63149-24-6

Usage

Uses

Used in Medical Imaging:
1,1,2-Trimethyl-3-(4-sulfobutyl)-1H-benz[e]indolium hydroxide, inner salt is used as a reactant in the preparation of liposomally formulated indocyanine green (LP-ICG) derivatives. This application is crucial for near-infrared fluorescence imaging of lymph nodes, which is an essential diagnostic tool in various medical procedures, including cancer staging and lymphatic system evaluation.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 1,1,2-trimethyl-3-(4-sulfobutyl)-1H-benz[e]indolium hydroxide, inner salt may be utilized as a building block or intermediate in the synthesis of various drug molecules. Its unique chemical properties can be harnessed to create new compounds with potential therapeutic applications.
Used in Research and Development:
1,1,2-Trimethyl-3-(4-sulfobutyl)-1H-benz[e]indolium hydroxide, inner salt can also be employed in research and development settings, where scientists explore its potential applications in various fields, such as materials science, nanotechnology, and biochemistry. Its unique structure and properties may lead to the discovery of new materials or processes with significant practical implications.

InChI:InChI=1/C19H23NO3S/c1-14-19(2,3)18-16-9-5-4-8-15(16)10-11-17(18)20(14)12-6-7-13-24(21,22)23/h4-5,8-11H,6-7,12-13H2,1-3H3

Synthetic route

1,4-butane sultone (1633-83-6) + 2,3,3-trimethylbenzo[e]indole (41532-84-7) → 4-(1,1,2-trimethyl-1H-benzo[e]indol-3-ium-3-yl)butane-1-sulfonate (63149-24-6)

Conditions	Yield
at 120℃; for 2h;	99%
In sulfolane at 120 - 130℃;	92%
With 1,2-dichloro-benzene In diethyl ether at 120℃; for 18h; Inert atmosphere; Darkness;	90%

1,2-oxathiane-2-oxide (24308-29-0) + 2,3,3-trimethylbenzo[e]indole (41532-84-7) → 4-(1,1,2-trimethyl-1H-benzo[e]indol-3-ium-3-yl)butane-1-sulfonate (63149-24-6)

Conditions	Yield
at 120℃; for 2h;	93%

Upstream product

• 1633-83-6 1,4-butane sultone 
• 41532-84-7 2,3,3-trimethylbenzo[e]indole 
• 4988-33-4 pentamethylene sulfone 
• 24308-29-0 1,2-oxathiane-2-oxide 

Downstream Products

• 1345697-56-4 C₅₃H₅₆N₂O₈S₃ 
• 162411-28-1 IR-820 
• 3599-32-4 cardiogreen 
• 3599-32-4 indocyanine green 
• 1351043-94-1 4-(1,1-dimethyl-2-((1E,3E,5E)-6-(N-phenylacetamido)hexa-1,3,5-trienyl)-1H-benzo[e]indolium-3-yl)butane-1-sulfonate 
• 1351043-94-1 4-(1,1-dimethyl-2-(6-(N-phenylacetamido)hexa-1,3,5-trien-1-yl)-1H-benzo[e]indol-3-ium-3-yl)butane-1-sulfonate 
• 1351043-94-1 2-(6-acetanilido-1,3,5-hexatrienyl)-3,3-dimethyl-1-(4-sulfobutyl)-4,5-benzo[e]indolium 

Relevant academic research and scientific papers

Protein triggered fluorescence switching of near-infrared emitting nanoparticles for contrast-enhanced imaging

Sub-100 nm colloidal particles which are surface-functionalized with multiple environmentally-sensitive moieties have the potential to combine imaging, early detection, and the treatment of cancer with a single type of long-circulating nanodevice . Deep tissue imaging is achievable through the development of particles which are surface-modified with fluorophores that operate in the near-infrared (NIR) spectrum and where the fluorophore's signal can be maximized by turning-on the fluorescence only in the targeted tissue. We present a general approach for the synthesis of NIR emitting nanoparticles that exhibit a protein triggered activation/deactivation of the emission. Dispersing the particles into an aqueous solution, such as phosphate buffered saline (PBS), resulted in an aggregation of the hydrophobic fluorophores and a cessation of emission. The emission can be reinstated, or activated, by the conversion of the surface-attached fluorophores from an aggregate to a monomeric species with the addition of an albumin. This activated probe can be deactivated and returned to a quenched state by a simple tryptic digestion of the albumin. The methodology for emission switching offers a path to maximize the signal from the typically weak quantum yield inherent in NIR fluorophores.

Visible diode laser-induced fluorescence detection in liquid chromatography after precolumn derivatization of amines

To fully exploit the attractive visible diode laser-induced fluorescence (LIF) detection technique in column liquid chromatography (LC), covalent labeling procedures need to be developed which are compatible with near-infrared fluorescence. For this purpose, several red-absorbing labels containing a single succinimidyl ester functionality were synthesized and used for the derivatization of primary and secondary amines. Oxazines/thiazines, squaraines, and dicarbocyanines were examined as redabsorbing fluorophores. The quality of the LC-diode LIF system for the analytes concerned is illustrated by the concentration detection limit of the labeled n-octylamine (a test compound), which was as low as 2 x 10-12 M. As expected in view of the limited reactivity of the succinimidyl ester group, the analyte concentrations required to obtain quantitative reaction with the label were equal to or higher than 2 x 10-8 M. To show the applicability of the method to biological samples, urine was spiked with 5 x 10-7 M 1-adamantanamine, extracted, derivatized with a dicarbocyanine-based label, and analyzed by LC-diode LIF.

Preparation and characterization of phospholipid-conjugated indocyanine green as a near-infrared probe

We have rationally designed and synthesized a novel near-infrared (NIR) photoactivating probe, designated by iDOPE, in which an indocyanine green (ICG) fluorophore is covalently conjugated with a phospholipid moiety, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), to incorporate into liposome bilayers. NIR irradiation showed that iDOPE retained the optical and fluorescence properties of ICG and demonstrated photoactivator characteristics: fluorescence emission at around 820 nm in a solvent, singlet oxygen production, and concentration-dependent heat generation. Additionally, iDOPE was incorporated into liposome bilayers and maintained stable liposomally formulated iDOPE (LP-iDOPE) over 1 week under physiological conditions. We also observed the tumor-specific biodistribution of LP-iDOPE of in vivo xenografts. These findings suggest that LP-iDOPE might be a promising tool for NIR optical imaging, photodynamic therapy, and photothermal therapy.

Deuterated Indocyanine Green (ICG) with Extended Aqueous Storage Shelf-Life: Chemical and Clinical Implications

Indocyanine Green (ICG) is a clinically approved near-infrared fluorescent dye that is used extensively for various imaging and diagnostic procedures. One drawback with ICG is its instability in water, which means that reconstituted clinical doses have to be used very shortly after preparation. Two deuterated versions of ICG were prepared with deuterium atoms on the heptamethine chain, and the spectral, physiochemical, and photostability properties were quantified. A notable mechanistic finding is that self-aggregation of ICG in water strongly favors dye degradation by a photochemical oxidative dimerization reaction that gives a nonfluorescent product. Storage stability studies showed that replacement of C?H with C?D decreased the dimerization rate constant by a factor of 3.1, and it is likely that many medical and preclinical procedures will benefit from the longer shelf-lives of these two deuterated ICG dyes. The discovery that ICG self-aggregation promotes photoinduced electron transfer can be exploited as a new paradigm for next-generation photodynamic therapies.

Cyanine Nanocage Activated by Near-IR Light for the Targeted Delivery of Cyclosporine A to Traumatic Brain Injury Sites

More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.

N-alkylated linear heptamethine polyenes as potent non-azole leads against Candida albicans fungal infections

In this study, eighteen heptamethine dyes were synthesised and their antifungal activities were evaluated against three clinically relevant yeast species. The eighteen dyes were placed within classes based on their core subunit i.e. 2,3,3-trimethylindolenine (5a-f), 1,1,2-trimethyl-1H-benzo[e]indole (6a-f), or 2-methylbenzothiazole (7a-f). The results presented herein imply that the three families of cyanine dyes, in particular compounds 5a-f, show high potential as selective scaffolds to treat C. albicans infections. This opens up the opportunity for further optimisation and investigation of this class compounds for potential antifungal treatment.

Preparation method and application of heptamethine benzo indole cyanine dye

The invention discloses a preparation method and application of a heptamethine benzo indole cyanine dye, and belongs to the field of polymethine indole cyanine dyes and preparation thereof. The methodcomprises the following steps: 1) carrying out a heating reaction on raw materials containing a 2,3,3-trimethyl-4,5-benzoindole derivative and a nucleophilic substituted compound under a vacuum condition to obtain an organic ammonium salt; and 2) carrying out a heating reaction on a solution containing the organic ammonium salt obtained in the step 1) and a cycloalkene derivative under a closed condition, wherein the structural formula of the heptamethine benzo indole cyanine dye is represented by a formula (I). According to the invention, the dye has near-infrared light absorption and fluorescence development performances and can be used as a probe auxiliary agent; and the method has the advantages of short synthesis route, environment-friendly solvent, simple process, avoidance of noblemetal catalysis, high yield, high product purity and the like, is high in applicability, and can be used for synthesizing products of various structure types.

Preparation method of heptamethine benzoindocyanine dye

The invention discloses a preparation method of a heptamethine benzoindocyanine dye. The method at least comprises the following steps that a 2,3,3-trimethyl-4,5-benzindole derivative reacts with a nucleophilic substitution compound and re-crystallized to obtain organic ammonium salt; the organic ammonium salt, a cyclohexene derivative and a sodium acetate solution react with one another, the product is mixed with alcohol and ether, the mixture is extracted many times, and the heptamethine benzoindocyanine dye is obtained. The method is short in synthetic route, simple in process, free of catalysis of precious metal and high in yield, the extraction method is simple, chromatographic column separation is not needed, the solvent consumption is low, the preparation efficiency of the dye is greatly improved, and low-cost batch production can be achieved. The method has great significance in the aspects of production and application research of heptamethine benzoindocyanine. The prepared heptamethine benzoindocyanine dye contains an aliphatic chain substituted N structure, and has or independently has near-infrared light absorption and fluorescent development functions.

PROCESS FOR THE PREPARATION OF SODIUM 4-(2-((1E,3E,5E,7Z)-7-(1,1-DIMETHYL-3-(4-SULFONATOBUTYL)-1H-BENZO[e]INDOL-2(3H)-YLIDENE) HEPTA-1,3,5-TRIENYL)-1,1-DIMETHYL-1H-BENZO[e]INDOLIUM-3-YL) BUTANE-1-SULFONATE (INDOCYANINE GREEN)

A process for the preparation of substantially pure Indocyanine green of formula with purity greater than 99.0% is provided. More particularly, the embodiments relate to the process for the preparation of Indocyanine green of formula and its intermediates thereof. It further provides crystalline form I of Indocyanine green of formula and process thereof.

Heptamethine benzoindocyanine dye and preparation method and application thereof

The invention discloses a heptamethine benzoindocyanine dye and a preparation method and application thereof. The heptamethine benzoindocyanine dye contains an aliphatic chain substituted N structure,and has or independently has near-infrared light absorption and fluorescent development functions. The preparation method is short in synthetic route, simple in process, free of catalysis of preciousmetal, high in yield and large in single reaction amount, the preparation efficiency of the dye is greatly improved, and low-cost batch production can be realized. The dye and the preparation methodhave great significance in the aspects of production and application research of heptamethine benzoindocyanine.