This document discusses different types of metal ion complexes and protein binding. It describes inorganic complexes containing ligands such as ammonia and cyanide. Chelates form more stable complexes due to multiple bonding sites for the metal. Organic molecular complexes involve weaker interactions like hydrogen bonding or charge transfer. Inclusion complexes trap one component within the lattice structure of the other. Common examples discussed include hexamine cobalt chloride, caffeine complexes, and drug polymer interactions.
Sanjo College of Pharmaceutical Studies, Physical Pharmaceutics I , 3rd semester B.Pharm, Complexation & protein binding, Classification in detail, determination methods, application of complexes in pharmacy.
PHYSICAL PHARMACEUTICS II COARSE DISPERSION VijayaKumarR28
R. VIJAYAKUMAR., M Pharm,
Research Scholar
department of Pharmaceutical Technology.
Anna university- BIT
Tiruchirappalli.
As per PCI syllabus for B Pharm / 2nd Year ,III Semester.
UNIT-III / Coarse dispersion
State of matter and properties of matter (Part-6)(Relative humidity, Liquid ...Ms. Pooja Bhandare
RELATIVE HUMIDITY, Humidity, Wet and Dry Hygrometer, LIQUID COMPLEX, LIQUID CRYSTALS, Types of liquid crystals, GLASSY STATES, Characteristics glassy state, Types of glassy state, What is the Glass Transition Temperature?
Complexation and Protein Binding [Part-1](Introduction and Classification an...Ms. Pooja Bhandare
Complexation: Classification of complexation:
Metal ion or co-ordination complexes :
Inorganic type Organic molecular complexes :
Quinhydrone type
Picric acid type
Caffeine and other drug complexes
Polymer type
Inclusion or occlusion compound
Channel lattice type
Layer type
Monomolecular type
Macromolecular type
Chelates
Olefin type
Aromatic type
Pi (п) complexes
Sigma (б) complexes
Sandwich complexes
Complexation and protein binding (Physical Pharmaceutics - I)Rakesh Mishra
Complexation and protein binding: Introduction, Classification of Complexation, Applications, Methods of analysis, Complexation and drug action, protein binding, Method of estimation for protein binding.
Powder Technology
Particle analysis in pharmaceuticals
Determination of particle size and surface area
Large scale equipment for powders
Types of powders
Solubility of drugs: Solubility expressions, mechanisms of solute solvent interactions, ideal solubility parameters, solvation & association, quantitative approach to the factors
influencing solubility of drugs, diffusion principles in biological systems. Solubility
of gas in liquids, solubility of liquids in liquids, (Binary solutions, ideal solutions)
Raoult’s law, real solutions. Partially miscible liquids, Critical solution temperature . Distribution law, its limitations and applications
Sanjo College of Pharmaceutical Studies, Physical Pharmaceutics I , 3rd semester B.Pharm, Complexation & protein binding, Classification in detail, determination methods, application of complexes in pharmacy.
PHYSICAL PHARMACEUTICS II COARSE DISPERSION VijayaKumarR28
R. VIJAYAKUMAR., M Pharm,
Research Scholar
department of Pharmaceutical Technology.
Anna university- BIT
Tiruchirappalli.
As per PCI syllabus for B Pharm / 2nd Year ,III Semester.
UNIT-III / Coarse dispersion
State of matter and properties of matter (Part-6)(Relative humidity, Liquid ...Ms. Pooja Bhandare
RELATIVE HUMIDITY, Humidity, Wet and Dry Hygrometer, LIQUID COMPLEX, LIQUID CRYSTALS, Types of liquid crystals, GLASSY STATES, Characteristics glassy state, Types of glassy state, What is the Glass Transition Temperature?
Complexation and Protein Binding [Part-1](Introduction and Classification an...Ms. Pooja Bhandare
Complexation: Classification of complexation:
Metal ion or co-ordination complexes :
Inorganic type Organic molecular complexes :
Quinhydrone type
Picric acid type
Caffeine and other drug complexes
Polymer type
Inclusion or occlusion compound
Channel lattice type
Layer type
Monomolecular type
Macromolecular type
Chelates
Olefin type
Aromatic type
Pi (п) complexes
Sigma (б) complexes
Sandwich complexes
Complexation and protein binding (Physical Pharmaceutics - I)Rakesh Mishra
Complexation and protein binding: Introduction, Classification of Complexation, Applications, Methods of analysis, Complexation and drug action, protein binding, Method of estimation for protein binding.
Powder Technology
Particle analysis in pharmaceuticals
Determination of particle size and surface area
Large scale equipment for powders
Types of powders
Solubility of drugs: Solubility expressions, mechanisms of solute solvent interactions, ideal solubility parameters, solvation & association, quantitative approach to the factors
influencing solubility of drugs, diffusion principles in biological systems. Solubility
of gas in liquids, solubility of liquids in liquids, (Binary solutions, ideal solutions)
Raoult’s law, real solutions. Partially miscible liquids, Critical solution temperature . Distribution law, its limitations and applications
1.1 Introduction
1.2 Classification of Complexation
1.3 Applications, Methods of Analysis
1.4 Protein Binding
1.5 Complexation and the drug actions
1.6 Crystalline Structures of Complexes and Thermodynamic Treatment of Stability Constants.
Biocidal Evaluation of Mixed Ligand Metal Complexes of Mercaptans/ThiolsTope A
Abstract: Coordination complexes are compounds which consists of a (usually metallic) central atom or ion and a surrounding array of bound molecules or ions known as ligands. A mixed ligand complex are chemical entities which consists of a central metal atom and at least two donor groups capable of chelation to metal atom. Sulphur containing 5-membered heterocyclic are known to exhibit useful biological activity. This work discusses the biocidal activities of some mixed ligand complex of Mercaptans/Thiols.
Download the full study for free here: http://topeakintayo.com/res/mixedligand.pdf
Nature of coordination compounds, coordination sphere, coordination number, oxidation state of central metal atom, lewis acids, types of ligands, types of complex(cationic and anionic), Valance bond theory, crystal field theory, werner theory of coordination compounds, Nomenclature of coordination compounds.Eg and t2g ,CFSE, Degeneracy, Application of coordination compounds, Charge of the coordination sphere.
Spatial arrangements, inner and outer orbital complexes, low and high spin complex, spin pair and spin free complexes, isomerism, types of isomerism.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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3. CLASSIFICATION OF COMPLEXES
Metal ion complexes:
Metal-ion coordination complexes are also called metal ion complexes, which consist of a
central metal ion bonded to one or more Ligands.
The coordination number of the complex is the number of bonds between the metal
ion and the ligand, which can be more than one .
This number depends on the size, charge and electronic structure of the metal ion.
Coordination numbers are normally between 2 and 9 with the most common coordination
numbers being 4 and 6.
4. 1. Inorganic complexes:
This group was first described by Werner in 1891
There are some examples of Complex ions belonging to this groups are
[Ag(NH3)2]+, [Fe(CN)6]4-,Co(NH3)6]3+ and [Cr(H2O]6]3+
In hexammine cobalt III chloride Co(NH3)6]3+Cl3- , ammonia molecules are known
as Ligands and are coordinated with cobalt ion.
The number of ammonia groups coordinated with metal ions is six hence,
coordination number of cobalt ion is six.
The metal ions which lack sufficient bonding orbital’s, Hybridization plays an
important role in coordination compounds.
5. The sp3 hybridisation of carbon Electronic configuration of d2sp3 hybridized
Hexamine cobalt III chloride
For example cobalt ion, co(III), has ground state electronic configuration. The electronic
configuration of metal ion with filled 3D levels and Thus, d2sp3 or octahedral structure is predicted
as the structure of this complex.
6. Pauling suggested that one of the 2s electron is promoted to 2p orbital to form four
equivalent orbitals.
This structure is known as sp3 hybrid as one S and three P orbital’s are involved.
These bonding orbitals are directed towards the corners of a tetrahedron.
Similarly, in a double bond, there is sp2 hybridized carbon and geometry is
triangular.
In transition elements, such as cobalt, zinc, nickel and copper 3d, 4s and 4p orbitals
are involved in forming hybrids.
Differently hybridized metal ions results in different geometries
H2O, NH3, CN-, or CL- like ligands donate a pair of electrons in forming a complex
with a metal ion, by filling the empty orbitals of the metal ion.
7. 2. Chelates:
Chelation means that the anion has two or more separate sites to which the metal is
bonded.
A molecular entity in which there is chelation is called a "chelate".
Chelates are more stable than nonchelated compounds of comparable composition
This phenomenon is called the chelate effect.
The stability of a chelate is also related to the number of atoms in the chelate ring.
8. Cis–trans isomerism occurs in octahedral and square planar complexes
Only cis-coordinated (ligands-ligands adjacent on a molecule) were
readily replaced by reaction with a chelating agent.
Vitamin B12 and the hemoproteins are incapable of reacting since
only the trans-coordination positions of the metal are available for
complexation.
In contrast, the metal ion in certain enzymes, such as alcohol
dehydrogenase, which contains zinc, can undergo chelation, suggesting
that the metal is bound in such a way as to leave two cis positions
available for chelation.
9. Chelates are more stable than comparable complexes containing only one binding site.
They are also used in formulations for increasing the shelf-life of the drug product.
Examples of such chelating agents include citric acid, tartaric acid and EDTA
(ethylenediamine tetraacetic acid).
It can also affect the solubility and absorption of both drug and metal ion, and can lead to
either increased or decreased absorption.
Therapeutic chelators are used in metal poisoning. For example, ethylenediamine
tetraacetic acid (EDTA) as the monocalcium disodium salt is used in the treatment of lead
poisoning. Deferiprone chelates iron.
Tetracycline chelation with metal ions leads to decreased drug absorption:
Polyvalent cations such as Fe2+ and Mg2+, and anions such as the trichloracetate or
phosphate interfere with absorption.
The antibacterial action of the tetracyclines depends on their metal-binding activity, as
their main site of action is on the ribosomes, which are rich in magnesium.
10. Organic molecular complexes
In organic molecular complexes, substrate and ligand are bonded together by weak
forces of the donor-acceptor type e.g., electrostatic interaction, charge-transfer
or hydrogen bonding.
Substrate and ligand forming the complex can be a small molecule-small molecule,
small molecule-macromolecule, enzyme-substrate, and drug-receptor and
antigen-antibody interaction.
The energy of attraction between them is probably less than 5 kcal/mole for most
organic complex and the bond distance is usually hence a covalent link is not
involved. greater than 3A°;
11. One molecule polarizes the other, resulting in a type of ionic interaction or
charge transfer, and is referred to as charge transfer complexes.
For example, the polar nitro groups of trinitrobenzene induce a dipole in
benzene molecule, and the electrostatic interaction that results in complex
formation.
Electrostatic interaction between Charge transfer complex between
Trinitrobenzene and Benzene Trinitrobenzene and Hexamethylbenzene due to
resonance.
Resonance makes the main contribution to complexation in charge-transfer
complex, while in the donor-acceptor complex, London dispersion forces and dipole-
dipole interactions contribute more to the stability.
13. •Picric acid complexes
When 2,4,6 trinitro phenol(Picric acid), reacts with weak bases it forms molecular
complexes where as when it reacts with strong bases to form salts.
For example Butesin picrate which is 2:1 complex is a molecular complex formed with
picric.
Eg. In Picric acid complex Butesin picrate, Butesin act as anaesthetic and picrate as
antiseptic and is used as a 1% ointment for burns and pain.
Carcinogen+ picric=carcinogenic activity
Substitution carcinogenic + picric=interfere with complex
Reduce carcinogenicity of carcinogen
It was observed that the stability of the complexes formed between carcinogenic agents
and picric acid leads to carcinogenic activity
and any substitution on the carcinogen molecule that interfere with Picrate
complexation also reduces carcinogenicity.
Butesin picrate (2:1 complex)
14. •Caffeine & other drug complexes
Complexation of caffeine with number of acidic drugs was studied by Higuchi and his associates.
According to them interaction between caffeine and acidic drug is due to the Dipole-Dipole force
or hydrogen bonding between the carbonyl group of caffeine and hydrogen atom of acid.
Secondary interaction may occur between the nonpolar parts of the molecules.
Many important drugs belong to ester class and many complexes formed between esters and
Amines, phenols, ethers and ketones is due to hydrogen bonding between carbonyl oxygen and
active hydrogen.
But it does not explain complexation of caffeine with Benzocain, Procaine and Tetracaine as there
is no active hydrogen on caffeine and hydrogen at 8 position is very weak to form a complex.
Formula I- Numbering in caffiene molecule.
Formula II-Strongly electrophilic nature of nitrogen at 2 position due to withdrawal of electrons by oxygen at 1 and 3 position.
Formula III-In benzocaine, carboxyl oxygen is nucleophilic which interacts with electophilic nitrogen of caffeine.
15. Polymer complexes
Polymers containing nucleophilic oxygen can form complexes with various drugs,
polymers like Polystyrene, PEG, carboxymethyl cellulose.
Some of them are incompatible with several drugs due to these interactions
Eg. Certain polyethers, such as carbowaxes, pluronics and tweens with tannic acid,
salicylic acid & phenol are incompatible.
This incompatibility may be due to undesirable physical, chemical or pharmacological
effects, like precipitation, flocculation, loss of preservative action, delayed biological
absorption etc.
Fromming et.al. Studied interaction of Crosspovidone with acetaminophen, benzocaine,
caffeine, tannic acid & Papavaine HCl.etc.
Crosspovidone is used as a disintegrant in pharmaceutical granules & tablets, does not
interfere with gastrointestinal absorption because the binding to drug is reversible.
Drug polymer interaction may used to modify biopharmaceutical parameters of drug
eg. dissolution rate of ajmaline is increased by complexation with PVP.
This interaction is due to amide group of PVP & aromatic ring of ajmaline to yield a
dipole-dipole induced complex.
16. Inclusion complexes
There are the compounds which are formed, as one constituent of complex get trapped in
the open lattice or cage like structure of the other to yield stable arrangement .
These complexes generally do not have any adhesive forces working between their
molecules and are therefore also known as no-bond complexes.
Deoxycholeic Acid, which forms channel lattice type complex.
1. Channel lattice type:
• The deoxycholeic acids (bile acids) can form complexes with paraffins, organic acids,
esters, ketones and aromatic compounds, and with solvents like ether, alcohol and
dioxanes.
• The crystals of deoxychloleic acid arrange to form a channel into which complexing
molecule can fit.
17. 2. Layer type:
In this type of complex, complexing agent trap the compounds between the layers of their
lattices.
Such as clay montmorillonite, the principle constituent of bentonite, trap hydrocarbon,
alcohol & graphites between its layers.
Similarly, graphites can also trap compounds between its layers.
Layer type complex
18. 3. Clathrates:
Some complexing agents have ability to crystallize as a cage like lattice, and coordinating
compound get entrapped inside this cage.
Molecular size of entrapped component is important and no chemical bonds are involved.
The stability of the complex formed is because higher amount of energy is required to
decompose the compound, due to strong structure.
Whereas Powell and Palin made a detailed study of clathrate, he showed that highly toxic
agent hydroquinone (quinol) crystallize in a cage like hydrogen-bonded structure.
These quinol molecules allow entrapment of one small molecule between two quinol
molecules .
These holes have diameter of 4.2 A therefore, very small molecules like H2 and large
molecules like ethanol cannot be accommodated in the cavity but small molecules like
methyl alcohol,CO2 & HCL may be trapped
Another example is official drug warfarin sodium USP is a clathrate of water and isopropyl
alcohol .
20. • Monomolecular complexes.
Cyclodextrins: According to Davis and Brewstar, Cyclocdextrins are cyclic oligomers of glucose that can form
water soluble inclusion complexes with small molecules and portions of large compound monomolecular inclusion
compound involve the entrapment of single guest molecule in the cavity of one host molecule.
β-Cyclodextrin
21. • Cyclodextrins are cyclic oligosaccharides consisting of (α-1,4)-linked D-glucopyranose units, with a
hydrophilic outer surface and a hydrophobic central cavity.
• The cavity entrance is hydrophilic due to presence of primary and secondary hydroxyl groups,
whereas interior of the cavity is relatively hydrophobic due to CH2 groups.
• The natural -cyclodextrin, β-cyclodextrin and -cyclodextrins consist of six, seven, and eight units of
glucose and diameters of the central cavities are about 5, 6, and 8 Å for α-, β-, and γ-cyclodextrin,
respectively.
• Ability to form inclusion compounds is due to typical arrangement of the glucose units.
• The molecule actually exists as a truncated cone and can accommodate drug molecule to form
inclusion compounds.
22. Macro molecular inclusion compounds
Macromolecular inclusion compounds are commonly called as molecular sieves.
They include zeolites, dextrins, silicagels and related substances.
The arrangement of these compounds is three dimensional and produces cages and channel like
structures.
Synthetic zeolites are made to have a definite pore size so as to separate molecules of different
dimensions and these are also capable of ion exchange.