Transcript 0-P01_crowmether-hos..

crowmether-host1.ppt
Distiguishing
features forwith
Chirality
Such small
molecules
are complexed
larger
host molecules
and
Chiralchiral
Recognition
by NMR
SpectroscopyA
Theoretical
approach.
the NMR spectra
of the resulting
used
for recognizing
Illustrating
modelingcomplex
strategiesiswith
organic
molecules the chiral
form, the R or S. with overtones for Modeling of Bio-molecules
S.Aravamudhan
Amino
acids are designated by L An
or DAbstract
optical isomers (equivalent to R,S
Departmentthat
of Chemistry
S.Aravamudhan
designation)
corresponds to
the presence of asymmetric carbon / a chiral
North Eastern Hill University
centre.
SHILLONG 793022 Meghalaya
material may
be available
as Internet
Resource:chemistry is
Most of themThis
experimental
studies
and not much
Computational
the web subdirectory:
http://www.ugc-inno-nehu.com/CRNMR/
reported on Display
such systems
for the calculation
of chemical shifts of un
complexed
forfilea require
comparison
with“ARGUSLAB”
the complexes.
Some of thehost
linkedand
filesligand,
in this .ppt
the Software
be installed in your
system. Download the MS Windows installer “setup.exe” file by clicking on the link below:
http://www.ugc-inno-nehu.com/arguslab/
Thus this presentation is
a study reporting a small molecule docking with a
larger molecule and the use of calculation of chemical shifts on certain model
And download the all the contents of this directory into the same and single
systems.
folder in the resident disc of the P.C. for the hyperlinks in the presentation file
to display
thespectroscopy
appropriateasfile.
Just as much as experimentalists
use NMR
an analytical tool for structure
determination, it is being pointed out that trends using Chemical shift calculations can be
Download
thesestudies
presentation
files
from my
internet
so much useful
in modeling
even if the
calculated
shift
values resource:
do not reproduce
http://www.ugc-inno-nehu.com/wmbs-II-mzu/
the experimental shift
values.
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Aravamudhan: Chiral Recognition by NMR
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D3d
Crown Ether
18Crown6 Ether
C12H24O6
In the D3d all oxygen are disposed
towards the cavity of the molecule
Cs
D3d
In the Cs there are interatomic distances for favorable
hydrogen bonding
JPG Image
Full publication by
Bagatur Yants et al
7/6/2012 11:49:36 AM
Aravamudhan: Chiral Recognition by NMR
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The JPG Image
The several perspective
views of the D3d
structure which seems
to be occurring more in
the polar media
The JPG image
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Crown Ether-18crown6-D3d-webmo computational result
Aravamudhan: Chiral Recognition by NMR
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The JPG Image
The several perspective
views of the Cs
structure which seems
to be occurring more in
the nonpolar media
18crown6-Cs form-computational results
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Aravamudhan: Chiral Recognition by NMR
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The two-line spectrum of the 18-crown-6 ether, due to the fluctuations and
conformational dynamics in solution gives a single averaged line spectrum as much
as the cyclohexane (Chair) . The experimental PMR spectrum of 18crown6ether
displays a single line spectrum at 3.691ppm, this value is higher than the average
value of the two-line theoretical spectrum {~(2.0+2.5 )/2=2.25ppm}. Such
differences can be reconciled by using a better QM method of calcualtion (-and a
scaling seems inevitable in any case) . Link:- data base experimental spectrum
Cyclohexane- CHAIR conformation with similar two line spectrum, requires 5.9 secs CPU time (a fctor of 9 times less). Crown
Ether has 42 atoms and Cyclohexane has 18 atoms in the molecule (atom count includes oxygen hetero atom in Crown ether)
The JPG Image
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Crown Ether-18crown6-D3d-webmo computational result
Aravamudhan: Chiral Recognition by NMR
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Job106639-Str-PMR-CMR-C12H24O6Crownether-form2-65.JPG
The NMR spectrum has relatively
more complex pattern: A consequence
of reduced symmetry of the Molecule.
Computationally this requires more
CPU time: a difference of about 5 secs
as compared to the D6 d symmetry
Cyclohexane-boat for comparison
The JPG Image
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18crown6-Cs form-computational results
Aravamudhan: Chiral Recognition by NMR
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The 18crown6ether in the PMR spectrum
has simply a single line; it is not
necessary that the derivatives should
also have similar single line.
Characteristic variations in certain
specific nmr line is often possible to
recognize the chirality (of the host)
dependent variations (as in next slide #7)
Typically referred to as
NMR titration: A specific
line in the spectrum of
the complex displays a
variation with the
relative guest/host
concentration ratio.
The JPG Image
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The variety of Derivatives of 18crown-6 ether which are used in the
experimental methods; For complexing
with chiral molecules and proceed to
obtain NMR of the complex.
The Full publication by Koylu et al
Aravamudhan: Chiral Recognition by NMR
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Hence the query as to whether theoretical calculations would reduce the
uncertainties; the quest for appropriate theoretical method is duly the initiative
required; Is it then simply a matter of calculating chemical shifts accurately, or the
better G.O . possibilities?
What makes these kind
of studies tedious and
prone with ambiguities
is: the experimental
search for appropriate
Guest and Host
molecules which would
enable some line in the
spectrum to be tagged
on to distinguish chiral dependence
The JPG Image
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The specific NMR
line position
variation for the S
and R conformers.
The actual complex
(the Host and gust)
can be seen in the
next slide #8
The Full publication by Koylu et al
Aravamudhan: Chiral Recognition by NMR
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This docked complex does indicate that a Theoretical
Calculation would entail the complications of docking studies in
the macromolecular regime (the hyperlinks should display the AGL files and
the corresponding exported images). Thus such a supra molecule
studies could derive benefit by modeling with small molecules
for favorable features to know the specifics which can then be
integrated into a set of conditions for a tangible study of the
large molecule. This indication for the necessity for a modeling
was pursued to gain some insight; and, the full comprehension
of the actualities (regarding the Chiral Recognition by NMR
using theoretical methods) would require several compilations
of the type presented now, and in the remaining parts.
CPUtime-CalcNMRchemShifts.JPG
Hyperlink-1
The JPG Image
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Hyperlink-2
The Full publication by Koylu et al
Aravamudhan: Chiral Recognition by NMR
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CYCLOHEXANE-analogous symmetry
and conformational disposition
The JPG Image
Computation on
Cyclohexane-chair
A boat conformation
requires more CPU time; a
marginal difference of
about 0.2 secs
Return to Slide #5
1,3,5 trioxane also
gives a 2 line NMR
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Aravamudhan: Chiral Recognition by NMR
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CYCLOHEXANE-analogous symmetry
and conformational disposition
The JPG Image
Computation on
Cyclohexane-boat
Return to Slide #6
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Aravamudhan: Chiral Recognition by NMR
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