Simijonović Dušica, Petrović Zorica D, Milovanović Vesna M, Petrović Vladimir P, Bogdanović Goran A
University of Kragujevac, Faculty of Science, Department of Chemistry R. Domanovića 12 34000 Kragujevac Serbia
Vinča Institute of Nuclear Sciences, University of Belgrade P. O. Box 522 11001 Belgrade Serbia.
RSC Adv. 2018 May 4;8(30):16663-16673. doi: 10.1039/c8ra02702a. eCollection 2018 May 3.
Pyrazolyl-phthalazine-dione derivatives (PPDs) were synthetized in the ionic liquid catalyzed one-pot multicomponent reaction of acetylacetone, 2,3-dihydrophthalazine-1,4-dione, and different aldehydes in moderate to good yields. Six new PPDs were obtained, and the crystal structure of 2-acetyl-1-(4-fluorophenyl)-3-methyl-1-pyrazolo[1,2-]phthalazine-5,10-dione (PPD-4) was determined. The most interesting structural features of the novel PPD-4 is the formation of a rather short intermolecular distance between the F atom of one molecule and the midpoint of the neighbouring six-membered heterocyclic ring. This interaction arranges all molecules into parallel supramolecular chains. UV-Vis spectra of all PPDs were acquired and compared to the simulated ones obtained with TD-DFT. All synthetized compounds were subjected to evaluation of their antioxidative activity using a stable DPPH radical. It was shown that PPD-7, with a catechol motive, is the most active antioxidant, while PPD-9, with two neighbouring methoxy groups to the phenolic OH, exerted a somewhat lower, but significant antioxidative potential. The results of DFT thermodynamical study are in agreement with experimental findings that PPD-7 and PPD-9 should be considered as powerful radical scavengers. In addition, the obtained theoretical results (bond dissociation and proton abstraction energies) specify SPLET as a prevailing radical scavenging mechanism in polar solvents, and HAT in solvents with lower polarity. On the other hand, the obtained reaction enthalpies for inactivation of free radicals suggest competition between HAT and SPLET mechanisms, except in the case of the ˙OH radical in polar solvents, where HAT is labeled as prefered.
吡唑基酞嗪二酮衍生物（PPDs）是在离子液体催化下，通过乙酰丙酮、2,3 - 二氢酞嗪 - 1,4 - 二酮与不同醛的一锅多组分反应合成的，产率适中至良好。得到了六种新的PPDs，并测定了2 - 乙酰基 - 1 -（4 - 氟苯基）- 3 - 甲基 - 1 - 吡唑并[1,2 - ]酞嗪 - 5,10 - 二酮（PPD - 4）的晶体结构。新型PPD - 4最有趣的结构特征是一个分子的F原子与相邻六元杂环中点之间形成了相当短的分子间距离。这种相互作用将所有分子排列成平行的超分子链。获取了所有PPDs的紫外 - 可见光谱，并与用TD - DFT得到的模拟光谱进行了比较。所有合成的化合物都使用稳定的DPPH自由基进行了抗氧化活性评估。结果表明，具有儿茶酚结构的PPD - 7是最具活性的抗氧化剂，而酚羟基邻位有两个甲氧基的PPD - 9具有稍低但显著的抗氧化潜力。DFT热力学研究结果与实验结果一致，即PPD - 7和PPD - 9应被视为强大的自由基清除剂。此外，所获得的理论结果（键离解和质子夺取能）表明，在极性溶剂中，SPLET是主要的自由基清除机制，而在低极性溶剂中是HAT。另一方面，所获得的自由基失活反应焓表明，HAT和SPLET机制之间存在竞争，但在极性溶剂中˙OH自由基的情况下除外，在这种情况下HAT被认为是首选机制。
