Fluorescence Approaches for Determining Protein Conformations ...
Chapter 3 webpeople.ysu.edu/~pnorris/Semesters/3719F2009/Slides/... · 3.1 Conformational analysis...
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1 Carey Chapter 3 – Conformations of Alkanes and Cycloalkanes YSU YSU Figure 3.5 – Energy distribution vs. Temp. G = H - TS YSU YSU Conformational Analysis – Towards Structural Biology Cytosine (C) (from TGCA alphabet in DNA
Transcript of Chapter 3 webpeople.ysu.edu/~pnorris/Semesters/3719F2009/Slides/... · 3.1 Conformational analysis...
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Carey Chapter 3 – Conformations of Alkanes and Cycloalkanes
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Figure 3.5 – Energy distribution vs. Temp.
G = H - TS
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Conformational Analysis – Towards Structural Biology
Cytosine (C) (from TGCA alphabet in DNA
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Conformational Analysis – Towards Structural Biology
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Cytosine (C) (from TGCA alphabet in DNA
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Conformational Analysis – Towards Structural Biology
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Conformational Analysis – Medicinal Chemistry
Thymidine – incorporated into DNA as “T”
Zidovudine (AZT) – incorporated into DNA instead of T – stops chain growth
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Conformational Analysis – Medicinal Chemistry
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3.1 Conformational analysis of Ethane
Since single bonds can rotate around the bond axis, different conformations are possible ‐ conformational analysis
Figure 3.1 – Different representations of ethane ‐ ChemDraw
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Different 3‐D depictions of Ethane
Rotation around the central C‐C bond will cause the hydrogens to interact ‐rotamers or conformers
“Wedge/dash”“Sawhorse”
“Newman”
3.1 Conformational Depictions of Acyclic Molecules
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3.1 Definitions for Using Newman Projections
Gauche
torsion angle 60oEclipsed
torsion angle 0oAnti
torsion angle 180o
Both gauche and anti conformers are staggered
Eclipsed conformers are destabilized by torsional strain
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3.1 – Conformational Analysis of Ethane
Figure 3.4 – Rotation around the C‐C bond of Ethane
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3.2 Conformational Analysis of Butane
Figure 3.4 – Rotation around the C‐C bond of Ethane
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3.3 Conformations of higher alkanes
Anti(staggered)
eclipsed eclipsed
Applicable for any
acyclic molecule
Gauche(staggered)
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3.4 Cycloalkanes – most are not planar
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3.5 Cyclopropane and Cyclobutane
Figure 3.10 – Depictions of Cyclopropane and Cyclobutane
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3.6 Conformations of Cyclopentane
Figure 3.12 – Important conformations of Cyclopentane
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3.7 Conformations of Cyclohexane
Conformationally flexible (without breaking bonds)
Chair Boat Chair
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3.7-3.8 Cyclohexane – axial and equatorial positions
Figures 3.13 & 3.14 – Axial and Equatorial positions in cyclohexane chair and boat conformations
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3.7-3.8 Cyclohexane – axial and equatorial positions
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3.9 Conformational inversion – ring flipping
Figure 3.18 – Energeticsof the ring‐flip
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3.10 Equilibrium constants for ring-flips
G = H – TS
G = ‐ RTlnK
Reactants Products
Equilibrium Constant (K) = [Products][Reactants]
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3.10 Equilibrium constants for ring-flips
G = ‐ RTlnK
Equilibrium Constant (K) = [Right‐Side][Left‐Side]
Left-Side Right-Side
K > 1, RHS favoured; K ~ 1, equal; K < 1, LHS favoured
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3.10 Analysis of monosubstituted cyclohexanes
G = ‐0.24 Kcal/mol
K = 1.5
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3.10 Analysis of monosubstituted cyclohexanes
G = ‐7.3 Kcal/mol
K = 19
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3.10 Analysis of monosubstituted cyclohexanes
G = ‐8.6 Kcal/mol
K = 32.3
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3.10 Analysis of monosubstituted cyclohexanes
G = ‐8.6 Kcal/mol
K = 32.3
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3.10 Analysis of monosubstituted cyclohexanes
G = ‐22.8 Kcal/mol
K = >9999
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3.10 Analysis of monosubstituted cyclohexanes
G = ‐22.8 Kcal/mol
K = >9999
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3.10 Analysis of monosubstituted cyclohexanes
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3.11 Disubstituted Cyclopropanes – Stereoisomers
Figure 3.20
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3.12 Disubstituted Cycloalkanes - Stereoisomers
Cis‐1,2‐dimethylcyclopropane is less stable than the trans isomer
Cis‐1,2‐dimethylcyclohexane is less stable than the trans isomer
Cis‐1,3‐dimethylcyclohexane is more stable than the trans isomer
Cis‐1,4‐dimethylcyclohexane is less stable than the trans isomer
All based on interactions between substituents and other groups on the ring
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3.12 Disubstituted Cyclohexanes – Energy Differences
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3.13 Medium and large rings - Cyclodecane
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3.13 Medium and large rings - Erythromycin
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3.13 Medium and Large Rings – YSU Chemistry
O
O O
O
O
Ph
N
O
OO
O
O
Ph
N
O
O O
O
O
N2
NNN
Rh2+
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3.14 Polycyclic Ring Systems
adamantane
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3.14 Polycyclic Ring Systems - Cholesterol
cholesterol
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3.14 Polycyclic Ring Systems - Bicyclics
Bicyclobutane
Bicyclo[3.2.0]heptane
Bicyclo[2.2.2]octane
Bicyclo[2.1.0]pentane
Bicyclo[4.1.0]heptane
Bicyclo[4.2.2]decane
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3.15 Heterocyclic Compounds
tetrahydrofuran pyrrolidine piperidine indole
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morphine ritilin librium
3.15 Heterocyclic Compounds
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3.15 Heterocyclic Compounds - Carbohydrates
O
OH
HOHO
OHOH
D‐Glucose (dextrose, blood sugar)
