Structural properties of flutamide molecule and analysis of its vibrational spectra

In this thesis study, the stable confomers of flutamide molecule were theoretically searched through a series of systematic geometry optimizations referred to as "Flexible Potential Energy Surface Scan". Afterwards, "geometry optimization" and "Hessian (harmonic frequency)" calculations were performed at different levels of theory for each of the determined stable conformers. The relative energies of the five conformers of the molecule, whose stabilities were confirmed, were theoretically determined through these systematical calculations, in which the HF-SCF, MP2 and DFT-B3LYP calculation methods and the 6-31G(d), 6-311++G(d,p), m-aug-cc-pvTZ and aug-cc-pvTZ basis sets were used. The optained results have shown that in all the stable conformers of the molecule, the fluoromethyl (CF3) and nitro (NO2) groups locate at "gauche" position to each other, and that the "trans" positions of these two functional groups correspond to the unstable states of the molecule, while their "cis" positions correspond to the transition states of the molecule. For each of the determined stable conformers of flutamide molecule, some important electronic structure calculations such as "Electronic energy (SCF energy)", "Total energy", "Electrical dipole moment", "First ionization energy", "Electron affinity", "Electronegativity" and "Chemical hardness", the equilibrium optimized geometry parameters and vibrational spectral data (vibrational modes and corresponding vibrational wavenumbers, Infrared (IR) intensity values, Raman intensity values and Potential energy distribution values) were optained with a high accuracy by means of theoretical molecular modelling calculations. The calculation results have indicated that two of the stable conformers of the molecule provide the largest contribution to its experimental spectra recorded at room temperature. The experimental part of the thesis study consists of the processes of recording the Infrared (IR) and Raman spectra of flutamide at room temperature. The IR and Raman spectra of the samples prepared of solid and KBr disc forms were recorded by using Jasco 6300 model FT-IR, Brucker MultiRAM model FT-Raman and Jasco NRS 3100 model Dispersif Mikro-Raman spectrometers in our research laboratory so as to obtain the highest resolution values. The results we obtained from the theoretical calculations have indicated that only two of the five stable conformers of flutamide molecule provide the major contribution to its vibrational spectra to be recorded at room temparature and lower temparatures and that the populations of the other three conformers at these temperature values should be lower than the 10% of the total population of the molecules in the medium. This means that these three conformers cannot povide a measurable contribution to the recorded spectra of the molecule. Considering these results, the analysis of the experimental vibrational spectra of flutamide molecule, which were recorded at room temparature, have been based on only the calculation results optained for the determined most stable two conformers of the molecule. The vibrational modes of these two conformers and the associated spectral data were calculated within the "Harmonic oscilator" approach at different levels of theory by using the methods and basis sets defined above. The force field, wavenumbers, IR and Raman intensity values calculated in this approach were refined by using an emprical scaling technique called "SQM-FF" in the literature. Also, the calculated harmonic wavenumbers were directly scaled by using another emprical scaling technique called "Dual Scaling Factors" in the literature. A correct assignment for all the fundamental bands observed in the recorded room-temperature IR and Raman spectra of the molecule was achieved on the basis of the theoretical vibrational spectral data refined by using two different emprical scaling techniques.