Study On Synthesis And Property Of Organic Fluorescent Probe Based On Isolongifolanone And Camphor

Isolongifolanone and camphor serve as two important turpentine derivatives with some merits including good biocompatibility,high reactivity,low cytotoxicity,low cost,and green environmental protection.Until now,isolongifolanone and camphor have been exploited to prepare many value-added derivatives,which are mainly used in the fields of anophelifuges and antineoplastics.However,the development of fluorescent molecules using isolongifolanone and camphor has rarely been reported.In this paper,a series of novel small organic fluorescence probes,which could be used for chemical sensing and bio-fluorescence imaging,have been synthesized from isolongifolanone and camphor.Moreover,the structures of these target compounds were fully characterized by NMR,GC-MS,FT-IR,HRMS and X-ray single crystal diffraction.These new fluorescent compounds based on isolongifolanone and camphor have been successfully applied in the detection of metal ion,reactive oxygen speciation,toxic gas and pH value,and the imaging of animal,plant and cell,and it greatly increases the application value of turpentine.The main research contents and results are as follows.?1?7-?pyridine-4?-ylmethylene?-isolongifolanone?2I?was synthesized by the aldol condensation reaction of isolongifolanone and 4-pyridinecarboxaldehyde,and then6,6,10,10–tetramethyl-4-?pyridine-4?-yl?-5,7,8,9,10,10a-hexahydro-6H-6a,9-methanobenzo[h]q uinazolin-2-amine?2II?was synthesized by the reaction of guanidine hydrochloride and7-?pyridine-4?-ylmethylene?-isolongifolanone in the presence of potassium tert-butylate.The compound 2II is highly selective and sensitive for Cu²⁺ion with a rapid response?30 s?and a wide pH range?5-11?.With the increasing concentration of Cu²⁺ion in system,the fluorescence intensity quenched gradually.Moreover,there was a good linear relationship between the fluorescence intensity and Cu²⁺ion concentration(0¹×10^-4M),and the LOD was 4×10^-8M.Furthermore,based on the good biocompatibility,compound 2II could be used for the fluorescence imaging in living mice.?2?7-?4'-?dimethylamino?benzylidene?-isolongifolanone?3I?was synthesized by an aldol condensation reaction between isolongifolanone and p-dimethylaminobenzaldehyde.Then,3-?4'-?dimethylamino?phenyl?-5,5,9,9-tetramethyl-2,4,5,6,7,8,9,9a-octahydro-8H-5a,8-methano-indazole?3IIa?was next synthesized and prepared by hydrazine monohydrate and7-?4'-?dimethylamino?benzylidene?-isolongifolanone via a simple cyclization reaction.4-?4?-?dimethylamino?phenyl?-6,6,10,10-tetramethyl-5,7,8,9,10,10a-hexahydro-6H-6a,9-methan obenzo[h]quinazolin-2-amine?3IIb?was then synthesized by a simple reaction of7-?4'-?dimethylamino?benzylidene?-isolongifolanone and guanidine hydrochloride.Compounds3IIa and 3IIb showed the positive solvatochromism phenomenon because of their D-?-A molecular configurations in different solvents.Thanks to the nitrogen heterocyclic structures,compounds 3IIa and 3IIb exhibited the obvious UV-vis and fluorescence responses towards acidic pH value.The fluorescence intensity ratio(F_{445 nm}/F_{373 nm})of compound 3IIa and pH value?1.5-4.0?showed an excellent linear relationship,the pKa was 2.59.The fluorescence intensity of compound 3IIb at 434 nm and pH value?3.5-7.0?exhibited a good linear relationship,pKa was 3.69.Meanwhile,these two solid-state compounds were applied to the detection of TsOH solid and TFA vapour.?3?7-?2'-hydroxybenzylidene?-isolongifolanone?4Ia?and 7-?pyridine-2?-ylmethylene?--isolongifolanone?4Ib?were first synthesized by the condensation reaction of isolongifolanone with salicylaldehyde and pyridine-2-aldehyde,respectively.Then,6,6,10,10-tetramethyl-4--?2'-hydroxyphenyl?-5,7,8,9,10,10a-hexahydro-6H-6a,9-methanobenzo[h]quinazolin-2-amine?4IIa?and6,6,10,10–tetramethyl-4-?pyridine-2?-yl?-5,7,8,9,10,10a-hexahydro-6H-6a,9--methanobenzo[h]quinazolin-2-amine?4IIb?were synthesized by the cyclization reactions of compounds 4Ia and 4Ib with guanidine hydrochloride in the catalysis of potassium tert-butylate,respectively.Compounds 4IIa and 4IIb could serve as two fluorescence probes for BF₃.Upon reaction with BF₃,compound 4IIa exhibited obviously enhanced fluorescence,while compound4IIb showed a red-shifted fluorescence emission from blue to green.Meanwhile,the fluorescence intensity of compound 4IIa at 428 nm and BF₃ concentration?0-10?M?had a good linear relationship,and the LOD was 1.37×10^-88 M.The fluorescence intensity ratio(F_490nm/F_{415 nm})of compound 4IIb and BF₃ concentration?0-10?M?also exhibited a good linear relationship,and the LOD was 6.21×10^-88 M.Moreover,compounds 4IIa and 4IIb could be used as two simple and rapid methods for detecting BF₃ vapour with the help of non-emissive filter paper.?4?A series of 7-?benzylidene?-isolongifolanone derivatives 5Ia-5Ie were synthesized by a aldol condensation reaction of isolongifolanone and aromatic aldehydes.Then a series of pyrimidine-based derivatives 5IIa-5IIe were synthesized by the reaction of guanidine hydrochloride and compounds 5Ia-5Ie using potassium tert-butylate as a catalyst.Finally,Five schiff bases 5IIIa-5IIIe were obtained by the reaction of 2-hydroxy-1-naphthaldehyde and compounds 5Ia-5Ie.From the measurements of their solid-state fluorescence emission,the fluorescence of compounds 5IIIa-5IIIe was greatly affected by the para-substituted groups on the phenyl.With the increase of electron donating ability of the para-substituted groups,their solid states exhibited an enhanced emission and a dark green to bright yellow color range.In addition to good thermal stability,their solid-state fluorescence was very stable.By adjusting water content in solution system,compound 5IIIe demonstrated obvious aggregation-induced emission?AIE?characteristic.These compounds were successfully applied to image Zn²⁺ion in plants.?5?7-?pyridine-3?-ylmethylene?-isolongifolanone?6I?was synthesized by a condensation reaction of isolongifolanone with 4-pyridinecarboxaldehyde in the presence of potassium tert-butylate.Then,6,6,10,10–tetramethyl-4-?pyridine-3?-yl?-5,7,8,9,10,10a-hexahydro-6H-6a,9-methanobenzo[h]quinazolin-2-amine?6II?was synthesized by reaction of compound6II and guanidine hydrochloride in the presence of potassium tert-butylate.Finally,1-6,6,10,10–tetramethyl-4-?pyridine-3?-yl?-5,7,8,9,10,10a-hexahydro-6H-6a,9-methanobenzo[h]quinazolin-2-imino)methyl)naphthalen-2-ol?6III?was afforded by reaction of compound 6II and 2-hydroxy-1-naphthaldehyde.Compound 6III exhibited strong green fluorescence in the presence of Zn²⁺ion,and it could be used as a fluorescence probe for the detection of Zn²⁺ion.There was an excellent linear relationship between fluorescence intensity of compound 6III and Zn²⁺concentration?0-9.5?M?,and the LOD was 5.12×10^-99 M.The spectral response behaviors of compound 6III towards Zn²⁺ion were rationally studied by the density functional theory?DFT?calculations.The compound 6III was used to image Zn²⁺ion in living mice.?6?7-?4'-?diethylamino?benzylidene?-isolongifolanone?7I?was first synthesized by an aldol condensation reaction between isolongifolanone and 4-diethylaminobenzaldehyde,and4-?4?-?N,N-diethylamino?phenyl?-6,6,10,10-tetramethyl-5,7,8,9,10,10a-hexahydro-6H-6a,9-met hanobenzo[h]quinazolin-2-amine?7II?was synthesized by a reaction of compound 7I and guanidine hydrochloride in the presence of potassium tert-butylate in tert-butyl alcohol.Finally,1-6,6,10,10–tetramethyl-4-?4?-?N,N-diethylamino?phenyl?-5,7,8,9,10,10a-hexahydro-6H-6a,9-m ethanobenzo[h]quinazolin-2-imino)methyl)naphthalen-2-ol?7III?was obtained by a reaction of compound 7II and 2-hydroxy-1-naphthaldehyde.Compound 7III was an excellent fluorescence probe for detecting ClO^-and exhibited strong blue fluorescence.With the fluorescence titration experiment,a good linear relationship between the fluorescence intensity of compound 7III at435 nm and ClO^-concentration?0-40?M?was obtained,and the LOD was 5.86×10^-9M.Meanwhile,the sensing mechanism of compound 7III for ClO^-was fully studied by FT-IR,HRMS and density functional theory?DFT?calculations.Inspired by low cytotoxicity and excellent cell membrane permeability,compound 7III was successfully used for fluorescence imaging of ClO^-in HeLa and RAW264.7 cells.?7?3-?2'-hydroxybenzylidene?-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one?8Ia?,3-?3'--hydroxybenzylidene?-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one?8Ib?and 3-?4'-hydroxy-benzylidene?-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one?8Ic?were synthesized by the aldol condensation reactions of camphor with salicylaldehyde,3-hydroxybenzaldehyde and4-hydroxybenzaldehyde under the presence of alkaline catalysts.Then,4-?2'-hydroxy-benzylidene?-8,9,9-tetramethyl-5,6,7,8-tetrahydro-5,8-methanoquinazolin-2-amine?8IIa?,4-?3'-hydroxybenzylidene?-8,9,9-tetramethyl-5,6,7,8-tetrahydro-5,8-methanoquinazolin-2-amin e?8IIb?and 4-?4'-hydroxybenzylidene?-8,9,9-tetramethyl-5,6,7,8-tetrahydro-5,8-methano-quinazolin-2-amine?8IIc?were synthesized by the reactions of compounds 8Ia-8Ic with guanidine hydrochloride.Compounds 8IIa-8IIc could serve as three colorimetric and ratiometricc fluorescence probes for ClO^-.Moreover,compounds 8IIa-8IIc showed excellent selectivity towards ClO^-,and they could be used for the quantitative detection of ClO^-concentration in solution.The fluorescence intensity of compound 8IIa at 489 nm and ClO^-concentration?10-50?M?showed an enhanced linear relationship,and the LOD was 5.16×10^-9M.The fluorescence intensity of compound 8IIb at 547 nm and ClO^-concentration?20-50?M?also exhibited an excellent linear relationship,and the LOD was 6.85×10^-99 M.The fluorescence intensity of compound 8IIc at 435 nm and ClO^-concentration?0-50?M?offered a good linear relationship,and the LOD was 3.55×10^-99 M.Proved by the experiments,compounds 8IIa-8IIc were successfully used for fluorescence imaging of exogenous ClO^-in HeLa cells and endogenous ClO^-RAW264.7 cells.