Oleksandr P. Kozynchenko

Effect of oxygen functional groups on synthetic carbons on liquid phase oxidation of cyclohexanone

Abstract Synthetic carbons from phenolic resins were used as catalysts for the aqueous phase oxidation of cyclohexanone to C4–C6 dicarboxylic acids (adipic, glutaric and succinic acids) at 413 K under 50 bar total air pressure. The changes in microporous structure and surface chemistry, produced as a consequence of activation or heat treatment processes, were analyzed. Using CO2 or air as activating agent increased significantly the surface area and the total pore volume responsible for the activity. The surface chemistry of the samples was also modified and was characterized by titration with bases of different strength and with HCl, by temperature programmed desorption, and by X-ray photoelectron spectroscopy. To determine the role of surface oxygen functionalities on the catalytic behavior of the carbons, heat treatments in nitrogen at different temperatures were used to selectively eliminate oxygenated groups. Thus, treatment at temperatures of 1173 K eliminating the carbonyl/quinone groups decreased the selectivity to adipic acid and dicarboxylic acids. Introducing quinone groups during the synthesis of the carbons also improved the selectivity to adipic acid, proving that the mechanism of oxidation involves the quinone type groups on the carbon surface.

Activation-dependent adsorption of cytokines and toxins related to liver failure to carbon beads.

In the course of severe pathological conditions, such as acute liver failure and sepsis, toxic metabolites and mediators of inflammation are released into the patients circulation. One option for the supportive treatment of these conditions is plasmapheresis, in which plasma, after being separated from the cellular components of the blood, is cleansed by adsorption of harmful molecules on polymers or activated carbon. In this work, the adsorption characteristics of activated carbon beads with levels of activation ranging from 0 to 86% were assessed for both hydrophobic compounds accumulating in liver failure (bilirubin, cholic acid, phenol and tryptophan) and cytokines (tumor necrosis factor α and interleukin-6). Progressive activation resulted in significant gradual reduction of both bulk density and mean particle size, in an increase in the specific surface area, and to changes in pore size distribution with progressive broadening of micropores. These structural changes went hand in hand with enhanced adsorption of small adsorbates, such as IL-6 and cholic acid and, to a lesser extent, also of large molecules, such as TNF-α.

Composites with macroporous poly(vinyl alcohol) cryogels with attached activated carbon microparticles with controlled accessibility of a surface

A set of glutaraldehyde (GA) cross-linked poly(vinyl alcohol)/activated carbon (PVA/GA/AC) composites prepared in the form of monolithic rods using a cryogelation technique and studied using adsorption, mercury porosimetry, scanning electron microscopy (SEM), and quantum chemistry methods display porosity similar to that of PVA/GA cryogel at a high GA content (content ratio GA/AC = 1 and GA/PVA = 0.2). GA cross-linked PVA multilayer coverage is an effective barrier for adsorption on AC particles. Variations in surface chemistry (AC initial and oxidized in air at 300 °C for 12 h) and content (14-62.5%w/w) of ACs in PVA/GA/AC composites relatively weakly affect their textural characteristics at a high GA content (specific surface area S(BET) < 120 m²/g, pore volume V(p) < 0.35 cm³/g). However, PVA/GA/AC composite rods formed with a lower concentration of GA (content ratio GA/AC = 1/6 and GA/PVA = 1/10) have significantly greater S(BET) (∼500 m²/g) and V(p) (>0.55 cm³/g) values because of improved accessibility of the AC surface. This provides better adsorption of methylene blue as a probe compound.

Nanoporous activated carbon beads and monolithic columns as effective hemoadsorbents for inflammatory cytokines.

The aim of the present study was to develop and investigate nanoporous activated carbon materials for their ability to adsorb inflammatory cytokines directly from blood, for a range of therapeutic applications, including: systemic inflammatory response syndrome (SIRS) related to sepsis, cardio-pulmonary by-pass surgery, or ischemic reperfusion injury. Building on the previously established relationship between the porous structure of beaded polymer-derived activated carbon and its capacity to adsorb inflammatory molecules, we have developed and characterized monolithic porous carbon columns produced from the same polymer precursor matrix as carbon microbeads. The monolithic columns developed were assessed for their ability to adsorb inflammatory molecules from blood in a circulating system. Preliminary findings demonstrated good removal of the inflammatory cytokines IL-8 (100% removal), IL-6 (80% removal), and TNF (51% removal) from blood. The efficiency of cleansing is dependent on the size of the adsorbed molecule and the porous structure of the monolith, highlighting their potential for use as a hemoadsorption device.

PMO-127 Biological effects of oral nanoporous carbon in bile duct ligated rats

Introduction Gut-derived bacterial products and associated dysregulated inflammatory response play a central role in the pathogenesis of cirrhosis. Therapeutic options to target these factors are currently limited to long-term antibiotics. Nanoporous carbons are non-absorbable, synthetic materials which are safe with porosity manipulated for adsorption of middle and high molecular weight molecules and surface chemistry modified to alter adsorption capacity for biological molecules such as cytokines and endotoxin. We sought to determine their biological effects in bile-duct ligated rats as a model of cirrhosis. Methods 131 male Sprague-Dawley rats underwent bile duct-ligation or sham biliary surgery. Animals were pair fed with or without oral carbon therapy 2 weeks from surgery until completion of the experiment at 4–5 weeks. Intra-peritoneal lipopolysaccharide (LPS) was administered to four subgroups 3.5 h prior to completion of the study. The following groups were studied: Sham (n=16), Sham + carbon (n=15), Sham + LPS (n=11), Sham+LPS+carbon (n=10), BDL (n=27), BDL + carbon (n=26), BDL+LPS (n=10), BDL+LPS+carbon (n=16). Portal haemodynamics were performed on 93 rats and Kupffer cell (KC) numbers and Reactive oxygen species (ROS) production assessed by flow cytometry in a sub-group of animals. Liver biochemistry and portal venous cytokines were performed. Results A significant reduction in portal pressure was observed in BDL+LPS (mean 18.05±0.88 mm Hg untreated, 10.17±1.07 mm Hg with carbon, p<0.05) and BDL (mean 12.57±0.43 mm Hg untreated, 11.02±0.28 mm Hg with carbon, p<0.05) groups following carbon treatment. A significant reduction in ALT was observed in the carbon treated BDL+LPS (p<0.05) and BDL groups (p<0.05). Carbon treatment in BDL rats was associated with a significant reduction in LPS-induced ROS production. A trend towards reduction in portal venous IL-4 and IL-10 was observed in carbon-treated BDL rats. No significant difference in portal venous TNF-α was observed. Finally, a significant increase in body mass was observed in the BDL carbon-treated group (p<0.05). Conclusion Oral nanoporous carbon therapy results in a significant reduction in portal pressure and liver biochemistry associated with a reduction in endotoxin-induced KC ROS production. We postulate therefore, that the effect of nanoporous carbon is possibly via a reduction in endotoxin induced KC stimulation. Competing interests None declared.

EFFECTS OF ORAL NANOPOROUS CARBON THERAPY IN LEPTIN NULL MICE AS A MODEL OF NON-ALCOHOLIC STEATOHEPATITIS

Introduction Endotoxaemia is implicated in the pathogenesis of non-alcoholic fatty liver disease. Modulation of intra-luminal factors driving bacterial translocation may have the capacity to impact on the natural history of the disease. Nanoporous carbons are non-absorbable, synthetic materials which are safe with porosity manipulated for adsorption of middle and high molecular weight molecules and surface chemistry modified to alter adsorption capacity for biological molecules. We sought to determine their biological effects in leptin null mice, which are hyperphagic and obese with evident steatohepatitis and to ascertain whether nanoporous carbons can reverse established non-alcoholic steatohepatitis (NASH) in these animals. Methods 10 lep−/lep− null and 10 heterozygote male mice were randomised to receive powdered chow ± carbon (0.4 g/100 g body weight/day) for 4 weeks. Extent of liver injury was assessed by serum levels of ALT. Additionally, non-parenchymal cells were isolated and the Kupffer cell (KC) population characterised by flow cytometry as those cells expressing F4/80, CD68 and CD11b. Reactive oxygen species (ROS) production by isolated KCs was also assayed. Hepatic TLR-4 expression as a surrogate of endotoxaemia was determined by immunohistochemistry. Results In lep−/lep− mice, oral carbon treatment was associated with a significant reduction in ALT 889±280 IU/ml to 408±42 IU/ml (p<0.05). Total KC population was found to be increased in lep−/lep− mice compared to heterozygote control with a significant reduction observed with carbon treatment (p<0.05). A significant reduction in KCs ROS production was also observed in carbon treated lep−/lep− mice (p<0.05) compared to untreated lep−/lep− controls. A significant reduction in the F4/80+, CD68−, CD11b+ cell sub-population in lep−/lep− in the presence of carbon treatment group was also observed (p<0.05). Moreover, hepatic TLR-4 expression was reduced in carbon-treated lep−/lep− mice compared to non-treated controls. Finally, we observed a trend towards reduction in final body weight in carbon-treated lep−/lep− mice compared to untreated controls group (p=0.095). Conclusion Oral nanoporous carbon through modulating endotoxaemia and KC function may be a promising therapy in NASH. Competing interests None declared.