Lejcher Connor A, Villa Eric M, Fletcher James T
Department of Chemistry, Creighton University, 2500 California Plaza, Omaha, NE 68178, U.S.A.
Med Chem Res. 2022 Mar;31(3):474-484. doi: 10.1007/s00044-022-02855-5. Epub 2022 Feb 5.
Bioactive molecules displaying visible wavelength emission can be useful for bioimaging, chemosensing and photodynamic therapy applications. Reported herein are 1,3,4-trisubsituted-1,2,3-triazolium salts displaying both antimicrobial and visible emission properties. Using a click chemistry approach, 2-fluorenyl, 1-naphthyl, 2-naphthyl, 2-anthracenyl and 1-pyrenyl units were incorporated at the N1 position, imparting visible emission properties to their triazolium bromide salts with Stokes shifts greater than 100 nm relative to the emission of their triazole precursors. The increasing size of such hydrophobic aryl units impacts minimum inhibitory concentration (MIC) values against Gram-positive bacteria, Gram-negative bacteria and yeast, and can be counterbalanced by hydrophobic substituent variation at other positions of the molecule in order to preserve bioactivity. Among the series of compounds studied are analogs displaying blue, green and yellow colored emission and MIC values as low as 0.4 μM (Gram-positive bacteria), 8 μM (Gram-negative bacteria) and 2 μM (yeast). XRD analysis validates the regioselective benzylation at the N3 position of the 1,2,3-triazole ring and the ability of such compounds to associate through dimeric intermolecular π-stacking interactions.
具有可见波长发射的生物活性分子可用于生物成像、化学传感和光动力治疗应用。本文报道了具有抗菌和可见发射特性的1,3,4-三取代-1,2,3-三唑鎓盐。采用点击化学方法,在N1位置引入了2-芴基、1-萘基、2-萘基、2-蒽基和1-芘基单元,赋予其三溴化三唑鎓盐可见发射特性,相对于其三唑前体的发射,斯托克斯位移大于100 nm。这种疏水性芳基单元尺寸的增加会影响对革兰氏阳性菌、革兰氏阴性菌和酵母的最低抑菌浓度(MIC)值,并且可以通过分子其他位置的疏水取代基变化来抵消,以保持生物活性。在所研究的一系列化合物中,有显示蓝色、绿色和黄色发射的类似物,其MIC值低至0.4 μM(革兰氏阳性菌)、8 μM(革兰氏阴性菌)和2 μM(酵母)。X射线衍射分析验证了1,2,3-三唑环N3位置的区域选择性苄基化以及此类化合物通过二聚体分子间π-堆积相互作用缔合的能力。