MOLECULAR MODELING OF THE ABSTRACTION OF DOUBLE STRANDED DNA BY MANGAN(IV) AND MANGAN(V) PYRAZOLIUM PORPHYRIN

• Main Author: Caroline
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78485
• Institution: Institut Teknologi Bandung

The photodynamic therapy, had been developed, a novel technique cancer therapy which does not interfere the normal cells, the technique is based on activation of a photosensitive compound that interacts with the DNA of cancer cells by electromagnetic radiation of appropriate wavelength. Pyrazolium porphyrin, had been demonstrated to interact with double-stranded DNA, modifying the site of the geometry of the DNA or cutting the DNA. Mangan(III)-porphyrin can be oxydized into a mangan-oxo(V), which will cleave the double-stranded DNA at the segments rich of adenine - thymine present in DNA of many cancer cells. Mangan-oxyl(IV) oxydizes hydrogen atoms of the deoxyribose unit, resulting in formation of hydroxyl at the carbon atom of the position 5’ or 1’ (C5’ or C1’) of the deoxyribose unit or at the carbon atoms of C4’ or C1’ of the deoxyribose unit at the end of the DNA chain. This study was aimed to modeling molecular interaction of double stranded DNA and mangan-oxyl(IV) and mangan-oxo(V) pyrazolium porfirin and to specify the interactions between the activated porphyrin complex and the double stranded DNA d(5’-TCGTCAAACCGC)-d(5”-GCGGTTTGACGA). Geometry of the porphyrins was optimized by the abinitio subprogram and the double stranded DNA was optimized by the Amber 99 subprogram. The optimized structures were interacted at the minor groove of the DNA, at the cytosine 9 - adenine 8 and guanine 8 - thymine 7 base step, and further optimized by the Amber 99 subprogram with addition of the 18 sodium ions. The interacted complex was analyzed in terms of the interatomic distance and angle of mangan and oxygen of oxyl or oxo form, and hidrogen atoms of the deoxyribose unit. Partial charges of the interacting atoms were evaluated to assume that the interaction took place. The observed geometry and the partial charges indicated that the interaction possibly occured. The probable interaction was then evaluated by molecular dynamic method using Amber 99 subprogram at a temperature of 300 oK and an equilibration time of 65 picosecond and the interatomic bonds and interaction energy were observed. The results confirmed the occurence of interaction between oxyl of the mangan(IV) pyrazolium porphyrin and hydrogen 5’ of the deoxyribose units of the cytosine 9. DNA conformations were analyzed the interaction before and after by molecular dynamic simulation in terms of torsion angle of backbone and widths of the groove. The observation showed that conformation DNA backbone always changed if mangan (IV) pyrazolium porfirin interacted with the cytosine 9 – adenine 8 base step. All the data indicated that abstraction of the double stranded DNA interacted with mangan(IV) pyrazolium porphyrin could occured at hydrogen 5’ of deoxyribose units of the cytosine 9.