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Usage

Uses

Used in Chemical Industry:
Lactobionic acid is used as a chelating agent for metal ions, which helps in preventing the formation of scale and corrosion in various industrial processes.
Used in Food Industry:
Lactobionic acid is used as a humectant to retain moisture in food products, enhancing their texture and shelf life. It also serves as an emulsifier, promoting the stability of food emulsions.
Used in Pharmaceutical Industry:
Lactobionic acid is used as a chelating agent in the synthesis of targetable and biocompatible drug delivery systems, improving the solubility and bioavailability of drugs.
Used in Organ Transplantation:
Lactobionic acid is used in preservation solutions for organ transplantation, helping to maintain the viability of organs during the transplantation process.
Used in Production of Erythromycine Lactobionate:
Lactobionic acid is used in the production of erythromycine lactobionate, a pharmaceutical compound with antibiotic properties.
Used in Neurobiology Research:
Lactobionic acid serves as an arginine metabolite in bovine brain and is involved in clonidine-displacing substance activity, which is important for studying neurotransmitter interactions and neurobiological processes.
Used as a Matrix Metalloproteinase Inhibitor:
Lactobionic acid acts as an inhibitor of matrix metalloproteinases, which are enzymes involved in the breakdown of extracellular matrix proteins. This property makes it useful in the development of therapeutic agents for various diseases, including cancer and inflammatory conditions.

Properties

Lactobionic acid has a molecular weight of 358.296 g/mol and a monoisotopic mass of 358.111 g/mol, which is also its exact mass. The compound has a heavy atom count of 24. Lactobionic acid has a melting point of 113-118°C and a boiling point of about 410.75°C. It is a white to off-white powder with a solubility of 10 g/100 mL in water and a density of about 1.4662. It is also slightly soluble in anhydrous methanol and ethanol. Lactobionic acid is hygroscopic, and it has a good water retention potential hence its applicability to cosmetic products. The compound and its constituent mineral salts (Ca, Na, and K lactobionate) are produced commercially for medical and industrial applications and in some cases for research purposes.

Preparation

The selective transformation of lactose into Lactobionic acid entails the oxidation of the radical aldehyde category of glucose on the lactose molecule to the carboxylic classification. The production of Lactobionic acid entails various processes which may include enzymatic synthesis, microbial production, biocatalytic oxidation, electrochemical oxidation and heterogeneous catalytic oxidation.

Extraction and Purification

To enhance the productive capacity of Lactobionic acid, the enzymatic reaction can be cut off after several hours of activity and the unchanged substrates can be re-injected into the cycle after the elimination of useful products. The effective process of separation is through liquid chromatography particularly because the recovered species are pure. Exposing the solution made of lactobionate ions through a sequence of ion-transfer resins produces a pure solution of Lactobionic acid with minimal amounts of calcium ions. Different techniques such as crystallization, evaporation, electrodialysis and ethanol precipitation can be employed to obtain Lactobionic acid.

Physiological & Commercial Applications

Lactobionic acid is an essential compound based on its chelating properties and its ability to form complex bonds with Ca, Fe, Cu, and Mn. Its incorporation into food additives can stimulate mineral absorption and Ca2+ in the intestines hence enhancing one’s health. Lactobionic acid is unaffected by digestive enzymes hence it is a valuable ingredient in the preparation of functional foods. It is poorly absorbed into the linings of the intestines hence it can also be a Bifidus booster molecule for functional beverages and foods. It enhances the healing process of wounds hence it is valuable in oral, skin, nail, hair and vaginal mucosa care. As an antioxidant, Lactobionic acid acts by suppressing the synthesis of hydroxyl radicals due to its iron chelating ability. As a food additive, Lactobionic acid functions as an acidifier in products containing fermented milk, an aging suppressor for bread, an antioxidant, and as a gelling or stabilizing medium in desserts. In cosmetics, Lactobionic acid is applied as an active ingredient in regenerative and antiaging skin-care products based on its therapeutic properties. Its metal chelation potential suppresses the degeneration potential of metalloproteinase enzymes, which decreases the appearance of aging wrinkles. In the chemical industry, Lactobionic acid is an active ingredient (sugar-based surfactant) in biodegradable detergents. It may also be used in drug delivery systems, nanoparticle diagnosis and tissue engineering.

Biotechnological Production

Currently, lactobionic acid is produced by chemical synthesis using refined lactose as feedstock. This process is expensive due to the energy demand. Alternatively, Acidic Organic Compounds in Beverage, Food, and Feed Production 111 enzymatic processes have been suggested. For example, lactose could be reacted to lactobionic acid using an enzymatic system with co-factor regeneration. First, lactose is converted to lactobionolactone by a cellobiose dehydrogenase. This reaction requires an electron acceptor, which is regenerated by a laccase reducing oxygen to water. Finally, lactobionolactone spontaneously hydrolyzes to lactobionic acid. Moreover, microbial production of lactobionic acid has been described. In a fed-batch cultivation of Burkolderia cepacia growing in a complex medium (lactose, salts, peptone, and yeast extract), a final titer of 400 g.L-1, a yield of approximately 1.0 g of lactobionic acid per gram of lactose, and a productivity of 1.67 g.L-1.h-1 have been achieved. Another promising strategy for an inexpensive biotechnological process is the utilization of cheap raw materials. For example, lactobionic acid could be obtained from concentrated cheese whey by fermentation with Pseudomonas taetrolens. In a fed-batch process, a product concentration of 164 g.L-1 with a productivity of 2.05 g.L-1.h-1 and a yield of 0.82 g of lactobionic acid per gram of lactose have been observed. Furthermore, whole-cell biocatalysis using permeabilized Zymonmonas mobilis cells and an equimolar mixture of lactose and fructose has been tested. In a batch process, a maximum lactobionic acid concentration of 268 g.L-1 and a conversion rate of 72 % within 24 h have been measured. The productivity of lactobionic acid was 11.2 g.L-1.h-1 .

Clinical Use

Erythromycin lactobionate is a salt with enhanced water solubility that is used for injections.

Purification Methods

Crystallise lactobionic acid from water by addition of EtOH. [NMR: Taga et al. Bull Chem Soc Jpn 51 2278 1978, Beilstein 17 III/IV 3392, 17/7 V 436.]

InChI:InChI=1/C12H22O12/c13-1-3(15)10(7(18)8(19)11(21)22)24-12-9(20)6(17)5(16)4(2-14)23-12/h3-10,12-20H,1-2H2,(H,21,22)/t3-,4-,5+,6+,7-,8-,9-,10-,12+/m1/s1

Upstream product

• 6057-48-3 3-O-β-D-galactopyranosyl-D-arabinose 
• 63-42-3 D-(+)-lactose 
• 5965-66-2 LACTOSE 
• 5965-65-1 lactobionolactone 

Downstream Products

• 5965-65-1 lactobionolactone 
• 888616-12-4 N-[1-(dodecylcarbamoyl-2-(trityl)imidazolyl)ethyl]-22-lactobionamido-12,12,13,13,14,14,15,15,16,16,17,17,18,18,19,19-hexadecafluorodocosanamide 
• 918802-82-1 N-galactosylamino-N'-phenylpiperazine 
• 173543-54-9 lactoseamidemethylbenzoic acid 
• 148526-30-1 C₂₂H₃₄N₂O₁₃ 
• 3847-29-8 erythromycin lactobionate 

Relevant academic research and scientific papers

Aqueous oxidation of sugars into sugar acids using hydrotalcite-supported gold nanoparticle catalyst under atmospheric molecular oxygen

Hydrotalcite-supported gold nanoparticles show good activity as a heterogeneous catalyst for the oxidation of monosaccharides (xylose, ribose, galactose and mannose) and disaccharides (lactose and cellobiose) into the corresponding sugar acids under external base-free conditions in water solvent using atmospheric pressure of molecular oxygen. The produced sugar acids were thoroughly identified by 1H-, 13C-, and HMQC-NMR and ESI-FT-ICR MS spectroscopic techniques.

Gold as active phase of BN-supported catalysts for lactose oxidation

Au/h-BN catalysts have been prepared by wet impregnation in order to combine the high activity of gold with the promising h-BN support to optimize the catalytic performances in lactose oxidation. After 1 h reaction, the catalysts were more active than all the Pd/h-BN catalysts described in previous works: 100% yield was reached after 2 h for a Au/h-BN catalyst prepared in water and containing only 1 wt.% of gold. The influence of α-Al2O3, γ-Al2O3 and Cblack as supports for Au was compared to h-BN and Au/α-Al2O3 was the most active. All of them exhibited 100% selectivity toward lactobionic acid. After a second run, Au/γ-Al2O3 presented a loss of selectivity and all were less active than during their first run. Au/h-BN and Au/α-Al2O3 have been regenerated and a thermal treatment permits to keep the catalysts active with 100% selectivity. Au/h-BN was the most active after regeneration thanks to the more facile poison removal from its surface and the high stability of boron nitride.

Boron nitride as an alternative support of Pd catalysts for the selective oxidation of lactose

The potential of boron nitride as innovative support for the selective oxidation of carbohydrates has been evaluated. Pd/h-BN catalysts as well as Pd/α-Al2O3 have been synthesized by two different methods for comparison: dry impregnation and deposition-precipitation. It is shown that BN is a suitable alternative to alumina and carbon for sugar oxidation in liquid phase. Very active and selective Pd/h-BN catalysts were obtained by the two synthetic methods under consideration.

Selective production of lactobionic acid by aerobic oxidation of lactose over gold crystallites supported on mesoporous silica

Partial oxidation of lactose over Au-based catalyst system using nanostructured silica materials with improved activity, selectivity and stability was investigated as a novel chemo-catalytic approach for selective synthesis of lactobionic acid (LBA) for therapeutic, pharmaceutical and food grad applications. Highly active gold crystallites dispersed on mesoporous silica (SiO2-meso) using bis-[3-(triethoxysilyl) propyl] tetrasulfide (BTSPT), a silane coupling agent to immobilize gold, were successfully formulated, and their catalytic activity was evaluated in an agitated semi-batch reactor. The catalysts were characterized by N2 physisorption, XRD, XPS and TEM. The influence of the reaction conditions, i.e., temperature, pH value, metal loading and catalyst/lactose ratio on lactose conversion were investigated. After 100 min of reaction, the catalyst containing 0.7% Au showed the highest catalytic activity (100% lactose conversion) and a 100% selectivity towards LBA, when it was used at a catalyst/lactose ratio of 0.2 under alkaline (pH 9.0) and mild reaction temperature (65 °C).

Production of lactose-free galacto-oligosaccharide mixtures: comparison of two cellobiose dehydrogenases for the selective oxidation of lactose to lactobionic acid

Galacto-oligosaccharides, complex mixtures of various sugars, are produced by transgalactosylation from lactose using β-galactosidase and are of great interest for food and feed applications because of their prebiotic properties. Most galacto-oligosaccharide preparations currently available in the market contain a significant amount of monosaccharides and lactose. The mixture of galacto-oligosaccharides (GalOS) in this study produced from lactose using recombinant β-galactosidase from Lactobacillus reuteri contains 48% monosaccharides, 26.5% lactose and 25.5% GalOS. To remove efficiently both monosaccharides and lactose from this GalOS mixture containing significant amounts of prebiotic non-lactose disaccharides, a biocatalytic approach coupled with subsequent chromatographic steps was used. Lactose was first oxidised to lactobionic acid using fungal cellobiose dehydrogenases, and then lactobionic acid and monosaccharides were removed by ion-exchange and size-exclusion chromatography. Two different cellobiose dehydrogenases (CDH), originating from Sclerotium rolfsii and Myriococcum thermophilum, were compared with respect to their applicability for this process. CDH from S. rolfsii showed higher specificity for the substrate lactose, and only few other components of the GalOS mixture were oxidised during prolonged incubation. Since these sugars were only converted once lactose oxidation was almost complete, careful control of the CDH-catalysed reaction will significantly reduce the undesired oxidation, and hence subsequent removal, of any GalOS components. Removal of ions and monosaccharides by the chromatographic steps gave an essentially pure GalOS product, containing less than 0.3% lactose and monosaccharides, in a yield of 60.3%.

Catalytic Wet Oxidation of Lactose

A process for converting lactose into carbon dioxide and/or carbon monoxide using catalytic wet oxidation. Oxygen gas and an aqueous solution of lactose are fed to a reactor comprising a Pt/Al2O3 catalyst, a Mn/Ce catalyst or a Pt/Mn—Ce catalyst, and the lactose is oxidized in the reactor at elevated temperature and pressure to produce at least one of small organic acids, carbon dioxide, carbon monoxide, water and combinations thereof. The small organic acids may be further degraded by feeding the small organic acids and oxygen gas into a reactor containing a Mn/Ce catalyst and oxidizing the small organic acids to water and at least one of carbon dioxide, carbon monoxide and combinations thereof.

Synthesis and preliminary biological studies of hemifluorinated bifunctional bolaamphiphiles designed for gene delivery

The multistep synthesis of a new series of dissymmetric hemifluorocarbon bolaamphiphiles designed for gene transport is described. The dissymmetric functionalization of diiodoperfluoroctane leads to bolaamphiphile molecules composed of a partially fluorocarbon core end-capped with a glycoside and an ammonium salt derived from histidine or lysine. Initial biological results indicate that one of the bolaamphiphile - end-capped with a lysine and a lactobionamide residue - induces a remarkably low cytotoxicity on COS-7 cells and, when self-assembled with DNA plasmid, generates a significant in vitro transfection efficiency without the addition of any fusogenic lipid. the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2006.

METHOD FOR SELECTIVE CARBOHYDRATE OXIDATION USING SUPPORTED GOLD CATALYSTS

The invention relates to a method for the selective oxidation of a carbohydrate in the presence of a gold catalyst comprising gold particles distributed in a nanodispersed manner on a metal oxide support, and to a method for the selective oxidation of an oligosaccharide in the presence of a gold catalyst comprising gold particles distributed in a nanodispersed manner on a carbon or metal oxide support. The invention also relates to aldonic acid oxidation products produced using said method.

Pd(II) inhibition during hexacyanoferrate (III) oxidation of sugars: a kinetic study

An inhibition effect of PdCl2 on the rate of oxidation of sugars, by alkaline hexacyano-ferrate(III) has been observed. The order of reactions in hexacyanoferrate(III) and OH- is zero and unity, respectively, while that in sugars decreases from unity at higher sugar concentration. The kinetic data and spectrophotometric evidence support the formation of {PdII - (sugar)} and {PdII - sugar)2} complexes and their resistance to react with Fe(CN)63-.