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.
Complexation and Protein Binding [Part-2](Method of analysis, Complexation a...Ms. Pooja Bhandare
Method of Analysis: Methods of continuous variation / JOB’S method of continuous variation.
pH titration method.
Distribution method.
Solubility method.
Spectroscopy and charge transfer complexation.
Miscellaneous method
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 [Part-2](Method of analysis, Complexation a...Ms. Pooja Bhandare
Method of Analysis: Methods of continuous variation / JOB’S method of continuous variation.
pH titration method.
Distribution method.
Solubility method.
Spectroscopy and charge transfer complexation.
Miscellaneous method
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
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?
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.
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
4th (30.10.2014) on eutectic mixture by Diptarco SinghaDiptarco Singha
this ppt is very simple and has immence importance in physical pharmacy. it has been prepared based on the syllabus of WBUT & consists of informations of elimentary label...
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.
State of matter and properties of matter (Part-2) (Latent Heat, Vapour pressu...Ms. Pooja Bhandare
Latent Heat, Vapour pressure, Factor affecting vapour pressure, Surface area, Types of molecule, Temperature and Intermolecular forces, Sublimation Critical point
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?
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.
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
4th (30.10.2014) on eutectic mixture by Diptarco SinghaDiptarco Singha
this ppt is very simple and has immence importance in physical pharmacy. it has been prepared based on the syllabus of WBUT & consists of informations of elimentary label...
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.
State of matter and properties of matter (Part-2) (Latent Heat, Vapour pressu...Ms. Pooja Bhandare
Latent Heat, Vapour pressure, Factor affecting vapour pressure, Surface area, Types of molecule, Temperature and Intermolecular forces, Sublimation Critical point
Effect of substituents and functions on drug structure activity relationshipsOmar Sokkar
The replacement, in an active molecule, of a hydrogen atom by a substituent (alkyl, halogen, hydroxyl, nitro, cyano, alkoxy, amino, carboxylate, etc.) or a functional group can deeply modify The potency, The duration, Perhaps even the nature of the pharmacological effect.
Level of structural organization of proteins in descriptionjaygawhale
Primary Structure: This is the most fundamental level and refers to the linear sequence of amino acids linked together by peptide bonds. The specific sequence of amino acids in a protein is determined by the genetic code of an organism. A change in even a single amino acid can significantly alter the protein's function.
Secondary Structure: This level describes the localized folding of the polypeptide chain due to hydrogen bonding between the carbonyl (C=O) and amino (N-H) groups of the peptide backbone. Two main types of secondary structures are alpha helices and beta sheets. These repetitive folding patterns provide stability and serve as building blocks for higher-order structures.
Tertiary Structure: This level refers to the three-dimensional arrangement of the entire polypeptide chain, including all its folds and bends. Interactions like hydrogen bonding, ionic bonds, disulfide bridges, and hydrophobic interactions determine how the secondary structures fold and assemble in space. The tertiary structure creates a unique shape for each protein, essential for its specific function.
Quaternary Structure:** This level applies only to proteins with multiple polypeptide chains. It describes how these individual polypeptide chains (each with its own tertiary structure) come together to form a functional protein complex. The interactions between these chains are similar to those seen in the tertiary structure. An example is hemoglobin, where four polypeptide chains assemble to form the oxygen-carrying molecule in red blood cells.
Understanding these levels of structural organization is crucial for comprehending protein function. The specific sequence of amino acids (primary structure) dictates how the protein folds (secondary and tertiary structures), ultimately determining its three-dimensional shape and its ability to interact with other molecules or perform its biological role.
Delving Deeper into Protein Structural Organization: Beyond the Basics
While the four-level hierarchy provides a solid foundation, protein structural organization has fascinating intricacies. Here's a closer look:
1. Primary Structure: The Blueprint in Every Bond
Amino Acid Sequence: The primary structure is the amino acid sequence, like a string of beads with unique side chains. The order and type of these amino acids (20 different types) determine the protein's potential to fold and function.Side Chain Chemistry: The side chains of amino acids have diverse chemical properties (hydrophobic, hydrophilic, charged, etc.). These properties influence how the chain folds and interacts with its environment.Disulfide Bridges: In some proteins, cysteine residues (amino acids with a sulfhydryl group) can form covalent disulfide bridges, further stabilizing the primary structure.
2. Secondary Structure: The Local Folds
Hydrogen Bonding: The key player in secondary structure formation is hydrogen bonding between the carbonyl (C=O) and amino (N-H) groups of the peptide backbo
he reaction involving combination of two or more monomer units to form a long chain polymer is termed as polymerization. These are widely used as Pharmaceutical aids like suspending agents, Emulsifying agents, Adhesives, Coating agents, Adjuvants etc.
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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
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.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
1. PHYSICAL PHARMACEUTICS-I
(THEORY)
COMPLEXATION AND PROTEIN BINDING.
1.1 INTRODUCTION
1.2 CLASSIFICATION OF COMPLEXATION
1.3 APPLICATIONS, METHODS OF ANALYSIS
1.4 PROTEIN BINDING
1.5 COMPLEXATION AND DRUG ACTIONS,
1.6 CRYSTALLINE STRUCTURES OF COMPLEXES AND THERMODYNAMIC
TREATMENT OF STABILITY CONSTANTS.
2. 1.1 INTRODUCTION
COMPLEXATION – Complexation is defined as the association
of two of more species capable of independent existence.
• Complexes result from a DONOR-ACCETOR MECHANISM or a
LEWIS ACID- BASE REACTION between 2 or more different chemical
constituents, forming co-ordination compounds.
• In this the DONOR Compound is a NON-METALLIC ATOM/ION which can
donate an electron pair and an ACCEPTOR is a METTALIC ION/NEUTRAL
ATOM which is capable of accepting a pair of electrons.
3. 1.2 CLASSIFICATION OF COMPLEXES
(I) Metal Ion Complexes (II) Organic Molecular Complexes (III) No-Bond
Complexes
- Inorganic type - Quinhydrone type - Clathrate
- Chelates - Picric Acid Type - Channel Lattice
- Olefin Type - Caffeine Type & Other Drug Complexes - Layer Type
- Aromatic Type - Polymer Type - Monomolecular
Pi-bond type - Macromolecular
Sigma-bond type
Sandwich compounds
4. (I) METAL ION COMPLEXES
a. Inorganic Type: In this type of complex the central atom(ACCEPTOR)in the
complex is a metal/metal ion which accepts electron from the donor.
Donor compound is also known as LIGAND coordinated with the acceptor molecule
Electrostatic/covalent bonding
Metal Ligand
Example of inorganic type complexes is Hexamine Cobalt III Chloride [Co(NH3)6]Cl is
formed due to reaction between ammonia and cobalt chloride.
The coordination no. of Cobalt ion = 6 (i.e. no. of ammonia groups coordinated with
cobalt ion).
5. b. Chelates: A substance containing 2 or more donor groups may combine with a metal
ion to form a complex is known as a chelate.
Ionic/Primary covalent type
Metal Ligand
Ligands may have more than one group capable of bonding with the metal ion. A molecule
with 2 DONOR Groups is k/a BIDENTATE
A molecule with 3 DONOR Groups is k/a TRIDENTATE
Example of chelate/chelating agent is Ethylenediamine Tetra acetic Acid (EDTA). It has 6 points
for attachment for the metal ion (2N &4 O2) and is therefore called HEXADENTATE. Both
metal & ligand molecules or complexes may exhibit isomerism, due to this only cis-coordinated
ligands are readily replaced by reaction with chelating agents.
6. Vitamin B12 and Haemoproteins, the trans coordination positions of the metal are
available & they are not able to react with chelating agents.
Another example of chelates involved in life processes of plants and animals are
Chlorophyll and Haemoglobin are 2 important naturally occurring compounds.
Albumin is the main carrier of various metal ions & small molecules in blood serum.
c. Olefin Complexes : Aqueous solution of certain metal ion such as Platinum, Iron,
Palladium, Mercury and Silver can absorb olefins such as ethylene to yield water
soluble complexes. Example: Silver-olefin complex.
Silver-Olefin Complexes
7. d. Aromatic Complexes:
Pi-bond complexes: Aromatic bases such as Benzene, toluene, xylene form pi-bond
complexes with metal ion such as silver by Lewis acid-base reactions.
Stability of complex increases with increasing strength of aromatic hydrocarbon.
-Iodine forms pi-bond complex with benzene to give RED-COLOURED SOLUTION,
whereas no such complexation takes place when iodine reacts with chloroform and
CCL4 (Carbon Tetrachloride) to give VIOLET-COLOURED SOLUTION.
-Toluene forms a pi-bond complex with HCl.
Pi-bond complexes between toluene and HCl
8. Sigma-bond complexes:
These complexes involve the formation of a sigma bond between an
ion & a carbon of the aromatic ring.
-These complexes are very reactive and difficult to isolate.
-Toluene forms a sigma-bond complex with a catalyst couple
(HCl.AlCl3)
Sigma-bond complexes of toluene with HCl.AlCl3
9. Sandwich compounds: These are STABLE COMPLEXES involving a delocalized
covalent bond between the d-orbital of a transition metal and a molecular
orbital of the aromatic ring.
An example of sandwich complexes is Ferrocene or Bisdicyclopentadienyl iron II
Here 1 Pi-electron of each ring is used to bind with the metal atom.
Ferrocene exhibits an aromatic character, such compounds are known as
sandwich compounds, because of the layered structure of ring-metal complexes.
Ferrocene
10. (II) ORGANIC MOLECULAR COMPLEXES.
(ADDITIONAL COMPLEXES)
These are formed by union of 2 organic molecules held together, either by
electrostatic force or hydrogen bonding.
a. Quinhydrone Complex: Formed by mixing of alcoholic solutions of
equimolar quantities of benzoquinone & hydroquinone, when green crystals
of crystals of quinhydrone complex settle done.
Quinhydrone
11. b. Picric acid type complexes: Picric acid (2,4,6 Trinitrophenol) forms
complexes with many polynuclear aromatic compounds.
Stability increases with increased No. of EWG (Electron Withdrawing Groups) on
the nitro group and ring complexity.
Stability increases with increases presence of EDG (Electron Donating Groups) on
the second compound.
Example of Picric Acid Complex is Butesin Picrate, a local anaesthetic.
Butesin picrate
12. C. Hydrogen Bonded Complexes: A large no. of compounds containing the
-OH and -NH- linkage exhibit hydrogen bonding. Hydrogen bonding is an example
of Dipole-Dipole Interaction. In this, one molecules positive hydron (H+) are
attracted to the negative oxygen atom of a second molecule. Complex formation in
such compounds occurs only if INTERMOLECULAR HYDROGEN BONDS are formed.
Caffeine and other drug Complexes – The most extensively studied example of
hydrogen bond complexes is that of caffeine compounds. Caffeine forms complexes
with a no. of drugs such as benzocaine, tetracaine or procaine and it enhances the
stability & appearance of pharmaceutical preparations of these drugs.
Caffeine complex
13. d. Polymer Type Complexes:
Polymeric materials such as PEG (Polyethylene glycols), Polystyrene,
Polyvinylpyrrolidone and sodium carbomethyl cellulose which are
usually present in suspensions, emulsions, suppositories and some
solid dosage forms, can form complexes with large no. of drugs.
Such interactions can result in precipitation, flocculation,
solubilisation, alteration in bioavailability, undesirable physical,
chemical and pharmacological effects.
14. (III) INCLUSION COMPOUNDS (NO BOND
COMPLEXES)
These complexes are formed due to the ability of one of the constituents of the
complex to get entrapped in the open lattice or cage-like crystals structure of the
other.
There are no adhesive force acting between their constituent molecules. Therefore
they are known as NO-BOND.
a. Clathrates- A molecules of a ‘guest’ compounds gets entrapped within the cage
like structure formed by the association/union of several molecules of a ‘host’
compound. The size of guest molecule is very important for complex formation.
If the size is too small, it will escape from the cage-lie structure of the host and
if the size of guest molecule is too big, it will not be accommodated inside the
cage.
15. For Example: Hydroquinone crystallizes in cage like structure (hydrogen bonded)
leaving holes of diameter 4.2 Armstrong. This permits the entrapment of
molecules such as methyl alcohol, HCl and CO2 but SMALLER molecules such as
H2 & LARGER molecules such as ethanol cannot be entrapped.
b. Channel Lattice Complexes:
In this the host component crystallizes to form a channel-like structure into
which the guest molecule can fit. Channel lattice complexes offers a
number of applications, in separation of petroleum products.
Examples: Starch iodine solution is a channel lattice type complex
consisting of iodine molecules entrapped within the spirals of starch
molecules.
16. C. Layer-type Complexes: In this complex the guest molecule is diffused
between the layers of carbon atom, hexagonally oriented to form alternate
layer of guest & host molecules. Example: Clay, Graphite.
D. Monomolecular type compounds: These compounds involve the
entrapment of one guest molecule into the cage like structure formed from a
single host molecule.
Example: Cyclodextrin molecule represents a monomolecular host structure into
which a no. of guest molecules can get entrapped.
E. Macromolecular Inclusion compounds: These are commonly k/a Synthetic
Zeolites, dextrin, silica gels and related substances. The atoms in these are
arranged n 3D to provide cages and channels and the guest molecule are
entrapped within.
17. 1.3 APPLICATIONS & METHODS OF ANALYSIS
Applications of Complexation:
a. Physical state- Complexation process improves processing characteristics by converting
liquid into solid complex, 𝛽-cyclodextrin complexes with nitro-glycerine.
b. Volatility- Complexation process reduces drug volatility for following benefits: Stabilize
system & Overcome unpleasant odour (iodine complexes with PVP Polyvinyl Pyrrolidone)
c. Solid state stability- Complexation process enhances the solid state stability of drug. β-
cyclodextrin complexes with Vitamin A & D
d. Chemical stability- Complex formation inhibit chemical reactivity (mostly inhibit). The
hydrolysis of Benzocaine is decreased by complexing with caffeine.
e. Solubility- Enhances solubility of drug. Caffeine enhances solubility of PABA (Para Amino
Benzoic Acid) by complex formation.
f. Dissolution- Enhances dissolution of drug. 𝛽 -cyclodextrin increases dissolution of
phenobarbitone by inclusion complex.
18. g. Partition Co-efficient: Complexation process enhances the Partition Co-efficient of
certain drugs. Permanganate ion with benzene.
h. Absorption & Bioavailability: Complexation process reduces the absorption of
tetracycline by complexing cations like Ca2+, Mg2+ and Al3+. Enhances the
absorption of indomethacin and barbiturates by complexing with 𝛽-cyclodextrin.
i.Reduced toxicity: 𝛽-cyclodextrin reduces ulcerogenic effects of indomethacin. 𝛽-
cyclodextrin reduces local tissue toxicity of chlorpromazine.
j. Antidote for metal poisoning: BAL (British Anti Lewisite) reduces toxicity of heavy
metals by complexing with gold, mercury and antimony.
k. Drug acting through metal poisoning: 8-Hydroxy quinoline complexes with Fe
exhibit greater antimalarial activity.
l. Anti-tubercular activity- PAS (Para Amino Salicylic Acid) complexes with Cupric ion
exhibit greater antitubercular activity.
19. ASSAY OF DRUGS/METHODS OF ANALYSIS
COMPLEXATION
1. Dielectric constant, Referactive index, Spectrophotometric extinction coefficient-
When there is complexation between the species, the value property is ADDITIVE.
On complexation these properties CHANGE but additive rule do not hold good.
The change in characteristics proves that the complexation has taken place.
2. pH Titration Method- This method is applicable for that complex that produces the
change in pH will determine that complexation has been taken place.
3. Distribution method- the distribution behaviour of a solute between two immiscible
liquid is expressed by distribution coefficient or partition coefficient. When a solute
complexes with an added substance, the solute distribution pattern changes
depending on the nature of complex.
20. 4. Solubility method- When the mixture form complexes solubility may
increase/decreases.
5. Spectroscopy method- The UV Spectroscopy is used as extensively in
determining rate constant, equilibrium constant, acid-bbase dissociation constant
etc for chemical reaction.
6. Miscellaneous method- Several other methods are available for the analysis
of complexes like NMR and IR spectroscopy, Polarography, Circular dicromism,
kinetics, X-Ray diffraction and electron diffraction.
21. 1.4 PROTEIN BINDING
The binding of drug to protein in the body is called as protein binding.
OR
The phenomenon of complex formation of drug with protein is called as protein
binding of drug. The interacting molecules are generally the macromolecules
such as proteins (Albumin, Globulins, ∝1 acid glycoproteins also called as AGP
OR lipoproteins) are present in blood, DNA, Adipose. These molecules have
been known to bind with the large number of drug molecules.
As a protein bound drug is neither metabolized nor excreted hence it is
pharmacologically INACTIVE due to its pharmacokinetic and pharmacodynamics
inertness.
22. The protein binding alters the biological properties of drug molecules as free
drugs concentration is reduced the bound drug inherits the diffusional
characteristics of the protein molecules.
KINETICS OF PROTEIN BINDING
An equation relating reaction velocity to Drug Concentration (Mol/L) for a
system where a Drug D binds reversibility to any Protein (P) of to form a
Protein-Drug Complex.
This system can be represented schematically as follows:
Protein + Drug ==== Protein-Drug Complex
P + D ==== PD
23. Applying the law of mass action, the equilibrium or association constant (K) is:
K= [PD]/[P] [D]
25. The graph is plotted between 1/R versus 1/[D], called Klotz reciprocal plot,
gives a straight line whose slope is 1/VK and intercept is V.
26. 1.5 COMPLEXATION AND DRUG ACTION
Protein binding inactivates the drugs because sufficient concentration of drug
cannot be build up in the receptor sight for action. Ex. Naphthoquinone.
Only free drug participate in the drug action. Complexation can alter the
pharmacological action of drug by interfering the interaction with the receptor
the action of drug to remove the toxic effect of metal ion from the human
bodies is through the complexation reaction
It has been seen that in some instance complexation can also lead to poor
solubility or decreased absorption of drug in the body, which decreases the bio
availability of drug in blood. Thus, the drug action gets altered.
27. Drug complex with hydrophilic drug also enhance the drug elimination, thus
helps in drug action termination and reduction in drug toxic action.
Examples:
• Tetracycline and Calcium – Poor absorbed complex
• Polar drug and complexing agent - Well absorbed lipid soluble complex
• Carboxy methyl cellulose and amphetamine - Poor absorbed complex
• PVP and Iodine – Better Absorption
28. 1.6 THERMODYNAMIC TREATMENT OF STABILITY
CONSTANTS COMPLEXES
The relationship between the standard free energy change of complexation
and the overall stability constant K is related as;
∆𝐺 = −2.303𝑅𝑇 𝐿𝑜𝑔𝐾
The standard enthalpy change maybe obtained from the slope of a plot of
Log K versus 1/T, thus the equation will be ;
Log K=-(∆H/2.303R) × (1/T) + Constant
When the value of K at two temperatures are known , the following equation
can be written as;
Log (𝐾1/𝐾2) = -(∆H/2.303R) × (𝑇2-𝑇1/ 𝑇1𝑇2)
29. The Standard Entropy change maybe obtained from the expression
∆𝐺 = ∆H−T ∆S
• As the stability constant for molecular complexation increases, ∆H and ∆S
becomes more negative
• As binding between the donor and receptor becomes stronger , ∆H becomes
more negative
• Since the specificity of interacting sites become negative, ∆S also becomes
more negative
But extent of change in ∆H is large enough to overcome the un favourable
entropy change resulting in negative ∆G value and hence complexation