DFT and MP2 based quantum mechanical calculations and a theoretical vibrational spectroscopic investigation on roscovitine, a potential drug to treat cancers


Balci K. , Akkaya Y. , Akyuz S., Palavan-Unsal N.

Journal of Raman Spectroscopy, cilt.42, ss.719-732, 2011 (SCI Expanded İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 42 Konu: 4
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1002/jrs.2774
  • Dergi Adı: Journal of Raman Spectroscopy
  • Sayfa Sayıları: ss.719-732

Özet

Theoretically possible stable conformers of free roscovitine molecule in its electronic ground state were searched by means of molecular dynamics and energy minimization calculations performed using the MM2 force field. Afterwards, geometry optimization and thermochemistry calculations were carried out at room temperature for each of the found minimum-energy conformers using the MP2 and DFT based electronic structure methods and different Pople-style basis sets. The results obtained from these calculations confirmed that the strong intramolecular hydrogen bonding between the purine-nitrogen and hydroxyl-hydrogen atoms plays an important role on the rigidity of roscovitine molecule and causes a dramatic reduction in the number of the possible stable conformers of this molecule at room temperature. Furthermore, the same calculation results also revealed that two of the found seven stable conformers are considerably more favorable in energy than the others and thus dominate the experimental room-temperature spectra of the molecule. In the light of the theoretical vibrational spectral data obtained for these two conformers, a successful assignment of the fundamental bands observed in the experimental IR and Raman spectra recorded at room temperature for solid roscovitine and for its ethanol solution is given, and the effects of the substitution and intramolecular hydrogen bonding on the fundamental bands associated with purine and phenyl group vibrations are discussed in detail. In the fitting of the calculated harmonic wavenumbers to the corresponding experimental wavenumbers, two different scaling procedures, called 'dual scale factors' and `Scaled Quantum Mechanical Force Field(SQMFF) methodology', were applied independently. Both procedures yielded results generally in good agreement with the experiment; however, the SQM FF methodology proved its superiority over the other. Copyright (C) 2010 John Wiley & Sons, Ltd.

 

Theoretically possible stable conformers of free roscovitine molecule in its electronic ground state were searched by means
of molecular dynamics and energy minimization calculations performed using the MM2 force ?eld. Afterwards, geometry
optimization and thermochemistry calculations were carriedout at room temperature for each of the found minimum-energy
conformers using the MP2 and DFT based electronic structure methods and different Pople-style basis sets. The results
obtained from these calculations con?rmed that the strong intramolecular hydrogen bonding between the purine-nitrogen and
hydroxyl-hydrogen atoms plays an important role on the rigidity of roscovitine molecule and causes a dramatic reduction in
the number of the possible stable conformers of this molecule at room temperature. Furthermore, the same calculation results
also revealed that two of the found seven stable conformers are considerably more favorable in energy than the others and
thus dominate the experimental room-temperature spectra of the molecule. In the light of the theoretical vibrational spectral
data obtained for these two conformers, a successful assignment of the fundamental bands observed in the experimental IR
and Raman spectra recorded at room temperature for solid roscovitine and for its ethanol solution is given, and the effects of
the substitution and intramolecular hydrogen bonding on the fundamental bands associated with purine and phenyl group
vibrations are discussed in detail. In the ?tting of the calculated harmonic wavenumbers to the corresponding experimental
wavenumbers, two different scaling procedures, called ‘dual scale factors’ and ‘Scaled Quantum Mechanical Force Field (SQM FF)
methodology’, were applied independently. Both procedures yielded results generally in good agreement with the experiment;
however, the SQM FF methodology proved its superiority over the other. Copyrightc 2010 John Wiley & Sons, Ltd.