Morphine is a natural opium alkaloid first isolated in 1805. It is a powerful pain reliever that acts on opioid receptors in the brain and nervous system. Spectroscopy techniques like IR, NMR, and mass spectrometry are used to characterize the molecular structure of morphine. IR spectroscopy identifies functional groups based on vibrational frequencies. NMR spectroscopy provides information on bonding and stereochemistry. Mass spectrometry identifies molecular mass and fragmentation patterns. Together these techniques allow for full structural elucidation of morphine.
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
Strategies to synthesize 5 & 6 membered heterocyclic.pptxPrabhjotKaur934413
M. Pharm Pharmaceutical Chemistry ppt on Organic chemistry first semester strategies to synthesize heterocyclic rings A presentation on heterocyclic chemistry
Active constituent of drugs used in diabetic therapyAkshay Kank
In this slide the active constituents which is isolated from herbal sources used for to treat the type 1 and type 2 diabetes is covered. 'Gymnema' and 'swerita chirata' herbal plant is also covered in the slide.This work help in to focus the herbal emphasis on diabetes.
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
Strategies to synthesize 5 & 6 membered heterocyclic.pptxPrabhjotKaur934413
M. Pharm Pharmaceutical Chemistry ppt on Organic chemistry first semester strategies to synthesize heterocyclic rings A presentation on heterocyclic chemistry
Active constituent of drugs used in diabetic therapyAkshay Kank
In this slide the active constituents which is isolated from herbal sources used for to treat the type 1 and type 2 diabetes is covered. 'Gymnema' and 'swerita chirata' herbal plant is also covered in the slide.This work help in to focus the herbal emphasis on diabetes.
Presented by Shikha Popali and Harshpal singh Wahi students from Gurunanak college of pharmacy, Nagpur in Department of pharmaceutical Chemistry. The explained topic is seful for every chemistry student and for others too
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’.-cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis.- trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
Contents includes at least three strategies of synthesis for each of three, four, five and six membered heterocylic ring with one or two heteroatoms. One mechanism described out of the three strategies. Few name reactions are described and the other are simple synthetic methods. This presentation was prepared for the partial fulfillment of Master of Pharmacy. The content was taken from the various books, mentioned in slide with the title of references.
Cardiovascular drugs as a lead for new pharmaceuticals (Antiihyperlipidemic a...Pooja Dhamade
Mainly focuses on drugs obtained from natural resources such as lovastatin and dicoumarol covering its history, extraction and structure activity relationship to give new modified drug molecules.
Presented by Shikha Popali and Harshpal singh Wahi students from Gurunanak college of pharmacy, Nagpur in Department of pharmaceutical Chemistry. The explained topic is seful for every chemistry student and for others too
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’.-cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis.- trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
Contents includes at least three strategies of synthesis for each of three, four, five and six membered heterocylic ring with one or two heteroatoms. One mechanism described out of the three strategies. Few name reactions are described and the other are simple synthetic methods. This presentation was prepared for the partial fulfillment of Master of Pharmacy. The content was taken from the various books, mentioned in slide with the title of references.
Cardiovascular drugs as a lead for new pharmaceuticals (Antiihyperlipidemic a...Pooja Dhamade
Mainly focuses on drugs obtained from natural resources such as lovastatin and dicoumarol covering its history, extraction and structure activity relationship to give new modified drug molecules.
Porphyrins are organic pigments, of both natural and
synthetic origin, all of which contain the porphyrin ring
as part of their structure.
In addition, porphyrin chemistry deals with various
analogues and derivatives of porphyrins and,
particularly, with their metal complexes.
In view of the medical and social problem caused by the increasing number of drug addicts the determination of opium alka-loids is of special importance. Morphine is known as a highly addictive and potent narcotic but drug users prefer heroin because of its more intense immediate effect. As heroin is hydrolysed in the organism to morphine the knowledge of the morphine content of biological fluids and tissues is indispensable for forensic and therapeutic purposes. The methods recently used for the determination of morphine in urine are gas-liquid chromatography 1, high-pressure liquid chromatography with fluorimetric determination 2 and gas chromatography mass spectrometry 3. In this paper a simple and inexpensive kinetic method is presented , based on the decomposition of the coloured compound formed by the reaction of hydrogen peroxide with cobalt(II) and morphine, in the presence of carbonate buffer. There is a definite concentration range over which the decomposition rate of the compound mentioned is a linear function of the morphine concentration.
MORPHINE AS A LEAD DRUG MOLECULE COMPOUNDShikha Popali
THE ADDICTED DRUG MORPHINE AN ALKALOID USED TO TREAT SOME DISEASE , HERE WE HAVE ATTEMPT ALL DATA ITS STURECTURE MECHANISM OF ACTION, SAR AND APPLICATIONS.
Microwave Assisted Synthesis and Characterisation of Ofloxacin Carboxamide De...Dr.M.Geethavani
Tuberculosis (TB) remains a significant global health threat, especially with
the emergence of drug-resistant strains. In this study, we aimed to address
the pressing need for novel antitubercular agents targeting multidrug-
resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). The
quinoxaline nucleus was selected for its unique mechanism of binding with
nucleic acid residues and lower reported toxicity. Seven quinoxaline
derivatives were synthesized through eight synthetic schemes and
screened for antimycobacterial activity against Mycobacterium tuberculosis
using the microplate Alamar Blue Assay (MABA) method. Standard strains
and concentrations were utilized for comparison: Pyrazinamide
(3.125µg/mL), Ciprofloxacin (3.125µg/mL), and Streptomycin (6.25µg/mL).
Our results indicate that all synthesized compounds, including derivatives
of Histidine, Glutamic Acid, Glycine, Valine, Alanine, Aspartic Acid, and
Cysteine, exhibited potent antimycobacterial activity at concentrations as
low as 0.8µg/mL, surpassing the efficacy of standard drugs. Particularly,
synthetic derivatives of ofloxacin demonstrated significant inhibition against
drug-resistant Mycobacterium tuberculosis, highlighting their potential as
promising candidates for further investigation. This study underscores the
importance of exploring novel chemical entities, such as ofloxacin
derivatives with amino acids, to combat the escalating threat of drug-
resistant tuberculosis. Further research in this direction holds promise for
the development of more effective treatments against virulent TB strains.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
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Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
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Home assignment II on Spectroscopy 2024 Answers.pdf
Structural characterization of morphine by using different types of spectroscopy techniques.
1. GURU JAMBHESHWAR UNIVERSITY OF
SCIENCE AND TECHNOLOGY, HISAR
STRUCTURAL CHARACTERISATON OF MORPHINE
BY USING DIFFERENT TYPES OF SPECTROSCOPIES
SUBMITTED TO- Dr. Sandeep Jain Sir
SUBMITTED BY- Shikha Kamboj
M Pharm 1st Sem
Pharmaceutical Chemistry
2. CONTENTS: 1. Introduction
2. Classification
3.Physical and chemical properties
4. Mechanism of action
5. Stereochemistry
6. Constitution
7. SAR
8. Spectroscopy
(a) IR
(b) NMR
(c) MS
9. Uses of morphine
10. Adverse effect of morphine
3. INTRODUCTION:-
• 1. INTRODUCTION
• MORPHINE:- It is a natural opium alkaloid, was first
obtained from opium poppy (Papaver somniferum) in 1805
by German pharmacist Friedrich Serturner. This is generally
believed to be the first isolation of an active ingredient from
plant. The term morphine is derived from Greek word
“Morpheus” which means “god of dreams”.
• In opium, it is present in a quantity of 10-23% along with
other substances.
• Morphine is said to be the most powerful pain reliever
medicine.
• It can be administered by mouth, by injection into a muscle,
by injection under the skin, intravenously etc.
• Its maximum effect is reached after about 20 mins when
administered IV and 60 mins when administered by mouth.
6. 3. PHYSICAL AND CHEMICAL
PROPERTIES OF MORPHINE
• It is solid, white crystalline alkaloid and needle shaped crystals.
• It is odorless and bitter in taste.
• Boiling point is 190°C.
• It is insoluble in water and soluble in alcohol and alkali
solutions.
• Its molecular formula is C17H19NO3 and molecular mass is
• 285.34 g/mol.
• Morphine is laevorotatory.
• SOLUBILITY: When exposed to air morphine sulfate gradually
loses its water of hydration. The drug darkens on prolonged
exposure too.
• DECOMPOSITION: When heated it emits toxic fumes of nitrogen
oxide.
• pH: pH of saturated solution is 8.5
7. 4. MECHANISM OF ACTION
Morphine is considered the classic opioid analgesic with
which other painkillers are compared. Like other
medications in this class, morphine has an affinity for
delta, kappa and mu opioid receptors.
Opioids activate 7 transmembrane GPCRs located
presynaptically and postsynaptically along pain
transmission pathways. High densities of opioid
receptors known as mu, delta and kappa are found in
the dorsal horn of the spinal cord and higher CNS
centers.
8. • Opioids cause hyper polarization of nerve cells,
inhibition of nerve firing and presynaptic
inhibition of transmitter release.
• Cellular effects of these drugs involve
enhancement of neuronal potassium
efflux(hyperpolarizes neurons and makes them
less likely to respond to a pain stimulus) and
inhibition of calcium influx (decreases neuro-
transmitter release from neurons located along
the pain transmission pathway).
• Constipation results from activation of opioid
receptors in the CNS and in the GIT.
9.
10.
11. 5. STEREOCHEMISTRY
• Morphine- The molecular formula of morphine is
C17H19NO3 and it is a ‘T’ shaped molecule.
• The three dimensional structure of morphine is
fascinating and in all morphine alkaloids,
phenanthrene nucleus is present. Due to this, these
are also known as phenanthrene alkaloids.
• It consists of five rings, three of which are
approximately in the same plane.
• The other two rings, including the nitrogen one, are
such at right angles to the other trio.
• It also consist of phenolic, ether and alcoholic group
and tertiary amine.
12. • Natural morphine molecule exists as a single
isomer.
• Naturally occurring levorotatory (-) morphine has
5R, 6S, 9R, 13S, 14R configuration.
• It undergoes epimerization at 14position, but not
beneficial to analgesic activity.
• Carbons at 5,6,9,13,14 position are chiral centers.
13.
14.
15. 6. CONSTITUTON
• MOLECULAR FORMULA: C17H1903N
• NATURE OF NITROGEN ATOM: As morphine adds
on one mole of methyl iodide to form a quaternary
salt, this shows that it contains tertiary nitrogen atom.
The tertiary nature of the nitrogen is further confirmed
by Hofmann degradation of codeine derivative which
also reveals the presence of nitrogen in the ring.
• NATURE OF OXYGEN ATOM: 1. Morphine when
acetylated or benzoylated yields the diacetyl or
benzoyl derivative, indicating that the morphine
contains two hydroxyl groups.
16. • 2. Morphine is also soluble in aqueous sodium
hydroxide solution to form monosodium salt
which is reconverted into morphine by passing
CO2 through it. All these facts reveals that one of
the two hydroxyl groups is phenolic in nature.
• PRESENCE OF ETHYLENIC BOND: When codeine
is reduced catalytically in the presence of
palladium, it takes up one molecule of hydrogen,
suggesting that both codeine and morphine
contain one ethylene bond.
17. • PRESENCE OF BENZENE NUCLEUS: Morphine when
brominated yields, a mono-bromo derivative along
with evolution of a molecule of hydrogen bromide,
suggesting that morphine possesses a benzene
nucleus.
• PRESENCE OF PHENANTHERENE: 1) When morphine
is distilled with zinc dust, it yields phenanthrene and
a no of bases suggesting that morphine may contain
phenanthrene nucleus.
• 2) When codeine is treated with methyl iodide, it
yields codeine methiodide. The later compound
when boiled with sodium hydroxide solution, yields
alpha- methylmorphimethine.
• 3) Which on further heating with acetic anhydride
yields an mixture of methyl morphol and
ethanoldimethylamine.
18. • PRESENCE OF THREE OXYGEN ATOMS: 1) B-
methylmorphimethine when heated by water,
yields a mixture of trimethylamine, ethylene and
methylmorphenol. Methylmorphenol when
demethylated by the hydrochloric acid yields
morphenol, a compound which contains one
phenolic hydroxyl group and an inert oxygen
atom.
• 2)
19. • 3) Codeine methiodide : a codeinone methiodide
on heating separately with a mixture of Ac2O-
AcONa gives 3-methoxy-4-acetoxyphenantthrene
an 3-methoxy-4, 6-diacetoxyphenanthrene
respectively. The addition of the acetoxyl group in
position 6 latter indicates the secondary alcoholic
group which further lost as water molecule during
dehydrogenation.
20. 7. SAR (STRUCTURAL ACTIVITY
RELATIONSHIP)
• 1. THE PHENOL MOIETY
• R=H Morphine
• R=Me Codeine
• An aromatic phenyl ring
is essential for activity.
• Any other substitution on phenyl ring diminishes
activity.
• Esterification at C3 decrease the analgesic
activity but increase the anti-tussive activity.
21. 2. THE 6-ALCOHOL
• The alcoholic group at C-6
when methylated, esterified,
Oxidized, removed analgesic
activity as well as toxicity of
the compound increase.
• The saturation of the double bond at C-7 position
gives more potent compound.
• Bridging of C-6 and C-14 through ethylene
linkage gives potent derivatives.
22. 3.MODIFICATION OF 3 NITROGEN
• Nitrogen is essential for the Activity, the removal
of nitrogen Atom results in decreases in
Analgesic activity.
• Double bond at 7 and 8 Position is not important
to binding.
23. • The substitution of certain bulky groups on
nitrogen 17 converts an opioid agonist into an
opioid antagonist. The most important of which
is naloxone.
• Additionally, substitution of certain very bulky
groups on carbon 6 converts naloxone into a
peripherally-selective opioid antagonist i.e.
naloxegel.
24. 4.EPOXIDE BRIDGE
• Removal of epoxide bridge (4,5) in morphine
structure result in the compound that is referred
to as morphinans.
• As the synthetic procedure, only levo isomer
possesses opioid activity while the dextro isomer
has useful antitussive activity, for eg.
Levorphanol and butorphanol.
• Levorphanol is more potent analgesic than
morphine.
26. 8. SPECTROSCOPY
• There are a number of techniques that can help
us to determine the molecular structure,
molecular mass, bond angle, bond length,
functional group etc. of an unknown compound.
• IR spectroscopy
• UV/Vis spectroscopy
• NMR spectroscopy
• Mass spectroscopy
• X-Ray diffraction
• Emission spectroscopy
27. STRUCTURAL CHARACTERIZATION OF
MORPHINE BY USING IR SPECTROSCOPY
• IR spectroscopy is one of the most powerful
analytical techniques which offers the possibility of
chemical identification.
• PRINCIPLE: In any molecule, it is known that atoms or
groups of atoms are connected by bonds. These
bonds are analogs to springs. Because of the
continuous motion of the molecule they maintain
some vibrations with some frequency, characteristic
to every portion of the molecule. This is called the
natural frequency of vibration.
• Applied IR frequency = Natural frequency of
vibration.
• Change in dipole moment
28.
29. The first plane in the case of morphine involves C4,
C9 to C14, O19, O21, O19 do not know enough
about the subject. comprising benzene (R1), oxide
(R2), and carboxylic (R3) rings. The second part
includes C5 to C9, C13 to C7, O20 and N22 and
contains the cyclohexenyl (R4) and ethenamine (R5)
rings. The two planes are nearly perpendicular to
each other and the molecule has a T shape.
The atoms in ring R1 are already coplanar, however
the pentagonal ring R2 is distorted, this is due to
the anti-bonding electron (oxygen) repulsion.
The ring R5 has typical chair form, and ringR4 has a
boat form.
30. This is caused by the 4, 5 ether bridge, which is also
responsible for the rigidity of morphine. The calculated
values match well with the experimental values. For
example in morphine, the optimized bond lengths of C-C of
the rings I made some changes; hope they are ok. R1, R2,
R3, R4, and R5 lie, respectively, between 1.36–145 ˚A,
1.37–1.55 ˚A, 1.33–1.56 ˚A, 1.34–156 ˚A, and 1.52–155 ˚A,
however the respective experimental data lies between
1.36–1.41 ˚A, 1.37–1.46 ˚A, 1.36–1.55 ˚A, 1.36–1.55 ˚A,
and 1.52–155 ˚A. In the case of heroin the optimized bond
lengths of C-C for the rings R1, R2, R3, R4, and R5 lie
between 1.38–1.40 ˚A, 1.38–1.50 ˚A, 1.33–1.55 ˚A, 1.38–
1.56 ˚A, 1.52–1.55 ˚A, and the corresponding experimental
data lies in between 1.36–1.42 ˚A, 1.38–1.51˚A, 1.29–1.55
˚A, 1.36–1.62 ˚A, and 1.52–1.55 ˚A, respectively.
31. As expected the two adjacent bonds of C7=C8 are
slightly shorter than the other bond in ring R3, e.g., the
bond lengths between 14C-8C, 7C-6C, and 6C-20O (23O
in case of heroin) are shorter than the C-C bond of ring
R3.
The bond length between C-C in the ring R5 is slightly
greater than the bond length between C-N in the same
ring of both the molecules. The bond lengths of each C-H
bond in the methyl group are not the same, but the
bond lengths between the hydrogen which is in plane
are .01 ˚A greater than the hydrogen which is out of
plane. Because of ring R2, which is distorted in shape,
some bond is elongated and its adjacent bond is
contracted a bit. The calculated substituent impact on
the C-C-C bond angles of the benzene ring is summarized
in table.
32. The data reflects the well-known trends observed for the
various substituents: morphine becomes heroin when two
O-H groups are attached at the position of C3 and C6, and
in morphine they are replaced by –OCOCH3. This causes
decrease in ortho, and it also results in a small increase in
para in the case of heroin, e.g.,
the calculated value of the ipso bond angle between C2-C3-
4C of morphine is 116◦ which
increases in the case of heroin and becomes 117◦. The bond
angle ortho at position C3 of
morphine is 121◦, and it decreases in the case of heroin and
becomes 119◦. The bond angle
para at position C3 of morphine is 119◦ and, due to a small
increment, in the case of heroin it becomes 119.21◦.
33. Bond lengths between oxygen attached with carbon at
the position 3, 6 are greater than in the case of heroin.
The bond lengths between C3-O19, C6-O20 in the case
of morphine are 1.37 ˚A, 1.42 ˚A, however the bond
lengths between C3-O23, C6-O26
are 1.39 ˚A, 1.44 ˚A in the case of heroin. It was
suggested by Bye (1976) at this
short bond distance resulted from a strong O-H...N
hydrogen bond in the case of morphine.
However, most of the substituents in the present study
have a mixed / character, and
the geometrical parameters of the ring are a result of
the superposition of overall effects.
Based on the above comparison, although there are
some differences between the theoretical
values and the experimental values.
34.
35.
36.
37.
38. STRUCTURAL CHARACTERIZATION OF
MORPHINE BY USING MASS
SPECTROSCOPY
Mass spectroscopy is an instrumental technique in which
sample is converted to rapidly moving positive ions by
electrons bombardment and charged particles are
separated according to their masses. Mass spectrum is a
plot of relative abundance OR intensity against the ratio
of mass/charge.
PRINCIPLE: Conversion of neutral molecule into a
charged molecule to a positively charged
molecule.
Separation of positively charged fragments
formed, based on their masses.
39. • Despite the importance of morphine and its biosynthetic
relatives, the literature dealing with electrospray
ionization mass spectrometry is limited. A number of
studies reported on identification and quantification of
morphine and related metabolites. Accurate mass data
of selected morphinans were obtained by quadrupole,
time-of-flight and FT-ICR mass spectrometry,
respectively.
• The substances under investigation are alkaloids with a
basic nitrogen, which makes them predestined for
electrospray ionization (ESI) in positive ion mode.
• Morphine and codeine show a very similar
fragmentation pattern since codeine contains only one
additional methyl group. Therefore, most fragments
found for morphine were also detected for codeine.
40. • The [M H H2O] ion formed by the loss of water
from position 6 is only found in the ion trap MS2.
The fragments of the type a are formed by
cleavage of the piperidine ring and loss of an
amine (CH2CHNHCH3, m 57). Such a fragment is
found for all morphinans and plays a crucial role
in further fragmentation pathways. Fragments of
the type (a-2H) are not found in case of ion trap
but for triple quadrupole MS/MS. Loss of water
from ion a leads to the key ion b, expulsion of
carbon monoxide to the fragment c. Both
pathways come together in the e-type fragment,
representing a loss of CO and water/MeOH from
the a fragment, respectively.
41. • The ion of type (e-H2O) with the elemental composition of
[C13H9] represents the most prominent fragment ion in
triple quad, and FT-ICR. The (e-CO) fragment is especially
abundant in triple quadrupole MS/MS. Another way leads
independently from [M H] to the key ion of type d.
• Ion trap MS3 of the [M HH2O] ion and ion a results in b,
whereas fragment c is only formed from a. In case of
morphine, MS3 of the base peak at m/z 201 (c) gives rise
to peaks at m/z 183 (e, 100), m/z 173 (c-CO, 18), m/z 165
(e-H2O, 5),m/z 155 (e-CO, 20), m/z 145 (8), and m/z 123
(10), (relative intensities in brackets). While MS4 of m/z
183 (e) results in m/z 165 (e-H2O) and m/z 155 (e-CO),
MS3 of m/z 211 (b) generates m/z 193 (b-H2O), m/z 183
(e), and m/z 165 (e-H2O). MS4 of m/z 183 (e) gives 165 (e-
H2O) and 155 (e-CO), indicating that this ion with
[C13H11O] plays a key role in the fragmentation.
42.
43.
44. fragmented ions m/z ratio Relative abundance (%)
[M H]+ 286 13
a 229 68
b 211 36
c 201 100
d 185 10
Table1: showing relative abundance and m/z ratio of morphine
45. STRUCTURAL CHARACTERIZATION OF
MORPHINE BY USING NMR
SPECTRSCOPY
• Nuclear Magnetic Resonance (NMR) spectroscopy is an
analytical chemistry technique used in quality control and
research for determining the content and purity of a
sample as well as its molecular structure.
• PRINCIPLE: The principle behind NMR is that many nuclei
have spin and all nuclei are electrically charged. If an
external magnetic field is applied, an energy transfer is
possible between the base energy to a higher energy level.
• The energy transfer takes place at a wavelength that
corresponds to radio frequencies and when the spin
returns to its base level, energy is emitted at the same
frequency.
46.
47. • Morphine Systems - The two aromatic protonated
carbons, C-1 (d) and C-2 (d), of morphine (la) and codeine
(lb) were easily differentiated from the olefinic carbons C-
7 (d) and C-8 (d) by the upfield shift of the latter
resonances on reduction of the double bond.
• Carbon 1 and C-2 were distinguished by the larger ortho
effect from the C-3 hydroxyl substituent compared to the
para effect from the C-4 0-alkyl moiety. Likewise, the
even larger ortho effect of the C-3 methoxyl substituent
caused the C-2 resonance in lb (and 2b) to appear upfield
relative to that in la (and 2a). Carbon 7 and C-8 of la (and
lb) were differentiated by the upfield shift of the C-7
resonance on going from la to either 3,6-
diacetylmorphine (IC) or 6-acetylmorphine(ld). The
upfield shift was due to the y effect of the C-6 acetoxyl
group.
48. • The assignment of the C-3 (s) and C-4 (s)
resonances was accomplished by comparing the
compounds possessing a C-3 hydroxyl group to
those containing a C-3 methoxyl group. On
changing the hydroxyl group to the methoxyl
group, substituent constants for methine carbons
in substituted benzenes predict that the C-3
resonance should be shifted downfield. 3-4 ppm
while the C-4 resonance should go upfield. 2 ppm
owing to the larger ortho effect of the C-3
methoxyl substituent.
49.
50.
51.
52.
53. Morphine rule
• A tertiary nitrogen with small alkyl substitution.
• A quaternary carbon
• A phenyl group directly attached to the quaternary
carbon.
• A 2 carbon spacer between the quaternary carbon
an the tertiary nitrogen.
54. 9. USES OF MORPHINE
• Antitussive effect
• Analgesic
• Sedation
• Nausea and Vomiting- Higher dose of morphine
inhibit the vomiting Centre.
• Papillary construction- Miosis.
• Respiration- Resulting in increase in plasma CO2
concentration.
• Heat regulation- It shift the equilibrium point of
heat.
56. Recent advancements
• 1. Dual Naked-Eye and Optical Chemo-sensor for
Morphine Detection in Biological Real Samples
Based on Cr(III) Metal–Organic Framework
Nanoparticles:
57. • 2. Vibrational Spectroscopy for Identification of
Metabolites in Biologic Samples.
• The average Raman spectra of five semen
samples (black) (a–e), and the Raman spectra of
blood (f) and saliva (g) spectroscopic signature.