40846-94-4

Usage

Uses

Used in Bioconjugation:
Alpha-lipoic acid-NHS is used as a bioconjugation agent for the formation of amide bonds between primary amine groups and other molecules. This application is particularly useful in the fields of pharmaceuticals, diagnostics, and research, where the creation of stable covalent bonds between biomolecules is essential.
Used in Drug Delivery Systems:
In the pharmaceutical industry, alpha-lipoic acid-NHS can be utilized as a component in the development of drug delivery systems. Its ability to form amide bonds can be harnessed to create targeted drug carriers, enhancing the specificity and efficacy of therapeutic agents.
Used in Chemical Synthesis:
Alpha-lipoic acid-NHS can also be employed in chemical synthesis processes, where its reactive NHS group can be used to introduce lipoic acid moieties into various molecules. This can be particularly beneficial in the synthesis of complex organic compounds and the development of novel pharmaceuticals.
Used in Material Science:
In the field of material science, alpha-lipoic acid-NHS may find applications in the development of novel materials with specific properties. The ability to form amide bonds can be exploited to create new polymers, coatings, or other materials with tailored characteristics.
Overall, alpha-lipoic acid-NHS is a versatile compound with a wide range of potential applications across various industries, thanks to its unique ability to form amide bonds with primary amine groups.

Upstream product

• 6066-82-6 1-hydroxy-pyrrolidine-2,5-dione 
• 1077-28-7 Thioctic acid 
• 74124-79-1 di(succinimido) carbonate 

Downstream Products

• 691410-93-2 5-([1,2]dithiolan-3-yl)pentanoic acid N-{3-[5-([1,2]dithiolan-3-yl)pentanoylamino]propyl}amide 
• 948565-65-9 C₁₈H₂₇O₃NS₂ 
• 1200-22-2 (R)-1,2-dithiolane-3-pentanoic acid 
• 1085381-76-5 2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl dihydrogen phosphate 
• 1085381-74-3 2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl 1-(4,5-dimethoxy-2-nitrophenyl)ethyl hydrogen phosphate 
• 1342764-64-0 C₁₆H₃₁NO₅S₂ 
• 1589517-79-2 5-(1,2-dithiolan-3-yl)-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)pentan-1-one 
• 1589517-80-5 5-(1,2-dithiolan-3-yl)-1-(4-(2-methylbenzyl)piperazin-1-yl)pentan-1-one 
• 1589517-81-6 5-(1,2-dithiolan-3-yl)-1-(4-(3-methylbenzyl)piperazin-1-yl)pentan-1-one 
• 1589517-82-7 5-(1,2-dithiolan-3-yl)-1-(4-(4-methylbenzyl)piperazin-1-yl)pentan-1-one 
• 1589517-83-8 5-(1,2-dithiolan-3-yl)-1-(4-(2-fluorobenzyl)piperazin-1-yl)pentan-1-one 
• 1589517-85-0 5-(1,2-dithiolan-3-yl)-1-(4-(3-fluorobenzyl)piperazin-1-yl)pentan-1-one 
• 1589517-86-1 5-(1,2-dithiolan-3-yl)-1-(4-(4-fluorobenzyl)piperazin-1-yl)pentan-1-one 
• 1589517-87-2 1-(4-(4-chlorobenzyl)piperazin-1-yl)-5-(1,2-dithiolan-3-yl)pentan-1-one 

Relevant academic research and scientific papers

Lipoyl-Homotaurine Derivative (ADM-12) Reverts Oxaliplatin-Induced Neuropathy and Reduces Cancer Cells Malignancy by Inhibiting Carbonic Anhydrase IX (CAIX)

Oxaliplatin (OXA) is a valuable and largely used cancer drug which induces a serious and intractable neuropathy. The lipoyl-homotaurine derivative (ADM-12) reverts in vivo OXA-induced neuropathy, and it is an effective antagonist of the nociceptive sensor channel TRPA1. Unprecedentedly, this safe analgesic showed a synergy with OXA in vitro and proved to inhibit CA IX, a relevant therapeutic target, clearly interfering with pancreatic cancer cells' aggressiveness.

Biotin Decorated Gold Nanoparticles for Targeted Delivery of a Smart-Linked Anticancer Active Copper Complex: In Vitro and in Vivo Studies

The synthesis and anticancer activity of a copper(II) diacetyl-bis(N4-methylthiosemicarbazone) complex and its nanoconjugates are reported. The copper(II) complex is connected to a carboxylic acid group through a cleavable disulfide link to enable smart delivery. The copper complex is tethered to highly water-soluble 20 nm gold nanoparticles (AuNPs), stabilized by amine terminated lipoic acid-polyethylene glycol (PEG). The gold nanoparticle carrier was further decorated with biotin to achieve targeted action. The copper complex and the conjugates with and without biotin, were tested against HeLa and HaCaT cells. They show very good anticancer activity against HeLa cells, a cell line derived from cervical cancer and are less active against HaCaT cells. Slow and sustained release of the complex from conjugates is demonstrated through cleavage of disulfide linker in the presence of glutathione (GSH), a reducing agent intrinsically present in high concentrations within cancer cells. Biotin appended conjugates do not show greater activity than conjugates without biotin against HeLa cells. This is consistent with drug uptake studies, which suggests similar uptake profiles for both conjugates in vitro. However, in vivo studies using a HeLa cell xenograft tumor model shows 3.8-fold reduction in tumor volume for the biotin conjugated nanoparticle compared to the control whereas the conjugate without biotin shows only 2.3-fold reduction in the tumor volume suggesting significant targeting.

Pyrene-modified quartz crystal microbalance for the detection of polynitroaromatic compounds

The synthesis of a dithiol-functionalized pyrene derivative is reported, together with studies of interactions between this receptor (and other related pyrenes) and nitroaromatic compounds (NACs), in both solution and in the solid state. Spectroscopic analysis in solution and X-ray crystallographic analysis of cocrystals of pyrene and NACs in the solid state indicate that supramolecular interactions lead to the formation of defined π-π stacked complexes. The dithiol-functionalized pyrene derivative can be used to modify the surface of a gold quartz crystal microbalance (QCM) to create a unique π-electron rich surface, which is able to interact with electron poor aromatic compounds. For example, exposure of the modified QCM surface to the nitroaromatic compound 2,4-dinitrotoluene (DNT) in solution results in a reduction in the resonant frequency of the QCM as a result of supramolecular interactions between the electron-rich pyrenyl surface layer and the electron-poor DNT molecules. These results suggest the potential use of such modified QCM surfaces for the detection of explosive NACs.

Lipoylcarnosine: Synthesis, Study of Physico-Chemical and Antioxidant Properties, Biological Activity

Abstract—: Synthesis of lipoylcarnosine (LipС), a conjugated molecule based on two natural antioxidants, carnosine and α-lipoic acid, is described and its physico-chemical, antioxidant properties and biological activity are characterized. According to reversed-phase HPLC with a UV detector, purity of the final product was 89.3%. The individuality of the obtained sodium salt of LipС was confirmed by tandem HPLC-mass spectrometry. LipC demonstrated high resistance to hydrolysis with serum carnosinase. The antioxidant activity of LipC evaluated by the reaction with the formation of thiobarbituric acid reacting substances and kinetic parameters of iron-induced chemiluminescence was higher than that of carnosine and lipoic acid. LipC did not affect viability of SH-SY5Y human neuroblastoma cells, differentiated to the dopaminergic phenotype, at concentrations not exceeding 5 mM. In the concentration range of 0.1–0.25 mM LipC protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity.

Carbonic anhydrase activators: Gold nanoparticles coated with derivatized histamine, histidine, and carnosine show enhanced activatory effects on several mammalian isoforms

Lipoic acid moieties were attached to amine or amino acids showing activating properties against the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The obtained lipoic acid conjugates of histamine, l-histidine methyl ester, and l-carnosine methyl ester were attached to gold nanoparticles (NPs) by reaction with Au(III) salts in reducing conditions. The CA activators (CAAs)-coated NPs showed low nanomolar activation (KAs of 1-9 nM) of relevant cytosolic, membrane-bound, mitochondrial, and transmembrane CA isoforms, such as CA I, II, IV, VA, VII, and XIV. These NPs also effectively activated CAs ex vivo, in whole blood experiments, with an increase of 200-280% of the CA activity. This is the first example of enzyme activation with nanoparticles and may lead to biomedical applications for conditions in which the CA activity is diminished, such as aging, Alzheimer's disease, or CA deficiency syndrome.

Enzyme Activated Gold Nanoparticles for Versatile Site-Selective Bioconjugation

A new enzymatic method is reported for constructing protein- and DNA-AuNP conjugates. The strategy relies on the initial functionalization of AuNPs with phenols, followed by activation with the enzyme tyrosinase. Using an oxidative coupling reaction, the activated phenols are coupled to proteins bearing proline, thiol, or aniline functional groups. Activated phenol-AuNPs are also conjugated to a small molecule biotin and commercially available thiol-DNA. Advantages of this approach for AuNP bioconjugation include: (1) initial formation of highly stable AuNPs that can be selectively activated with an enzyme, (2) the ability to conjugate either proteins or DNA through a diverse set of functional handles, (3) site-specific immobilization, and (4) facile conjugation that is complete within 2 h at room temperature under aqueous conditions. The enzymatic oxidative coupling on AuNPs is applied to the construction of tobacco mosaic virus (TMV)-AuNP conjugates, and energy transfer between the AuNPs and fluorophores on TMV is demonstrated.

Synthesis and characterization of new and potent α-lipoic acid derivatives

α-Lipoic acid [5-[1,2]-dithiolan-3-yl-pentanoic acid (LA)] is a natural antioxidant and cofactor of several enzymes. It increases the glucose transport activity in skeletal muscles and adipocytes in a non-insulin dependent manner. Therefore, LA is widely used in Type 2 diabetic patients as an oral auxiliary drug. However, large doses of LA (0.8-1.8 gr/day po) are required due to its unfavorable pharmacokinetic parameters. In order to improve these parameters, we synthesized ester and amide LA derivates. Two of these newly synthesized compounds, 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]dithiolan-3yl-pentanoylamino)-propyl]-amide (AN-7) and 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]-dithiolan-3yl-pentanoyloxy)- propyl ester (AN-8) augmented the rate glucose transport in myotubes in culture in the absence or presence of insulin. Their potency was 12-fold higher than that of the parent compound; their maximal stimulatory effect was 1.5-fold higher than that of LA. When tested in vivo in streptozotocin-diabetic C57/ Black mice, AN-7 (10 mg/kg/day for 2 weeks, sc) reduced blood glucose level by 39% while a higher dose of LA (50 mg/kg/day for 2 weeks, sc) lowered it by 30%. These results indicate that AN-7 is more potent than LA in augmenting glucose transport in skeletal muscles and reducing blood glucose in diabetic animals.

Plasmon resonance scattering spectroscopy at the single-nanoparticle level: Real-time monitoring of a click reaction

A method based on plasmon resonance Rayleigh scattering (PRRS) spectroscopy and dark-field microscopy (DFM) was established for the real-time monitoring of a click reaction at the single-nanoparticle level. Click reactions on the surface of single gold nanoparticles (GNPs) result in interparticle coupling, which leads to a red-shift of the λmax (Δλ max=43nm) in the PRRS spectra and a color change of the single gold nanoparticles in DFM (from green to orange). Copyright

Compact biocompatible quantum dots functionalized for cellular imaging

We present a family of water-soluble quantum dots (QDs) that exhibit low nonspecific binding to cells, small hydrodynamic diameter, tunable surface charge, high quantum yield, and good solution stability across a wide pH range. These QDs are amenable to covalent modification via simple carbodiimide coupling chemistry, which is achieved by functionalizing the surface of QDs with a new class of heterobifunctional ligands incorporating dihydrolipoic acid, a short poly(ethylene glycol) (PEG) spacer, and an amine or carboxylate terminus. The covalent attachment of molecules is demonstrated by appending a rhodamine dye to form a QD-dye conjugate exhibiting fluorescence resonance energy transfer (FRET). High-affinity labeling is demonstrated by covalent attachment of streptavidin, thus enabling the tracking of biotinylated epidermal growth factor (EGF) bound to EGF receptor on live cells. In addition, QDs solubilized with the heterobifunctional ligands retain their metal-affinity driven conjugation chemistry with polyhistidine-tagged proteins. This dual functionality is demonstrated by simultaneous covalent attachment of a rhodamine FRET acceptor and binding of polyhistidine-tagged streptavidin on the same nanocrystal to create a targeted QD, which exhibits dual-wavelength emission. Such emission properties could serve as the basis for ratiometric sensing of the cellular receptor's local chemical environment.

Synthesis of new lipoic acid conjugates and evaluation of their free radical scavenging and neuroprotective activities

A series of new lipoic acid derivatives were designed and synthesized as multitarget ligands against Alzheimer's disease. In particular, analogues combining both lipoic acid and cysteine core structures were synthesized. The antioxidant properties of these compounds were evaluated by 1,1-diphenyl-2- picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS?+) radical cation scavenging assays and ferrous ion chelation. The antioxidant potential of the synthesized compounds was also evaluated in a cellular context and compared to α-lipoic acid and its reduced form, dihydrolipoic acid. The antioxidant effects observed for these compounds in vitro confirmed the importance of free thiol functions for effective antioxidant capacities. However, these promising in vitro results were not mirrored by the antioxidant activity in T67 cell line. This suggests that multiple factors are at stake and warrant further investigations. A series of new lipoic acid derivatives have been synthesized and evaluated for their potential antioxidant and neuroprotective activities. Structure-activity relationship studies comparing lipoic acid derivatives and their corresponding reduced analogues revealed the importance of free thiol functions.