Synthesis Of Nitrogen Naphthalene Compounds And Their Application In Chemical Small Molecular Recognition

Quinoline compounds, as a typical representative of nitrogen naphthalene compounds, not only have very good biological and pharmacological activity, but also possess excellent optical properties and coordination performance, as a result, they have a wide range of application in medicine, pesticide, luminescence materials, dyes, molecular recognition, and other fields. Therefore, synthesis of new quinoline compounds and their performance has been the research focus in the field of organic chemistry. In this paper, we designed and synthesized a series of nitrogen naphthalene (including quinoline and naphthylamine) compounds with active functional groups, and systematically studied their application in chemical small molecular recognition. The concrete research content is as follows:1. Nine quinoline compounds with reactive functional groups were synthesized by reacting 2-chloro and 3-aldehyde of 2-chloro-6,7-difluoro-3-quinoline-carboxaldehyde, and characterized by NMR and MS methods. These compounds were used in the subsequent application research in chemical small molecular recognition.2. The recognition ability of 2-chloro-6,7-difluoro-3-quinoline-carboxaldehyde (2-1),2-chloro-6,7-difluoro-3-quinolinecarboxaldehyde (2-4) and ethyl 3-(2-chloro-6,7-difluoroquinolin-3-yl) acrylate (2-7) for H2S was studied owing to the strong reactive ability of 2-chloro of quinoline. Experimental results showed that compared with compound 2-4 and 2-7, compound 2-1 could quickly detect S2-with high selectivity over other anions (F-, Cl-, Br-, I-, CO32- HCO3-, NO3-, SO42-, CH3CO2-, SCN-, CN-, S2O32-, NO2-) and biothiols (Cys, Hcy, GSH). Moreover, the detection mechanism of 2-1 to H2S was proposed and demonstrated by 1H NMR analysis. H2S could replace 2-chloro of quinoline by nucleophilic substitution reaction owing to the strong nucleophilic property of H2S resulting in the change of the optical property of quinoline compounds3. The recognition ability of sodium 6,7-difluoro-3-formyl-2-oxo-2H-quinolin-1-ide (2-8) for pH was studied owing to the strong alkaline of nitrogen anion of 2-8. Experimental results showed that compound 2-8 could launch strong fluorescence in neutral and weak acid conditions, but the fluorescence intensity decreased gradually in extremely acidic conditions, and had a pKa value of 1.85 and the best pH response range in 1.3-2.6. Moreover, compound 2-8 showed high selectivity for H+ over other metal ions, including K+, Na+, Ca2+, Zn2+, Ni2+, Cu2+, Mn2+, Cd2+, Pb2+, Mg2+, Al3+ Fe2+, Fe3+, Cr3+, Co2+, Hg2+, and good light stability.4. The recognition ability of 3-(1H-benzo[d]imidazol-2-y1)-6,7-difluoroquinolin-2(1H)-one (2-5) for metal ions were studied owing to the nitrogen of quinoline and benzoimidazole easily complexing with metal ions. Experimental results indicated that compound 2-5 showed high selectivity for Hg2+ over other metal ions, including Zn2+, Ni2+, Cu2+, Cu+, Mn2+, Ru3+, Cd2+ Pb2+, La3+, Ce4+, Er3+, Mg2+, Sn2+, Al3+, Nd3+, K+, Sm3+, Fe2+, Fe3+, Eu3+, Ag+, VO2+, Cr3+, Zr4+, Bi3+, Co2+. Moreover, the detection mechanism of 2-5 to Hg2+ was proposed and demonstrated by ESI-MS and 1H NMR analysis, which was consistent with fluorescence quenching of Hg2+due to the effect from spin-orbit coupling of Hg2+ after the oxygen of the 2-quinolinone and the nitrogen of benzoimidazole in 2-5 coordinated with Hg2+5. A new type fluorescent probe containing binaphthalene fluorophore and maleimide binding group (6-1) was designed and synthesized from 1,1’-naphthalene-4,4’-diamine as the starting material and used for detecting biothiols (Cys, Hey, GSH) owing to the C=C double bond of the maleimide easily attacked by nucleophilic reagent. Experimental results indicated that compound 6-1 showed high selectivity and sensitivity for thiol-containing amino acids (Cys, Hey, GSH) over other amino acids. Moreover, the detection mechanism was proposed and proved by ESI-MS and 1H NMR analysis. After addition of thiols, the fluorescence of 6-1 was enhanced due to the thiol reacting with the C=C double bond of the maleimide group, and blocking the ICT process from the binaphthalene moiety to the maleimide group, resulting in a recovery of the emission of the binaphthalene fluorophore. More importantly, the application in bioimaging was illustrated: probe 6-1 has good cell membrane permeability, and it can be used to mark thiols within living cells.