Transcript P04 - S.Aravamudhan

crowmether-host1.ppt
Chiral Recognition by NMR Spectroscopy- A Theoretical approach.
Illustrating modeling strategies with organic molecules
with overtones for Modeling of Bio-molecules
An Abstract
S.Aravamudhan
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7/6/2012 11:49:36 AM
Aravamudhan: Chiral Recognition by NMR
1
The Chiral recognition by NMR require:
1. NMR spectrum of the Host molecule
2. NMR spectrum of the Guest (Chiral) molecule
3. NMR spectrum of the Host-guest complex. Slide#3
4. Identifying the spectral lines/region which indicates the dependence on
the complexing by the guest. (typically from Slide # 6)
5. And, monitoring the indicator peaks with the concentration of the Guest
molecule (illustrated in Slide# 10). This means a theoretical calculation
would require calculation of the NMR of the complex molecule for
various Stoichio metric proportions and hence Host to Guest molar
ratios - 1:2, -1:1, - 2:1, -etc ., to be specifying a few typical ratios. To
cover non-integral ratio values, the required integral number of cluster
molecules would demand handling large sized molecular cluster than
for the above simple integral ratios. For such clusters Host-host, guestguest interactions and changes in structures of host and guest
molecule structures would be factors to reckon with.
6. This would mean the super molecular system to handle would increase
in size depending on the complex as compared to the size of the guest
molecule alone or the host molecule alone. The increase in computation
time, and while trying to optimize the time factor, what options could be
exercised on the theoretical method and basis sets, must be spelt out
with the corresponding advantages/disadvantages.
8/9/2012 10:22AM
S.Aravamudhan
CRNMR
2
In the optimized structures
on the right hand side, the
guest and host are placed
at shorter inter molecular
distances. Note the
crowding of lines between
4 & 5ppm. On the left hand
side the spectral lines are
more spread out in the
region 2.5-6 ppm
As also seen in SLIDE # 6
Host-guest complex STRUCTURE and NMR
To Slide#2
8/9/2012
Only chemical shifts calculated : No spin-spin coupling
10:22AMincluded
S.Aravamudhan
CRNMR
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Alanine- an amino
acid: Small molecule
unit of biological
macromolecules
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S.Aravamudhan
CRNMR
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S.Aravamudhan
CRNMR
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S
R
An expanded view of
this region is in Slide #7
To Slide#2
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S.Aravamudhan
CRNMR
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Slide #3
The third spectrum (lower) seems an addition of the features of the first two spectrum
(above) as much as the third structure consists of both the individual molecules of the
above two molecules. Hence a guest-host distance dependence is in sequence for the
8/17/2012
Dr S Aravamudhan
CRNMR
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trends
determining differentiating features
in PMR
SLIDE # 6
These expanded regions are
part of the full spectrum
obtained using the calculated
chemical shifts. Next slide
depicts a simulated
spectrum obtained using an
“FID Simulator” with the
same set of chemical shifts.
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S.Aravamudhan
CRNMR
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With this illustration of a simulation, for the
complexation of two chiral forms of the
ligand ( above and below in the respective
columns), the next stage is set for looking
for the trends of variations in Chemical
shifts for different stoichiometric
composition, and the calculable chemical
variations.
To Slide#2
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S.Aravamudhan
CRNMR
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