Zayed M A, Hawash M F, Fahmey M A, El-Habeeb Abeer A
Chemistry Department, Faculty of Education of Girls, El-Qaseem, Borida, Saudi Arabia.
Spectrochim Acta A Mol Biomol Spectrosc. 2007 Nov;68(3):970-8. doi: 10.1016/j.saa.2007.01.010. Epub 2007 Jan 20.
Sertraline (C(17)H(17)Cl(2)N) as an antidepressant drug was investigated using thermal analysis (TA) measurements (TG/DTG and DTA) in comparison with electron impact (EI) mass spectral (MS) fragmentation at 70eV. Semi-empirical MO-calculations, using PM3 procedure, has been carried out on neutral molecule and positively charged species. These calculations included bond length, bond order, bond strain, partial charge distribution and heats of formation (DeltaH(f)). Also, in the present work sertraline-iodine product was prepared and its structure was investigated using elemental analyses, IR, (1)H NMR, (13)C NMR, MS and TA. It was also subjected to molecular orbital calculations (MOC) in order to confirm its fragmentation behavior by both MS and TA in comparison with the sertraline parent drug. In MS of sertraline the initial rupture occurred was CH(3)NH(2)(+) fragment ion via H-rearrangement while in sertraline-iodine product the initial rupture was due to the loss of I(+) and/or HI(+) fragment ions followed by CH(2)NH(+) fragment ion loss. In thermal analyses (TA) the initial rupture in sertraline is due to the loss of C(6)H(3)Cl(2) followed by the loss of CH(3)-NH forming tetraline molecule which thermally decomposed to give C(4)H(8), C(6)H(6) or the loss of H(2) forming naphthalene molecule which thermally sublimated. In sertraline-iodine product as a daughter the initial thermal rupture is due to successive loss of HI and CH(3)NH followed by the loss of C(6)H(5)HI and HCl. Sertraline biological activity increases with the introduction of iodine into its skeleton. The activities of the drug and its daughter are mainly depend upon their fragmentation to give their metabolites in vivo systems, which are very similar to the identified fragments in both MS and TA. The importance of the present work is also due to the decision of the possible mechanism of fragmentation of the drug and its daughter and its confirmation by MOC.
将舍曲林（C₁₇H₁₇Cl₂N）作为一种抗抑郁药物，使用热分析（TA）测量（TG/DTG和DTA）进行了研究，并与70eV下的电子轰击（EI）质谱（MS）碎裂进行了比较。使用PM3程序对中性分子和带正电的物种进行了半经验分子轨道计算。这些计算包括键长、键级、键应变、部分电荷分布和生成热（ΔHf）。此外，在本研究中制备了舍曲林 - 碘产物，并使用元素分析、红外光谱、¹H NMR、¹³C NMR、质谱和热分析对其结构进行了研究。还对其进行了分子轨道计算（MOC），以便与舍曲林母体药物相比，通过质谱和热分析确认其碎裂行为。在舍曲林的质谱中，最初的断裂是通过H重排产生CH₃NH₂⁺碎片离子，而在舍曲林 - 碘产物中，最初的断裂是由于I⁺和/或HI⁺碎片离子的丢失，随后是CH₂NH⁺碎片离子的丢失所致。在热分析（TA）中，舍曲林的最初断裂是由于C₆H₃Cl₂的丢失，随后是CH₃ - NH的丢失，形成四氢萘分子，该分子热分解生成C₄H₈、C₆H₆，或者是由于H₂的丢失形成萘分子，该分子热升华。在作为子代的舍曲林 - 碘产物中，最初的热断裂是由于HI和CH₃NH的相继丢失，随后是C₆H₅HI和HCl的丢失。舍曲林的生物活性随着碘引入其骨架而增加。该药物及其子代的活性主要取决于它们在体内系统中碎裂生成代谢产物，这与质谱和热分析中鉴定出的碎片非常相似。本研究的重要性还在于确定了该药物及其子代可能的碎裂机制，并通过分子轨道计算对其进行了证实。
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