مطالعه نظري بر روي سه فرم توتومري داروي لناليدومايد با روش تئوري تابعي چگال

A Theoretical Study on Three Tautomeric Forms of Lenalidomide with Density Functional Theory

در اﯾﻦ ﺗﺤﻘﯿﻖ ، ﺳﺎﺧﺘﺎر ﺗﻮﺗﻮﻣﺮي، ﺧﻮاص ﻧﻮري و اﻟﮑﺘﺮوﻧﯽ، ﻃﯿﻒ ﺟﺬﺑﯽ اﻟﮑﺘﺮوﻧﯽ، ﻓﺮﮐﺎﻧﺲ ﻫﺎي ارﺗﻌﺎﺷﯽ، ﺧﻮاص ﺗﺮﻣﻮدﯾﻨﺎﻣﯿﮑﯽ و ﺗﻮزﯾﻊ ﺑﺎر ﺳﻪ ﺳﺎﺧﺘﺎر آﻣﯿﺪي واﯾﻤﯿﺪﯾﮏ اﺳﯿﺪ داروي ﻟﻨﺎﻟﯿﺪوﻣﺎﯾﺪ از ﻃﺮﯾﻖ ﻣﺤﺎﺳﺒﺎت ﺷﯿﻤﯽ ﮐﻮاﻧﺘﻮﻣﯽ ﺑﺎ اﺳﺘﻔﺎده از ﺗﺌﻮري ﺗﺎﺑﻌﯽ ﭼﮕﺎﻟﯽ )DFT( و ﺗﺌﻮري ﺗﺎﺑﻌﯽ ﭼﮕﺎﻟﯽ واﺑﺴﺘﻪ ﺑﻪ زﻣﺎن )TDDFT( ﺑﺎ ﺗﺎﺑﻊ ﻫﯿﺒﺮﯾﺪي B3LYP و ﻣﺠﻤﻮﻋﻪ ﭘﺎﯾﻪ )6-311+G(d,p در ﻓﺎز ﮔﺎزي ﻣﻮرد ﺑﺮرﺳﯽ ﻗﺮار ﮔﺮﻓﺘﻨﺪ. ﻧﺘﺎﯾﺞ ﻣﺤﺎﺳﺒﺎت ﻧﺸﺎن ﻣﯽدﻫﺪ ﮐﻪ ﺳﺎﺧﺘﺎر آﻣﯿﺪي ﻟﻨﺎﻟﯿﺪوﻣﺎﯾﺪ ﺧﻮاص ﮐﻮاﻧﺘﻮﻣﯽ ﻣﻨﺎﺳﺒﯽ دارد ﮐﻪ ﻣﯽ ﺗﻮاﻧﺪ ﺑﻪ ﻋﻨﻮان دارو ﻋﻤﻞ ﮐﻨﺪ. اﻧﺮژي ﻫﺎي ﺳﺎﺧﺘﺎرﻫﺎي آﻣﯿﺪ و اﯾﻤﯿﺪﯾﮏ اﺳﯿﺪ ﻟﻨﺎﻟﯿﺪوﻣﺎﯾﺪ ﻧﺸﺎن ﻣﯽ دﻫﺪ ﮐﻪ ﺳﺎﺧﺘﺎر آﻣﯿﺪ ﺑﺎ اﺧﺘﻼف اﻧﺮژي ﮐﻤﯽ، ﭘﺎﯾﺪارﺗﺮ از ﺳﺎﺧﺘﺎر اﯾﻤﯿﺪﯾﮏ اﺳﯿﺪ ﻣﯽ ﺑﺎﺷﺪ. ﻣﺤﺎﺳﺒﺎت ﺣﺎﻻت ﺑﺮاﻧﮕﯿﺨﺘﻪ ﻧﺸﺎن ﻣﯽ دﻫﺪ ﮐﻪ ﺳﺎﺧﺘﺎر آﻣﯿﺪ ﻟﻨﺎﻟﯿﺪوﻣﺎﯾﺪ ﺧﻮاص ﺟﺬﺑﯽ ﺑﻬﺘﺮي دارد. ﺧﻮاص ﻧﻮري ﻏﯿﺮﺧﻄﯽ ﺳﺎﺧﺘﺎر آﻣﯿﺪ ﻟﻨﺎﻟﯿﺪوﻣﺎﯾﺪ ﻧﯿﺰ ﺑﺎﻻﺗﺮ از ﺳﺎﺧﺘﺎر اﯾﻤﯿﺪﯾﮏ اﺳﯿﺪ ﻟﻨﺎﻟﯿﺪوﻣﺎﯾﺪ ﺑﻪ دﺳﺖ آﻣﺪه وﻟﯽ ﺳﺨﺘﯽ ﺷﯿﻤﯿﺎﯾﯽ ﺳﺎﺧﺘﺎر آﻣﯿﺪ ﮐﻤﺘﺮ از ﺳﺎﺧﺘﺎر اﯾﻤﯿﺪﯾﮏ ﻣﯽ ﺑﺎﺷﺪ ﮐﻪ ﻧﺸﺎن ﻣﯽ دﻫﺪ واﮐﻨﺶ ﭘﺬﯾﺮي و اﻧﺘﻘﺎل ﺑﺎر ﺳﺎﺧﺘﺎر آﻣﯿﺪ ﺑﯿﺸﺘﺮ از ﺳﺎﺧﺘﺎر اﯾﻤﯿﺪﯾﮏ اﺳﯿﺪ ﻣﯽ ﺑﺎﺷﺪ.

In this study, the totemic structure, optical and electron properties, electron absorption spectrum, vibrational frequencies, thermodynamic properties and charge distribution of three amide and imidic acid structures of lenalidomide via quantum chemistry calculations using density functional theory (DFT) Time-dependent (TDDFT) hybridization with B3LYP function and base set 6-311 + G ** were investigated. The computational results show that the amide structure of lenalidomide has good quantum properties that can act as a drug. The energies of the amide and imidic acid structures of lenalidomide indicate that the amide structure with little energy difference is more stable than the imidic acid structure. Calculations of excited states show that the structure of the amide lenalidomide has better adsorption properties. The nonlinear optical properties of the amide structure of lenalidomide are also higher than the imidic acid structure of lenalidomide but the chemical hardness of the amide structure is lower than that of the imidic structure, indicating that the reactivity and charge transfer of the amide structure are higher than the imidic acid structure.