• Theoretical and Experimental Vibrational and Theoretical Conformational Analysis of Some Molecules That are Used in Cancer Treatments


• Conformational Analysis and Vibrational Spectral Investigation of Some Biological Active Molecules
  

In this study the conformational preferences of Anastrozole (Arimidex), Doxorubicin (Adriamycin) and Epirubicin (4'-epi-isomer of doxorubicin molecule) molecules which are known to be used as drugs in cancer treatments will be investigated in their electronic ground states by means of scanning potential energy surface with DFT method and their possible conformers will be determined.

In the experimental part of this study, the FT-IR and FT-Raman spectra of the molecules will be recorded and compared with the calculated spectra of the molecules. The results will enable us to determine possible structures of the molecules at room temperature in solid phase.

Some of the instruments that will be used in this project are available in the Atomic and Molecular Physics Research Laboratoiries. Within this project an FT-Raman Spectrometer will be purchased. The instrument is not present in any unit of our university and it exists only in a few universities in Istanbul.

Researches:

1. The results of this study are important since it will reveal the conformational structures of the title molecules on which their chemical activities are dependent. Therefore this study will form a basis to other studies that will deal with the intermolecular interactions.
2. The title molecules have drug properties so they are of great importance in drug industry. To reveal the physical grounds of their biological activity will therefore help to improve their biological activities and to synthesize more active molecules.
3. Within the framework of this project, the FT-Raman spectrometer, will activate the scientific conditions in our division and in this context our participation to TUBITAK, DPT, and EU funded projects will significantly be more possible.
4. In all the studies where the behavior of the biologically active molecules in physiological environment is studied, molecules must be examined in aqueous solutions. This is best done using FT-Raman Spectrometers. Hence for all the future projects involving the molecular studies in physiological conditions, FT-Raman spectrometers will be necessary. Therefore within this project we will be able to prepare an infrastructure for the future projects.
5. There are only a few FT-Raman spectrometers in Istanbul and there is none in our university. It will be an important contribution to our university in terms of adapting to new technological developments.
6. Forming necessary laboratory equipment of this type in our university will provide opportunities to conduct joint studies with international centers.

FT-Raman Spectrometer

In this study, the potential energy surfaces of the dipeptides L-Carnosine (ß-Alanine-Histidine) and Anserine (N-methyl carnosine), which are known to have antioxidant property, and Valine-Tyrosine showing antihipertensive influence, will be theoretically constructed using some appropriate semi-emprical and density functional theory based calculation methods. Afterwards, the preferable conformers of these biologic active molecules at different temperatures will be determined. Since these dipeptides are molecules of large size, calculations on them can only be possible by the use of a High Performance Computation (HPC) platform which has appropriate softwares.  Before this project, in our department there was a HPC platform consisting of six server computers. During this project, a new server computer with four  processors of Itanium-2 (dual core) possing memory capacity of 192 GB and hard disk capacity of 576 GB, which includes appropriate softwares and provides paralel computing and use of multi-processor, was included into our HPC platform.

Researches:

1. The conformational analysis of the biologic-active molecules will be carried out by using molecular calculation methods of high level of theory.
2. The possible chemical reactions of the macro-molecules can be simulated in the computational environment.
3. The theoretical data to be used in the analysis of the molecular interactions and their experimentally observed results will be obtained.
4. The structure-functionality relation of the molecules and the environmentinol factors effecting it will be computationally simulated.
5. Theoretical molecular modelling supported by computer platforms, which is getting to be one of the standard methods used in the analysis of the molecular structures, enable us to do collective studies between different dissiplines. From this point of view, the server computers bought during this project have been providing a very significant support.