Citrulline activates adenosine receptors: New insight into metabolic pathways interaction.

Citrulline is a non-proteinogenic amino acid that forms as by-product in nitric oxide (NO) synthesis from arginine and may act in concert with NO as an independent signaling molecule that involves in the mechanism of vascular smooth muscle vasodilation. In this study we examined the effects of citrulline on pulmonary artery smooth muscles. Experimental design comprised outward potassium currents measurements in enzymatically isolated rat pulmonary artery smooth muscle (PASMc) cells using whole-cell patch clamp technique, isometric contractile force recordings on rat pulmonary artery rings and method of molecular docking simulation. Citrulline in a concentration 10-9-10-5 M relaxed phenylephrine (PHE)-preactivated SM of rat pulmonary artery in a dose-dependent manner (EC50 0,67 µM). This citrulline-induced relaxation was dependent on an intact endothelium. Bath application of citrulline (10-8-10-5 M) on isolated PASMc induced a significant increase in the amplitude of outward potassium current (Ik). The adenosine antagonist caffeine (10-6 M) effectively blocked both the citrulline-induced relaxation response and Ik increment. Molecular docking modeling suggests that caffeine blocking the potent activity of citrulline results from competitive interactions at the A2 adenosine receptor binding site. In summary, our data suggest that citrulline, released with NO at low concentrations, can effectively interact with adenosine receptors in smooth muscle cells, causing their relaxation, indicating surprising interaction between NO and adenosine pathways.

Skin Cancer Induction by the Antimycotic Drug Voriconazole is Caused by Impaired DNA Damage Detection Due to Chromatin Compaction.

Phototoxicity and skin cancer are severe adverse effects of the anti-fungal drug voriconazole (VOR). These adverse effects resemble those seen in xeroderma pigmentosum, caused by defective DNA nucleotide excision repair (NER), and we show that VOR decreases NER capacity. We show that VOR treatment does not perturb the expression of NER, or other DNA damage-related genes, but that VOR localizes to heterochromatin, in complexes containing histone acetyltransferase general control of amino-acid synthesis 5-like 2. Impairment of general control of amino-acid synthesis 5-like 2 binding to histone H3 reduced acetylation of H3, restricting damage-dependent chromatin unfolding, thereby reducing NER initiation. Restoration of H3 histone acetylation using histone deacetylase inhibitors, rescued VOR-induced NER repression, thus offering a preventive therapeutic option. These findings underline the importance of DNA damage-dependent chromatin remodeling as an important prerequisite of functional DNA repair.

Selection of Aptamers for Use as Molecular Probes in AFM Detection of Proteins.

Currently, there is great interest in the development of highly sensitive bioanalytical systems for diagnosing diseases at an early stage, when pathological biomarkers are present in biological fluids at low concentrations and there are no clinical manifestations. A promising direction is the use of molecular detectors-highly sensitive devices that detect signals from single biomacromolecules. A typical detector in this class is the atomic force microscope (AFM). The high sensitivity of an AFM-based bioanalysis system is determined by the size of the sensing element of an atomic force microscope-the cantilever-the radius of the curvature of which is comparable to that of a biomolecule. Biospecific molecular probe-target interactions are used to ensure detection system specificity. Antibodies, aptamers, synthetic antibodies, and peptides can be used as molecular probes. This study has demonstrated the possibility of using aptamers as molecular probes for AFM-based detection of the ovarian cancer biomarker CA125. Antigen detection in a nanomolar solution was carried out using AFM chips with immobilized aptamers, commercially available or synthesized based on sequences from open sources. Both aptamer types can be used for antigen detection, but the availability of sequence information enables additional modeling of the aptamer structure with allowance for modifications necessary for immobilization of the aptamer on an AFM chip surface. Information on the structure and oligomeric composition of aptamers in the solution was acquired by combining small-angle X-ray scattering and molecular modeling. Modeling enabled pre-selection, before the experimental stage, of aptamers for use as surface-immobilized molecular probes.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Detection of Circulating Serum microRNA/Protein Complexes in ASD Using Functionalized Chips for an Atomic Force Microscope.

MicroRNAs, which circulate in blood, are characterized by high diagnostic value; in biomedical research, they can be considered as candidate markers of various diseases. Mature microRNAs of glial cells and neurons can cross the blood-brain barrier and can be detected in the serum of patients with autism spectrum disorders (ASD) as components of macrovesicles, macromolecular protein and low-density lipoprotein particles. In our present study, we have proposed an approach, in which microRNAs in protein complexes can be concentrated on the surface of AFM chips with oligonucleotide molecular probes, specific against the target microRNAs. MicroRNAs, associated with the development of ASD in children, were selected as targets. The chips with immobilized molecular probes were incubated in serum samples of ASD patients and healthy volunteers. By atomic force microscopy (AFM), objects on the AFM chip surface have been revealed after incubation in the serum samples. The height of these objects amounted to 10 nm and 6 nm in the case of samples of ASD patients and healthy volunteers, respectively. MALDI-TOF-MS analysis of protein components on the chip surface allowed us to identify several cell proteins. These proteins are involved in the binding of nucleic acids (GBG10, RT24, RALYL), in the organization of proteasomes and nucleosomes (PSA4, NP1L4), and participate in the functioning of the channel of active potassium transport (KCNE5, KCNV2).

Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs.

Cytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study their immunopharmacological properties. 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDSPA) and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) were used as reversible chain transfer agents. Experiments were carried out in Wistar rats. The MTT assay was used to evaluate the cytotoxic effect of the polymeric systems on peritoneal macrophages. An experimental tumor model was obtained by grafting RMK-1 breast cancer cells. Serum cytokine levels of tumor-bearing rats were analyzed. The chain transfer agents employed in classical radical polymerization substantially reduced the molecular weight of the resulting polymers, but a narrow molecular weight distribution was achieved only with CDSPA and high CPDT concentrations. Toxicity was not observed when incubating peritoneal macrophages with polymeric systems. In tumor-bearing rats, the IL-10 concentration was 1.7 times higher and the IL-17 concentration was less than half that of intact rats. Polymeric systems decreased the IL-10 concentration and normalized the IL-17 concentration in tumor-bearing rats. The maximum effect was observed for a MAA homopolymer with a high molecular weight. The anion-active polymers proposed as carrier constituents are promising for further studies and designs of carrier constituents of drug derivatives.

Effect of Spherical Elements of Biosensors and Bioreactors on the Physicochemical Properties of a Peroxidase Protein.

External electromagnetic fields are known to be able to concentrate inside the construction elements of biosensors and bioreactors owing to reflection from their surface. This can lead to changes in the structure of biopolymers (such as proteins), incubated inside these elements, thus influencing their functional properties. Our present study concerned the revelation of the effect of spherical elements, commonly employed in biosensors and bioreactors, on the physicochemical properties of proteins with the example of the horseradish peroxidase (HRP) enzyme. In our experiments, a solution of HRP was incubated within a 30 cm-diameter titanium half-sphere, which was used as a model construction element. Atomic force microscopy (AFM) was employed for the single-molecule visualization of the HRP macromolecules, adsorbed from the test solution onto mica substrates in order to find out whether the incubation of the test HRP solution within the half-sphere influenced the HRP aggregation state. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was employed in order to reveal whether the incubation of HRP solution within the half-sphere led to any changes in its secondary structure. In parallel, spectrophotometry-based estimation of the HRP enzymatic activity was performed in order to find out if the HRP active site was affected by the electromagnetic field under the conditions of our experiments. We revealed an increased aggregation of HRP after the incubation of its solution within the half-sphere in comparison with the control sample incubated far outside the half-sphere. ATR-FTIR allowed us to reveal alterations in HRP's secondary structure. Such changes in the protein structure did not affect its active site, as was confirmed by spectrophotometry. The effect of spherical elements on a protein solution should be taken into account in the development of the optimized design of biosensors and bioreactors, intended for performing processes involving proteins in biomedicine and biotechnology, including highly sensitive biosensors intended for the diagnosis of socially significant diseases in humans (including oncology, cardiovascular diseases, etc.) at early stages.

AFM study of changes in properties of horseradish peroxidase after incubation of its solution near a pyramidal structure.

In our present paper, the influence of a pyramidal structure on physicochemical properties of a protein in buffer solution has been studied. The pyramidal structure employed herein was similar to those produced industrially for anechoic chambers. Pyramidal structures are also used as elements of biosensors. Herein, horseradish peroxidase (HRP) enzyme was used as a model protein. HRP macromolecules were adsorbed from their solution onto an atomically smooth mica substrate, and then visualized by atomic force microscopy (AFM). In parallel, the enzymatic activity of HRP was estimated by conventional spectrophotometry. Additionally, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) has been employed in order to find out whether or not the protein secondary structure changes after the incubation of its solution either near the apex of a pyramid or in the center of its base. Using AFM, we have demonstrated that the incubation of the protein solution either in the vicinity of the pyramid's apex or in the center of its base influences the physicochemical properties of the protein macromolecules. Namely, the incubation of the HRP solution in the vicinity of the top of the pyramidal structure has been shown to lead to an increase in the efficiency of the HRP adsorption onto mica. Moreover, after the incubation of the HRP solution either near the top of the pyramid or in the center of its base, the HRP macromolecules adsorb onto the mica surface predominantly in monomeric form. At that, the enzymatic activity of HRP does not change. The results of our present study are useful to be taken into account in the development of novel biosensor devices (including those for the diagnosis of cancer in humans), in which pyramidal structures are employed as sensor, noise suppression or construction elements.

AFM and FTIR Investigation of the Effect of Water Flow on Horseradish Peroxidase.

Atomic force microscopy (AFM)-based fishing is a promising method for the detection of low-abundant proteins. This method is based on the capturing of the target proteins from the analyzed solution onto a solid substrate, with subsequent counting of the captured protein molecules on the substrate surface by AFM. Protein adsorption onto the substrate surface represents one of the key factors determining the capturing efficiency. Accordingly, studying the factors influencing the protein adsorbability onto the substrate surface represents an actual direction in biomedical research. Herein, the influence of water motion in a flow-based system on the protein adsorbability and on its enzymatic activity has been studied with an example of horseradish peroxidase (HRP) enzyme by AFM, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) and conventional spectrophotometry. In the experiments, HRP solution was incubated in a setup modeling the flow section of a biosensor communication. The measuring cell with the protein solution was placed near a coiled silicone pipe, through which water was pumped. The adsorbability of the protein onto the surface of the mica substrate has been studied by AFM. It has been demonstrated that incubation of the HRP solution near the coiled silicone pipe with flowing water leads to an increase in its adsorbability onto mica. This is accompanied by a change in the enzyme's secondary structure, as has been revealed by ATR-FTIR. At the same time, its enzymatic activity remains unchanged. The results reported herein can be useful in the development of models describing the influence of liquid flow on the properties of enzymes and other proteins. The latter is particularly important for the development of biosensors for biomedical applications-particularly for serological analysis, which is intended for the early diagnosis of various types of cancer and infectious diseases. Our results should also be taken into account in studies of the effects of protein aggregation on hemodynamics, which plays a key role in human body functioning.

AFM Imaging of Protein Aggregation in Studying the Impact of Knotted Electromagnetic Field on A Peroxidase.

The phenomenon of knotted electromagnetic field (KEMF) is now actively studied, as such fields are characterized by a nontrivial topology. The research in this field is mainly aimed at technical applications - for instance, the development of efficient communication systems. Until present, however, the influence of KEMF on biological objects (including enzyme systems) was not considered. Herein, we have studied the influence of KEMF on the aggregation and enzymatic activity of a protein with the example of horseradish peroxidase (HRP). The test HRP solution was irradiated in KEMF (the radiation power density was 10-12 W/cm2 at 2.3 GHz frequency) for 40 min. After the irradiation, the aggregation of HRP was examined by atomic force microscopy (AFM) at the single-molecule level. The enzymatic activity was monitored by conventional spectrophotometry. It has been demonstrated that an increased aggregation of HRP, adsorbed on the AFM substrate surface, was observed after irradiation of the protein sample in KEMF with low (10-12 W/cm2) radiation power density; at the same time, the enzymatic activity remained unchanged. The results obtained herein can be used in the development of models describing the interaction of enzymes with electromagnetic field. The obtained data can also be of importance considering possible pathological factors that can take place upon the influence of KEMF on biological objects- for instance, changes in hemodynamics due to increased protein aggregation are possible; the functionality of protein complexes can also be affected by aggregation of their protein subunits. These effects should also be taken into account in the development of novel highly sensitive systems for human serological diagnostics of breast cancer, prostate cancer, brain cancer and other oncological pathologies, and for diagnostics of diseases in animals, and crops.

Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells.

TP53 deficiency is the most common alteration in cancer; however, this alone is typically insufficient to drive tumorigenesis. To identify genes promoting tumorigenesis in combination with TP53 deficiency, we perform genome-wide CRISPR-Cas9 knockout screens coupled with proliferation and transformation assays in isogenic cell lines. Loss of several known tumor suppressors enhances cellular proliferation and transformation. Loss of neddylation pathway genes promotes uncontrolled proliferation exclusively in TP53-deficient cells. Combined loss of CUL3 and TP53 activates an oncogenic transcriptional program governed by the nuclear factor κB (NF-κB), AP-1, and transforming growth factor ß (TGF-ß) pathways. This program maintains persistent cellular proliferation, induces partial epithelial to mesenchymal transition, and increases DNA damage, genomic instability, and chromosomal rearrangements. Our findings reveal CUL3 loss as a key event stimulating persistent proliferation in TP53-deficient cells. These findings may be clinically relevant, since TP53-CUL3-deficient cells are highly sensitive to ataxia telangiectasia mutated (ATM) inhibition, exposing a vulnerability that could be exploited for cancer treatment.

Hypoxic pulmonary vasoconstriction is lacking in rats with type 1 diabetes.

Hypoxic pulmonary vasoconstriction (HPV) is the most important feature of intact lung circulation that matches local blood perfusion to ventilation. The main goal of this work was to study the effects of diabetes on the development of HPV in rats. The experimental design comprised diabetes mellitus induction by streptozotocin, video-morphometric measurements of the lumen area of intrapulmonary arteries (iPAs) using perfused lung tissue slices and patch-clamp techniques. It was shown that iPA lumen size was significantly reduced under physical and chemical hypoxia (7-10 mm Hg) in normal iPA, but, on the contrary, it clearly increased in diabetic lung slices. The amplitude of the outward K+ current in diabetic iPAs smooth muscle cells (SMCs) was two-fold greater than that seen in healthy cells. Chemical hypoxia led to significant decrease in the amplitude of the K+ outward current in healthy iPA SMCs while it was without effect in diabetic cells. The data obtained clearly indicate a significant dysregulation of vascular tone in pulmonary circulation under diabetes, ie diabetes damages the adaptive mechanism for regulating blood flow from poorly ventilated to better ventilated regions of the lung under hypoxia. This effect could be clinically important for patients with diabetes who have acute or chronic lung diseases associated with the lack of blood oxygenation.

Analysis of the adhesion activity of peritoneal macrophages after exposure to radiation from a gas-discharge plasma and mercury lamp.

The aim of the work was to study the influence of UV radiation of a spark discharge plasma and a mercury lamp on the state of membrane structures of peritoneal macrophages. The objects of the study were peritoneal macrophages of rats. The total number of cells after exposure and their viability were analyzed. Oxidative modification of proteins was recorded by fluorescence of tryptophan, tyrosine and products of non-enzymatic glycosylation of proteins. The concentration of sialic acids was determined spectrophotometrically, and the intensity of adhesion properties of cells was estimated by the ability to adhere to the plastic. It was shown that the radiation of a spark discharge plasma and UV lamp with the selected exposure regimes affect the structural components of membranes of peritoneal macrophages. The ability to adhere is enhanced by short exposure regimes, and under long-term conditions, adhesion properties decrease. The change in adhesion is probably associated with a decrease in the concentration of sialic acids on the cell surface, as well as with the intensification of oxidative modification of proteins. It has been established that spark plasma and UV lamp radiation promote the oxidation of aromatic amino acids and the accumulation of glycosylation products of proteins.

UVA, metabolism and melanoma: UVA makes melanoma hungry for metastasis.

Ultraviolet (UV) radiation has a plethora of effects on human tissues. In the UV spectrum, wavelengths above 320 nm fall into the UVA range, and for these, it has been shown that they induce reactive oxygen species (ROS), DNA mutations and are capable to induce melanoma in mice. In addition to this, it was recently shown that UVA irradiation and UVA-induced ROS also increase glucose metabolism of melanoma cells. UVA irradiation causes a persistent increase in glucose consumption, accompanied by increased glycolysis, increased lactic acid production and activation of the pentose phosphate pathway. Furthermore, it was shown that the enhanced secretion of lactic acid is important for invasion of melanoma in vitro. The current knowledge of this link between UVA, metabolism and melanoma, possible mechanisms of UVA-induced glucose metabolism and their starting points are discussed in this review with focus on ROS- and UVA-induced cellular stress signalling, DNA damage signalling and DNA repair systems. When looking at the benefits of UVA-induced glucose metabolism, it becomes apparent that there are more advantages of these metabolic changes than one would expect. Besides the role of lactic acid as initiator of protease expression and invasion, its role for immune escape of melanoma cells and the pentose phosphate pathway-derived nicotinamide adenine dinucleotide phosphate (NADPH) as part of a ROS detoxification strategy are discussed.

Chronic Hepatitis Due to Gluten Enteropathy - a Case Report.

BACKGROUND: Celiac disease is an immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. CASE DESCRIPTION: A 45-year-old Caucasian woman presented with severe iron-deficient anemia and mild elevation of liver enzymes. Upper endoscopy was done in the context of evaluation of anemia, which revealed reduced duodenal folds and mosaic pattern of the mucosa, but also grade II esophageal varices and portal hypertensive gastropathy. Duodenal biopsy showed total villous atrophy, diffuse mainly lymphocytic infiltrate, presence of intra-epithelial lymphocytes. Serology test confirmed celiac disease by the typical pattern of high titer positive IgA and IgG antibodies to tissue transglutaminase. Liver biopsy was performed for staging and etiological evaluation, because laboratory screening ruled out common viral, metabolic and autoimmune liver disease. Liver morphology was consistent with chronic hepatitis without findings for extensive fibrosis. Our patient had poor dietary compliance, so we failed to established improvement of liver enzymes and resolution of anemia during follow-up. CONCLUSIONS: We would like to stress on the diverse clinical manifestations of celiac disease and the importance of serologic screening with antibodies to tissue transglutaminase in differential diagnosis of chronic liver disease.

Immune responses to polyclonal T-cell vaccination in patients with progressive multiple sclerosis.

The overall objective of disease management in autoimmune diseases is to suppress chronic inflammation and prevent organ damage. Therapies often revolve around five drug classes: non-steroidal anti-inflammatory drugs (NSAIDS), anti-malarials, steroids, immunosuppressants, and bio-therapies. However, none of these is a 'cure' and each displays a potential for adverse events. In particular, while all of them suppress harmful autoimmune responses, they also impact on useful protective immune responses. T-Cell receptor (TCR) immunogenicity provides a rationale for T-cell vaccinations to induce anti-idiotypic immune responses with the purpose of down-regulating functionality of idiotype-bearing self-reactive T-cells. To explore this, in this study, 39 patients with progressive (chronic) multiple sclerosis (MS) were multiply immunized with autological polyclonal T-cell vaccines (TCVs). None of the TCV-treated patients experienced any significant side-effects during the entire follow-up period (2 years). T-Cell vaccination had no significant effects on T-cell sub-population contents in the blood of MS patients after 2 years of immunotherapy initiation. However, a substantial reduction in the frequency of CD4+ and CD8+ memory T-cells able to produce interferon (IFN)-γ following activation were noted in the blood of TCV-treated patients. Moreover, significant and sustained reduction in plasma IFNγ levels and concomitant increases in interleukin (IL)-4 levels were documented in these samples. The TCV-treated subjects, however, exhibited no significant changes in plasma IL-17 and IL-18. More importantly was a significant decline in proliferative T-cell responses to myelin antigens in the TCV-treated patients, indicating attenuation of myelin-specific T-cell activity. Collectively, the results suggest that polyclonal T-cell vaccination is safe to use, able to induce measurable, long-lasting, anti-inflammatory immune effects in patients with advanced MS.

Ag-Promoted ZrBEA Zeolites Obtained by Post-Synthetic Modification for Conversion of Ethanol to Butadiene.

1,3-Butadiene was synthesized from ethanol using zirconium-containing zeolite beta (ZrBEA) catalysts doped with 1 wt % silver. The Zr was planted using post-synthesis modification by dealumination of the parent zeolite followed by treatment with ZrOCl2 in a DMSO solution. FTIR and NMR spectroscopy were used to investigate the planting process by preparing materials with different Si/Al ratios and crystal sizes. The results showed preferential grafting of Zr to the terminal silanols present on the external surface of the zeolite crystals instead of incorporation of Zr into silanol nests. The grafting yielded highly accessible Zr(OSi)3 OH open sites with high Lewis acidity, as confirmed by FTIR spectroscopy of adsorbed CO. These sites are shown to be extremely active for the conversion of ethanol to butadiene. Ag/ZrBEA catalysts prepared using the post-synthesis method showed significant advantages compared with Ag/ZrBEA catalysts synthesized using a conventional hydrothermal procedure. The best catalyst performance in terms of butadiene formation rate (3 µmol g(-1) s(-1) ) was observed over Ag/Zr(3.5)BEA(75) (containing 3.5 wt % Zr), which had the smallest crystal size and the highest content of Zr open sites of the prepared catalysts.

Wilson's disease in association with anetoderma.

BACKGROUND: Wilson's disease is an autosomal recessive disorder of copper homeostasis with predominantly hepatic and neuropsychiatric involvement. Anetoderma is a rare benign condition with focal damage of dermal elastic tissue. Previous reports described this skin disorder in association with prolonged D-Penicillamine therapy. CASE PRESENTATION: A 26-year-old male was referred for evaluation of asymptomatic elevation of aminotransferase levels. Investigations showed negative markers for chronic viral and autoimmune hepatitis, low ceruloplasmin level, and increased copper urinary excretion. Liver biopsy revealed chronic hepatitis with moderate activity and severe bridging fibrosis. Mutation analysis found a compound heterozygote genotype and supported a diagnosis of Wilson's disease. At the time of the primary physical exam, skin lesions were also observed, consisting of numerous white to pale papules less than 7-8 mm in diameter with central protrusion located at the upper part of the body. Primary anetoderma was established based on presentation and skin biopsy findings. Therapy with D-Penicillamine at a daily dose of 1500 mg was started, and, during 12-month follow-up, aminotransferase decreased to normal and skin lesions remained unchanged. CONCLUSION: In our opinion the case is a first reported association between Wilson's disease and primary anetoderma. The possible mechanism behind this relationship is discussed.

Design of a metal-promoted oxide catalyst for the selective synthesis of butadiene from ethanol.

The synthesis of buta-1,3-diene from ethanol has been studied over metal-containing (M=Ag, Cu, Ni) oxide catalysts (MO(x)=MgO, ZrO2, Nb2O5, TiO2, Al2O3) supported on silica. Kinetic study of a wide range of ethanol conversions (2-90%) allowed the main reaction pathways leading to butadiene and byproducts to be determined. The key reaction steps of butadiene synthesis were found to involve ethanol dehydrogenation, acetaldehyde condensation, and the reduction of crotonaldehyde with ethanol into crotyl alcohol. Catalyst design included the selection of active components for each key reaction step and merging of these components into multifunctional catalysts and adjusting the catalyst functions to achieve the highest selectivity. The best catalytic performance was achieved over the Ag/ZrO2/SiO2 catalyst, which showed the highest selectivity towards butadiene (74 mol%).

Catalysis by coke deposits: synthesis of isoprene over solid catalysts.

A help rather than a hindrance: Carbonaceous deposits have been found to play a key role in the selective synthesis of isoprene from formaldehyde and isobutene over solid catalysts. They accumulate on the catalyst surface during the induction period and promote the interaction of the substrates at the steady state. The proposed mechanism shows the way forward for the design of efficient solid catalysts for the synthesis of isoprene.