Distribution Coefficient
Distribution Coefficient
TITLE PAGE
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TABLE OF CONTENTS
TITLE PAGE ............................................................................................................. 1
TABLE OF CONTENTS……………………………………………………………………………………………2
ABSTRACT ............................................................................................................... 4
INTRODUCTION ....................................................................................................... 5
THEORY ................................................................................................................... 8
EQUIPMENT .......................................................................................................... 13
MATERIALS ............................................................................................................ 13
PROCEDURE .......................................................................................................... 19
RESULT .................................................................................................................. 20
DISCUSSION........................................................................................................... 24
CONCLUSION ......................................................................................................... 26
RECOMMENDATION ............................................................................................. 27
REFERENCES .......................................................................................................... 28
APPENDIX ............................................................................................................. 29
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Figure 5: Burette................................................................................................... 15
Figure 9: Stopwatch.............................................................................................. 17
Table 1:Tabulation of Titration Result in The Use of Water For The Extraction.... 20
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ABSTRACT
Distribution coefficient also called a partition coefficient is the ratio of the
concentrations in the two phases of a mixture of two immiscible solvents at
equilibrium.
The distribution coefficient Kd was obtained by titrating the aqueous and organic
layer of iodine in carbon tetrachloride and water solution with 0.1N sodium
thiosulphate while For the equilibrium constant K c the procedures for Kd was
repeated using 0.1N solution of potassium iodide instead of water
Several volume and concentration data from the experimental titration of the flow
rate of aqueous and organic phase was required and was obtained. The
liquid/liquid extraction was maintained at constant flow rate of 10minutes so as to
help us to demonstrate the mass balance and mass coefficient and then the
sample was titrated against 0.1N Sodium Thiosulphate.
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INTRODUCTION
Solvent extraction is a very common laboratory separation procedure used when isolating or
purifying a product. It is extremely useful for very rapid and clean separation of both organic
and inorganic substances. It involves the distribution of a solute between two immiscible liquid
phases. A separation funnel is used for this process. The density of the phases must differ
appreciably so that they can separate easily after mixing.
Solvent extraction also known as partition coefficient is the ratio of the concentration of an
organic compound in two phases that are in equilibrium with each other. For Example in a two
system of water (bottom layer) and an organic solvent (top layer) as shown above, an organic
compound will be in one or the other of the layers. After stirring and allowing time for the layers
to settle, the organic compound could well be in both phases, albeit to a different extent
(concentration, C) in each phase. The partition coefficient (K) is
C organic
K= C aqueous
From this equation, a high value of K suggests that the compound is not very water soluble but
is more soluble in the organic solvent that is if the organic compound is lipophilic (or
hydrophobic).
Molecular partitioning occurs when an organic compound dissolves in each of two immiscible
solvent phases and is measured by the partition coefficient or distribution coefficient which is
the ratio of the concentrations of the compound in a mixture of the two immiscible phases at
equilibrium. This ratio is therefore a measure of the difference in solubility of the compound in
these two phases.
Most commonly, one of the solvent is water while the second is hydrophobic.
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For the distribution coefficient to determined, the amount (concentration) of the dots in the
organic phase is divided by the amount in the dots in the aqueous phase.
The organic solvent used for extraction must meet the following criteria:
Similarly, a partition coefficient can be derived for the partition of a chemical between a liquid
and a solvent adsorbent.
In the case of adsorption, the partition coefficient, Kd is the ratio of the amount of adsorbate
adsorbed per mass of adsorbent solid to the amount of the adsorbent remaining in the solution
per solution volume. Thus,
q
K d=
C
It is worthy of note, that Kd decreases with an increase in the amount of total suspended solids.
This effect, frequently referred to as the partition concentration effect (PCE) or the solids
concentration effect can have a noticeable influence on the solid-solution portioning.
The PCE is an unexpected decline in Kd as suspended particulate matter increases. This anomaly
has been attributed to a variety of causes, such as reaction kinetics, irreversible adsorption,
incomplete desorption, variations in surface chemistry, filtration artifacts, and particle-particle
interactions. However a prominent cause of the PCE is believed to be the existence of colloidal
forms of the adsorbate, which are included, in error, in the dissolved fraction when calculating
K d.
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The term solubility is sometimes used to refer to the partition coefficient, but this is incorrect
and misleading. Solubility has a precise meaning and has a unit of concentration. A partition
coefficient essentially has no units (has units of
concentr ation/concentration ).
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THEORY
A distribution coefficient also called a partition coefficient is the ratio of the concentrations in
the two phases of a mixture of two immiscible solvents at equilibrium.
This ratio is therefore a comparison of the solubilities of the solute in these two liquids.
The distribution coefficient is a relationship that is applied in the liquid-liquid extraction process
to separate two miscible liquids by going through a process of adding another immiscible liquid.
If the distribution coefficient is less than one, the solute to be separated is more easily extracted
from the aqueous phase, while if the distribution coefficient is greater than 1, it is more easily
extracted from the organic phase.
−
A complex ion, the tri-iodide (I3 ) ion, is formed from the reaction between I− and I2. In the
two-phase system two equilibriums occur simultaneously, each competing for I2. The
concentration of all species at equilibrium can be determined by titration, and the equilibrium
constant for the formation of the complex ion can be calculated. Titration of the aqueous layer
gives the total iodine present in the aqueous layer, that is;
The equilibrium constant (Kc) for the formation of the complex ion is then calculated with Eq **.
Actually the equilibrium constant should be written in terms of the activities and the activity
coefficients.
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concentration ∈ organic
�� = concentration ∈ aqueous Equation 1
In this experiment, the distribution coefficient was first found in a mixture where no reaction
occurred between the components, and then used as a basis for the determination of the
equilibrium constant in the reaction of KI and I2 to form KI3 according to the equation
�� + �� ⇌ ��� Equation 2
The equilibrium constant can be found as the ratio of the concentration of the product to the
concentration of the reactants using the relationship,
[KI 3]
Kc = [ KI ][ I 2 ] Equation 3
But since it is a reversible reaction which is at equilibrium, not all the reactants react to form the
product, so some of the original reactants still remain in the reaction.
The concentration of I2 is gotten from titration and relationship with the acid-base volume
concentration relationship1 with Na2S2O3 and should be designated as [I2]aqueous. But since
not all of this concentration is needed, because it is a combination of the concentration of I2
which takes part in the reaction (let this be designated as [KI3]) and the unreacted
concentration or free I2 (let this be designated as free[I2]aqueous, it can be written that,
From the above equation the value of [I2]aqueous is known, to find free[I2]aqueous, the
relationship of the distribution coefficient is used, relating the concentration of I2 in the organic
phase to free[I2]aqueous.
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[I 2∈organic]
Kd =
free [I 2] aqueous
And the concentration of unreacted KI ([KI]free) is given as the difference between the stated
stock concentration ([KI]stock) and the reacted concentration ([KI3]).
In the chemical and pharmaceutical sciences, both phases usually are solvents. Most
commonly , one of the solvents is water, while the second is hydrophobic, such as 1-
octanol.Hence the partition coefficient measures how hydrophilic ("water-loving") or
hydrophobic ("water-fearing") a chemical substance is.
Partition coefficients are useful in estimating the distribution of drugs within the body.
Hydrophobic drugs with high octanol/water partition coefficients are mainly distributed to
hydrophobic areas such as lipid bilayers of cells. Conversely,hydrophilic drugs (low
octanol/water partition coefficients) are found primarily in aqueous regions such as blood serum.
If one of the solvents is a gas and the other a liquid, a gas/liquid partition coefficient can
be determined. For example, the blood/gas partition coefficient of a general anesthetic measures
how easily the anesthetic passes from gas to blood.
Applications
Pharmacology
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A drug's distribution coefficient strongly affects how easily the drug can reach its
intended target in the body, how strong an effect it will have once it reaches its target, and
how long it will remain in the body in an active form. Hence, the log P of a molecule is
one criterion used in decision-making by medicinal chemists in pre-clinical
drug discovery, for example, in the assessment of druglikeness of drug candidates.
Pharmacokinetics
In the context of pharmacokinetics (what the body does to a drug), the distribution coefficient
has a strong influence on ADME properties of the drug. Hence the hydrophobicity of a
compound (as measured by its distribution coefficient) is a major determinant of how drug-like
it is. More specifically, for a drug to be orally absorbed, it normally must first pass through lipid
bilayers in the intestinal epithelium (a process known as transcellular transport). For efficient
transport, the drug must be hydrophobic enough to partition into the lipid bilayer, but not so
hydrophobic, that once it is in the bilayer, it will not partition out again. Likewise,
hydrophobicity plays a major role in determining where drugs are distributed within the body
after absorption and, as a consequence, in how rapidly they are metabolized and excreted.
Pharmacodynamics
In the context of pharmacodynamics (what a drug does to the body), the hydrophobic effect
is the major driving force for the binding of drugs to their receptor targets. On the other hand,
hydrophobic drugs tend to be more toxic because they, in general, are retained longer, have a
wider distribution within the body (e.g., intracellular), are somewhat less selective in their
binding to proteins, and finally are often extensively metabolized. In some cases the metabolites
may be chemically reactive. Hence it is advisable to make the drug as hydrophilic as possible
while it still retains adequate binding affinity to the therapeutic protein target. For cases where
a drug reaches its target locations through passive mechanisms (i.e., diffusion through
membranes), the ideal distribution coefficient for the drug is typically intermediate in value
(neither too lipophilic, nor too hydrophilic); in cases where molecules reach their targets
otherwise, no such generalization applies
Environmental science
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The hydrophobicity of a compound can give scientists an indication of how easily a compound
might be taken up in groundwater to pollute waterways, and its toxicity to animals and aquatic
life. Partition coefficient can also be used to predict the mobility of radionuclides in groundwater.
In the field of hydrogeology, the octanol–water partition coefficient Kow is used to predict and
model the migration of dissolved hydrophobic organic compounds in soil and groundwater.
Many other industries take into account distribution coefficients for example in the formulation
of make-up, topical ointments, dyes, hair colors and many other consumer products.
Measurement
A number of methods of measuring distribution coefficients have been developed, including
the shake-flask, separating funnel method, reverse-phase HPLC, and pH-metric techniques.
DESCRIPTION OF APPARATUS
EQUIPMENT
Beaker
Conical Flask
Separating Funnel
Burette
Funnel
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Retort Stand
Measuring Cylinder
Timer
MATERIALS
Carbon tetrachloride
Sodium thiosulphate
Starch indicator
Iodine
Potassium iodide
Water
BEAKER
A beaker is a cylindrical container used to store, mix and heat liquids in laboratories. Most are
made of glass, but other non-corrosive materials, such as metal and heatresistant plastic, are
also used. Beakers usually have a flat bottoms and a lip around the top.
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Figure 2: Beaker
CONICAL FLASK
An Erlenmeyer flask, also known as a conical flask (BrE) or a titration flask, is a type of laboratory flask
which features a flat bottom, a conical body, and a cylindrical neck. Flasks can be used for making
solutions or for holding, containing, collecting, or sometimes volumetrically measuring chemicals,
samples, solutions, etc.
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BURETTE: A burette is a graduated glass tube with a tap at one end, for delivering known
volumes of a liquid, especially in titrations. It is a long, graduated glass tube, with a stopcock at
its lower end and a tapered capillary tube at the stopcock's outlet.
Figure 5: Burette
FUNNEL
Funnels are apparatuses that have been made for use in the chemical laboratory. It is used to
channel liquid or fine-grained substances into containers with a small opening.
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Figure 6: Funnel
RETORT STAND
A retort stand, sometimes called a clamp stand or a ring stand, is a piece of scientific
equipment to which clamps can be attached to hold other pieces of equipment and glassware –
for instance, burettes, test tubes and flasks.
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TIMER: Stopwatch is a handheld timepiece designed to measure the amount of time that
elapses between its activation and deactivation.
Figure 9: stopwatch
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EXPERIMENTAL SET-UP
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PROCEDURES
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RESULTS
In a similar way, all the concentration for iodine both in aqueous and organic
phases for step 2 and step 3 are found and tabulated as shown in table 1.
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Average Kd =
∑f Kd
n
kd 1+kd 2+kd 3
Kd = 3
Kd = 110.889
KI + I2 ⇌ KI3
[ KI 3]
KC = [ KI ] [I 2] Equation 7
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From equation 6;
C AV A nA
C BV B nB
0.1 x 19.3 x 1
(CB) organic = 2 x 10
[ I 2∈organic]
free[I2]aqueous = Kd
0.0965
free (I2)aqueous = 110.889
(KI3) = 0.0196 N
From equation 5;
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(KI)free = 0.0804 N
From equation 7;
0.0196
(KC)1 = 0.0804 x 8.702 x 10 −4
(KC)1 = 280.1437 N
In a similar way,
(KC)2 = 193.7465 N
(KC)3 =86.9986 N
280.1437 + 193.7465+ 86.9986
The average (KC) = 3
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DISCUSSION
For determining the distribution coefficient, When a solute (the iodine in this case) is
mixed with two immiscible liquids in contact with each other (the water and carbon
tetrachloride), the solute dissolves in each solvent to some extent, and so distributes itself
between the layers. When equilibrium has been reached, the ratio
is constant, independent of the two individual concentrations but dependent upon the temperature
and the nature of the specific solute and solvents involved. Kd is the distribution coefficient.
In the experiment conducted, for to determine the distribution coefficient, the reaction
between the thiosulphate and the iodine was a redox reaction with the I2 been reduced and the
thiosulphate being oxidized. The concentration of the iodine in the organic phase was found to
be higher than that in the aqueous phase. The distribution coefficient(Kd) was observed to be
110.889, which clearly shows that the I2 molecules clearly tend to quantitative distribution in
carbon tetrachloride; this implies that a little percentage of the iodine was extracted into the
aqueous phase (water) and would take a series of extractions to appreciatively separate iodine
from carbon tetrachloride.
On the other hand, the result shows that carbon tetrachloride will effectively separate iodine
from water if there were to be an iodine-water mixture.
In the second test, to determine the equilibrium constant Kc the iodide was reacted directly
with the iodine in the carbon tetrachloride phase. This was done in order to bring about
extraction of most of the iodine into the KI solution phase. The carbon tetrachloride layer that
was drawn from the beaker was found to contain a large amount of the iodine. This was
observed from the large volume of the thiosulphate that was obtained in the titration. This
implies that the amount of the iodine that reacted with the second addition of the potassium
iodide was very large showing that little of the initial iodine present was extracted into the KI
solution phase. Hence, the total tri-iodide ion concentration was the addition of the iodide
concentration in the KI solution and the one that reacted with the thiosulphate solution.
Although the values of the equilibrium constant gotten for the three sets of titration involving KI
and a saturated solution of I2 and CCl4 which was carried out were expected to be the same
since it is an already proven and accepted theoretical fact that concentration (of reactants or
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products) has no effect on equilibrium constant, we have some variations from this fact, as the
values of the equilibrium constant showed differences ranging from 280.1437 N to 193.7465
N and then 86.9986 N.
This variation from standard can be attributed to various causes which are outlined as follows;
Possible over dripping of the Na2S2O4 from the burette during titration.
variations could also have arisen from improper measurements of some reactants
before use in performing a reaction.
Decomposition of Iodine molecule
PH and temperature is also another factor
With all the possible sources of errors already outlined above, various precautions were taken
to ensure accuracy and minimize errors.
Pharmacokinetics
Pharmacodynamics
Environmental science
Agrichemical research
Metallurgy
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CONCLUSION
The distribution coefficient (kd) was found to be 110.889; and the equilibrium
constant for the reaction (kc) was found to be 186.999.
RECOMMENDATIONS
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The following are recommended with same aim of the experiment for more
accuracy and time saving;
REFFERENCES
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Shargel L, Susanna WP, Yu AB (2012). "Chapter 10: Physiological Drug Distribution and
Protein Binding". Applied Biopharmaceutics & Pharmacokinetics (6th ed.). New York:
McGraw-Hill Medical. p. 211. ISBN 978-0-07-160393-5.
Martin YC (2010). "Chapter 4: The Hydrophobic Properties of Molecules". Quantitative
Drug Design: A critical introduction (2nd ed.). Boca Raton: CRC Press/Taylor & Francis.
pp. 66–73. ISBN 978-1-4200-7099-6.
General Chemistry Laboratories, University of Alberta;
http://www.chem.ualberta.ca/~ngee/Expt.N_05.html
Pandit NK (2007). "Chapter 3: Solubility and Lipophilicity". Introduction to the
Pharmaceutical Sciences. (secondary) (1st ed.). Baltimore, MD: Lippincott Williams &
Wilkins. pp. 34–37. ISBN 978-0-7817-4478-2.
APPENDIX
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Distribution coefficient is a ratio denoted by Kd and can be found using the relation
concentration ∈ organic
𝑲𝑲= concentration ∈aqueous
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[I2]aqueous the total concentration of iodine in the aqueous phase. Note, this can
be derived using [I2]aqueous = [KI3] + free[I2]aqueous
The averages of the distribution coefficient and the equilibrium constant can be gotten
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