Materials & Chemicals : Biochemicals


“Green” Catalytic Systems for Solvent-Free Alcohol Oxidations

Research from the University of Wisconsin-La Crosse has led to the discovery and development of a novel suite of catalytic systems for industrially-relevant green oxidations including the oxidative conversion of primary and secondary alcohols to value-added aldehydes and ketones. Similar systems have been developed for the oxidation of olefins to produce important epoxides, and for the oxidation of alkanes to produce alcohols. Specifically the team has developed a series of iron-based catalysts known as ‘helmet’ phthalocyaninaoto complexes of iron(III). Preliminary studies have focused on the use of what is commonly referred to as the ‘diiPc’ iron(III) system. Notably, the team has shown that this system is capable of catalytically oxidizing a diverse array of substrates including five non-benzylic alcohols (1-pentanol, 2-pentanol and cyclohexanol as well as 2,4-dimethyl-3-pentanol and 5-hydroxymethylfurfural) in the absence of added organic solvent. The presence of water as the monodentate axial ligand in the diiPc complex allows for markedly increased solubility in non-aromatic alcohols, making it an ideal catalyst for use with a much wider and more diverse range of substrates under solvent free conditions. It is envisaged that modification of the diiPc and related ligands will be undertaken to impart further enhancements to catalyst solubility in substrates or water, and/or superior stability in substrate alcohols. In addition to the diiPc system, the team have also developed a means of forming derivatized catalysts utilizing what is commonly referred to as a “helmet naphthalocyaninato” iron(III) complex. Specifically, a sulfonated version has been produced that possesses excellent solubility in water due to the added hydrophilic groups. To date, the sulfonated helmet naphthalocyaninato complex has been shown to provide for efficient formation of acetone from isopropanol as well as conversion of 2-pentanol to 2-pentanone using hydrogen peroxide as the primary oxidant. As such we anticipate that the same system would also be effective in the oxidation of 2-butanol to produce methyl ethyl ketone (MEK), an important commodity scale industrial chemical, and in many other commercially important transformations. Furthermore, preliminary studies have shown this molecule can be immobilized on various solid supports including anion-exchange resins, thereby resulting in a heterogeneous catalyst that can be utilized in the development of catalytic transformations that occur under flow conditions. Additionally, we now know that the sulfonated catalyst efficiently catalyzes the oxidation of phenol with hydrogen peroxide to produce para-benzoquinone. This transformation, along with other related reactions, is very important in the treatment of wastewater.

Modified E. coli for Enhanced Production of Pyruvate, Ethanol

UW–Madison researchers have developed a variety of new E. coli strains capable of producing pyruvate up to 95 percent of the maximum theoretical yield from renewable sources under aerobic conditions. This exceeds the highest previously reported yields of 78 percent.

The researchers used a genome-scale metabolic model of E. coli to identify multiple gene deletion targets that couple growth rate with pyruvate production. Further engineering of these new strains enabled them to produce ethanol at near maximum theoretical yields.

Skin Whitening Agent(s)

Following on from earlier research focused on development of stilbenoid-based derivatives for antimicrobial activity (isolated originally from the sweet fern Comptonia peregrina), researchers at UW-River Falls have generated a preclinical data package using zebrafish embryos which demonstrates lead analogues to possess potent skin-lightening activity. The zebrafish embryo model makes an excellent model for pigmentation studies due to the rapid and well-conserved melanocyte development and melanin synthesis. Lead compound, A11, has been shown to have more potent activity compared to a number of current skin-lightening compounds including arbutin which required a significantly higher concentration (300mM) to achieve comparable effects as A11 at 10M (70% versus 90% inhibition, respectively). Most importantly, A11 caused no detectable toxicity, whereas niaciamide and tretinoin caused strong toxicity to developing embryos while gallic acid killed the embryos at 50mM and arbutin caused cardiac degeneration. When tested for long-term efficacy, A11-incubated embryos demonstrated a 50% recovery of pigment 48 hours after wash, suggesting longer-acting skin-lightening effect as compared to other products which fully recovered (100%) their pigment within 24 hours after wash. Importantly, while A11 possessed these longer-acting effects, this study also demonstrated that the effects are reversible, which is an important factor for skin-whitening agents. Unlike most products on the market, A11 does not appear to act by inhibiting the tyrosinase enzyme and preliminary studies in a melanoma cell line suggest that the molecule may possess a different mechanism of action and may lead to skin-lightening via the control of melanocyte development and/or proliferation. Further studies are underway to better understand the molecular mechanisms of A11 using fish embryo and mouse melanoma cell lines. Interestingly, preliminary data from these studies also support potential use of these compounds in melanoma treatment. Additional in vivo studies utilizing a guinea pig or mouse model has been proposed to further validate the skin-lightening activity of A11 and related analogues.

Bio-Based Production of Non-Straight-Chain and Oxygenated Fatty Acids for Fuels and More

UW–Madison researchers have identified several enzymes in the bacterium Rhodobacter sphaeroides that can be purified to produce non-straight-chain fatty acids in vitro or expressed in genetically modified microorganisms including E. coli for synthesis in vivo. Strains may be ‘fine-tuned’ to produce a specific type of non-straight-chain fatty acid (e.g., furan-containing) by expressing, overexpressing or deleting the enzymes in various combinations.

Microbes Produce High Yields of Fatty Alcohols from Glucose

UW–Madison researchers have developed a method to produce fatty alcohols such as 1-dodecanol and 1-tetradecanol from glucose using genetically engineered microorganisms. The organism, e.g., a modified E. coli strain, overexpresses several genes (including FadD and a recombinant thioesterase gene, acyl-CoA synthetase gene and acyl-CoA reductase gene). Other gene products are functionally deleted to maximize performance.

The strain is cultured in a bioreactor in the presence of glucose.

New Disulfide-Bond Reducing Agent

UW–Madison researchers have developed a fast-working pyrazine dithiol that can be prepared from inexpensive starting material. The new reagent, 2,3-bis(mercaptomethyl)pyrazine (BMMP), is synthesized in three simple steps from the commonplace aromatic chemical 2,3-dimethylpyrazine.

Phosphine Ligands Made Cheaper, Better

UW–Madison researchers have developed methods for synthesizing novel classes of chiral phosphine ligands via enantioselective copper-catalyzed halogenation. The process is rapid and flexible, and also can be used to streamline the preparation of known phosphines.

The researchers previously described their ‘recycling’ method for use with aromatic compounds. Now, they have rendered the process enantioselective using an asymmetric bidentate phosphine ligand to produce scaffolds with high enantiomeric purity.

In essence, the use of the phosphine ligand helps form a chiral center in a complex product that is otherwise costly or impossible to create.

Two-Step Process Converts Lignin into Simple Aromatic Compounds

Building on their work, the researchers have now developed a two-step process for selectively converting lignin and lignin-type material into low molecular weight aromatic compounds.

The lignin is first selectively oxidized via the previously described method, then reacted with an organic carboxylic acid, salt or ester (e.g., formic acid) for a time and temperature sufficient to cleave carbon-carbon or carbon-oxygen bonds. The process results in high yields of simple aromatic compounds.

Concentrated C5 and C6 Sugars from Biomass

UW–Madison researchers have developed a process for producing C5 and C6 sugars from biomass at high yields (70 to 90 percent) in a solvent mixture of water, dilute acid and GVL (gamma-valerolactone). GVL is attractive because it is effective and derived from biomass.

The biomass and solvent system may be reacted at a temperature between 50 and 250oC for less than 24 hours.

The method yields liquid and solid fractions enriched in C5 and C6 sugar, respectively. The fractions are easily separated for post-treatment upgrading. This strategy is well-suited for catalytic upgrading to furans or fermentative upgrading to ethanol at near-theoretical yield.

Functional and Degradable ROMP Polymers for Plastics and Biomaterial

UW–Madison researchers have developed functionalized and degradable ROMP polymers. Specifically, monomers having a bicyclic oxazinone core structure have been found to be substrates for the ROMP process using a ruthenium or osmium carbene catalyst. This core may be chemically modified at a site away from the polymerizable moieties and bridgehead carbons. Polymers prepared from these monomers are both acid and base degradable.

Renewable Plastic from Glucose-Fed Microbes

UW–Madison researchers have developed recombinant E. coli capable of producing high yields of mcl-PHA from non-lipid, carbohydrate sources.

The researchers previously designed and built a bacterial strain that produces high levels of C12 fatty acids (see WARF reference number P09329US02). This strain has been further modified by deleting various fad genes implicated in the breakdown of fatty acids. Also, the bacteria cells incorporate several genes taken from other species to increase conversion efficiency.

Modified Microbes Tolerate 50-Fold More Organic Acid

UW–Madison researchers have genetically modified microorganisms to better tolerate organic acids like 3HP, acrylic acid and propionic acid. The modified microorganisms are cyanobacteria such as Synechococcus.

In the modified bacteria, the acsA gene is replaced or deleted. This leads to increased organic acid tolerance.

Improved Disulfide-Bond Reducing Agents

UW–Madison researchers have developed dithioamine reducing agents that can be prepared from inexpensive starting materials. The new reagent, dithiobutylamine (DTBA), is synthesized from the common amino acid, aspartic acid, by a short and simple route.

Biomass-Derived HMF Using Renewable Solvents

UW–Madison researchers have developed a process to convert biomass-derived sugars into HMF, furfural and other downstream chemicals using an organic solvent. In this way, both the sugars and solvent are sourced from renewable feedstock.

Biomass sugars (mostly fructose and glucose) are reacted in a one- or two-phase reaction solution containing water and the organic solvent. This solvent can comprise lactones, furans and pyrans derived from plant matter like starch and cellulose. The reaction is conducted in the presence of acid and dehydration catalysts. Under suitable conditions, a portion of the sugar is converted to HMF.

Moreover, the HMF may be readily separated and upgraded into other chemicals like FDCA (furandicarboxylic acid), which is used to make fiber and packaging polyesters.

Method for Renewably Sourced Diones as Fossil Chemical Alternative in Industry

UW–Madison researchers have developed a method for the conversion of 2,4-diones such as acetylacetone in high yield from renewable derivatives.

The process involves the acid catalysis or thermally induced ring opening of HMP derived from glucose. The molecule is reacted in a solvent selected from a group consisting of water, alcohols and tetrahydrofuran. In the absence of an acid, the reaction is conducted at mild temperature and pressure conditions to yield the corresponding dione.

A Supply of the Antibiotic Oligomycin

WARF has available for licensing a several hundred-gram quantity of the research chemical oligomycin. The available supply includes a mixture of oligomycins A, B and C, as well as purified preparations of oligomycin A and oligomycin B.