This document provides an overview of enantiomers, racemic mixtures, and methods for resolving racemic mixtures into individual enantiomers. It defines key terms like enantiomers, racemic mixtures, and resolution. It then describes several methods for resolving racemic mixtures, including mechanical separation, preferential crystallization, biochemical separation using microorganisms, chromatographic separation, kinetic resolution, precipitation, and using diastereomers. It discusses the need for resolution and provides examples like levocetrizine and levodopa.
STEREOSPECIFIC REACTION, STEREOSELECTIVE REACTION, OPTICAL PURITY, ENANTIOMERIC EXCESS.. all these topics are explained in this slide with examples and formula.
THIS PRESENTATION COVER INTRODUCTION, STRUCTURE, AROMATICITY, RESONANCE, BASICITY, PHYSICAL PROPERTIES, SYNTHESIS, CHEMICAL PROPERTIES AND MEDICAL USES OF PYRIDINE AND PYRIMIDINE
STEREOSPECIFIC REACTION, STEREOSELECTIVE REACTION, OPTICAL PURITY, ENANTIOMERIC EXCESS.. all these topics are explained in this slide with examples and formula.
THIS PRESENTATION COVER INTRODUCTION, STRUCTURE, AROMATICITY, RESONANCE, BASICITY, PHYSICAL PROPERTIES, SYNTHESIS, CHEMICAL PROPERTIES AND MEDICAL USES OF PYRIDINE AND PYRIMIDINE
This slide discusses about basic indole nucleus, its chemistry, synthesis, reactions and medicinal uses of Indolyl derivatives..Indole is basically fused heterocyclic compound
This slide discusses about fused heterocyclic compound Acridine..the structural analogue of anthracene with one carbon group is replaced with nitrogen atom.
This slide discusses about basic indole nucleus, its chemistry, synthesis, reactions and medicinal uses of Indolyl derivatives..Indole is basically fused heterocyclic compound
This slide discusses about fused heterocyclic compound Acridine..the structural analogue of anthracene with one carbon group is replaced with nitrogen atom.
Introduction: Most of the drugs substance single enantiomer is active. In such cases the inactive enantiomer is considered as an impurity, e. g. If Dextro form is active then in this case levo form is considered as an impurity.
An enantiomer can be named by the direction in which it rotates the plane of polarized light. An optical isomer can be named by the spatial configuration of its atoms. Clockwise rotation of the light traveling toward the viewer is labelled (+) or R (in Latin Rectus for right) also termed as d-isomer i.e. dextrorotatory enantiomer. Its mirror-image is labelled (−) or S (in Latin Sinister for left) also termed as l-isomer i.e. levorotatory enantiomer.
The R / S system is an important nomenclature system for representing enantiomers. This method labels each chiral centre R or S according to a system by which its substituents are each assigned a priority, according to the Cahn–Ingold–Prelog priority rules (CIP), based on atomic number.
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Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
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optics at visible wavelengths.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
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Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
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Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. Introduction
Enantiomers
Racemic Mixture
Resolution
Need for Resolution of Racemic Mixture
Methods of Resolution Of Racemic Mixture
Mechanical Separation or Spontaneous Resolution
Preferential Crystallization By Inclution.
Biochemical separation.
Chromatographic Separation
Kinetic Method
Precipitation
By Disateromers
2
3. A racemic mixture is a 50:50 mixture of two enantiomers.
Because they are mirror images, each enantiomer rotates
plane-polarized light in an equal but opposite direction and is
optically inactive.
Separation of racemates into their component enantiomers is a
process called resolution.
Moving from a racemic drug to a chiral specific drug may done
for a better safety profile or an improved therapeutic index. This
process is called chiral switching and the resulting enantiopure
drug is called a Chiral Switch.
To cite few examples, Esomeprazole is a chiral switch of (±)-
omeprazole; Levocetrizine is a chiral switch of (±)-cetirizine.
3
4. 4
In chemistry, racemization is a conversion, by heat or by
chemical reaction, of an optically active compound into
a racemic (optically inactive) form.
Half of the optically active substance becomes its mirror
image (enantiomer) referred as racemic mixtures (i.e.
contain equal amount of (+) and (−) forms).
If the racemization results in a mixture where the D and L
enantiomers are present in equal quantities, the resulting
sample is described as a Racemic mixture or a racemate.
Racemization can proceed through a number of different
mechanisms ,and it has particular significance in
pharmacology as different enantiomers may have different
pharmaceutical effects.
5. Isomers which are non-superimposable mirror images
of each other are called enantiomers.
Enantiomers are the chiral molecules that are mirror
images of one another and are not superimposable.
Eg.
5
ENANTIOMERS:-
(S)-(+)-Lactic Acid (left) and (R)-(–)-lactic acid (right)
are non-superposable mirror images of each other.
7. A equimolar (50/50) mixture of the two enantiomers
is called a racemic mixture or a racemate.
Examples include thalidomide, ibuprofen, cetirizine
and salbutamol.
Resolution:-
The process of seperation of pure enantiomer
from their racemic modification is called resolution.
7
10. Levodopa (i.e. L-DOPA) is used in the treatment of
Parkinson's disease and dopamine-responsive dystonia.
L-DOPA is converted to dopamine in the brain by
aromatic L-amino acid decarboxylase, also known as
DOPA decarboxylase (DDC).
Levodopa (L-dopa) is used in treatment of Parkinson’s
disease, its D-form causes serious side effects, such as
granulocytopenia 10
Levodopa
11. Mechanical Separation or Spontaneous
Resolution.
Preferential Crystallization By Inoculation.
Biochemical separation.
Chromatographic Separation
Kinetic Method
Precipitation
By Disateromers
11
12. This involved mechanical separation of the crystal of one
enantiomers from the other in racemic mixture based on
difference in their shapes.
Crystal of the two forms have different shapes
separated by magnifying lens and forceps.
This method first used by pasteur for he resolutiuon of
sodium ammonium tartarate which crystallise out in
the form of racemic mixture below 27 degree.
This methods is time consuming and every compound can
not be crystallized at room temperature.
12
13. 2.Preferential Crystallization By
Inoculation:-
This method involve seeding of a saturated solution of
the racemic mixture with a pure crystal of one the two
enantiomers.
The solution now become supersaturated with respect to
the added enantiomers.
It begins to crystallise out.
Eg. Harda obtained free from amino acid by adding
corresponding D/Lisomers of amino acid.
13
14. It was introduced by PASTEUR in 1858.
This method is based on fact that when certain micro
organisms like bacteria, fungi,yeast,moulds,etc are
grown in dilute solution of racemic mixture,They eat
up one enantiomer rapidly than other.
Example: The mould penicillium glaucum
preferentially destroys the (+) isomer of racemic
ammonium tartarate leaving (-) ammonium tartarate
in solution.
14
15. The racemic mixture can be separated by
chromatography on an optically active support.
The diastereomeric adsorbates which are formed have
different stabilities.
Thus one enantiomer will be held more tightly than the
other and would be eluted first.
15
16. This methodmis based on the fact that one of the
enantiomer of racemic mixture reacts faster with
optically active compound.
Methanol reacts faster with (+) mandelic acid with (-)
mandelic acid.
Thus with difference in kinetic of reaction , Racemic
mixture can be seperated.
Which form of compound get firstly reacted it should get
seperated first. In this way the Racemates get easily
seperated.
16
17. This method is based on formation of precipitate by
reaction between any reagent and racemic mixture.
Example: (+) & (-) narcotine when dissolved in
HCL,precipitates (+) narcotine.
17
18. When racemic mixture is allowed to interact with
optically active material, it give a diastereomeric
derivatives.
Distereomers have different physical properties and
hence can be easily seperated into two component by
fractional crystallization.
18
19. The most unremarkably used procedure for separating
enantiomers is to convert them to a mix of
diastereomers which will have totally different physical
properties, freezing point, boiling purpose, solubility,
and so on.
For example: If you have got a racemic or D,L
mixture of enantiomers of associate acid and convert
this to a salt with a chiral base having the D
configuration, the salt is a mixture of two
diastereomers, D acid. D base and L acid. D base.
19
20. These diastereomeric salts are not identical and that they are not
mirror pictures. Hence, they will take issue to a point in their
physical properties, and a separation by physical strategies, like
crystallization, could also be attainable.
If the diastereomeric salts is fully separated, the acid regenerated
from every salt is either completely the D or the L enantiomer.
20
21. To reduce the adverse drug reaction by making
optically inactive form of racemates.
To improve the Threpeutic effect of drug.
To improve the chemical stability of a compound; so it
can not change its chemical properties when come in
contact with the atmosphere or humidity.
21
22. Advantages of racemic modification:-
The use of a single isomer must be seriously taken after
long clinical assessments between racemate and single
enantiomer actions because in some cases, racemates
have more therapeutic advantages than single isomers.
Disadvantages of racemic modification:-
Side effects of “other” enantiomer could be dangerous.
Larger or double doses of the drug will have to be taken
if drug contains a mixture of enantiomers.
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