Introduce, properties, comparative analysis

1. COMPARATIVE ANALYSIS OF CAFFEINE
PRESENTED BY GUIDED BY
MR. SHUBHAM GAJANAN WAGH PROF. DR.K.B.GABHANE
VIDYA BHARATI COLLEGE OF PHARMACY, AMRAVATI-444602
2019-20

2. INDEX
Sr. No. Contents Page No.
1 Introduction 3
2 Structure & Properties of Caffeine 4
3 Structural-Activity Relationship 5
4 Mechanism of Action 6
5 Metabolism of Caffeine 7-8
6 Advantages 9
7 Disadvantages 10
8 Identification 11
9 Case studies 12 -15
10 Conclusion 16
11 Reference 17
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Sr. No. Contents Page No.
1 Introduction 3
2 Structure & Properties of Caffeine 4
3 Structural-Activity Relationship 5
4 Mechanism of Action 6
5 Metabolism of Caffeine 7-8
6 Advantages 9
7 Disadvantages 10
8 Identification 11
9 Case studies 12 -15
10 Conclusion 16
11 Reference 17

3. INTRODUCTION
Caffeine is a pharmacologically active substance and depending on the dose, can be a mild
central nervous system stimulant.
It is the world’s most consumed psychoactive drug which is legal and unregulated in most
parts of the world.
Caffeine is a bitter, white crystalline power and purine derivative which is a methylxanthine
alkaloid.
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4. STRUCTURE & PROPERTIES OF CAFFEINE
Sr.No. Properties Values/ Appearance
1 Molecular weight 194.19 g/mol.
2 Density 1.2gm/cm3
3 Melting Point 237 °C
4 pKa value 10.4
5 Solubility in water Slightly soluble
6 Boiling point 178 °C
7 Appearance White Needles/ Powder
IUPAC Name : 1,3,7-Trimethylpurine-2,6-dione
Synonyms : Guaranine
Methyltheobromine
1,3,7-TrimethylxanthineTheine
Molecular Formula :C8H10N4O2
Structure of caffeine
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5. STRUCTURAL-ACTIVITY RELATIONSHIP
Effects of the structural activity relationship of the
xanthenes molecule on adenosine antagonism and
systematic effects:
 Substitution in position 1 is necessary for high
affinity and selectivity towards adenosine receptor
sites
 Substitution in position 3 increases bronchodilator
effect
 Substitution in position 7 decreases both
adenosine receptor antagonism and bronchodilator
potency
 Substitution in position 9 results in decreased
adenosine receptor affinity
 Substitution in position 8 increases adenosine
antagonism and selectivity towards A1 receptors
Xanthines molecules
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6. MECHANISM OF ACTION
 Adenosine is a central nervous system neuromodulator that has a specific receptors.
 When adenosine is bind to its receptors neural activity slow down and you feel sleepy.
 Adenosine thus facilitates sleep and dilates the blood vessels.
 Caffeine act as a adenosine-receptor antagonist. This means that binds to same
receptors but without reducing neural activity.
 Fewer receptors are thus available to the natural braking action of adenosine and neural
activity therefore speed's up.
 Caffeine also stimulate the pituitary gland to secrete the hormones of adrenal gland to
produce more adrenaline so it increase your attention level and gives your entire system
an extra burst of energy
Similarity in double ring structure
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7. METABOLISM
Biosynthesis
 Biosynthesis of caffeine is as shown in Fig. Xanthosine is the
precursor for caffeine biosynthesis
 In the presence of 7-methylxanthosine synthase and S-adenosyl-
L-methionine enzymes 7-methylxanthosine is produce from
xanthosine.
 In the presence of methylxanthosine nucleotidase enzyme gives
7-methylxanthine from 7-methylxanthosine.
 Later 7-methylxanthine gives first gives Theobromine and then
caffeine in presence of enzymes caffeine synthase and S-
adenosyl-l-methionine
 Paraxanthine is an intermediate synthesized during caffeine
biosynthesis which also leads to the synthesis of caffeine.
Biosynthesis of Caffeine
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8. Catabolism
 The catabolism process is initiated by the
degradation of caffeine to xanthine as shown in Fig .
 Intermediates such as 3-methyl xanthine,
theophylline are formed.
 Before the formation of xanthine,then it is degraded
into uric acid,allantoin,allantoate and finally to
ammonia and carbondioxide.
 Caffeine is primarily metabolised in the liver by
cytochrome P450 enzymes, which are responsible
for more than 90% of caffeine clearance. Catabolism of Caffeine
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9. ADVANTAGES
When caffeine is consumed in lower doses (20-200) mg it has the following advantages on the body .
 Caffeine inhibits adenosine which has an inhibitory effect on neurotransmitters. This increases the
activity dopamine. It causes relief from tension and headache. The chances of suffering from
depression also reduce.
 The risk of hepatocellular and endometrial cancer also reduces.
 It acts as a thermogenic agent by inhibiting the degradation of intracellular cAMP caused by
phosphodiesterase .This helps in weight control
 Caffeine has an anticariogenic effect that helps in preventing dental caries which is caused by the
production of acid by various types of bacteria such as Streptococcus mutants, Actinomycetes.
 Caffeine helps in reducing blood cholesterol levels and fat absorption by the body and hence reduces
obesity. This helps in reducing the risk of a atherosclerosis.
 It acts as an antioxidant due to the presence of various polyphenols, it helps in preventing oxidative
stress in vivo. It also increases the activity of leucocytes.
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10. DISADVANTAGES
When caffeine is consumed in excess, it brings health hazards.They are as follows :
 Excess caffeine reduces the time a person is able to sleep. It is because of this phenomenon
that people suffering from insomnia.
 According to earlier studies,adenosine causes vasodilatation. Presence of caffeine stimulates
the release of nor epinephrine from the adrenal glands which causes vasoconstriction in turn
causes an increase in heart rate and blood pressure.
 Studies have shown that caffeine increases the stiffness of arteries causing a decrease in
elasticity of arteries.
 A high dose of caffeine (>1000 mg) causes caffeine addiction.
 Anxiety is the main symptom of caffeine addiction, there is an increase in the risk of bladder,
the condition of patients suffering from glaucoma is worsened by the increase in pressure
within the eye.
 There is an increase in the risk of osteoporosis due to decreased calcium absorption by bones
and increased calcium secretion in urine.
 The overdose of caffeine also causes premenstrual symptoms in women and there is an
increase in the secretion of insulin by the β cells of the pancreas, thus increasing the risk of
diabetes.
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11. IDENTIFICATION
Murexide Test
The murexide test is an analytical technique to identify the
presence of caffeine and other purine derivatives in a
sample.
These compounds do not respond to the common alkaloids
detecting tests such as Dragendorff’s reagents.
In this test the alkaloids are mixed with a tiny amount
of potassium chlorate and a drop of hydrochloric acid.
The sample is then evaporated to dryness and the resulting
residue is exposed to ammonia vapour.
Purine alkaloids produce a pink colour in this test.
Murexide (ammonium purpurate) with a purple colour is
also produced in this test.
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12. CASE STUDIES
 Fourier transform infrared spectroscopy has proved to be a good technique for quantifying a wide
range of materials especially pharmaceutical products when it is used in combination with
Attenuated Total Reflectance Accessory.
 TGA/DTA a combined technique in thermal analysis measures the physical changes and chemical
changes that occur in characterizing the samples to show thermal stability and material purity .
Apparatus
 FTIR Nicolet 6700 equipped with Attenuated Total Reflectance accessory designed for use with a
diamond crystal (200-30000 cm-1) to measure the reflectance of solid and liquid samples.
 The spectra can be transformed by recording the absorbance as a function of wavelength.
 The concentrations can be calculated from absorbance measurements using a calibration curve.
 The interferogram is equipped with KBr beam splitter and DTGS/KBr detector.
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13.  Preparation of standard caffeine:
Standard solutions of caffeine containing 0,2,4,6,8 and 10 mg in chloroform were pipette
separately in 100 mg dry KBr. The standard samples were mixed, crushed and dried under N2 gas
to remove traces of chloroform.
 Preparation of coffee samples:
Solid coffee samples finely powdered were used directly for analysis
 Conditions of measurements:
Wave numbers 400-4000 cm-1, Number of scans 32, Resolution 4 cm-1.
Preparation of Samples
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14. Determination of caffeine and active ingredient in different coffee samples by FTIR
Overlain FTIR spectra
FTIR/ATR spectra of solid samples of pure caffeine and coffee samples from top to bottom,
Arabian coffee blend, roasted coffee blend, Instant coffee and caffeine standard respectively
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15. TGA Analysis of caffeine samples
Above demonstrates the thermograms of the samples with percentages loss of masses
caused by heat flow through coffee samples.
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16. CONCLUSION
The aim of the comparative analysis has been focused on coffee samples containing spices to
know their effect on caffeine. The results showed the absence of any chemical effect on the
caffeine content of coffee samples as exhibited in the FTIR/ATR spectra. The purity of caffeine
in Arabian coffee and roasted was maintained in the thermogram whereas the Instant coffee
showed signs of impurity in the thermogram. Finally, the presence of spices in Arabian coffee
and roasted home made coffee offers curative benefits and preventive medication as presented
in the introduction which is good for the health of coffee consumers.
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17. REFERENCE
 International Journal of Engineering and Applied Sciences (IJEAS) ISSN: 2394-3661, Volume-2, Issue-12,
December 2015 (by Mohammad A. Abdulla)
 Hindawi Publishing Corporation International Journal of Analytical Chemistry Volume 2015, Article ID 170239, 7
pages http://dx.doi.org/10.1155/2015/170239 (by Showkat Ahmad Bhawani, SimSiong Fong,and Mohammad
Nassir Mohammad Ibrahim)
 https://www.hindawi.com/journals/ijac/2015/170239/
 International Journal of Research In Science & Engineering e-ISSN: 2394-8299Volume:2 Issue:6 p-ISSN: 2394-
8280
 https://www.ncbi.nlm.nih.gov/m/pubmed/1658821/
 https://en.m.wikipedia.org/wiki/Murexide_test
 https://www.mdpi.com/1420-3049/21/8/974/html
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