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Chapter 4
Conversion of the prepared compound into surfactant
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4.1 Introduction to surfactant
Surfactants are having wide array of pharmaceutical applications. Day
by day demand of surfactants is increasing drastically due to its recent
prevelance in developing formulations. Owing to the higher water
solubility of one of the most widely used surfactant (sodium lauryl
sulphate), interest have recently arisen to synthesize a compound
bearing quinazoline nucleus with lauryl group. Synthesized compound
when analyzed by QSAR exhibits the low water solubility which is a
major impediment in achieving low MIC values. Thus only few
compounds having higher antibacterial activity were transformed into
surfactant. These synthesized compounds can be further screened for
antimicrobial activity. The synthesized surfactant was further evaluvated
for physicochemical properties like surface tension, cloud point, foaming
height, wetting time and emulsification power which was used to improve
the stability of the whole system.
4.2 Experimental Work
4.2.1 Development of QD surfactant
On the basis of antibacterial activity, we emphasized on the synthesis of
new compounds such as QD-6 and QD-7 with improved water solubility.
However due to the poor yield and lack of knowledge regarding the
synthesis of QD-7, QD-6 were selected for further synthesis. Additionally
the structure of compound was deterimed by TLC, IR, Mass and NMR.
78
A solution of compound QD-6 (0.01M) and Sodium Lauryl
Sulphate (0.01 mole) were refluxed 12 hrs in boiling Ethanol (20ml) in
the presence of potassium hydroxide (Scheme 2). Then mixtures were
concentrated on water bath and finally recrystallized by ethanol. Yield:
45%; UV λmax: 245 nm; Rf: 0.77 (Pet.ether: ethyl acetate: methanol);
Mpt: 1600C
N
N
O
N
F
SO4C12H25
N
N
O
N
F
F
NaSO4C12H25 KOH
Ehanol
Reflux for 12 hrs
Surfactant3-{[bis(4-fluorophenyl)methylidene]amino}-2-phenylquinazolin-4(3H)-one
Scheme 2: Synthesis of surfactant
4.2.2 Determination of physical properties
4.2.2.1 Surface tension
Surface tension was measured using Stalgmometer with 0.1 % (w/v)
aqueous solution of surfactant at room temperature (25oC) {1}.
4.2.2.2 Cloud point
This can be envisaged by gradually heating 0.1 % (w/v) solution in a
controlled temperature bath and recording the time at which the clear or
nearly clear solutions became definitely turbid. The reproducibility of this
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temperature was checked by cooling the solutions until they become
clear again {2}.
4.2.2.3 Wetting time
Wetting time was determined by immersing a sample of cotton fabric in a
0.1 % (w/v) aqueous solution of surfactant {3}. So, they can find a wide
application in textile industry
4.2.2.4 Foaming properties
This method follows traditional method in which a 25 ml solution 0.1%
(w/v) was shaken vigorously for 10 seconds in a 100 ml glass stopper,
graduated cylinder, at 250C. The solution was allowed to stand for 30
seconds, and the foam height was measured {4}.
4.2.2.5 Emulsification stability
10 ml of a 0.1% (w/v) aqueous solution of surfactant and 5 ml of liquid
paraffin at 400C was prepared for Emulsification stability. The
emulsifying property was determined by the time it took for an aqueous
volume separating from the emulsion layer to reach 9 ml. counting from
the moment the shaking was stopped {5}.
4.2.2.6 Determination of Critical Micelle Concentration (CMC)
The critical micelle concentration of surfactant was determined by
plotting surface tension values against the concentration of each
surfactant.
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4.3 Biological activity
The antimicrobial activities of some synthesized compounds were
determined in vitro using the Cup plate method {6}. Different species of
Gram positive and Gram negative bacteria were used for screening
antibacterial activity. The compound in question was dissolved in
Dimethyl Formamide (DMF) and different concentrations were chosen
(10-250 μg/ml). Fresh broth culture of Gram positive and Gram negative
bacteria were used to inoculated uniform Agar plates. The discs were
incubated at 280C for 24 h. The formed zones of inhibition was measured
in mm scale.
4.4 Result and Discussion
Prior to this study () various related wok was done to improve the anti-
microbila activity of a compound by introducing new molecular
parameter such as heteroatoms {7}, chemical functions {8–11}, aromatics
{12} or non aromatic cyclic substituents {13}. In our study attempts were
made to synthesize a whole system wich acts as a drug as well as
surfactant.
4.4.1 Physicochemical properties
The investigation of the surface active properties of the compound has
been done in the neutral medium (pH 7.3), at a concentration of 0.1 %
(w/v) and 250C. These types of surfactants are especially interesting
81
because they are not the most common. Therefore the traditional
procedure was used to follow up the properties.
4.4.1.1 Surface tension
The surface tension of prepared compound is shown in Table 4.1. This
compound has low surface activity due to electrostatic repulsion between
ions in molecule.
4.4.1.2 Cloud point
An understanding of the property called cloud point is a very important
factor. This property can be used in various applications of surfactants
in aqueous system. The cloud point of the prepared surfactant is less
than 1000C because of presence of long alkyl chain. Its hydrophobicity
increase with increase in the alkyl chain.
4.4.1.3 Wetting time
For the prepared compound, at all points of the investigation, the
synthesized surfactant was efficient wetting agent.
4.4.1.4 Foam power
Foam power was also investigated for surfactant and is generally rated as
foamy. The foam height of the prepared surfactant was measured. A low
foaming height has an application in the dyeing industry {15}.
4.4.1.5 Emulsion stability
Studies are still being carried out on the use of surfactant in emulsion
formation which is of immense importance to technological development.
It was proven that the emulsifying stability of the prepared surfactant
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containing heterocyclic nucleus exhibit moderate emulsifying properties.
The results might lead to the application of the surfactant of choice in
the manufacturing of cosmetics.
Table 4.1 Physical properties of Surfactant
PHYSICAL PROPERTIES VALUE
Color White crystal
pH 7.3
CMC 0.4 %
Surface Tension (0.3%) 27 (dyne/cm)
Foam Height (0.1%) 3 cm
Emulsion Stability (0.1%) 25 min
Wetting Time 10 sec
Cloud point 600C
Log P 3.12
4.4.1.6 Critical Micelle Concentration
The surface tension decreases from its original value to a lower constant
one, which is attained at the CMC. The value of CMC for drug was found
to be 0.4 % (Fig. 4.1). Hydrophobic group is an important driving force in
micellization. Increase in hydrophobicity, decrease in CMC value. The
number of carbon atoms was found to be a determining factor in the
values of CMC {16}.
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0
10
20
30
40
50
60
70
0.00% 0.10% 0.20% 0.30% 0.40% 0.50% 0.60% 0.70%
conc.
surf
ace
tens
ion(
dyne
/cm
)
Series1
Figure 4.1 Effect of varying the concentration of drug on the surface
tension
4.5 Biological activity
Most of the antibiotics act by specific mechanism by showing
intereferance in the metabolic processes of micro organism. By keeping
this in view we here synthesized a compound which acts through specific
mechanism. Structure activity relationship of the designed compound is
basically depends on two factors.
The presence of heterocyclic moiety and the length of aliphatic chain
regulate the anti-microbial activity of synthesized product. Among the
two factors Carbon chain length plays a greater role by exhihibiting
absorption at the interface of cell membrane, which is responsible for the
decrease in permeability of cell leading to altered biological process and
cause cell death.
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Table 4.2 Zone of inhibition with different microbes
Micro-organism Zone of Inhibition
(mm)*
Ciprofloxacin DMF
S.aureus6571 25 25 -------
B.subtilisATCC6051 21 26 --------
S.dysenteriaeK12 29 29 ---------
E.coli6 20 22 --------
*Conc: 125µg/ml
0
5
10
15
20
25
30
35
S.aureus
B.subtilis
S.dysenteria
eE.co
li
zone
of in
hibi
tion
(mm
)
Zone of Inhibition(mm)*Ciprofloxacin
Figure 4.2 Activity of compound for different microbes
85
4.6 Conclusion
Our previous work lead to the conclusion that prepared surfactant
constituting hydrophilic (sulfate ion) and hydrophobic (long alkyl chain)
properties in a single frame work, demonstrates good emulsifing or
surface active properties which can be used as a topical agent as well as
anti-bacterial formulations.
86
4.7 References
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15, 317-320 (1987).
5. Takeshi H. Bull. Chem. Soc., 43, 2236-2239 (1970).
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14. Mao J European Patent Number EP0937912A2 (1999).
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