acs presentation march 2011
TRANSCRIPT
![Page 1: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/1.jpg)
Density functional calculations of the structural, thermodynamic & spectroscopic properties of spiroindolone
Fred L. Nesbitt & Rose A. NesbittNETA International,Seabrook, MD USA
![Page 2: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/2.jpg)
Introduction
• Spiroindolone has been shown to be effective against two species of malaria (Plasmodium falciparum and Plasmodium berghei)• 40% of the global population affected• Plasmodium falciparum - most virulent and
affects about half a billion people per year • A million deaths in 2008, 90% of these are
children• Most current effective drug is Artemisinin
combination therapies (ACT) shows resistance hence the need for a new drug
![Page 3: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/3.jpg)
All geometries were computed using the B3LYP densityfunctional theory method using Spartan 10
Geometries optimized were performed using the 6-31G*basis set
Computational Method
![Page 4: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/4.jpg)
Lewis structure of SpiroindoloneC19H14ClF2N3O
![Page 5: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/5.jpg)
RESULTSStructure of Spiroindolone
![Page 6: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/6.jpg)
RESULTSSpace filling model of Spiroindolone
![Page 7: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/7.jpg)
RESULTSThermodynamic properties
∆fH0 =843 kJ/Mole
S0 =638 J/Mole K
∆fG0 = 654 kJ/Mole
Cp0 = 352 J/Mole K
![Page 8: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/8.jpg)
RESULTSDipole moment
Dipole Moment = 5.37 Debye
![Page 9: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/9.jpg)
RESULTSInfrared spectra
![Page 10: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/10.jpg)
RESULTSRAMAN spectra
![Page 11: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/11.jpg)
RESULTSNMR spectra
![Page 12: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/12.jpg)
RESULTSUV-Vis spectra
![Page 13: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/13.jpg)
RESULTSDensity potential map
![Page 14: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/14.jpg)
RESULTSHOMO Surface
![Page 15: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/15.jpg)
RESULTSLUMO Surface
![Page 16: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/16.jpg)
RESULTSElectrostatic Potential
![Page 17: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/17.jpg)
Future Studies
Perform density functional calculations on the three other enantiomers of spiroindolone To determine the following properties IR spectra, NMR spectra, dipole moment and thermodynamic properties. These properties will be important in eliminating impurities (the other 3 enantiomers) of spiroindolone which may be responsible for side effects.
![Page 18: Acs presentation march 2011](https://reader031.vdocument.in/reader031/viewer/2022020218/55a5ea7f1a28abb6128b48f6/html5/thumbnails/18.jpg)
References
1.Bryan K.S. Yeung, et.al. Spirotetrahydro β-carolines (Spirindolones): A new class of potent and orally efficacious compounds for the treatment of malaria.,J.Med. Chem., 2010, 53, 1555 – 1564. 2.SPARTAN '08, build 131 (Jan 29 2009)Wavefunction Developers: B.J. Deppmeier, A.J. Driessen, T.S. Hehre, W.J. Hehre, J.A. Johnson, P.E. Klunzinger, J.M. Leonard, I.N. Pham W.J. Pietro, Jianguo Yu Q-Chem Developers: Y. Shao, L. Fusti-Molnar, Y. Jung, J. Kussmann, C. Ochsenfeld,S. T. Brown, A. T. B. Gilbert, L. V. Slipchenko, et. al., Wavefunction Inc.