?

They should be measured, then remeasured after a small quantity of the authentic material is added and the temp is remeasured, if pure temp range will not change, if not then it will broaden and lower the melting point and range

Why is care needed when measuring the boiling point of a liquid

The boiling temp of a liquid depends critically on the ambient pressure.

What do dissolved impurities in a liquid do to the boiling point usually?

They raise it

To increase purity of solids, what should be done

Recrystallisation

What inevitably happens after recrystallisation

Some of the desired compound remains in solution and is lost. This lowers the overall yield but provides a higher purity

How do you purify liquids

Distillation

What impurities does simple distillation work on

Non-volatile and impurities with higher boiling points than the liquid

What do you use when the impurities have a similar boiling point to the liquid

Fractional distillation

What is a redox titration

When you do a titration using coloured species to locate the end point

What oxidants in particular are used for redox titrations and why

• I2 for determination of unsaturation

• Cr2O7 2- or MnO4 - for determination of hydroxy groups

What is a standard solution

A solution with a concentration know to high precision and accuracy

What is a primary standard

A pure solute from which a standard solution can be prepared by precise weighing and dissolving

What is the endpoint

The point where some permanent change is observed that signals that titrant addition should be halted

What is the equivalence point

The point where the reactants have been combined in exactly the correct stoichiometric ratio

What is the aliquot

A fixed volume portion of solution, measured with a pipette previously raised with the soliton to be measured

What is the titre

The volume of titrant required to reach the end point, measured from a burette

What does a mass spectrometer do

It measures the mass of moving positive ions by measuring the deflection produced by the sideways force

What are the 4 steps of mass spectrometry

1. Ionisation - shooting of ions at the molecule to knock off electrons to leave them positively charged

2. Acceleration - an electric field gets these cations moving through the instrument with a fixed amount of kinetic energy

3. Deflection - magnetic field gives the moving cations a sideways kick that causes a deflection in their path

4. Detection - the stream of cations can be detected as current

What does the magnitude of the deflection depend on

• the mass of the cation with lighter particles deflected more

• The size of the charge on the cation. A 2+ ion will get a bigger kick from the magnetic field and undergo a deflection twice as large of a 1+ ion

Why does a mass spectrometer minimise the formation of charges larger than 1+

To avoid ambiguous signals where they have the same m/z

What is a molecular ion

• a positive charge

• An unpaired electron

What is a free radical

A species with an unpaired electron

When a molecule fragments what does it produce

One cation and one neutral fragment, however, only the positively charged fragments can produced a signal in the mass spectrum

What does a higher wave number mean in infrared spectroscopy

Large wave numbers represent higher frequency, and hence higher energy, photons

If placed in a strong magnetic field what happens to the spinning molecules

They will tend to align

What is electron shielding

The amount of electrons protecting the nucleus from external magnetic fields, which changes the frequencies which are absorbed

What does NMR give?

An indication of the bonding environments of the atoms whose nuclei are absorbing energy

What is TMS

Tetramethylsilane, a silicone atom with 4 methyl groups

Why is TMS used as an internal standard in HNMR

The hydrogen atoms in this molecule retain a large amount of electron density and so their nuclei are more strongly shielded than hydrogen atoms in most other compounds.

What is a chemical shift

A measure of how different the absorption frequency of a hydrogen atom from that of the hydrogen atoms in TMS

What does a low shift mean

A high electron density and a more shielded atom

What does the addition of a more electrodense atom do to the shielding of a atom

It makes it more deshielded as it withdraws more electron density from around the H atoms

What is peak intergration

The ration of the sizes of the peaks in a HNMR between different chemical environments

What are hydrogen environments (chemical environments)

Different bonding environments

What is the number of sub peaks in a group basically related to

One more than the number of hydrogens on adjacent carbon atoms

What are the three relevant points important when determining the number of sub peaks

• An absorption peak is only split by adjacent hydrogen atoms that are non-equivalent (in different environments)

• The effects of hydrogen atoms further away than one carbon are negligible

• Hydrogen atoms on other atoms than carbon do not cause splitting

What are the 3 key points of C13NMR

• the number of peaks in the C13 spectrum corresponds to the number of different carbon environments in the sample molecule

• There is no peak splitting in C13 spectra

• Chemical shifts are generally larger in C13NMR than HNMR

What is the material the mixture is added to called in chromatography

The stationary phase

What is the origin - chromatography

Origin

What is the mixture carried along by in chromatography

The mobile phase

What do molecule that from bonds to the stationary phase become

Adsorbed

What is the word you must use when referring to the want to bond of polar molecules to a polar stationary phase

Affinity

What is the mobile phase

It is typically a liquid solvent or solvent mixture in which the sample molecules dissolve and are carried through the stationary phase

What are molecules that are highly soluble to the mobile phase said to be

Desorpt

What is liquid chromatography

It is where the stationary phase is a thin layer of fine compacted powder on a solid sheet

What is the rf value

Distance travelled from the origin/ distance travelled by the solvent from the origin

What is a key factor that plays into the Rf value

The conditions under which it was recorded

How do you use Rf values to identify components

You run both the mixture and a pure substance, making them have identical conditions, thus you can compare

What is different about column chromatography

• it uses Rt not Rf

• The stationary phase is a powder that is packed into the tube

• The mobile phase is continuously added

• The mobile phase is called the eluent

What is HPLC

High performance liquid chromatography

What are the two reasons HPLC is closely related to column chromatography

• the SP is a finely divided solid or a viscous liquid coated onto a finely divided solid surface

• The mobile phase is liquid and called the eluent

How do you extract chemicals from their natural sources like plants

By dissolving them in appropriate solvents

What substances dissolve in polar solvents

It would only dissolve polar substance

What substances dissolve in non polar solvents

Only non-polar substances would dissolve

What are the key steps involved in extracting soluble compounds from a particular natural sources

• crush/grind up the plants/leafs

• Dissolve in suitable solvents

• Flitter away solid residue

• Distill off solvent (if solid recrystallisation, test purity with MP)

How does steam distillation work

Steam is generated and passed through finely divided plant material. Any volatile compounds in the sample are picked up and carried along by the steam. Leaving a layer of non polar oils onto of the water

What are structural isomers

• have different physical properties

• Can posses different functional groups which can result in very different properties

What are Stereoisomers

They have the same formula and same bonding connections, however they differ in some permanent difference in the way atoms are arranged spatially

What is a geometric isomer

When the isomers contain some structural feature that prevents rotation about one or more bonds, the most common is C=C

What happens to the properties of geometric isomers

Even though they share the same functional groups, they will tend to have the same physical properties but due to their different molecular shape they may not be identical

What is an optical isomer

They are when they are mirror images of each other - chiral

What is a Chiral carbon

When the carbon atom is bonded to four different substituents

What does a chiral carbon do to light

It causes rotation of this polarised light, in opposite directions

What is the difference between two optical isomers, and how does this effect their interactions

They interact differently with other chiral objects

This causes difference interactions between:

• chiral reactants colliding in a chemical reaction

• Chiral solutes and chiral solvents

• Chiral reactants and chiral catalysts

Why are amino acids named amino acids

Due to the presence of both:

• an amino group

• An acidic carboxyl group

What are amino acids from which human proteins are composed called? And why?

The are called Alpha Amino acids because the amino group is attached to the same carbon atom as the carboxy group

Why are Alpha amino acids generally chiral

As the alpha carbon has 4 different substituent groups

What happens to an amino acid in low pH acid solutions

The amino group gains a Hydrogen and the nitrogen becomes positively charged, creating a positively charged amino acid

What happens to an amino acid in high pH basic solutions

The hydrogen from the hydroxy group is lost, creating a negatively charged Oxygen, overall making the amino acid negatively charged

In aqueous solutions at neutral pHs what happens to the amino acids and what is this called

Both the amino and the carboxyl group are ionised and this is called a zwitterion

Can the Z side chain of an amino acid possess acid-base characteristics

Yes, allowing for ionisation like what happens to the alpha substituent groups

What is a fibrous protein

Where the protein chains are aligned and held together by strong bonds

What are globular proteins

they are proteins that fold into a compact, roughly spherical shape. It’s structure is stabilised by interactions such as hydrogen bonding, ionic interactions, hydrophobic interactions and sometimes disulfide bridges between amino acid chains

Are globular proteins soluble

Yes, as the hydrophilic amino acids side chains tend to face outwards while the hydrophobic side chains are tucked inside

What does the globular proteins precise shape do

The precise arrangement of the protein chain in an enzyme is essential to its ability to catalyse a chemical reaction

What is a primary structure, and what is it held together by

It is the sequence of amino acid residues in a chain, these are held together by the strong covalent bonds in peptide links

What is the secondary structure of a protein

It is the pleating or coiling of the protein chains tend into a helix, thus the secondary structure is a result of hydrogen bonding between distant peptide groups on the backbone of the chain

What is the tertiary structure of a protein

When the coiled protein chains becomes folded or twisted in specific ways to produce the final 3D shape, which is unlike the secondary as it involves the Z side groups

What are the important interactions for the tertiary structure

• strong covalent bonds in the form of disulfide linkages (s-s)

• Repulsion’s between bulky or like charged Z groups

• Attractions between oppositely charged Z groups - ionic attractions

• attractions between polar and charged Z groups - ion dipole

• Hydrogen bonds between polar z groups

• Hydrophobic interactions, where non polar side chains clump in the middle of the folded protein, bonded by dispersion forces

What is the quaternary structure

When multiple tertiary structures bond to form a single active form protein

Why are enzymes like all catalysts

• they increase the rate of chemical reaction

• Are unchanged by the reaction

Compared to inorganic catalysts, enzymes

• achieve much larger rate increases

• Are specific for action on a certain chemical species called the substrate

• Work best only within narrow ranges of temperature, pH

• Are readily destroyed (Denatured)

What does the bonding of the substrate to the enzyme do to the substrate

Weakens the bonds within the substrate molecule, thus the AE is lowered and the reaction occurs quicker

What does the lock and key model mean

The active site of the enzyme has a more or less fixed shape that the substrate must fit into

What cause denaturation

• heating - can break the bonds due to additional vibrational energy, disrupting tertiary and secondary structure

• Changes in pH - can alter the charges on the ionic side groups and disrupt the tertiary structure

• Certain chemical species - can bond to the side group and disrupt the normal bonding altering its shape completely

What is coagulation

When a protein is denatured and new bonds form between separate protein chains, causing them to clump together, making it likely to be solid and insoluble

At temps below optimum, what happens to enzyme activity

Going below the optimum lowers the rate of reaction, but as the temp increases towards the optimum, the kinetic energy increases, and the ROR increases

At above the optimum, what happens to the enzyme

As temperature increases past the optimum, the rate rapidly decreases due to the temperature causing the denaturation of the enzyme