The good fluorescence characteristics can be used to improve the detection sensitivity, which reduces background interference from intracellular environment or tissues. The photophysical behavior of the cyanines was investigated using uvvis and steadystate fluorescence in solution, as well as their association with bovine serum albumin bsa in phosphate buffer solution pbs. Optimal labeling conditions have been identified which yield probes with 2040. Benzc,dindoliumcontaining monomethine cyanine dyes. Cyanine dye dutp analogs for enzymatic labeling of dna. Maleimide groups react with sulfhydryls under neutral ph conditions to form a thioether linkage figure. The carbon chain contributes to the overall shape of the molecule being linear. All results demonstrated that asymmetric dye 5a possesses better photostability, which can be a good fluorescent labeling reagent for protein. Practical syntheses of lysineselective, succinimidyl ester derivatives. Synthesis of merocyanine dyes all the approaches to the synthesis of merocyanines relied on the socalled cyanine condensation. H 2 pc has a twodimensional geometry and a ring system consisting of 18. In this project a chemical analog to the already existing boxto has been synthesized via synthesis of a benzothiazolium salt and a quinolinium salt followed by a condensation of these into the final dye.
The scope of the previously reported catchandrelease method using. In this paper, we describe the synthesis and the photophysical properties of two novel nearinfrared nir cyanine dyes nir5. They are not the dyes that are directly seen in the photo, but the unseen dyes which are. Processes are described for synthesizing suitable heterocyclic and indole derivatives as precursors for the aforementioned cyanine dyes. Cyanine dyes are an interesting class of near infrared nir dyes that have captured the interest of the scientific community. Synthesis of different classes of fivesix membered. Novel nearinfrared cyanine dyes for fluorescence imaging. Kvach institute of physical organic chemistry, surganova, minsk 220072, belarus, fax.
The alkylated amide 2 was then converted to the thioketone 3 under reflux with phosphorous pentasulfide in pyridine. The cyanine dyes cy3 and cy5 have proven valuable in numerous applications involving conjugation with proteins. Herein we report the synthesis of seven monomethine cyanine dyes that have been successfully prepared with various heterocyclic moieties such as quinoline, benzoxazole, benzothiazole, dimethyl indole, and benzeindole adjoining benzc,dindol1ium, which was found to directly influence their optical and energy profiles. Novel nearinfrared cyanine dyes for fluorescence imaging in biological systems by nilmi t.
Synthesis of nearinfrared heptamethine cyanine dyes by jamie l. Phthalocyanine h 2 pc is a large, aromatic, macrocyclic, organic compound with the formula c 8 h 4 n 2 4 h 2 and is of theoretical or specialized interest. Cyanine dye cy3, possesses many excellent characteristics, such as good chemical stability, good fluorescence absorbance, and a high molar absorption coefficient 12. Reversible synthesis and characterization of dynamic imino analogues of trimethine and pentamethine cyanine dyes kamel meguellati, martin spichty, and sylvain ladame isis. Fluorogenic peptide nucleic acids pnas functionalized with indoline derivatives are used to specifically sense g. Synthesis of novel fluorescent benzothiazole cyanine dyes as. In an accompanying paper, we present a study of the dissociation of these dyes from dna under conditions typical for biotechnical application 35.
A series of mesochlorine substituted heptamethine cyanine dyes and related heptamethine cyanine dyes unsubstituted on the vinyl chain were synthesized by condensation of 2,3,3trimethyl indolenium salts with reactive intermediates, 2chloroformyl3hydroxymethylenecyclohexene or n5phenylamino2,4phentadienylidene aniline monohydroc hloride. Microwave synthesis of cyanine dyes january 2010 the journal of microwave power and electromagnetic energy. This short chapter provides a background to the subsequent. The word cyanin is from the english word cyan, which conventionally means a shade of bluegreen close to aqua and is derived from the greek. Synthesis of pentamethine cyanine dyes 34 and 35 containing a cyclopentene ring in the pentmethine chain was accomplished by condensing 2methylcylcopentane1,3diones 30, 31 with quaternary salts of 2methylbenzothiazolium 32, 33 at 210c in the presence of triethylamine equation 9. They are efficient substrates for dna polymerases and can be incorporated into. The synthesis of a geometrically constrained and near. Bibliography includes bibliographical references and index. The synthesis results in two variants of the probes. Reversible synthesis and characterization of dynamic imino. A method of the synthesis of taqman probes with the use of bisphosphoramidite of cyanine dye cy3 was proposed.
A dye which in the past have shown promising dnabinding and fluorescent is a cyanine dye called boxto. The synthesis of unsymmetrical carbocyanine dyes is excellent for modifying a dyes absorption wavelength, preparing it for conjugation, or altering the dyes polarity or solubility. Cyanine dye is the nonsystematic name of a family of fluorescent dyes with excellent photophysical properties such as high fluorescence quantum yield, emission at long wave lengths and high photostability. The asymmetric redshifted monomethine cyanine dyes were synthesized as shown in scheme 1.
Cyanine is the nonsystematic name of a synthetic dye family belonging to polymethine group. Synthesis and applications of benzothiazole containing. We also report a new and chemically distinct synthetic strategy, employing the stepwise attack of. International journal of organic chemistry, 8, 282297. Phthalocyanine h2pc is a large, aromatic, macrocyclic, organic compound with the formula c 8 h 4 n 2 4 h 2 and is of theoretical or specialized interest.
Cyanine 3 and cyanine 5 supports are also offered to allow simpler production of 3 cyanine dyelabelled oligonucleotides. Cyanine dye dutp analogs for enzymatic labeling of dna probes. Cyanine dyes are known best for their application in color photography. We report here a series of studies that explore solidphase methodologies for the synthesis of various cyanine dyes. Pdf four tetramethylindodicarbocyaninederived carboxylicacids have been prepared using a modified onepot procedure for the dye. Synthesis and characterization of heptamethine cyanine dyes. Solidphase methods for the synthesis of cyanine dyes the. The most commonly used nearinfrared cyanine dyes contain an aryl ether that is not fully stable towards nucleophiles.
New cyanines were prepared by an efficient and practical route with satisfactory overall yield from lowcost starting materials. Synthesis of new symmetrical mono, tri, and pentamethine cyanine dyes with two nammonioalkyl substituents was developed. Synthesis of a new beta naphthothiazole monomethine cyanine dye for the detection of dna in aqueous solution. It is composed of four isoindole units linked by nitrogen atoms. The photophysical behavior of the cyanines was investigated using. Cyanine dyes that have a thiolreactive group are typically maleimide derivatives. In dye chemistry, as is well known, many roads lead to the same goal. The scope of the previously reported catchandrelease method using sulfonyl chloride resin1 has now been extended to include pentamethine and watersoluble cyanine dyes. Synthesis, spectral properties, and use in the preparation of internally quenched fluorescent probes. The journal of physical chemistry c 2017, 121 28, 1504915062. A cyanine dye molecule consists of 2 nitrogencontaining heterocycles connected by an elongated, unsaturated carbon chain. In the last step of the synthesis, conditions for the removal of the phthalimide protecting group in cyanine dyes using hydrazine monohydrate and an ethanol solution of menh 2 were selected.
If dmfdg is used during synthesis, deprotect in ammonium. The synthesis of four cyanine phosphoramidites and activated esters cy3, cy3. Deprotection of oligos containing cyanine dyes may be carried out with ammonium hydroxide at room temperature, regardless of the base protecting groups on the monomers used. Synthesis and optical properties of pentamethine cyanine dyes.
Fernando under the direction of professor lucjan strekowski. Henary abstract carbocyanine dyes are organic compounds. Synthesis of nearinfrared heptamethine cyanine dyes. Compared with wellknown symmetric cyanine dye 6c, the asymmetric dyes 5a and 5b contain only one active group on their molecules, and should benefit from quantitative protein labeling. Facile synthesis of thiolreactive cy3 and cy5 derivatives. The word cyanin is from the english word cyan, which conventionally means a shade of blue. Pdf synthesis and optical properties of cyanine dyes with. Jan 01, 2016 synthesis of the chlorocyclohexenylcy7bisnorbornenylbromide 7 synthesis and characterization of heptamine cyanine dyes are well described by the li group 28. Solidphase methods for the synthesis of cyanine dyes. The synthesis of cyanine dye 22 was carried out by condensation reaction between compound 21 and 2,3dimethyl benzothiazole tetrafluoroborate in the presence of sterically hindered hunig base. Cyanine dyes featuring alkyl carboxylic acids have been previously explored extensively for both dyesensitized solar cells and conjugation of other groups onto the dye. Pdf six cyanine dyes with aromatic azonia skeleton 1a. The dye is useful in labeling a variety of target molecules. Cyanine dye should be dissolved in organic solvent first, and added to a solution of biomolecule protein, peptide, aminolabeled dna in appropriate aqueous buffer.
Synthesis and photophysical properties of novel highly stable. Synthesis of a novel heptamethinecyanine dye for use in. A cyanine dye having the formula wherein r 1 r 8 are each independently selected from a group consisting of hydrogen, c 1 c 6 alkyl group, and c 0 c 4 alkyl group having a hydrophilic. Heterocyclic polymethine dyes synthesis, properties and. Microwave synthesis of near infrared heptamethine cyanine dye.
We were surprised to observe that commercialavailable cyanine. Synthesis and optical properties of cyanine dyes with an. Synthesis and photophysical properties of novel highly. Synthesis, spectroscopic characterizations, and ionspecific cooperative adsorption at the surface of tio2 anatase nanoparticles.
This takes advantage of the presence of carboxylate co2 groups in silk and wool. Six cyanine dyes with an aromatic azonia skeleton 1af were obtained by the reaction of chlorinated heptamethylene cyanine and 2aminopyridine derivatives. The nir cyanine dye of interest, heptamethine cyanine dye nir1. Five of them 1ad and 1f emit red and nearinfrared fluorescence at 600800 nm. The electronic visible adsorption spectra of all the synthesized cyanine dyes were investigated in 95% ethanol solution. The presence of the pyridine ring in the pentamethine chain makes the dye more rigid and the cationic charge makes it water soluble.
Reagents for the labeling of biomolecules maksim v. Synthesis and optical properties of pentamethine cyanine. Synthesis of a novel heptamethinecyanine dye for use in near. The synthesis results in two variants of the probes consisting of either one or two oligonucleotide residues bearing a quencher at the 3 end attached to the dye, with the first variant being predominant. Synthesis of taqman probes using bisphosphoramidite of. Replacement of the aryl ether by a more stable carboncarbon bond can improve the stability. Cyanine dye is the nonsystematic name of a family of fluorescent dyes with excellent photophysical properties such as high fluorescence quantum yield, emission at long wave. The synthesis of an azo dye requires two organic compounds a diazonium salt and a coupling component. Reversible synthesis and characterization of dynamic imino analogues of trimethine and pentamethine cyanine dyes kamel meguellati, martin spichty, and sylvain ladame isis universite. Us6437141b2 cyanine dyes and synthesis methods thereof. A novel nearinfraredabsorbing heptamethinecyanine dye kfh3 that contains four nbutyl groups was synthesized for use in highly efficient dyesensitized solar cells with porous zinc oxide zno prepared at low temperature, and resulted in remarkable performance characteristics, such as a conversion effi. Synthesis of a new betanaphthothiazole monomethine cyanine.
Different methods in the synthesis of monobiheterocyclic six mem bered cyanine dyes. The synthesis began with the alkylation of benzc,dindol21hone 1 by reflux with. Compared with wellknown symmetric cyanine dye 6c, the asymmetric dyes 5a and 5b contain only one active group on their molecules, and should benefit from quantitative protein labeling and purifying. Cyanine dyes are amongst the earliest quaternary ammonium salts, which were evaluated against helminths. The synthesis began with the alkylation of benzc,dindol21hone 1 by reflux with iodobutane in acetonitrile. Synthesis of heptamethine cyanine dyes ubc open collections. A series of mesochlorine substituted heptamethinecyanine dyes and related heptamethine cyanine dyes unsubstituted on the vinyl chain were synthesized by condensation of 2,3,3.
The first bridged cyanine dye synthesis was published in 1933 where. They are efficient substrates for dna polymerases and can be incorporated into dna probes by standard nick translation, random priming and polymerase chain reactions. In an accompanying paper, we present a study of the dissociation. Dyes for dye sensitized solar cells synthesis and computational study corneliu i. However, cationic dyes can be used to dye protein fibres and, in fact, the first synthetic dye mauveine was a basic dye that was used for dyeing silk. Pdf photoexcitation processes in oligomethine cyanine.
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