Physical properties, analytical chemistry, purity determination and compounds separation Flashcards
Physical property
characteristic of matter that can be measured or observed without a change in its chemical composition
Examples of physical properties:
colour, hardness, mass, volume, malleability, solubility, electrical conductivity, density, lipophilicity, melting point, boiling point
flammability, toxicity, acidity (pH), reactivity (many types), heat of combustion
Intensive properties
not depend on the amount of substance (i.e. temperature)
Extensive properties
depend on the amount of substance (i.e. mass, volume)
Chemical property
can be measured by changing the chemical composition of a substance
Physical states
amorphous solid, crystalline solid, hygroscopic solid, liquid or gas
Intermolecular forces
attraction forces between molecules (non-bonding)
1) Dipole-dipole interactions
interactions between the positive end of one dipole and the negative end of another dipole
2) van der Waals Forces
relatively weak forces of attraction that exist between nonpolar molecules. Distance-dependent interactions. Called induced dipole–induced dipole interactions.
3) Hydrogen bonding
attractive force between the H attached to an electronegative atom of one molecule and an electronegative atom of the same (intramolecular) or a different molecule (intermolecular). i.e. H2O
Melting point (mp)
temperature at which a solid becomes a liquid
Melting point H2O (ice point)
at 1 atm is 0 °C (32 °F, 273.15 K)
Characterise organic compounds and confirm their _____
purity
mp pure compound
always higher than the mp of an impure compound
Increases as the molecular weight _____
increases
Packing:
how well the individual molecules in a solid fit together in a crystal lattice (symmetrical three-dimensional arrangement of atoms inside a crystal).
The _____ the crystal lattice, the _____ energy is required to break it and eventually melt the compound
tighter
more
Boiling point (bp)
temperature at which the vapour pressure of the liquid is equal to the atmospheric pressure. Temperature at which a substance can change its state from a liquid to a gas at a given pressure
Strongly influenced by intermolecular forces
bp increases as the molecular size _____
increases
What are the factors of VDW forces
area of contact between the molecules
the _____ the area of contact, the ______ are the van der Waals forces
greater
stronger
the ______ the amount of energy required to ______ these forces
greater
overcome
Branched alkane has
more compact, less surface area for force interactions. Boils at a lower temperature
Hydrogen bonding
OH hydrogen → strongly polarised → H-bond with a pair of nonbonding electrons from the O of another alcohol molecule increasing bp
Dipole–dipole attractions
polarised C-O and H-O bonds and the nonbonding electrons produce a dipole moment of 1.69 D in ethanol, compared with a dipole moment of only 0.08 D in propane
H-bonds
clearly much stronger intermolecular attractions than dipole–dipole attractions
Carboxylic acids high bp:
Carboxylic acids high bp:
H2O: high polar solvent
excellent solvent for polar and ionic molecules
poor solvent for nonpolar molecules
Hydrophilicity or lipophobicity?
ability of a chemical compound or drug to go into solution in H2O and polar solvents (e.g. MeOH) and have “fear of the fat “.
Hydrophilic or lipophobic molecule are polar or ionic, forms H-bonds and
dipole-dipole with solvent, fat insoluble, cannot cross cell membrane,
bind to receptor molecules on the outer surface of target cells
Biological membranes are
lipophilic and the rate of drug transfer for passively absorbed drugs is directly related to the lipophilicity of the molecule
µ=𝛿 x d
What is this equation used for? and what does each letter mean?
Bond polarity and bond dipole moments
𝛿 = amount of charge
d = distance between of charges
Polarity of a molecule
indicated by the molecular dipole moment of the entire molecule
Molecular dipole moment of a molecule
equal to the vector sum (sign is important) of the all individual bond dipole moments
Solubility
amount of a solute that can be dissolved in a specific solvent under given conditions.
Measure of how much of the solute can be dissolved into the solvent at a specific temp
“Like dissolves like.”
Polar substances dissolve in polar solvents, and
nonpolar substances dissolve in nonpolar solvents
1) Polar Solute in a Polar Solvent (Dissolves)
The process of dissolving solute in solvent is called solvation, or hydration when the solvent is H2O
H2O molecules surround each ion, with the appropriate end of the dipole moment next to the ion
2) Polar Solute in a Nonpolar Solvent (Does Not Dissolve)
Nonpolar molecules (no partial charges) do not solvate ions very strongly.
Attractions of the ions in the solid for each other are much greater than their attractions for the solvent
3) Nonpolar Solute in a Nonpolar Solvent (Dissolves)
Molecules of a nonpolar substance: weakly attracted to each other, and these van der Waals attractions are easily overcome by van der Waals attractions with the solvent
4) Nonpolar Solute in a Polar Solvent (Does Not Dissolve)
Nonpolar molecules: weakly attracted to each other, and little energy is required to separate them.
H2O molecules: strongly attracted to each other by their hydrogen bonding
“Like dissolves like also applies to the mixing of liquids. “
What is immiscible?
do not mix! NONPOLAR
e.g. H2O and gasoline (or oil)
Miscible liquids are POLAR molecules
Ethyl alcohol and H2O
n-hexane and dodecane: miscible in one another because….
they are nonpolar - not miceable TOGETHER
Partition coefficient
Substance added to a pair of immiscible solvents → distributes itself between the two solvents according to its affinity for each phase (solvent)
aqueous or polar phase is a…..
Polar compound (e.g. ionised drug or amino acids):
non-aqueous or organic phase is a….
Non-polar compound (e.g. non-ionised drug):
Partition law:
a given substance, at a given temperature, will partition itself between two immiscible solvents in a constant ratio of concentrations’.
Partition coefficient P= [ _____ / _____ ]
[organic]/ [aqueous]
Predict ADE of drugs within the body
Predict the onset of action of drugs or the duration of action of drugs
What is Drug design?
used in mathematical equations that try to relate the biological activity of a drug to its physical and chemical characteristics (QSAR)
Chemistry laboratory:
separate, purify or extract compounds
Calculation =
Consider the distribution of 100 mg of a drug between 50 mL of an organic solvent and 50 mL of H2O
In a separating funnel;
66.7mg (2) {unionised } ORGANIC 50ml <> 33.3mg (1) {unionied} WATER 50ml
a) organic]= 66.7/50 = 1.33 mg mL-1
[water]= 33.3/50 = 0.67 mg mL-1
b) P=[organic]/[aqueous]=1.33 mg mL-1/0.67 mg mL-1=2
c) % of drug extracted: simply the mass of drug in the organic phase divided by the total mass of drug, i.e. 66.7/100 x 100= 66.7%.
Weak acid or weak base
ionisation to form an anion or a cation alters the solubility profile of the drug
Partition coefficient depends;
vary depending on the pH at which the measurement is carried out
1] Adjust the experimental conditions;
measure P of the unionised molecule
P value for acids: measured at low pH when the acid is unionised
P value for bases: measured at high pH to prevent ionisation
2] Apparent partition coefficient (Papp)=
Ptrue x funionised
Ptrue:
true partition coefficient of the unionised species
Papp :
dependent on the proportion of substance present in solution, which in turn depends upon the pH of the solution
if funionised=1 Papp = Ptrue and the compound is ______
UNIONISED
shake flask method =
logP=[organic]/[aqueous]
e.g. 1-Octanol: results obtained seem to correlate best with biological data obtained in vivo.
Hydrophobic/ hydrophilic =
aqueous buffer (pH 7.4) = represents aqueous compartments within the body, e.g. blood plasma.
Partition coefficient step by step ( list 4 steps)
- The two phases are mixed
- Two phases separate→ the drug is added (flask shaken)
- Two phases allowed to separate → concentration of drug in the aqueous phase is then determined (titration, spectrometry).
- Concentration in the octanol phase: found by subtraction and the value of P is calculated.
Separation
purification of mixtures
Side-reactions and by-products is a results of
Incomplete chemical reaction
Drugs isolation from complex mixtures of chemicals e.g.
isolation of a drug metabolite from a blood or urine sample
Non-ionised
dissolve well in non-polar organic solvents (diethyl ether, chloroform or ethyl acetate)
Ionised acids (conjugated base-e.g.
COO-) and bases (conjugate acid-NH3+): more soluble in aqueous solvents (water or buffer)
Acidic molecules:
Soluble in organic solvents at low pH (unionised)
Soluble in polar solvents at high pH.
Basic molecules:
soluble in organic solvents when the pH is high (unionised)
Soluble in water at low values of pH
Separation: if our compound is not pure after partition
Is a purification required?
Yes
Purification
if our compound is pure after partition (solids and liquids)
Recrystallisation
Procedure for purifying an impure compound in a solvent (solids only).
Based on the principle that the solubility of most solids increases with increased temperature
If your compound A is contaminated of compound B, we use a solvent in which:
A: not soluble at room temperature (25˚C) but it is soluble in the hot solvent
B: soluble (or partially soluble) at room temperature and when the solvent is hot
A+B= adding hot solvent, A and B go in solution.
Solvent cool down: A is not soluble anymore and crystallises out pure. B stays in solution and does not precipitate back
Hot solvent > cooling > filtration =
pure compound A
Distillation
A process where liquids are converted into vapours by heating and followed by condensation of vapours through cooling
Non-volatile impurities from volatile liquid
= Mixtures with liquids having a difference in
boiling point
Explain what Chromatography is:
“Methods for separating a mixture into its components, which may also involve identify the components and measuring their concentration”
Partition coefficient P (K)=[
[solute phase 1]/[solute phase 2]
Mobile Phase flows through or over the stationary phase
Mobile Phase: gas or liquid
Stationary Phase: solid or liquid supported on a solid
Component of a mixture interact differently with the stationary phase →
move at different speeds and become separated as they pass down the column
Qualitative Chromatography: step by step
- thin layer of absorbent coating of SiO2 or Al2O3 *
1] TLC plate is prepared with a thin layer of absorbent coating
2] Small amount of the sample in solution is spotted on the plate
3] The end of the TLC plate is immersed in a pool of solvent
4] Out in a glass gar secured tightly with a lid
a) put chromatography paper in solvent BUT the line above surface of solvent
b) solvent rises up by caplillarity
Retention factor Rf= b/a
b = distance travelled by sample
a = distance travelled by solvent
What to use if compounds are colourless?
Fluorescence: stationary phase has a substance added which will fluoresce when exposed to UV light
Using fluorescence:
- No UV light: cannot see compounds
- Plate all glow apart from where the spots are. The spots show up as darker patches because they mask the glow
- Make the spots visible by reacting with something which produces a coloured product
Stationary Phase =
Free OH groups: can form hydrogen bonds, van der Waals forces and dipole-dipole attractions.
Very polar surface
More polar compounds = form H-bonds with silica → stick to the silica gel more firmly than the others. Adsorbed more strongly
Less polar compounds:
form only weak van der Waals interactions → stick less to the silica gel → more carried by the mobile phase
More strongly a compound is adsorbed (more polar is) →
less distance travelled up the plate. Low polarity compounds have higher Rf values (run more) than higher polarity compounds.
Mobile Phase
Ability to dissolve: solubility of compounds (Like dissolves like) in mobile phase influence how fast they move up the TLC plate.
The more soluble they are, the faster they move.
Polar compounds: run faster in polar solvent
Non-polar compounds: run faster in non-polar solvents
Ability to be adsorbed on the silica: affinity for the silica. Can displace the compounds “pushing” them up the plate.
Solvent too strongly adsorbed: fully displaces all compounds →they move up the plate together with the solvent front with no separation
Solvent too weakly adsorbed: its solvating power alone may be insufficient to move any compounds fast enough to effect separation
Separation - mobile phase to stationary phase
Less eluting strength (less polar solvents)
MOBILE PHASE»_space;>
Greatest Eluting strength (more polar solvents)
Less strongly adsorbed (less polar compounds)
Stationary Phase»_space;>
Most strongly Absorbed
Absorptivity of compounds:
increases with increased polarity (i.e. the more polar the compound then the stronger it binds to the silica)
Eluting power of solvents
increases with polarity
Low polarity compounds →eluted with low polarity solvents
Higher polarity compounds → solvents of higher polarity.
Solvents can be mixed together
The stronger a compound is bound to the silica , the _____ it moves up
slower
Non-polar compounds: move up the plate most ______ (higher Rf value)
rapidly
Polar compounds: travel up the TLC plate _____ or not at all (lower Rf value)
slowly
Column chromatography: purification method (solids and liquids)
Same principles of TLC:
Non-polar compounds: move down rapidly: will come out first from column
Polar compounds: travel down slowly or not at all: will come out very late or will stay in the column
Solvent collected in small fractions containing the pure compound
Gradient elution:
change the proportion of the solvents over a pre-determined timescale (i.e. 100% hexane, then 90 hexane: 10 ethyl acetate, etc
Analytical Chemistry
Deals with obtaining, processing, and presenting both the qualitative (which substances are in a sample?) and quantitative (how much?) data of substances
Analytical Chemistry
Deals with obtaining, processing, and presenting both the qualitative (which substances are in a sample?) and quantitative (how much?) data of substances
Melting point and boiling point:
any pure substance will have a specific melting and boiling point. Presence of impurities will cause a lower melting point as well as a change in boiling point
Purity determination = TLC
if your substance is pure (no impurities present), you should see only one spot in your plate after a run
More advanced light-based or spectroscopic methods:
UV-VIS spectroscopy, nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). Other methods used in testing the purity include mass spectroscopy, capillary electrophoresis, optical rotation, HPLC and particle size analysis
