Our research sits at the intersection of reaction discovery, physical organic chemistry, and scientific training. Each project in the lab generates new chemical knowledge while giving undergraduate researchers authentic ownership of open-ended problems. The threads below are interconnected: iodonium salts from one project feed into another, amines synthesized in the teaching lab become substrates for new bond-forming reactions, and computational models validate experimental measurements across the program.
Arynes are short-lived, highly strained aromatic intermediates that behave simultaneously as electrophiles and nucleophiles. This dual character allows them to insert directly into polarized sigma bonds, forming two new bonds in a single step. While aryne insertion into C-N, C-O, and N-Si bonds is well precedented, insertion into boron-heteroatom bonds had not been explored before our work.
We have demonstrated proof-of-concept for B-O bond activation using benzyne and trimethyl borate, observing an 8:1 selectivity for the insertion product. DFT calculations (M06-2X/6-311+G**) predict a concerted, highly exergonic pathway consistent with the experimental selectivity. We have since extended this chemistry to B-Cl bond activation with boron trichloride, and current work targets boronic esters, boroxines, and B-N bonds.
A practical challenge in this area is aryne precursor synthesis. The standard Kobayashi method requires cryogenic conditions and air-sensitive reagents, presenting real barriers for early-stage researchers. Our lab has transitioned to aryl(TMP)iodonium triflate salts, bench-stable crystalline solids prepared from simple aryl iodides without cryogenic handling. This switch has made aryne chemistry genuinely accessible in an undergraduate setting.
This chemistry also enables a modular route to medicinally relevant tertiary amines. Secondary amines prepared by green reductive amination (see CURE section below) serve as substrates, and iodonium salt-derived arynes insert into the N-H bond to form a new C-N bond. Tertiary amines appear in an extraordinary fraction of approved drugs, from cetirizine (Zyrtec) to clomipramine (Anafranil), making efficient routes to this pharmacophore broadly valuable.
Screening across a matrix of iodonium salts and inorganic bases has identified NaOtBu as the most broadly effective base, with 4-chloro (89%), 4-Me (97%), and 3-fluoro (100% with Cs₂CO₃) iodonium salts showing strong conversion at gram scale. Electron-deficient substrates (4-CN, 3-CN) show limited conversion, indicating sensitivity to arene electronics that will inform future optimization. This project is the convergence point of three lab threads: iodonium salt preparation, green amine synthesis, and aryne insertion chemistry.
Substrate scope expansion across symmetric borates, pinacol and catechol boronic esters, and boroxines. Regioselectivity studies with unsymmetric aryne precursors. Isolation and full characterization of the tertiary amine product library. One-pot sequences from primary amine, aldehyde, and aryl iodide.
Organoboron compounds are among the most versatile functional groups in modern synthesis, central to Suzuki coupling, oxidation, and a growing list of FDA-approved drugs. Yet the Hammett sigma values for common boryl substituents, the quantitative descriptors that tell chemists how electron-donating or withdrawing a group is, have never been experimentally determined. The A-value for pinacol boronic ester was only reported in 2020. We set out to fill this gap.
Our target set includes B(OH)₂, Bpin, Bcat, BF₃K, Bneop, Bdan, and Bmida, measured as both meta- and para-substituted benzoic acid derivatives (14 compounds total). We use two complementary methods: potentiometric titration for water-compatible substrates and UV-vis spectrophotometric titration (using P₄-t-Bu base and para-nitrobenzoic acid reference) for water-sensitive boronic esters.
In collaboration with Dr. Prajay Patel, DFT calculations and machine learning methods complement the experimental measurements, providing a mechanistic picture of why different boryl ligands produce different effects and extending predictive reach beyond the directly measured compounds.
This project is no longer an active experimental focus, but the accumulated dataset represents genuinely new physical organic data. Manuscript preparation is a clear priority, with undergraduate researchers from the original experimental campaigns as co-authors.
Reductive amination is one of the most important methods in organic chemistry for building C-N bonds. The standard undergraduate procedure uses sodium triacetoxyborohydride in dichloromethane, a probable human carcinogen classified by the EPA, IARC, and OSHA. In 2024, the EPA issued a final rule banning most consumer and industrial uses of DCM, with only a narrow laboratory exemption remaining. Training students to default to a probable carcinogen is at odds with the 12 Principles of Green Chemistry.
Students have developed a DCM-free alternative. We surveyed 13 alternative solvents and identified 2-MeTHF as the optimal replacement: renewable (derived from furfural), biodegradable, water-immiscible for straightforward workup, and delivering 78% isolated yield under the same mild conditions. The method has been validated across five aniline derivatives (80-100% yield) and nine structurally diverse aldehydes (45-100% yield), preserving all the pedagogical advantages of the original procedure.
This chemistry is the foundation of our NSF-supported Course-Based Undergraduate Research Experience (CURE) in Organic II. The CURE replaces cookbook labs with open-ended research: after instrument training and a benchmark reaction, students propose their own variables, run experiments across a 10-week campaign, and write up results in journal format. Every student generates data that has not been collected before. Fall 2023 pilot feedback was striking: engagement was high, and students reported that the experience made research feel accessible rather than intimidating.
Continued substrate scope expansion through the CURE; manuscript preparation for J. Chem. Educ. with undergraduate co-authors; NSF-funded instrument acquisition (benchtop NMR with autosampler, FTIR, rotary evaporator) to address bottleneck equity issues identified in the pilot.
Aviation fuel spills at airbases and airports cause lasting environmental harm, and no permanent, green remediation solution exists at scale. Pseudomonas aeruginosa, a bacterium abundant at contaminated sites, degrades jet fuel hydrocarbons through AlkB1 and AlkB2 monooxygenases, but the genes controlling when these enzymes are expressed remain poorly understood.
Dr. Cody's lab is mapping the regulatory pathway through insertional inactivation genetics. Our contribution is the analytical chemistry: developing extraction methods and GCMS protocols to quantify which hydrocarbons are degraded, at what rate, and to what extent by each mutant strain. Without rigorous quantification of degradation efficiency, the genetic screen cannot be interpreted.
This collaboration has been a productive training ground for students bridging chemistry and biology. Theo Nguyen has presented this work across five venues, earning 1st Place at both the ACS Southwest Regional Meeting (2024) and the ASM National Meeting (2025, Orville Wyss Award).
In collaboration with Dr. Prajay Patel, we are building machine learning models that predict Hammett sigma constants from readily obtainable inputs. The motivation grew directly from the experimental challenges of the Hammett project: pKₐ measurement by titration is demanding and slow. Can we predict sigma values instead from data that any synthetic chemist can generate?
Two descriptor classes are being developed in parallel. On the computational side, Hirshfeld atomic charges from DFT-optimized structures (CAM-B3LYP/def2-TZVP) serve as inputs to Random Forest, Multilayer Perceptron, and Lasso LARS models trained on 90 known sigma values. The MLP model achieves R² = 0.90 on para-substituted compounds. On the experimental side, ¹³C NMR chemical shifts of benzoic acid scaffold carbons serve as a complementary descriptor set. A library of 70 substituted benzoic acids has been characterized, with a custom Python workflow for automated scaffold atom identification and peak extraction.
The long-term vision is a multimodal model combining both DFT charges and NMR shifts as joint inputs, potentially outperforming either alone and applicable to novel substituents including the boryl groups from our Hammett project.
Commercial e-cigarette liquids report nicotine concentration and a general flavor description, but the dozens of chemical compounds that make up the flavor profile are neither identified nor disclosed. Many common flavoring agents are recognized as safe for ingestion but untested for inhalation, a fundamentally different exposure route. This matters directly to Dr. Toby's research on lung cellular physiology and disease signaling.
We are using GCMS to answer three questions: Does labeled nicotine concentration match what is in the bottle? What specific compounds make up the flavor profiles? And how does that composition change after heat exposure at temperatures reachable inside a parked car in summer (55-65°C)?
The thermal degradation question is especially underappreciated. Esters, aldehydes, terpenes, and other thermally labile flavor compounds can decompose or rearrange at these temperatures, meaning consumers may be inhaling a chemical mixture that differs substantially from what was manufactured and labeled.