Post on 11-Jun-2020
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Istituto di Scienze e Tecnologie Molecolari
ISTM-CNR, Università degli Studi di Padova
e-mail: silvia.gross@unipd.it
Silvia Gross
La chimica moderna e la sua comunicazione
Dipartimento di Scienze Chimiche
Università degli Studi di Padova
e-mail: silvia.gross@unipd.it
http://www.chimica.unipd.it/silvia.gross/
Silvia Gross
Colloid Chemistry
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Critical Micelle Concentration (CMC)
Souce of the table:
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Factors affecting the CMC
Hydrophobic group
The length of the hydrocarbon chain is a major factor determining the CMC. For a homologous
series of linear single-chain surfactants the CMC decreases logarithmically with carbon number.
The relationship usually fits the Klevens equation:
log10(CMC) = A- BnC
where A and B are constants for a particular homologous series and temperature, and nc is the
number of carbon atoms in the chain, CnH2n+2.
Constant A varies with the nature and number of hydrophilic groups
Constant B approximately equal to log102 (B≈0.29–0.30) for all paraffin chain salts having a single
ionic head group (i.e. reducing the CMC to approximately one-half per each additional --CH2--
group).
Alkyl chain branching and double bonds, aromatic groups or some other polar character in the
hydrophobic part produce noticeable changes in CMC.
In hydrocarbon surfactants, chain branching gives a higher CMC than a comparable straight-chain
surfactant.
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Factors affecting the CMC
Hydrophobic group
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Hydrophilic Group
For surfactants with the same hydrocarbon chain, varying the hydrophile nature (i.e. from ionic to
non-ionic) has an important effect on the CMC values.
C12 hydrocarbon, the CMC with an ionic head group lies in the range of 1*10-3 mol/dm3
C12 non-ionic material exhibits a CMC in the range of 1*10-4 mol/dm3.
Counter-ion Effects
In ionic surfactants micelle formation is related to the interactions of solvent with the ionic head
group. Since electrostatic repulsions between ionic groups are greatest for complete ionisation, an
increase in the degree of ion binding will decrease the CMC.
For a given hydrophobic tail and anionic head group, the CMC decreases asLi+ > Na+ > K+ > Cs+ > N(CH3)
+ > Ca2+ ≈ Mg2+ (lytropic series)
For a given hydrophobic tail and cationic head group, the CMC decreases as F- > Cl- > Br- > I-
Monovalent → divalent → trivalent: sharp decrease in CMC
Difference can be (partially) ascribed to degree of hydration of the head group
Factors affecting the CMC
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Hydration enthalpy (DHhyd in kJ/mol)
Ion Ionic Radius (pm)
Group 1A(1)
Group 2A(2)
Group 7A(17)
Li+
Na+
K+
Rb+
Cs+
Mg2+
Ca2+
Sr2+
Ba2+
F-
Cl-
Br-
I-
76
102
138
152
167
-510
-410
-336
-315
-282
72
100
118
133
-1903
-1591
-1424
-431
181 -313
196 -284
220 -247
DHhydr (kJ/mol)
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Critical Micelle Concentration (CMC)
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Effect of added salt
The presence of an indifferent electrolyte causes a decrease in the CMC of most surfactants.
The greatest effect is found for ionic surfactants. The principal effect of the salt is to partially screen
the electrostatic repulsion between the head groups and so lower the CMC. For ionics, the effect of
adding electrolyte can be empirically quantified. Ci = concentration of electrolyte
Effect of temperature
The influence of temperature on micellisation is usually weak, reflecting subtle changes in bonding,
heat capacity and volume that accompany the transition. This is, however, quite a complex effect. It
was shown, for example, that the CMC of most ionic surfactants passes through a minimum as the
temperature is varied from 0°C to 70° C. The major effects of temperature are the Krafft and
cloud points. For polymeric surfactants strong effects of temperature on CMC are observed and it is
common to define a critical micelle temperature (CMT) for this class of surfactants.
Factors affecting the CMC
log10(CMC) = -alog10Ci+ b
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Temperature-dependence
The solubility of ionic surfactants increases gradually with increasing
temperature, but at a critical temperature there is a rapid increase of
solubility with further increase in temperature (Krafft Temperature) (micelle
formation becomes possible)
Solutions of nonionic surfactants of the ethoxylate type show special
behaviour with increasing temperature, namely ‘‘clouding’’ above a certain
critical temperature.
This is defined as the cloud point (CP), which depends on the surfactant
concentration and its composition.
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Factors affecting the CMC
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Cloud point (CP) of surfactants
Temperature at which phase separation of the
surfactant takes place.
In the case of Pluronics, dehydration of the
polyoxyethylene chains is followed by more tight
coiling (=avvolgimento)
Electrolytes lower the CP.
Maximum surface activity close to CP.
Typically referred to 1% wt. solution
Above the cloud point, the system
consists of an almost micelle-free dilute solution at a
concentration equal to its CMC at that temperature,
and a surfactant-rich phase.
ASTM Norm: https://www.youtube.com/watch?v=6pCNB4OjpYg
https://www.youtube.com/watch?v=hIh95xS85y4American Society for Testing and Materials International
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Cloud point (CP) of surfactants
CP increases with increasing EO number of chains.
CP decreases with increasing electrolyte concentration (for most
electrolytes).
Origin:
With rising temperature, the PEO chain becomes dehydrated (breaking of
hydrogen bonds) and, at the CP, the dehydrated micelles aggregate, which
is probably the origin of the clouding phenomenon.
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Krafft temperature of surfactants
As for most solutes in water, increasing temperature produces an increase
in solubility.
However, for surfactants, which are initially insoluble, there is often a
temperature at which the solubility suddenly increases very
dramatically.
This is known as the Krafft point or Krafft temperature, TK, and is defined
as the intersection of the solubility and the CMC curves, i.e. it is the
temperature at which the solubility of the monomeric surfactant is
equivalent to its CMC at the same temperature.
Below TK surfactant monomers only exist in equilibrium with the hydrated
crystalline phase, and above TK micelles are formed providing much
greater surfactant solubility.
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Krafft point (IUPAC)
Krafft point
The temperature (more precisely, narrow temperature range) above
which the solubility of a surfactant rises sharply. At this temperature
the solubility of the surfactant becomes equal to the critical micelle
concentration. It is best determined by locating the abrupt change in
slope of a graph of the logarithm of the solubility against T or 1/T
https://goldbook.iupac.org/html/K/K03415.html
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Krafft point (IUPAC)
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Thermodynamics of micellization
DG is large and negative
DH is positive, indicating that the process is slightly endothermic
TDS is large and positive → in micellization process there is a net
increase in entropy
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
standard free energy of micellization increasingly negative as the chain length increases.
→ the c.m.c. decreases with increasing alkyl chain length (remind: log10(CMC) = A- BnC)
DHbecomes less positive and TDS becomes more positive with increasing surfactant chain length.
→the large negative free energy of micellization is made up of a small positive enthalpy (which
decreases slightly with increasing chain surfactant length) and a large positive entropy term TDS, which
becomes more positive as the chain is lengthened: why?
Thermodynamics of micellization
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Entropy change during micellization
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Thermodynamics of micellization
micelle formation must be predominantly
an entropy driven process
1.DG0 for micellization are negative: spontaneous
process
2.DH0 for micellization are negative/positive
3.DS0 for micellization are positive
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
𝚫𝑮𝒎𝒊𝒄𝟎 = 𝚫𝑯𝒎𝒊𝒄
𝟎 - T𝚫𝑺𝒎𝒊𝒄𝟎
nS ↔ Sn
𝚫𝑺𝒎𝒊𝒄𝟎 < 0 would be expected:
number of independent kinetic units
decreases upon micellization
n 1
Thermodynamics of micellization
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Entropy change during micellization
nS ↔ Snn = degree of aggregation
number on independent kinetic units decreases → DS < 0 (if we consider configurational entropy)
The system water/surfactant has to be considered. Extensive and dynamic hydrogen bonding
→ water must experience an increase in entropy to account for DSmic > 0
loose network of tetrahedra bound at the corners
thermal fluctuactions: various part continuously break and reform in
liquid water: relative “disorder”
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Hydrophobic effect
when alkyl groups of free surfactant
molecules are surrounded by water, the H2O
molecules form clathrate cavities (i.e.
stoichiometric crystalline solids in which
water forms cages around solutes).
→ predominant effect of the hydrocarbon
part of the molecule is to increase the
degree of structure in the immediately
surrounding water. It acts as “nucleation
site” for water network formation around
cavity.
During the formation of micelles, the reverse
process occurs: as lyophobic residues
aggregate, the highly structured water
around each chain collapses back to
ordinary (less ordered) bulk water thereby
accounting for the large overall gain in
entropy, DSmic. DHmic small (enhanced H-
bond)
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Hydrophobic effect
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Shape and size of micelles
Micelles are typically (but not always) spherical, with a radius
approximately equal to the chain length of R (for ionic
surfactants), and an aggregation number (n) of 50–100.
Central core: hydrocarbon (expulsion of hydorophobic tail
from the polar medium is an important driving force:
hydrophobic effect)
Further shapes:
rod-shaped micelles
lamellar micelles
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Shape and size of micelles
http://pubs.rsc.org/en/content/articlelanding/2008/pp/b717475f/unauth#!divAbstract
The cationic and anionic
regions of the micelle are
depicted by open and filled
circles, respectively.
Covalently bonded donor
(δ+) and acceptor (δ−) part
of the probe are indicated
by blank and shaded
squares, respectively.
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Shape and size of micelles
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Shape and size of micelles
Critical Packing Parameter (CPP)
For a surfactant with a tail volume, V, a head area A and a tail length l a
simple dimensionless number, the CPP, can be calculated:
CPP=V/(A*l)
If V ~ A·l then the surfactant is fairly symmetrical (CPP~1) and it's quite
easy for it to pack into cubic or simple Lα phases. If the head is very large
(e.g. a bulky ethoxylate) and the tail volume is fairly small then CPP<1/3
and it's easy to pack the surfactant into familiar o/w micelles. In between
these two cases (1/3<CPP<1/2) hexagonal packing becomes possible. At
the other extreme with a very bulky tail (V is large) and a small head
and/or short tail then CPP>1 and any attempt to pack the surfactant
molecules together is going to have difficulties and the phases are quite
complex - or you have reverse (w/o) micelles.
Souce of definition: https://www.stevenabbott.co.uk/practical-
surfactants/cpp.php
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Solubilization (referred to surfactants)
Above the surfactants' CMC, the solubility of (water)
poorly-soluble substances increases dramatically
due to the formation of surfactant micelles →
solubilization
surfactants → solubilizer
solutes→ solubilizates
Result: thermodynamic stable isotropic solution
Surfactants with HLB values 15~18 are the best
solubilizing agents.
The commonly used solubilizers: Tweens
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Solubilization
The mechanism for solubilization
Solubilization is the process of incorporation of the solubilizate into or onto
the micelles.
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Solubilization
Above a certain limit: phase separation of the solubilizate
Solubilizate may affect the value of CMC
Localization: solubilizate from polar water to unpolar hydrocarbon (gradient
of polarity): relevant for drug delivery
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Micellar solubilization of drugs
J Pharm Pharmaceut Sci 8(2):147-163, 200
At surfactant concentrations above the cmc the solubility increases linearly with
the concentration of surfactant, indicating that solubilization is related to micellization
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Thermodynamics of solubilization
Partitioning of a substance between micelle and aqueous phase according to a partitioning coefficient P:
Molar solubilization capacity: number of moles of the solute which can be solubilized by one mole of
micellar surfactant.
Stot = total solute solubility
Sw = solute solubility in water
Cs = molar concentration of surfactant in solution
CCMC = CMC
∆𝐺𝑠0 = −𝑅𝑇 ln𝑃
𝜒 =𝑆𝑡𝑜𝑡 − 𝑆𝑊𝐶𝑠 − 𝐶𝐶𝑀𝐶
𝑃 =𝑆𝑡𝑜𝑡 − 𝑆𝑊
𝑆𝑊𝑃 =
𝜒 𝐶𝑠 − 𝐶𝐶𝑀𝐶𝑆𝑊
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Micellar solubilization of drugs
Possible loci of solubilization of drugs in surfactant micelles, depending on drug hydrophobicity.
There is a gradient of polarity inside the micelle
Black bold lines (—) : drug at different sites in the micelle. The black circles represent the surfactant heads, the black
bold curved lines represent surfactant heads consisting of PEO, and the light black curved lines represent the
surfactant tails.
(1) hydrophilic drugs can be adsorbed on the surface of the micelle
(2) drugs with intermediate solubility should be located in intermediate positions within the micelle such as between
the hydrophilic head groups of PEO micelles
(3) in the palisade layer between the hydrophilic groups and the first few carbon atoms of the hydrophobic group, that
is the outer core
(4) completely insoluble hydrophobic drugs may be located in the inner core of the micelle
Micellar solubilization is an effective method for dissolving hydrophobic
drugs in aqueous environments
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Micellar solubilization of drugs
J Pharm Pharmaceut Sci 8(2):147-163, 200
The lower is the cmc value of a given surfactant, the more stable are the micelles. This is especially
important from the pharmacological point of view, since upon dilution with a large volume of the blood,
considering intravenous administration, only micelles of surfactants with low cmc value still exist, while
micelles from surfactants with high cmc value may dissociate into monomers and their content may
precipitate in the blood.
RSC Adv., 2014,4, 8165-8176
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Micellar solubilization of drugs
https://www.sciencedirect.com/science/article/pii/S0378517317308517
Silvia Gross – Chimica dei Colloidi – Laurea Triennale in Chimica
Micellar solubilization of drugs
RSC Adv., 2014,4, 17028-17038