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 This material may be available as Internet Resource: Display the web subdirectory: http://www.ugc-inno-nehu.com/CRNMR/ Some of the linked files in this .ppt file require the Software “ARGUSLAB” 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/ And download the all the contents of this directory into the same and single folder in the resident disc of the P.C. for the hyperlinks in the presentation file to display the appropriate file. 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR In the D3d all oxygen are disposed towards the cavity of the molecule In the Cs there are interatomic distances for favorable hydrogen bonding D3d Cs D3d JPG Image Full publication by Bagatur Yants et al 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR The JPG Image The several perspective views of the D3d structure which seems to be occurring more in the polar media The JPG image Crown Ether-18crown6-D3d-webmo computational result 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR 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 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR 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 The JPG Image Crown Ether-18crown6-D3d-webmo computational result 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR Job106639-Str-PMR-CMR-C12H24O6-Crownether-form2-65.JPG Cyclohexane-boat for comparison 18crown6-Cs form-computational results The JPG Image 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR 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) The variety of Derivatives of 18-crown-6 ether which are used in the experimental methods; For complexing with chiral molecules and proceed to obtain NMR of the complex. 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 The Full publication by Koylu et al 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR 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 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 The JPG Image 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR 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. Hyperlink-2 Hyperlink-1 The Full publication by Koylu et al The JPG Image 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR CYCLOHEXANE-analogous symmetry and conformational disposition The JPG Image Computation on Cyclohexane-chair Return to Slide #4 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR

Aravamudhan: Chiral Recognition by NMR CYCLOHEXANE-analogous symmetry and conformational disposition The JPG Image Computation on Cyclohexane-boat Return to Slide #5 7/6/2012 11:49:36 AM Aravamudhan: Chiral Recognition by NMR