This chapter discusses stereochemistry and chirality. It defines key terms like enantiomers, diastereomers, and meso compounds. Enantiomers are nonsuperimposable mirror images that have different properties. Compounds with multiple chiral carbons can have enantiomers, diastereomers, or meso isomers. Rules for assigning R and S configurations like CIP priorities are covered. The chapter also addresses topics like optical activity, resolving enantiomers, and properties of stereoisomers.
IMPORTANT NAMED REACTIONS in Organic synthesis with Introduction, General Mechanism, and their synthetic application covering more than 20 named reactions in it.
IMPORTANT NAMED REACTIONS in Organic synthesis with Introduction, General Mechanism, and their synthetic application covering more than 20 named reactions in it.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
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(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
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 .
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
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.
5. Chapter 5 5
Chiral Carbons
• Carbons with four different groups attached
are chiral.
• It’s mirror image will be a different
compound (enantiomer).
6. Chapter 5 6
Achiral Compounds
Take this mirror image and try to superimpose it
on the one to the left matching all the atoms.
Everything will match.
When the images can be superposed the
compound is achiral.
7. Chapter 5 7
Planes of Symmetry
• A molecule that has a plane of symmetry is
achiral.
8. Chapter 5 8
Cis and Trans Cyclic Compounds
• Cis-1,2-dichlorocyclohexane is achiral because the molecule
has an internal plane of symmetry. Both structures above can be
superimposed.
• Trans-1,2-dichlorocyclohexane does not have a plane of
symmetry so the images are nonsuperimposable and the
molecule will have two enantiomers.
9. Chapter 5 9
(R) and (S) Nomenclature
• Different molecules (enantiomers) must have different
names.
• Usually only one enantiomer will be biologically active.
• Configuration around the chiral carbon is specified
with (R) and (S).
10. Chapter 5 10
Cahn–Ingold–Prelog
Rules
• Assign a priority number to each group
attached to the chiral carbon.
• Priority is assigned according to atomic
number. The highest atomic number
assigned is the highest priority #1.
• In case of ties, look at the next atoms along
the chain.
• Double and triple bonds are treated like
bonds to duplicate atoms.
11. Chapter 5 11
Assign (R) or (S)
• Working in 3-D, rotate the molecule so that the lowest
priority group is in back.
• Draw an arrow from highest to lowest priority group.
• Clockwise = (R), Counterclockwise = (S)
12. Chapter 5 12
Assign Priorities
Atomic number: F > N > C > H
Once priorities have been assigned, the lowest priority
group (#4) should be moved to the back if necessary.
13. Chapter 5 13
Assign Priorities
Draw an arrow from Group 1 to Group 2 to Group 3 and
back to Group 1. Ignore Group 4.
Clockwise = (R) and Counterclockwise = (S)
Counterclockwise
(S)
16. Chapter 5 16
Example (Continued)
CH3
CH3CH2CH=CH
CH2CH2CH2CH3
H
1
2
3
4
Counterclockwise
(S)
17. Chapter 5 17
Draw the enantiomers of 1,3-dibromobutane and
label them as (R) and (S). (Making a model is
particularly helpful for this type of problem.)
The third carbon atom in 1,3-dibromobutane is
asymmetric. The bromine atom receives first
priority, the (–CH2CH2Br) group second priority,
the methyl group third, and the hydrogen fourth.
The following mirror images are drawn with the
hydrogen atom back, ready to assign (R) or (S) as
shown.
Solved Problem 1
Solution
18. Chapter 5 18
Properties of Enantiomers
• Same boiling point, melting point, and density.
• Same refractive index.
• Rotate the plane of polarized light in the same
magnitude, but in opposite directions.
• Different interaction with other chiral molecules:
– Active site of enzymes is selective for a specific
enantiomer.
– Taste buds and scent receptors are also chiral.
Enantiomers may have different smells.
19. Chapter 5 19
Optical Activity
• Enantiomers rotate the plane of polarized
light in opposite directions, but same
number of degrees.
21. Chapter 5 21
Specific Rotation
Observed rotation depends on the length
of the cell and concentration, as well as the
strength of optical activity, temperature,
and wavelength of light.
[ ] = (observed)
c l
Where (observed) is the rotation observed in
the polarimeter, c is concentration in g/mL and l is
length of sample cell in decimeters.
22. Chapter 5 22
When one of the enantiomers of 2-butanol is placed
in a polarimeter, the observed rotation is 4.05°
counterclockwise. The solution was made by
diluting 6 g of 2-butanol to a total of 40 mL, and
the solution was placed into a 200-mm polarimeter
tube for the measurement. Determine the specific
rotation for this enantiomer of 2-butanol.
Since it is levorotatory, this must be (–)-2-
butanol The concentration is 6 g per 40 mL = 0.15
g/ml, and the path length is 200 mm = 2 dm. The
specific rotation is
[ ]D
25=
–
4.05
°
(0.15
)(2)
= –13.5°
Solved Problem 2
Solution
24. Chapter 5 24
Racemic Mixtures
• Equal quantities of d- and l- enantiomers.
• Notation: (d,l) or ( )
• No optical activity.
• The mixture may have different boiling point (b. p.)
and melting point (m. p.) from the enantiomers!
25. Chapter 5 25
Racemic Products
If optically inactive reagents combine to
form a chiral molecule, a racemic mixture
is formed.
26. Chapter 5 26
Optical Purity
• Optical purity (o.p.) is sometimes called
enantiomeric excess (e.e.).
• One enantiomer is present in greater
amounts.
observed rotation
rotation of pure enantiomer
X 100o.p. =
27. Chapter 5 27
Calculate % Composition
The specific rotation of (S)-2-iodobutane is +15.90 .
Determine the % composition of a mixture of (R)-
and (S)-2-iodobutane if the specific rotation of the
mixture is -3.18 .
3.18
15.90
X 100o.p. = = 20%
2l = 120% l = 60% d = 40%
Sign is from the enantiomer in excess: levorotatory.
28. Chapter 5 28
Chirality of Conformers
• If equilibrium exists between two chiral
conformers, the molecule is not chiral.
• Judge chirality by looking at the most
symmetrical conformer.
• Cyclohexane can be considered to be
planar, on average.
29. Chapter 5 29
Chirality of Conformational
Isomers
The two chair conformations of cis-1,2-dibromocyclohexane
are nonsuperimposable, but the interconversion is fast and
the molecules are in equilibrium. Any sample would be
racemic and, as such, optically inactive.
30. Chapter 5 30
Nonmobile Conformers
• The planar conformation of the biphenyl derivative is too
sterically crowded. The compound has no rotation around
the central C—C bond and thus it is conformationally
locked.
• The staggered conformations are chiral: They are
nonsuperimposable mirror images.
31. Chapter 5 31
Allenes
• Some allenes are chiral even though
they do not have a chiral carbon.
• Central carbon is sp hybridized.
• To be chiral, the groups at the end
carbons must have different groups.
33. Chapter 5 33
Fischer Projections
• Flat representation of a 3-D molecule.
• A chiral carbon is at the intersection of
horizontal and vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.
35. Chapter 5 35
Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon is at top.
• Rotation of 180 in plane doesn’t
change molecule.
• Do not rotate 90 !
36. Chapter 5 36
180 Rotation
• A rotation of 180 is allowed because it will
not change the configuration.
37. Chapter 5 37
90 Rotation
• A 90 rotation will change the orientation of
the horizontal and vertical groups.
• Do not rotate a Fischer projection 90 .
38. Chapter 5 38
Fischer Mirror Images
• Fisher projections are easy to draw and make
it easier to find enantiomers and internal
mirror planes when the molecule has 2 or
more chiral centers.
CH3
H Cl
Cl H
CH3
39. Chapter 5 39
Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so
assignment rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise
1-2-3 is (R).
• Example:
(S)
(S)
CH3
H Cl
Cl H
CH3
40. Chapter 5 40
Diastereomers
• Molecules with two or more chiral carbons.
• Stereoisomers that are not mirror images.
41. Chapter 5 41
Alkenes
• Cis-trans isomers are not mirror images, so
these are diastereomers.
42. Chapter 5 42
Two or More Chiral Carbons
• When compounds have two or more chiral
centers they have enantiomers,
diastereomers, or meso isomers.
• Enantiomers have opposite configurations at
each corresponding chiral carbon.
• Diastereomers have some matching, some
opposite configurations.
• Meso compounds have internal mirror planes.
• Maximum number of isomers is 2n, where n =
the number of chiral carbons.
43. Chapter 5
43
Are the structures connected the same?Are the structures connected the same?
yesyes nono
Are they mirror images?Are they mirror images? Constitutional IsomersConstitutional Isomers
yesyes nono
EnantiomersEnantiomers
All chiral centers willAll chiral centers will
be opposite between them.be opposite between them.
Is there a plane of symmetry?Is there a plane of symmetry?
yesyes nono
DiastereomersDiastereomersMesoMeso
superimposablesuperimposable
Comparing Structures
44. Chapter 5 44
• Meso compounds have a plane of symmetry.
• If one image was rotated 180 , then it could be
superimposed on the other image.
• Meso compounds are achiral even though they have
chiral centers.
Meso Compounds
45. Chapter 5 45
Number of Stereoisomers
The 2n rule will not apply to compounds that may have a
plane of symmetry. 2,3-dibromobutane has only 3
stereoisomers: ( ) diastereomer and the meso diastereomer.
46. Chapter 5 46
Properties of Diastereomers
• Diastereomers have different physical
properties, so they can be easily separated.
• Enantiomers differ only in reaction with other
chiral molecules and the direction in which
polarized light is rotated.
• Enantiomers are difficult to separate.
• Convert enantiomers into diastereomers to be
able to separate them.
47. Chapter 5 47
Resolution of Enantiomers
React the racemic mixture with a pure chiral
compound, such as tartaric acid, to form
diastereomers, then separate them.