Nanoporous solid acid and base catalysts for sustainable biofuels production

Dwindling fossil fuel reserves, and growing concerns over CO2 emissions and associated climate change, are driving the quest for renewable feedstocks to provide alternative, sustainable fuel sources. Catalysis has a rich history of facilitating energy efficient, selective molecular transformations, and in a post-petroleum era will play a pivotal role in overcoming the scientific and engineering barriers to economically viable, and sustainable, biofuels derived from renewable resources. The production of second generation biofuels, derived from biomass sourced from inedible crop components, e.g. agricultural or forestry waste, or alternative non-food crops such as Switchgrass or Jatropha Curcas that require minimal cultivation, necessitate new heterogeneous catalysts and processes to transform these polar and viscous feedstocks [1]. Here we show how advances in the rational design of nanoporous solid acids and bases, and their utilisation in novel continuous reactors, can deliver superior performance in the energy-efficient esterification and transesterification of bio-oil components into biodiesel [2-4]. Notes: [1] K. Wilson, A.F. Lee, Cat. Sci. Tech. 2012 ,2, 884. [2] J. Dhainaut, J.-P. Dacquin, A. F. Lee, K. Wilson, Green Chem. 2010 , 12, 296. [3] C. Pirez, J.-M. Caderon, J.-P. Dacquin, A.F. Lee, K. Wilson, ACS Catal. 2012 , 2, 1607. [4] J.J. Woodford, J.-P. Dacquin, K. Wilson, A.F. Lee, Energy Environ. Sci. 2012 , 5, 6145.

Recent developments in heterogeneous catalysis for the sustainable production of biodiesel

The quest for energy security and widespread acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from combusting fossil derived carbon sources, is driving academic and commercial research into new routes to sustainable fuels to meet the demands of a rapidly rising global population. Biodiesel is one of the most readily implemented and low cost, alternative source of transportation fuels to meet future societal demands. However, current practises to produce biodiesel via transesterification employing homogeneous acids and bases result in costly fuel purification processes and undesired pollution. Life-cycle calculations on biodiesel synthesis from soybean feedstock show that the single most energy intensive step is the catalytic conversion of TAGs into biodiesel, accounting for 87% of the total primary energy input, which largely arises from the quench and separation steps. The development of solid acid and base catalysts that respectively remove undesired free fatty acid (FFA) impurities, and transform naturally occurring triglycerides found within plant oils into clean biodiesel would be desirable to improve process efficiency. However, the microporous nature of many conventional catalysts limits their ability to convert bulky and viscous feeds typical of plant or algal oils. Here we describe how improved catalyst performance, and overall process efficiency can result from a combination of new synthetic materials based upon templated solid acids and bases with hierarchical structures, tailored surface properties and use of intensified process allowing continuous operation.

Designer catalysts for biodiesel synthesis

The combination of dwindling oil reserves and growing concerns over carbon dioxide emissions and associated climate change is driving the urgent development of clean, sustainable energy supplies. Biodiesel is a non-toxic and biodegradable fuel, with the potential for closed CO2 cycles and thus vastly reduced carbon footprints compared with petroleum. However, current manufacturing routes employing soluble catalysts are very energy inefficient, with their removal necessitating an energy intensive separation to purify biodiesel, which in turn produces copious amounts of contaminated aqueous waste. The introduction of non-food based feedstocks and technical advances in heterogeneous catalyst and reactor design are required to ensure that biodiesel remains a key player in the renewable energy sector for the 21st century. Here we report on the development of tuneable solid acid and bases for biodiesel synthesis, which offer several process advantages by eliminating the quenching step and allowing operation in a continuous reactor. Significant progress has been made towards developing tuneable solid base catalysts for biodiesel synthesis, including Li/CaO [1], Mg-Al hydrotalcites [2] and calcined dolomite [3] which exhibit excellent activity for triglyceride transesterification. However, the effects of solid base strength on catalytic activity in biodiesel synthesis remains poorly understood, hampering material optimisation and commercial exploitation. To improve our understanding of factors influencing solid base catalysts for biodiesel synthesis, we have applied a simple spectroscopic method for the quantitative determination of surface basicity which is independent of adsorption probes. Such measurements reveal how the morphology and basicity of MgO nanocrystals correlate with their biodiesel synthesis activity [4]. While diverse solid acids and bases have been investigated for TAG transesterification, the micro and mesoporous nature of catalyst systems investigated to date are not optimal for the diffusion of bulky and viscous C16-C18 TAGs typical of plant oils. The final part of this presentation will address the benefits of designing porous networks comprising interconnected hierarchical macroporous and mesoporous channels (Figure 1) to enhance mass-transport properties of viscous plant oils during biodiesel synthesis [5]. References: [1] R.S. Watkins, A.F. Lee, K. Wilson, Green Chem., 2004, 6, 335. [2]D.G. Cantrell, L.J. Gillie, A.F. Lee and K. Wilson, Appl. Catal. A, 2005, 287,183. [3] C. Hardacre, A.F. Lee, J.M. Montero, L. Shellard, K.Wilson, Green Chem., 2008, 10, 654. [4] J.M. Montero, P.L. Gai, K. Wilson, A.F. Lee, Green Chem., 2009, 11, 265. [5] J. Dhainaut, J.-P. Dacquin, A.F. Lee, K. Wilson, Green Chem., 2010, 12, 296.

Studies on the thermal decomposition behaviour, kinetics and electrical conductivity of the non-isothermal decomposition of pyridine mono carboxylic acids and some of their transition metal complexes

The thesis is divided into four chapters. They are: introduction, experimental, results and discussion about the free ligands and results and discussion about the complexes. The First Chapter, the introductory chapter, is a general introduction to the study of solid state reactions. The Second Chapter is devoted to the materials and experimental methods that have been used for carrying out tile experiments. TIle Third Chapter is concerned with the characterisations of free ligands (Picolinic acid, nicotinic acid, and isonicotinic acid) by using elemental analysis, IR spectra, X-ray diffraction, and mass spectra. Additionally, the thermal behaviour of free ligands in air has been studied by means of thermogravimetry (TG), derivative thermogravimetry (DTG), and differential scanning calorimetry (DSC) measurements. The behaviour of thermal decomposition of the three free ligands was not identical Finally, a computer program has been used for kinetic evaluation of non-isothermal differential scanning calorimetry data according to a composite and single heating rate methods in comparison with the methods due to Ozawa and Kissinger methods. The most probable reaction mechanism for the free ligands was the Avrami-Erofeev equation (A) that described the solid-state nucleation-growth mechanism. The activation parameters of the decomposition reaction for free ligands were calculated and the results of different methods of data analysis were compared and discussed. The Fourth Chapter, the final chapter, deals with the preparation of cobalt, nickel, and copper with mono-pyridine carboxylic acids in aqueous solution. The prepared complexes have been characterised by analyses, IR spectra, X-ray diffraction, magnetic moments, and electronic spectra. The stoichiometry of these compounds was ML2x(H20), (where M = metal ion, L = organic ligand and x = water molecule). The environments of cobalt, nickel, and copper nicotinates and the environments of cobalt and nickel picolinates were octahedral, whereas the environment of copper picolinate [Cu(PA)2] was tetragonal. However, the environments of cobalt, nickel, and copper isonicotinates were polymeric octahedral structures. The morphological changes that occurred throughout the decomposition were followed by SEM observation. TG, DTG, and DSC measurements have studied the thermal behaviour of the prepared complexes in air. During the degradation processes of the hydrated complexes, the crystallisation water molecules were lost in one or two steps. This was also followed by loss of organic ligands and the metal oxides remained. Comparison between the DTG temperatures of the first and second steps of the dehydration suggested that the water of crystallisation was more strongly bonded with anion in Ni(II) complexes than in the complexes of Co(II) and Cu(II). The intermediate products of decomposition were not identified. The most probable reaction mechanism for the prepared complexes was also Avrami-Erofeev equation (A) characteristic of solid-state nucleation-growth mechanism. The tempemture dependence of conductivity using direct current was determined for cobalt, nickel, Cl.nd copper isonicotinates. An activation energy (ΔΕ), the activation energy (ΔΕ ) were calculated.The ternperature and frequency dependence of conductivity, the frequency dependence of dielectric constant, and the dielectric loss for nickel isonicotinate were determined by using altemating current. The value of s paralneter and the value of'density of state [N(Ef)] were calculated. Keyword Thermal decomposition, kinetic, electrical conduclion, pyridine rnono~ carboxylic acid, cOlnplex, transition metal compJex.

Progress in the development of mesoporous solid acid and base catalysts for converting carbohydrates into platform chemicals

This chapter provides a general overview of recent studies on catalytic conversion of fructose, glucose, and cellulose to platform chemicals over porous solid acid and base catalysts, including zeolites, ion-exchange resins, heteropoly acids, as well as structured carbon, silica, and metal oxide materials. Attention is focused on the dehydration of glucose and fructose to HMF, isomerization of glucose to fructose, hydrolysis of cellulose to sugar, and glycosidation of cellulose to alkyl glucosides. The correlation of porous structure, surface properties, and the strength or types of acid or base with the catalyst activity in these reactions is discussed in detail in this chapter.

Quantification of hydroxycinnamic acids and lignin in perennial forage and energy grasses by Fourier-transform infrared spectroscopy and partial least squares regression

Levels of lignin and hydroxycinnamic acid wall components in three genera of forage grasses (Lolium,Festuca and Dactylis) have been accurately predicted by Fourier-transform infrared spectroscopy using partial least squares models correlated to analytical measurements. Different models were derived that predicted the concentrations of acid detergent lignin, total hydroxycinnamic acids, total ferulate monomers plus dimers, p-coumarate and ferulate dimers in independent spectral test data from methanol extracted samples of perennial forage grass with accuracies of 92.8%, 86.5%, 86.1%, 59.7% and 84.7% respectively, and analysis of model projection scores showed that the models relied generally on spectral features that are known absorptions of these compounds. Acid detergent lignin was predicted in samples of two species of energy grass, (Phalaris arundinacea and Pancium virgatum) with an accuracy of 84.5%.

Milk feeding, solid feeding, and obesity risk:a review of the relationships between early life feeding practices and later adiposity

Childhood obesity is a major health issue with associated ill-health consequences during childhood and into later adolescence and adulthood. Given that eating behaviors are formed during early childhood, it is important to evaluate the relationships between early life feeding practices and later child adiposity. This review describes and evaluates recent literature exploring associations between child weight and the mode of milk feeding, the age of introducing solid foods and caregivers’ solid feeding practices. There are many inconsistencies in the literature linking early life feeding to later obesity risk and discrepancies may be related to inconsistent definitions, or a lack of control for confounding variables. This review summarizes the literature in this area and identifies the need for large scale longitudinal studies to effectively explore how early life feeding experiences may interact with each other and with nutritional provision during later childhood to predict obesity risk.

Chemometric modelling to relate antioxidants, neutral lipid fatty acids and flavour components in chicken breast

Relationships among quality factors in retailed free-range, corn-fed, organic, and conventional chicken breasts (9) were modeled using chemometric approaches. Use of principal component analysis (PCA) to neutral lipid composition data explained the majority (93%) of variability (variance) in fatty acid contents in 2 significant multivariate factors. PCA explained 88 and 75% variance in 3 factors for, respectively, flame ionization detection (FID) and nitrogen phosphorus (NPD) components in chromatographic flavor data from cooked chicken after simultaneous distillation extraction. Relationships to tissue antioxidant contents were modeled. Partial least square regression (PLS2), interrelating total data matrices, provided no useful models. By using single antioxidants as Y variables in PLS (1), good models (r2 values > 0.9) were obtained for alpha-tocopherol, glutathione, catalase, glutathione peroxidase, and reductase and FID flavor components and among the variables total mono and polyunsaturated fatty acids and subsets of FID, and saturated fatty acid and NPD components. Alpha-tocopherol had a modest (r2 = 0.63) relationship with neutral lipid n-3 fatty acid content. Such factors thus relate to flavor development and quality in chicken breast meat.

Optimising the nanoporous architecture of solid acid and base catalysts for biodiesel synthesis

Dwindling oil reserves and growing concerns over CO2 emissions and associated climate change are driving the utilisation of renewable feedstocks as alternative, sustainable fuel sources. While rising oil prices are improving the commercial feasibility of biodiesel production, many current processes still employ homogeneous acid and/or base catalysts to transform plant or algae oil into the fatty acid methyl ester (FAME) components of biodiesel. Fuel purification requires energy intensive aqueous quench and neutralization steps, thus the rational design of new high activity catalysts is required to deliver biodiesel as a major player in the 21st century sustainable energy portfolio. Advances in the development of heterogeneous catalysts for biodiesel synthesis require catalysts with pore architectures designed to improve the accessibility of bulky viscous reactants typical of plant oils. Here we discuss how improvements to active site accessibility and catalyst activity in transesterification or esterification reactions can be achieved either by designing hierarchical pore networks or by pore expansion and use of interconnected pore architectures.

Ageing, adipose tissue, fatty acids and inflammation

A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults.

Combinatorial solid phase synthesis of multiply substituted 1,4-benzodiazepines and affinity studies on the CCK2 receptor (Part 1)

One hundred sixty-eight multiply substituted 1,4-benzodiazepines have been prepared by a five-step solid-phase combinatorial approach using syn-phase crowns as a solid support and a hydroxymethyl-phenoxy-acetamido linkage (Wang linker). The substituents of the 1,4-benzodiazepine scaffold have been varied in the -3, -5, -7, and 8-positions and the combinatorial library was evaluated in a cholecystokinin (CCK) radioligand binding assay. 3-Alkylated 1,4-benzodiazepines with selectivity towards the CCK-B (CCK2) receptor have been optimized on the lipophilic side chain, the ketone moiety, and the stereochemistry at the 3-position. Various novel 3-alkylated compounds were synthesized and [S]3-propyl-5-phenyl-1,4-benzodiazepin-2-one, [S]NV-A, has shown a CCK-B selective binding at about 180 nM. Fifty-eight compounds of this combinatorial library were purified by preparative TLC and 25 compounds were isolated and fully characterized by TLC, IR, APCI-MS, and 1H/13C-NMR spectroscopy.

Solid dispersions: formulation, characterisation, permeability and genomic evaluation

Poor water solubility is characterised by low dissolution rate and consequently reduced bioavailability. Formulation of solid dispersion of the drug has attracted considerable interest as a means of improving dissolution process of a range of poorly water soluble drugs. This current study investigates the formulation of solid dispersion for a range of poorly water soluble drugs with varying physicochemical properties including paracetamol, sulphamethoxazole, phenacetin, indomethacin, chloramphenicol, phenylbutazone and succinylsulphathiazole. Solid dispersions were prepared using various drugs to polymer ratios. PEG 8000 was selected as a carrier in the solid dispersions. The study revealed that inclusion of drug within the polymeric matrix, ratio of drug to polymer and physicochemical properties of the drug molecules enhance the dissolution rate. Characterisations of the solid dispersions were performed using DSC, FTIR and SEM. These studies revealed that all seven drugs were present in the amorphous form within the solid dispersions and there was a lack of interaction between the PEG 8000 and drug. Stability studies for solid dispersions showed that all seven drugs studied were unstable at accelerated conditions (40°C±2°C/75%RH±5%RH) whereas, they were found to be stable for 12 months at room conditions. Permeability of indomethacin, phenacetin, phenylbutazone and paracetamol were higher for solid dispersions as compared to drug alone across Caco-2 cell monolayers. From the cell uptake studies it was shown that PEG 8000 enhanced rhodamine123 uptake which suggested that PEG 8000 may increase the permeability of these drugs in solid dispersions. Gene expression profiles analyzing the expression changes in the ABC and solute carrier transporter during permeability studies.ABCA10, ABCB4, ABCC12, SLC12A6, MCT13, SLC22A12 and SLC6A6 gene expression were increased by indomethacin alone whereas solid dispersion of indomethacin resulted in a slight increase in expression. ABCC12 and SAMC gene expression was increased in case of paracetamol alone but slightly increased when exposed to solid dispersion of paracetamol.

Purification and characterisation of two cancer cachexia factors

Cachexia is a wasting phenomenon that often accompanies malignant disease. Its manifestation is associated with shortened survival and reduced responsiveness to anti-tumour therapy and as yet there is no established, effective amelioratory treatment. The MAC 16 model of cancer cachexia has been shown by many studies to closely mirror the human condition. Thus, cachexia is mediated by the presence of a small, slow-growing solid tumour that is mainly resistant to chemotherapy. In addition, the condition is largely attributable to aberrations in metabolic processes, while weight loss due to anorexia is negligible. Cachexia induced by the MAC 16 tumour, has been shown to be mediated by the production of tumour-derived circulatory catabolic factors, and the further elucidation of the structure of these molecules contributes towards the main content of this report. Thus, a factor with in vitro lipid-mobilising activity has been purified from the MAC 16 tumour, and has been found to have similarities to tumour-derived lipolytic factors published to date. Further work demonstrated that this factor was also purifiable from the urine of a patient with pancreatic cancer, and that it was capable of inducing weight loss in non tumour-bearing mice. Sequence analysis of the homogeneous material revealed an identity to Zn-α-2-glycoprotein, the significance of which is discussed. An additional factor, first detected as a result of its specific reactivity with a monoclonal antibody produced by fusion of splenocytes from MAC 16 tumour-bearing mice with mouse BALB/c myeloma cells, was identified as a co-purificant during studies to isolate the lipolytic factor. Subsequent purification of this material to homogeneity resulted in the determination of 18 of the N-terminal amino acids and revealed the highly glycosylated nature of its structure. Thus, this material (P24) was found to have an apparent molecular mass of 24kD of which 2kD was due to protein, while the remainder (92%) was due to the presence of carbohydrate groups. Sequence analysis of the protein core of P24 revealed an identity with Streptococcal pre-absorbing antigen (PA-Ag) in 11 of the amino acids, and the significance of this is discussed. P24 was shown to induce muscle protein breakdown in vitro and to induce cachexia in vivo, as measured by the depletion of fat (29%) and muscle (14%) tissue in the absence of a reduction of food and water intake. Further studies revealed that the same material was purifiable from the urine of patients with pancreatic cancer and was found to be detectable in the urine of cancer patients with weight loss greater than l.Skg/month. Thus, cachexia induced by the MAC 16 tumour in mice and by malignant disease in humans may be induced by similar mediators. Attempts to isolate the gene for P24 using information provided by the N-terminal protein sequence were unsuccessful. This was probably due to the low abundance o[ the material, as determined by protein purification studies; and the nature of the amino acids of the N-terminal sequence, which conferred a high degree o[ degeneracy to the oligonucleotides designed for the polymerase chain reaction.

Absorption and metabolism of chlorogenic acids in cultured gastric epithelial monolayers

Gastric absorption of feruloylquinic acid and di-O-caffeoylquinic acid analogs has never been investigated despite their potential contribution to the proposed beneficial health effects leading to reduced risk of type 2 diabetes. Using a cultured gastric epithelial model, with an acidic apical pH, the relative permeability coefficients (P(app)) and metabolic fate of a series of chlorogenic acids (CGAs) were investigated. Mechanistic studies were performed in the apical to basal direction and demonstrated differential rates of absorption for different CGA subgroups. For the first time, we show intact absorption of feruloylquinic acids and caffeoylquinic acid lactones across the gastric epithelium (P(app) ~ 0.2 cm/s). Transport seemed to be mainly by passive diffusion, because good linearity was observed over the incubation period and test concentrations, and we speculate that a potential carrier-mediated component may be involved in uptake of certain 4-acyl CGA isomers. In contrast, absorption of intact di-O-caffeoylquinic acids was rapid (P(app) ~ 2-10 cm/s) but nonlinear with respect to time and concentration dependence, which was potentially limited by interaction with an efflux transporter and/or pH gradient dependence. For the first time, methylation is shown in gastric mucosa. Furthermore, isoferulic acid, dimethoxycinnamic acid, and ferulic acid were identified as novel gastric metabolites of CGA biotransformation. We propose that the stomach is the first location for the release of hydroxycinnamic acids, which could explain their early detection after coffee consumption.

Amino acids in oral drug delivery:salts, ion-pairs and transcriptomics

Oral drug delivery is considered the most popular route of delivery because of the ease of administration, availability of a wide range of dosage forms and the large surface area for drug absorption via the intestinal membrane. However, besides the unfavourable biopharmaceutical properties of the therapeutic agents, efflux transporters such as Pglycoprotein (P-gp) and multiple resistance proteins (MRP) decrease the overall drug uptake by extruding the drug from the cells. Although, prodrugs have been investigated to improve drug partitioning by masking the polar groups covalently with pre-moieties promoting increased uptake, they present significant challenges including reduced solubility and increased toxicity. The current work investigates the use of amino acids as ion-pairs for three model drugs: indomethacin (weak acid), trimethoprim (weak base) and ciprofloxacin (zwitter ion) in an attempt to improve both solubility and uptake. Solubility was studied by salt formation while creating new routes for uptake across the membranes via amino acids transporter proteins or dipeptidyl transporters was the rationale to enhance absorption. New salts were prepared for the model drugs and the oppositely charged amino acids by freeze drying and they were characterised using FTIR, 1HNMR, DSC, SEM, pH solubility profile, solubility and dissolution. Permeability profiles were assessed using an in vitro cell based method; Caco-2 cells and the genetic changes occurring across the transporter genes and various pathways involved in the cellular activities were studied using DNA microarrays. Solubility data showed a significant increase in drug solubility upon preparing the new salts with the oppositely charged counter ions (ciprofloxacin glutamate salt exhibiting 2.9x103 fold enhancement when compared to the free drug). Moreover, permeability studies showed a 3 fold increase in trimethoprim and indomethacin permeabilities upon ion-pairing with amino acids and more than 10 fold when the zwitter ionic drug was paired with glutamic acid. Microarray data revealed that trimethoprim was absorbed actively via OCTN1 transporters while MRP7 is the main transporter gene that mediates its efflux. The absorption of trimethoprim from trimethoprim glutamic acid ion-paired formulations was affected by the ratio of glutamic acid in the formulation which was inversely proportional to the degree of expression of OCTN1. Interestingly, ciprofloxacin glutamic acid ion-pairs were found to decrease the up-regulation of ciprofloxacin efflux proteins (P-gp and MRP4) and over-express two solute carrier transporters; (PEPT2 and SLCO1A2) suggesting that a high aqueous binding constant (K11aq) enables the ion-paired formulations to be absorbed as one entity. In conclusion, formation of ion-pairs with amino acids can influence in a positive way solubility, transfer and gene expression effects of drugs.