Organocatalytic Asymmetric Synthesis of Si-Stereogenic Siloxanols.

We report the organocatalytic synthesis of Si-stereogenic compounds via desymmetrization of a prochiral silanediol with a chiral imidazole-containing catalyst. This metal-free silylation method affords high yields with enantioselectivity up to 98:2 for various silanediol and silyl chloride substrate combinations (including secondary alkyl, vinyl, and H groups), accessing products with potential for further elaboration. NMR and X-ray studies reveal insight into the H-bonding interactions between the imidazole organocatalyst and the silanediol and the dual activating role of the Lewis basic imidazole to account for the high enantioselectivity.

Immobilization of Diatom Phaeodactylum tricornutum with Filamentous Fungi and Its Kinetics.

Immobilizing microalgae cells in a hyphal matrix can simplify harvest while producing novel mycoalgae products with potential food, feed, biomaterial, and renewable energy applications; however, limited quantitative information to describe the process and its applicability under various conditions leads to difficulties in comparing across studies and scaling-up. Here, we demonstrate the immobilization of both active and heat-deactivated marine diatom Phaeodactylum tricornutum (UTEX 466) using different loadings of fungal pellets (Aspergillus sp.) and model the process through kinetics and equilibrium models. Active P. tricornutum cells were not required for the fungal-assisted immobilization process and the fungal isolate was able to immobilize more than its original mass of microalgae. The Freundlich isotherm model adequately described the equilibrium immobilization characteristics and indicated increased normalized algae immobilization (g algae removed/g fungi loaded) under low fungal pellet loadings. The kinetics of algae immobilization by the fungal pellets were found to be adequately modeled using both a pseudo-second order model and a model previously developed for fungal-assisted algae immobilization. These results provide new insights into the behavior and potential applications of fungal-assisted algae immobilization.

Synthesis of Functionalized Silsesquioxane Nanomaterials by Rhodium-Catalyzed Carbene Insertion into Si-H Bonds.

We report carbene insertion into Si-H bonds of polyhedral oligomeric silsesquioxanes (POSS) for the synthesis of highly functionalized siloxane nanomaterials. Dirhodium(II) carboxylates catalyze insertion of aryl-diazoacetates as carbene precursors to afford POSS structures containing both ester and aryl groups as orthogonal functional handles for further derivatization of POSS materials. Four diverse and structurally varied silsesquioxane core scaffolds with one, three, or eight Si-H bonds were evaluated with diazo reactants to produce a total of 20 new POSS compounds. Novel diazo compounds containing a fluorinated octyl group and boron-dipyrromethene (BODIPY) chromophore demonstrate the use of highly functionalized substrates. Transformations of aryl(ester)-functionalized POSS compounds derived from this method are demonstrated, including ester hydrolysis and Suzuki-Miyaura cross-coupling.

NMR Quantification of Hydrogen-Bond-Accepting Ability for Organic Molecules.

The hydrogen-bond-accepting abilities for more than 100 organic molecules are quantified using 19F and 31P NMR spectroscopy with pentafluorobenzoic acid (PFBA) and phenylphosphinic acid (PPA) as commercially available, inexpensive probes. Analysis of pyridines and anilines with a variety of electronic modifications demonstrates that changes in NMR shifts can predict the secondary effects that contribute to H-bond-accepting ability, establishing the ability of PFBA and PPA binding to predict electronic trends. The H-bond-accepting abilities of various metal-chelating ligands and organocatalysts are also quantified. The measured Δδ(31P) and Δδp(19F) values correlate strongly with Hammett parameters, pKa of the protonated HBA, and proton-transfer basicity (pKBH+).

NMR Quantification of Halogen-Bonding Ability To Evaluate Catalyst Activity.

Quantification of halogen-bonding abilities is described for a series of benzimidazolium-, imidazolium- and bis(imidazolium) halogen-bond donors (XBDs) using 31P NMR spectroscopy. The measured Δδ(31P) values correlate with calculated activation free energy ΔG‡ and catalytic activity for a Friedel-Crafts indole addition. This rapid method also serves as a sensitive indicator for Brønsted acid impurities.

NMR quantification of H-bond donating ability for bioactive functional groups and isosteres.

The H-bond donating ability for 127 compounds including drug fragments and isosteres have been quantified using a simple and rapid method with 31P NMR spectroscopy. Functional groups important to medicinal chemistry were evaluated including carboxylic acids, alcohols, phenols, thioic acids and nitrogen group H-bond donors. 31P NMR shifts for binding to a phosphine oxide probe have a higher correlation with equilibrium constants for H-bonding (log KHA) than acidity (pKa), indicating that these binding experiments are representative of H-bonding ability and not proton transfer. Additionally, 31P NMR binding data for carboxylic acid isosteres correlates with physicochemical properties such as lipophilicity, membrane permeability and plasma protein binding. This method has been used to evaluate the H-bond donating ability of small molecule drug compounds such as NSAIDs and antimicrobials.

Enantioselective Si-H Insertion Reactions of Diarylcarbenes for the Synthesis of Silicon-Stereogenic Silanes.

We report the first example of enantioselective, intermolecular diarylcarbene insertion into Si-H bonds for the synthesis of silicon-stereogenic silanes. Dirhodium(II) carboxylates catalyze an Si-H insertion using carbenes derived from diazo compounds where selective formation of an enantioenriched silicon center is achieved using prochiral silanes. Fourteen prochiral silanes were evaluated with symmetrical and prochiral diazo reactants to produce a total of 25 novel silanes. Adding an ortho substituent on one phenyl ring of a prochiral diazo enhances enantioselectivity up to 95:5 er with yields up to 98%. Using in situ IR spectroscopy, the impact of the off-cycle azine formation is supported based on the structural dependence for relative rates of diazo decomposition. A catalytic cycle is proposed with Si-H insertion as the rate-determining step, supported by kinetic isotope experiments. Transformations of an enantioenriched silane derived from this method, including selective synthesis of a novel sila-indane, are demonstrated.

NMR Quantification of the Effects of Ligands and Counterions on Lewis Acid Catalysis.

The relative Lewis acidity of a variety of metal-ligand catalyst complexes is quantified using 31P NMR spectroscopy. Three 31P NMR probes, including two new bidentate binding probes, are compared on the basis of different binding modes (i.e., monodentate vs bidentate) and the relative scale of their downfield shift upon binding to Lewis acid complexes. Bidentate coordination of catalyst complexes including metal catalysts, ligands, and counterions were assessed due to their importance to asymmetric catalysis. The effect of ligands, counterions, and additives on Lewis acidity is quantified and correlated to reaction yield at an early time point as an approximation for catalytic activity/efficiency and chelation mode in two organic transformations. Binding studies were performed under catalytically relevant conditions, giving further applicability to synthesis. Insight into activation modes are revealed through this analysis.

Catalytic Asymmetric Synthesis of Cyclopentene-spirooxindoles Bearing Vinylsilanes Capable of Further Transformations.

We report a scandium-catalyzed [3 + 2] annulation of alkylideneoxindoles with allenylsilanes for the enantioselective formation of cyclopentene-spirooxindoles containing vinylsilanes. Using a Sc(OTf)2/PyBOX/BArF complex, the spiroannulation of allenylsilanes affords products with >94:6 dr and >90:10 er. The effect of the counterion and ligand to control selectivity is discussed. The transformation of the vinylsilane is demonstrated using cross-coupling, epoxidation, and Tamao-Fleming oxidation reactions. A series of competition experiments provide a comparison of nucleophilicity between allyl- and allenylsilanes.

Metal-Free Synthesis of 1,3-Disiloxanediols and Aryl Siloxanols.

The first example of metal-free oxidative hydrolysis of hydrido-siloxanes is reported. Both base-catalyzed and organocatalytic hydrolysis methods are demonstrated to transform 1,3-dihydrido-disiloxanes into 1,3-disiloxanediols. The first example of a chemoselective silane hydrolysis is demonstrated.

Kinetic and Binding Studies Reveal Cooperativity and Off-Cycle Competition for H-Bonding Catalysis with Silsesquioxane Silanols.

The catalytic activity, kinetics, and quantification of H-bonding ability of incompletely condensed polyhedral oligomeric silsesquioxane (POSS) silanols are reported. POSS-triols, a homogeneous model for vicinal silica surface sites, exhibit enhanced H-bonding compared with other silanols and alcohols as quantified using a 31 P NMR probe. Evaluation of a Friedel-Crafts addition reaction shows that phenyl-POSS-triol is active as an H-bond donor catalyst whereas other POSS silanols studied are not. An in-depth kinetic study (using RPKA and VTNA) highlights the concentration-dependent H-bonding behavior of POSS-triols, which is attributed to intermolecular association forming an off-cycle dimeric species. Binding constants provide additional support for reduced H-bond ability at higher concentrations, which is attributed to competitive association. POSS-triol self-association disrupts H-bond donor abilities relevant for catalysis by reducing the concentration of active monomeric catalyst.

Conversion of Microbial Lipids to Biodiesel and Basic Lab Tests for Analysis of Fuel-Quality Parameters.

This chapter describes lab-scale procedures for the direct conversion of microbial lipids to fatty acid methyl esters (FAMEs) for use as biodiesel fuel. Methods for the gas chromatography analysis of FAME profiles and equations to predict several fuel-quality parameters are detailed herein. This chapter also provides a complete list summarizing each of the fuel quality tests (e.g., sample size and equipment) that are required by ASTM International D6751 regulations for pure biodiesel fuel (B100) or blend stock. Recommendations for the decolorization of microbial lipid sources containing pigments are also included. This resource should provide a guide to basic conversion and characterization of microbial-derived biodiesel fuels and a roadmap for more-detailed testing required to assess commercial feasibility.

Producing Oleaginous Microorganisms Using Wastewater: Methods and Guidelines for Lab- and Industrial-Scale Production.

Cultivation of oleaginous microorganisms on wastewater provides alternative biofuel options while also acting as a remediation technique for alternative wastewater treatment. This chapter describes guidelines and methods for the production of oleaginous microorganisms-with a focus on microalgae-using wastewater as a growth medium while considering a variety of general challenges for both lab- and industrial-scale production. Cultivation techniques described here range in scale from microplates with 10-mL working volumes, up to multigallon, industrial-scale microorganism cultivation, with a focus on microalgae. This chapter includes guidelines for the preparation of wastewater and selection of oleaginous microorganisms combined with methods for the production of oleaginous microorganisms cultivated using wastewater.

Sodium-Catalyzed Friedel-Crafts Reactions and Mechanistic Insight.

Sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF) demonstrates catalytic activity for Friedel-Crafts addition reactions of phenolic and other aromatic nucleophiles to trans-ß-nitrostyrene. Solubility studies demonstrate a chelating effect between the Na+ cation and the nitro group of trans-ß-nitrostyrene as the basis for catalytic activation. Mechanistic studies are presented, including a comparison with other sodium salts, additive effects, and reaction progress kinetics analysis using 19F NMR spectroscopy.

NMR Quantification of Hydrogen-Bond-Activating Effects for Organocatalysts including Boronic Acids.

The hydrogen-bonding activation for 66 organocatalysts has been quantified using a 31P NMR binding experiment with triethylphosphine oxide (TEPO). Diverse structural classes, including phenols, diols, silanols, carboxylic acids, boronic acids, and phosphoric acids, were examined with a variety of steric and electronic modifications to understand how the structure and secondary effects contribute to hydrogen-bonding ability and catalysis. Hammett plots demonstrate high correlation for the Δδ 31P NMR shift to Hammett parameters, establishing the ability of TEPO binding to predict electronic trends. Upon correlation to catalytic activity in a Friedel-Crafts addition reaction, data demonstrate that 31P NMR shifts correlate to catalytic activity better than p Ka values. Boronic acids were investigated, and 31P NMR binding experiments predicted strong hydrogen-bonding ability, for which catalytic activity was confirmed, resulting in the greatest rate enhancement observed in the Friedel-Crafts addition of all organocatalysts studied. A detailed investigation supports that boronic acid activation proceeds through hydrogen-bonding interactions and not coordination with the Lewis acidic boron center. Using 31P NMR spectroscopy offers a simple and rapid tool to quantify and predict hydrogen-bonding abilities for the design and applications of new organocatalysts and supramolecular synthons.

Reaction Progress Kinetics Analysis of 1,3-Disiloxanediols as Hydrogen-Bonding Catalysts.

1,3-Disiloxanediols are effective hydrogen-bonding catalysts that exhibit enhanced activity relative to silanediols and triarylsilanols. The catalytic activity for a series of 1,3-disiloxanediols, including naphthyl-substituted and unsymmetrical siloxanes, has been quantified and compared relative to other silanol and thiourea catalysts using the Friedel Crafts addition of indole to trans-ß-nitrostyrene. An in-depth kinetic study using reaction progress kinetic analysis (RPKA) has been performed to probe the catalyst behavior of 1,3-disiloxanediols. The data confirm that the disiloxanediol-catalyzed addition reaction is first order in catalyst over all concentrations studied with no evidence of catalyst self-association. 1,3-Disiloxanediols proved to be robust and recoverable catalysts with no deactivation under reaction conditions. No product inhibition is observed, and competitive binding studies with nitro-containing additives suggest that 1,3-disiloxanediols bind weakly to nitro groups but are strongly activating for catalysis.

Synthesis of Structurally Varied 1,3-Disiloxanediols and Their Activity as Anion-Binding Catalysts.

A series of new 1,3-disiloxanediols has been synthesized, including naphthyl-substituted and unsymmetrical siloxanes, and demonstrated as a new class of anion-binding catalysts. In the absence of anions, diffusion-ordered spectroscopy (DOSY) displays self-association of 1,3-disiloxanediols through hydrogen-bonding interactions. Binding constants determined for 1,3-disiloxanediol catalysts indicate strong hydrogen-bonding and anion-binding abilities with unsymmetrical siloxanes displaying different hydrogen-bonding abilities for each silanol group.

Combined nitrogen limitation and hydrogen peroxide treatment enhances neutral lipid accumulation in the marine diatom Phaeodactylum tricornutum.

Exogenous application of dilute hydrogen peroxide (H2O2) increases neutral lipid production in Phaeodactylum tricornutum. Exposing early stationary phase cultures of P. tricornutum to 0.25-2mM H2O2 increases the amount of neutral lipids per biomass (mg/mg) by >100% at 24h post H2O2 treatment as determined upon lipid extraction and analysis using a neutral lipid assay. H2O2 treatment increased the total levels of neutral lipids harvested up to 50%, from 64mg/L to 96mg/L, demonstrating its possible effectiveness as a pre-harvest strategy to enhance the biofuel feedstock potential of P. tricornutum. The effects of H2O2 on biomass are concentration dependent; increasing concentrations of H2O2 reduce the levels of isolated biomass. Analysis of combined stressors demonstrates that H2O2 treatment exhibits synergistic effects to enhance neutral lipid production under nitrogen-depleted, but not phosphorus-depleted conditions, suggesting that the effects of hydrogen peroxide on lipid production are influenced by environmental nitrogen levels.

Lanthanum(III)-Catalyzed Three-Component Reaction of Coumarin-3-carboxylates for the Synthesis of Indolylmalonamides and Analysis of Their Photophysical Properties.

New methodology has been developed for the Lewis acid catalyzed synthesis of malonamides. First, the scandium(III)-catalyzed addition of diverse nucleophiles (e.g., indoles, N,N-dimethyl-m-anisidine, 2-ethylpyrrole, and 2-methylallylsilane) to coumarin-3-carboxylates has been developed to afford chromanone-3-carboxylates in high yields as a single diastereomer. Upon investigating a subsequent lanthanum(III)-catalyzed amidation reaction, a new multicomponent reaction was designed by bringing together coumarin-3-carboxylates with indoles and amines to afford indolylmalonamides, which were identified to exhibit fluorescent properties. The photophysical properties for selected compounds have been analyzed, including quantum yield, molar absorptivity, and Stokes shift. Synthetic studies of several reaction byproducts involved in the network of reaction equilibria for the three-component reaction provide mechanistic insight for the development of this methodology.

Chlorella vulgaris production enhancement with supplementation of synthetic medium in dairy manure wastewater.

To identify innovative ways for better utilizing flushed dairy manure wastewater, we have assessed the effect of dairy manure and supplementation with synthetic medium on the growth of Chlorella vulgaris. A series of experiments were carried out to study the impacts of pretreatment of dairy wastewater and the benefits of supplementing dairy manure wastewater with synthetic medium on C. vulgaris growth increment and the ultrastructure (chloroplast, starch, lipid, and cell wall) of C. vulgaris cells. Results showed that the biomass production of C. vulgaris in dairy wastewater can be enhanced by pretreatment and using supplementation with synthetic media. A recipe combining pretreated dairy wastewater (40 %) and synthetic medium (60 %) exhibited an improved growth of C. vulgaris. The effects of dairy wastewater on the ultrastructure of C. vulgaris cells were distinct compared to that of cells grown in synthetic medium. The C. vulgaris growth in both synthetic medium and manure wastewater without supplementing synthetic medium was lower than the growth in dairy manure supplemented with synthetic medium. We anticipate that the results of this study will help in deriving an enhanced method of coupling nutrient-rich dairy manure wastewater for biofuel production.