Zadykowicz Beata, Czechowska Justyna, Ożóg Agnieszka, Renkevich Anton, Krzymiński Karol
Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63 St., 80-308 Gdańsk, Poland.
Org Biomol Chem. 2016 Jan 14;14(2):652-668. doi: 10.1039/c5ob01798j.
A series of 10-methyl-9-(phenoxycarbonyl)acridinium trifluoromethanesulfonates (XAEs), bearing substituents of various characteristics in the lateral benzene ring (2-halogen, 2,6-dihalogen, 2-trifluoromethyl, 2-nitro, 2-methoxy, 3-halogen and 4-halogen) were synthesized with high yields, identified and subjected to a physicochemical and theoretical investigation. The main task of the work was to assess the mechanism and optimal conditions of light emission in various liquid systems based on the above salts in order to evaluate their potential usefulness as chemiluminescence (CL) labels and indicators in ultra-sensitive analyses. Density functional theory (DFT) calculations were performed to investigate the detailed mechanism of the oxidation of 9-substituted 10-methylacridinium cations involved in XAEs by hydrogen peroxide in alkaline media. Three general pathways were drawn, which are termed the "light path" (chemiluminogenic) and there were two "dark paths" (non-chemiluminogenic): hydrolytic and "pseudobase". The CL time profiles, triggered in alkaline solutions containing hydrogen peroxide, enabled us to establish crucial physicochemical parameters, including pseudo-first order kinetic constants of CL decay and relative efficiencies of emission. In order to optimize the systems' luminogenic performance, different bases, such as sodium hydroxide, tetrabutylammonium hydroxide (TBAOH) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), as well as enhancers, such as cationic, zwitterionic and neutral surfactants (cetyltrimethylammonium chloride (CTAC), N,N-dimethyldodecylammonio-1,3-propane sulfonate (DDAPS) and Triton X-100, respectively) were tested. The results revealed the optimal CL systems, which enabled us to obtain substantially higher emissions than typical ones, based on acridinium esters or luminol. The derived parameters, characterizing the potential utility of the acridinium esters, such as stability in aqueous environments and usefulness (the product of emission efficiency and stability at a given pH), enabled us to reveal the best candidates and their practical applications. The post-reaction mixtures, analyzed by means of chromatography (RP-HPLC) and mass spectrometry (ESI-MS), allowed us to verify the occurrence and population of the products that were theoretically predicted, i.e. 10-methyl-9-acridinone (NMAON), 10-methylacridinium-9-carboxylic acid (NMACA) and substituted phenols (RPhOHs).
合成了一系列10-甲基-9-(苯氧羰基)吖啶三氟甲磺酸盐(XAEs)，这些化合物在侧链苯环上带有各种不同特性的取代基(2-卤素、2,6-二卤素、2-三氟甲基、2-硝基、2-甲氧基、3-卤素和4-卤素)，产率很高，并对其进行了鉴定以及物理化学和理论研究。该工作的主要任务是评估基于上述盐类的各种液体体系中的发光机制和最佳条件，以评估它们作为化学发光(CL)标记物和超灵敏分析中的指示剂的潜在用途。进行了密度泛函理论(DFT)计算，以研究碱性介质中过氧化氢对XAEs中涉及的9-取代10-甲基吖啶阳离子氧化的详细机制。绘制了三条一般途径，分别称为“光路”(化学发光)和两条“暗路”(非化学发光)：水解和“假碱”。在含有过氧化氢的碱性溶液中引发的CL时间曲线，使我们能够确定关键的物理化学参数，包括CL衰减的假一级动力学常数和发射的相对效率。为了优化体系的发光性能，测试了不同的碱，如氢氧化钠、四丁基氢氧化铵(TBAOH)和1,8-二氮杂双环[5.4.0]十一碳-7-烯(DBU)，以及增强剂，如阳离子、两性离子和中性表面活性剂(分别为十六烷基三甲基氯化铵(CTAC)、N,N-二甲基十二烷基铵-1,3-丙烷磺酸盐(DDAPS)和Triton X-100)。结果揭示了最佳的CL体系，与基于吖啶酯或鲁米诺的典型体系相比，该体系能使我们获得更高的发射强度。所推导的表征吖啶酯潜在用途的参数，如水环境中的稳定性和实用性(发射效率与给定pH下稳定性的乘积)，使我们能够找出最佳候选物及其实际应用。通过色谱法(RP-HPLC)和质谱法(ESI-MS)对反应后的混合物进行分析，使我们能够验证理论预测的产物的出现和含量，即10-甲基-9-吖啶酮(NMAON)、10-甲基吖啶-9-羧酸(NMACA)和取代酚(RPhOHs)。
