Syntheses And Properties Of The Derivatives Of Meso-Chlorine Containing Heptamethine Cyanines By Substitution Nitrogen Or Oxygen For The Chlorine

Heptamethine indocyanines?Cy-Cls?have been widely used in biological analysis,clinical medicine,food safety,environmental monitoring and pH detection for their large extinction coefficient,good biocompatibility,absorption and emission wavelengths in the near-infrared region.But they usually have small Stokes shift and low fluorescence quantum yield and this will affect their detection sensitivity.In order to further improve these spectral properties,12 novel heptamethine indocyanine derivatives?Cy-Ns and Cy-Os?with large Stokes shift and high fluorescence quantum yield by substitution N or O atoms for the meso-chlorine of Cy-Cls have been designed and synthesized.Their spectral properties,pH response,and the effect of surfactants and metal oxide colloidal particles on them are studied.The details are as follows:Firstly,three symmetrical Cy-Cls with N-methyl,N-ethyl and N-p-carboxybenzyl were synthesized by the reaction of 2-chloro-1-formyl-3-hydroxymethyl-ene-cyclohex-1-ene with the corresponding indoline intermediates in acetic anhydride?anhydrous sodium acetate as the catalyst?.Then,nine heptamethine cyanine derivatives from Cy-Cls by substitution N for Cl with benzylamine,taurine or n-butylamine were synthesized in dichloromethane or ethanol,with or without the catalysis of anhydrous sodium carbonate.Three heptamethine cyanine derivatives from Cy-Cls by substitution O for Cl were synthesized in DMF at room temperature under the catalysis of anhydrous sodium acetate and N-hydroxy succinimide.All of the dyes were purified and confirmed by ¹HNMR and ESI-MS.The maximum Uv-Vis absorption wavelengths(?_ab)of Cy-Cls,Cy-Os and Cy-Ns in methanol are in 774 nm-792 nm,518-528 nm and 589-637 nm,respectively,and the maximum emission wavelengths(?_em)of them are in 801-818 nm,617-623 nm and728-740 nm,respectively.Compared to Cy-Cls,Cy-Ns show shorter?_ab and?_em,larger Stokes shift?100-139 nm?and higher fluorescence yield?0.09-0.16?.The electron donating group of-NHR can form good?push-pull?structure with the main conjugated polymethine chain,and make the energy level of the ground state of the molecule decrease,so the excitation energy increases and the?_ab and?_em take blue shift.Furthermore,stronger electron donating ability of-NHR group can make greater blue shift of?_ab.Cy-Os show shorter wavelengths?79-100 nm?and higher fluorescence yield?0.41-0.47?than Cy-Cls because their polymethine chain is influenced by the carbonyl group and exhibits the characteristic of tricarbonay cyanine.With the increasing of polarity of the solvent,the?_ab and?_em of Cy-Ns show blue shift and exhibit negative solvatochromism,while those of Cy-Os show red shift and exhibit positive solvatochromism.In all of the dyes,Cy-Os have the best photostability due to the strong electron-withdrawing ability of carbonayl group and the short conjugated chain of Cy-Os.The?_ab and?_em can keep basically the same in neutral,weak basic and weak acidic conditions.Under extremely acidic condition?pH=2.11-4.28?,the?_ab and?_em of Cy-Os shift to near-infrared region?709-760 nm?and the color of the solutions turns from purple red to green because Cy-Os take reversible tautomerization to Cy-OHs by the protonation of meso-carbonyl group of Cy-Os to hydroxyl,and the large?conjugated system through the whole molecule backbone is recovered to the structure characteristic of heptamethine cyanine.Under extremely basic condition?pH=9.53-13.55?,the?_abb of Cy-Ns shifts to about 420 nm and the color of the solutions turns from blue to yellow because Cy-Ns turn to their reversible basic structures by attacking the 2 position of the indole ring with OH^-.While,the color of Cy-Cls solutions turns from green to yellow.The spectral properties,photostability and pH response of the dyes can be affected by surfactants through the formation of the micelles.In CTAB solutions,the?_ab and?_em of Cy-Os show blue shift,and those of Cy-Ns and Cy-Cls show red shift.With the increasing concentration of CTAB,the absorption and emission intensity decrease first,then increase at a certain value.Cy-Os,Cy-Ns and Cy-Cls show better photostability and pH response at smaller values in CTAB solutions,and also the critical micelle concentration of CTAB is reduced due to the dye joining the formation of micelle of CTAB.In TiO₂ and SiO₂ sol,the?_ab and?_em of Cy-Os show blue shift,while Cy-Ns and Cy-Cls show red shift,and the rigid and emission intensity of the dyes are increased because the dyes can well disperse in the sol-gel and combine with the TiO₂ and SiO₂ colloid particles.The Cy-Os can not convert to their enol tautomers in TiO₂ gel due to the strong action between the carbonyl with TiO₂.The novel derivatives by substitution nitrogen or oxygen for the chlorine of heptamethine cyanines designed in the thesis all show large Stokes shift and high fluorescence quantum yield,they also exhibit sensitive pH response in extremely acidic or basic conditions.The spectral properties and pH response range can be effectively adjusted by surfactants or metal oxide colloid particles.Therefore,it is expected that they will be widely applied in the fields of biological analysis,food safety and environmental monitoring,and so on.