Experimental and Theoretical Studies on the Nature of Weak Nonbonded Interactions between Divalent Selenium and Halogen Atoms
摘要:
To investigate the nature of weak nonbonded selenium(...)halogen interactions ((SeX)-X-... interactions; X = F Cl, and Br), three types of model compounds [2-(CH2X)C6H4SeY (1-3), 3-(CH2X)-2-C10H6-SeY (4-6), and 2-XC6H4CH2SeY (7-9); Y = CN, Cl, Br, SeAr, and Me] were synthesized, and their Se-77 NMR spectroscopic behaviors were analyzed in CDCl3. The gradual upfield shifts of Se-77 NMR absorptions observed for series 1-3 and 4-6 suggested that the strength of (SeX)-X-... interaction decreases in the order of (SeF)-F-... > (SeCl)-Cl-... > (SeBr)-Br-.... The quantum chemical calculations at the B3LYP/631H level using the polarizable continuum model (PCM) revealed that the most stable conformer for 1-3 is the one with an intramolecular short (SeX)-X-... atomic contact in CHCl3 (epsilon = 4.9) and also that the n(x) --> sigma*(se-y) orbital interaction (E-Se...X) can reasonably explain the order of strength for the (SeX)-X-... interactions. On the other hand, the Se-77 NMR absorptions observed for series 7-9 did not shift significantly from the reference compounds (C6H5CH2SeY), indicating the absence of the (SeX)-X-... interaction for 7-9 presumably due to attenuation of basicity for the halogen atom that is substituted directly to the aromatic ring. These observations suggested that the n(x) --> sigma*(se-y) orbital interaction is a dominant factor for formation of weak (SeX)-X-... interactions. Electron correlation was also suggested to be important for the stability.
Herein, based on the theory of bioisosterism, a series of novel miconazole analogues containing selenium were designed, synthesized and their inhibitory effects on thirteen strains of pathogenic fungi were evaluated. It is especially encouraging that all the novel target compounds displayed significant antifungal activities against all tested strains. Furthermore, all the target compounds showed excellent
A fast and direct iodide-catalyzed oxidative 2-selenylation of tryptophan
作者:Yu-Ting Gao、Shao-Dong Liu、Liang Cheng、Li Liu
DOI:10.1039/d1cc00700a
日期:——
We have developed a novel methodology for the synthesis of valuable 2-selenylated tryptophans from diselenides under the catalysis of iodide.
我们已经开发出一种新颖的方法,可以在碘化物的催化下,从二硒化物合成具有价值的2-硒基色氨酸。
Design, synthesis and antifungal activities of novel triazole derivatives with selenium-containing hydrophobic side chains
作者:Meng-bi Guo、Zhong-zuo Yan、Xin Wang、Hang Xu、Chun Guo、Zhuang Hou、Ping Gong
DOI:10.1016/j.bmcl.2022.129044
日期:2022.12
In this work, a series of novel 1,2,4-triazole derivatives with selenium-containing hydrophobic side chains were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). All compounds were characterized by HRMS, 1H NMR and 13C NMR. Then, their antifungalactivities against eight human pathogenic fungi were evaluated in vitro by testing the minimal inhibitory concentrations
本工作基于羊毛甾醇 14α-脱甲基酶 (CYP51) 的结构,设计并合成了一系列具有含硒疏水侧链的新型 1,2,4-三唑衍生物。所有化合物均通过 HRMS、1 H NMR和13 C NMR进行了表征。然后,在体外评估了它们对八种人类病原真菌的抗真菌活性通过测试最小抑菌浓度。结果表明,几乎所有测试的化合物被发现比对照药物氟康唑更有效地对抗所有测试的真菌菌株。进一步的机理研究表明,目标化合物具有真菌CYP51抑制活性。同时,代表性化合物显示出对哺乳动物细胞系的低细胞毒性作用。此外,对接结果表明,目标化合物与白色念珠菌CYP51 的结合模式优于氟康唑,尤其是在狭窄的疏水裂缝中。总的来说,可以进一步开发具有含硒疏水侧链的新型 1,2,4-三唑衍生物,用于治疗侵袭性真菌感染。
Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections