This summer, Auden, Bryn, Danielle, and Emily have taken over the Organic Chemistry Lab, working hard and having fun doing research with Dr. Funk. We are working on two main projects: Sustainable Oxidations and Reductions using Iron-based Catalysts and Lipid Synthesis. Keep reading to find out what each Funk Lab member does!
Project 1: Sustainable Alcohol Oxidation
Danielle Kleinberg ’23
Danielle is a rising junior double-majoring in Chemistry and Environmental Studies. With an interest in green chemistry, working in Dr. Funk’s lab is a perfect fit for her! This summer, Danielle is oxidizing alcohols using a sustainable iron catalyst.
What’s so great about oxidizing alcohols? Alcohol oxidation is a very common step in the synthesis of important molecules. Making oxidations more sustainable is an important stride towards greener chemistry. What makes iron so sustainable? Historically, alcohols have been oxidized using heavy transition metals such as ruthenium, palladium, or rhodium. These precious metals are rare, making them not only unsustainable but also quite expensive. Iron is a much cheaper and more sustainable option for a catalyst in these oxidation reactions. Making up 5% of the Earth’s crust, iron is the 2nd most abundant metal in it. In addition, iron is typically viewed as environmentally friendly due to its generally low toxicity. If iron-catalyzed oxidations can be performed just as effectively as oxidations catalyzed by rare metals, we can reduce both the financial and environmental cost of this chemistry.
Now that you have some background on these reactions, let’s go into some specifics. Below is the general mechanism for reactions Danielle is running:
Danielle oxidizes alcohols (I) with varying functional groups, sterics, and electronics in order to explore the substrate scope of this iron catalyst. Compound II, our iron catalyst, becomes activated once trimethylamine N-oxide (III) removes one of its carbonyl ligands, creating an active site where the alcohol can react. After II gets reduced, it must be reoxidized in order to keep working as a catalyst – this is where furfural (IV) comes in handy! The use of furfural as a terminal oxidant increases the sustainability of this reaction, since it is produced on an industrial scale using cellulosic biomass waste. After these reactions run overnight, Danielle isolates the carbonyl product (A) in order to see how well the reaction worked. In order to isolate A, she rinses away any water-soluble products and then performs column chromatography in order to separate the remaining products. After isolating A, Danielle calculates an isolated yield, which is the percent of alcohol (I) that is converted to ketone or aldehyde (A). Based on this calculation, she can see how well the reaction worked and identify the reactivity trends of this catalyst.
Along with using the iron catalyst, Danielle is working to further improve the sustainability of this process by testing it in different solvents. As seen in the reaction scheme, Danielle runs these reactions in toluene or water with 2% TPGS-750-M. Toluene is an organic solvent – organic solvents are convenient for these oxidations because our reagents dissolve in them and can therefore readily interact and react with each other. Although convenient, organic solvents derived from fossil fuels are not sustainable. Danielle is working to make these oxidations more sustainable by performing them in water mixed with a vitamin E-based lipid, TPGS-750-M, which creates tiny spheres of grease, known as “micelles”, which act as nanoreactors where the reagents can dissolve and interact. This process is known as micellar catalysis. TPGS-750-M is also non-toxic, making it even more environmentally friendly.
Project 2: Steric Bulk and Chemoselectivity in Alcohol Oxidations
Auden Cameron Lampariello ’22
Auden is a rising senior majoring in Chemistry. For Auden’s project, he synthesizes catalysts whose ligands have differences in steric bulk near the active site of the catalyst.
The list of catalysts Auden has synthesized and will be synthesizing may be seen below. It is expected that the increase in steric bulk near the active site of the catalyst will increase the catalyst’s selectivity towards oxidizing primary alcohols over secondary alcohols.
This study is based on a paper previously published by Professor Funk that showed that a catalyst with a trimethylsilyl ligand was able to selectively oxidize primary alcohols over secondary alcohols in diols to form lactones. This is contrary to the catalysts usual behavior as other forms of this catalyst normally favor the oxidation of secondary alcohols since this forms more stable products. It is the hope of this project to make a catalyst that can reliably oxidize primary alcohols over secondary alcohols, such that the catalyst may be used in more complex molecules for oxidations.
As each catalyst is obtained, it is used in a conversion experiment to determine how well it can oxidize primary alcohols over secondary alcohols when both are present. The conversions for each catalyst are monitored by extracting samples for gas chromatography analysis before the reaction has started and 24 hours after the reaction has started. The specific conditions may be seen below. The conversions for each catalyst are compared to one another to determine which catalyst converts more primary alcohols for every secondary alcohol converted.
Based on current findings, the increased steric bulk in the catalyst had minimal impact on the conversions for the primary alcohol but greatly decreased the conversions for the secondary alcohol. While the bulkiest ligand for this project has yet to be synthesized, Auden is optimistic that it will have the highest selectivity towards primary alcohols. This is based on the trends we have seen for three of the catalysts synthesized.
Project 3: Reactivity of a Novel Trimethylamine Adduct
Bryn Werley ’23
Bryn is a rising junior double majoring in Chemistry and Music who joined the Funk lab to pursue her interests in chemical synthesis. This summer, Bryn is working with both oxidations and reductions catalyzed by (cyclopentadienone)iron carbonyl catalysts.
Bryn’s work centers on our catalysts’ performance in oxidations and reductions. By tuning the electronic properties of our cyclopentadienone ligands, we are able to improve the reactivity of our catalysts. In general, increases in electron density increase catalytic activity.
Bryn is also investigating the catalytic activity of different versions of our tricarbonyl catalysts. Our tricarbonyl catalysts (Structure A) must be activated using trimethylamine N-oxide through a process that produces carbon dioxide and trimethylamine (two gases). Because trimethylamine is a gas, we assumed that it would just float away after the catalyst was activated (i.e., go from A to C directly, skipping Structure B), but this does not seem to be the case! Bryn recently isolated crystals in which trimethylamine had stuck to the iron atom of the catalyst (Structure B)!
She is currently using this trimethylamine-bound species (B) as a catalyst and has found that it 1) does not need to be activated in order to catalyze oxidations or reductions and 2) has faster initial reaction rates than our tricarbonyl compounds in both oxidations and reductions. Overall, the trimethylamine-bound species is much more effective for reductions than it is for oxidations. Bryn is currently working to explain these differences in reactivity and also hopes to compare the reactivity of similar catalysts later this summer! She is also planning experiments that may allow her to better understand the mechanisms behind these reactions (i.e., how the molecules and their electrons physically interact during the course of each reaction).
Project 4: Lipid Synthesis
Emily Howe ’23
Emily is a rising junior double major in BMB and Spanish, and is a lab TA for the Chem department. She’s working on creating a library of synthetic lipids based on the compound cyanuric chloride.
Lipids are characterized by having a hydrophobic region (the “tail”) and a hydrophilic region (the “head). Synthetic lipids can be created by attaching a fatty acyl tail (which are generally long, greasy, and hydrophobic) and some kind of hydrophilic group to a “linker” molecule which holds the two groups together. The linker my research focuses on is cyanuric chloride, a molecule with three potential positions that can be functionalized. A tri-substituted ring could lend itself to synthetic lipids of diverse geometries, one of which is shown below. This research is partially collaborative with Dr. Vince Venditto of the University of Kentucky College of Pharmacy, whose lab focuses on creating liposomes to use in vaccine delivery.
Based on the data that Dr. Venditto’s lab has obtained regarding the types of lipids that spontaneously self-assemble into liposomes, we are tailoring the types of lipids that we make to give us the greatest chance of producing lipids applicable to this branch of drug/vaccine delivery research.
Now That You Know Us, Let’s Get to Know You!
To conduct our work, we use many different analytical instruments. Each instrument has its own important purpose in our work. In fact, our instruments are so central to our work that we consider them honorary lab members, each with their own personality and quirks! So, let’s find out…
Congratulations on making it through the quiz! As your reward, we have created an alignment chart for each of our instruments, as well one for our most used solvents.
Funk Lab Instruments Alignment Chart
Lawful Good: Detail-oriented and reliable, the Gas Chromatograph has never led us astray. Bryn and Auden use this instrument to quantitatively monitor the progress of their reactions over time. The instrument uses mere microliters of their reaction mixtures to operate and allows for automated analysis of their samples.
Neutral Good: Running iron-catalyzed reactions means that we have some unique cleaning to do in the Funk Lab. In order to clean any oxidized iron from our reaction flasks, only hydrochloric acid can do the trick! But, we can’t dispose of HCl without first making it neutral. Meeting our needs of acid neutralization, Sodium Sesquicarbonate has surely gained our respect in the lab.
Chaotic Good: Though he appears intimidating at first, the NMR Spectrometer is a favorite instrument in the Funk Lab! It can take some time to understand the complicated spectra produced by this instrument, but the data provided by this instrument is integral to elucidating the structures of numerous compounds.
Lawful Neutral: Thin Layer Chromatography is a technique that helps us to determine the best method to separate compounds based on their polarities and identify the compounds present in the fractions we obtain during column chromatography. A simple method that produces consistent results, this is one of the first techniques that organic chemistry students learn in the lab!
True Neutral: Keeping us safe from any dangerous chemicals in the air, the Fume Hood keeps the atmosphere truly neutral.
Chaotic Neutral: The Rotavap (or Rotary Evaporator) combines the power of a vacuum pump with a heated water bath and rotating flask to evaporate solvents quickly. By lowering the pressure in a flask, heating a solution, and rotating the flask to form a thin layer of solvent, we remove solvents from solutions in order to isolate our products. While the rotation of the flask can certainly be hypnotizing, we must be careful not to get distracted and “bump” the solution, which refers to violent, rapid boiling of solvents under low pressure. Bumping can occur if we create too strong of a vacuum too quickly.
Lawful Evil: Many of our reactions are sensitive and do not run well when exposed to air. Our Gas Lines help to ensure that our reactions take place under nitrogen, an inert atmosphere.
Neutral Evil: A grown-up version of TLC, Column Chromatography is a technique that we use to isolate and purify the products of our reactions. Arguably the prettiest lab technique, column chromatography requires us to collect a series of (often colorful) fractions. Fractions are small amounts of a solution that drips out of the bottom of the column. We then use TLC to identify the contents of each fraction to see which fractions contain our target product.
Chaotic Evil: Kugelrohr… the name says it all. “Hot N Cold” by Katy Perry is this instrument’s favorite song. This instrument uses extreme temperature differences in order to distill small samples.
Funk Lab Solvents Alignment Chart
Lawful Good: This was an easy choice! Ethyl Acetate is one of our favorite solvents in the Funk Lab. It is super useful for cleaning grease and oil, and comes in a pretty green squirt bottle! In a pinch, Danielle has been known to use this solvent to remove old nail polish that she is tired of.
Neutral Good: Another useful solvent, Acetone is used for a majority of our glassware cleaning in the Funk lab. It is dependable and pretty harmless if accidentally gotten on the skin. It smells like nail polish remover, too – mmmm, tasty!
Chaotic Good: Auden has used Tetrahydrofuran (THF) as a solvent in some pretty intense reactions, but it has never let him down.
Lawful Neutral: Deuterated Chloroform gets the job done as a solvent when using the NMR. With an added bonus of tetramethylsilane, you can be sure that your chemical shifts will be on lock!
True Neutral: Deionized Water… with a pH of 7, you can’t get any more neutral than this solvent.
Chaotic Neutral: Sometimes, Bryn just doesn’t feel like using deuterated chloroform for her NMR experiments. To better mirror the experiments that her NMR studies model, she adds Deuterated Benzene (C6D6) to isopropanol. A bit hard to come by, C6D6 comes in glass ampules, which Bryn has to break open in order to access this helpful solvent.
Lawful Evil: Toluene works well in our alcohol oxidation reactions, but is a bit of an attention-seeker. Every morning, Auden or Danielle takes around 10 minutes to “degas” the toluene, which is the process of flushing out any air bubbles in the toluene through bubbling it with nitrogen. Each morning, one of the most common questions on Auden and Danielle’s side of the lab is: “Has the toluene been degassed yet?”
Neutral Evil: When you need to quench an oxidation or reduction, look no further than Hexanes! Bryn uses this nonpolar solvent to ensure the accuracy of her kinetic experiments, but it comes in the same color bottle as her dichloromethane! This devious mimicry can get quite confusing if she isn’t careful!
Chaotic Evil: Dichloromethane (DCM) introduces herself as the solvent that’s able to rinse permanent marker off of glassware – how handy! Unfortunately, the more you get to know her, the more she tries to give you chemical burns. You know how you wear gloves in chem lab to protect yourself from dangerous substances? Well, DCM has a special trick up her sleeve! She likes to soak right through your gloves to begin burning your skin; while it initially feels similar to the cool mist of acetone evaporating from your hand, it simply gets worse and worse even after you run to the sink to wash your hands! These days, Emily finds that wearing gloves while dispensing DCM actually works against her, forcing her to first rip off her gloves before dashing to get soap and running water while yelling, “Oh god, make it stop!”