Department of Chemical and Biomolecular Engineering

In vivo cell engineering enables chimeric antigen receptor (CAR) production directly within the body. Most in vivo CAR approaches target broad T cell populations. However, antigen-presenting nanoparticles could be used to engineer specific T cell subsets, leveraging the phenotypic and functional properties of the cells for T cell therapy.

Inverse ZrO₂/Cu catalysts, where Zr oxide is deposited on Cu particles, show a high catalytic performance converting CO₂ to methanol. We employ density functional theory (DFT) calculations to investigate the CO₂ hydrogenation reaction mechanisms on a model of highly dispersed Zr oxide clusters on Cu (111). The exploration is not performed on a single active site configuration but across an ensemble of 83 formate configurations accessible under reaction conditions. Detailed reaction-pathway analysis reveals that structural sensitivity is pronounced, and only 10 of the catalyst configurations are significantly active across the full pathway. The turnover frequency of the studied inverse structures is largely determined by reaction steps after methoxy formation, rather than the formate hydrogenation steps, and the energy of the methoxy intermediate is a key reactivity descriptor. Two hypotheses are presented for the ensemble average activity: where the probabilities of site populations are determined at the formate intermediate, or at the methoxy resting state. The latter, compared to the former, drastically changes the site distribution, eliminating active structures and decreasing the average rate by a factor of 1000. Catalyst rigidity helps maintain activity by slowing down the structural evolution from the more active formate-bound states to the less active methoxy-bound states.

ABSTRACT Inverse ZrO 2 /Cu catalysts, where Zr oxide is deposited on Cu particles, show a high catalytic performance converting CO 2 to methanol. We employ density functional theory (DFT) calculations to investigate the CO 2 hydrogenation reaction mechanisms on a model of highly dispersed Zr oxide clusters on Cu (111). The exploration is not performed on a single active site configuration but across an ensemble of 83 formate configurations accessible under reaction conditions. Detailed reaction‐pathway analysis reveals that structural sensitivity is pronounced, and only 10 of the catalyst configurations are significantly active across the full pathway. The turnover frequency of the studied inverse structures is largely determined by reaction steps after methoxy formation, rather than the formate hydrogenation steps, and the energy of the methoxy intermediate is a key reactivity descriptor. Two hypotheses are presented for the ensemble average activity: where the probabilities of site populations are determined at the formate intermediate, or at the methoxy resting state. The latter, compared to the former, drastically changes the site distribution, eliminating active structures and decreasing the average rate by a factor of 1000. Catalyst rigidity helps maintain activity by slowing down the structural evolution from the more active formate‐bound states to the less active methoxy‐bound states.

The atomic-scale structure of a metal catalyst surface controls its catalytic performance. Through a combination of high-pressure scanning tunneling microscopy (HP-STM), ambient-pressure X-ray photoelectron spectroscopy (AP-XPS), and machine learning-accelerated computational studies, we uncovered that Pt nanoclusters, formed by restructuring of hex-Pt(100) under reaction conditions involving CO, experience major structural evolution when exposed to increasing CO pressure in the range of 2 × 10^-8-750 Torr. Atom-resolved images and simulations demonstrate that CO binds strongly on these nanoclusters, leading to a CO coverage of one molecule per Pt atom, while the lateral CO-CO repulsion is released by tilting CO molecules outward at the nanocluster edge. Metal nanoclusters break down along as CO pressure is increased from 2 × 10^-8 to 1 Torr with the average size decreasing from 3.2 ± 1.5 to 2.3 ± 1.0 nm, consistent with Pt 4f_7/2 photoemission feature evolution observed with AP-XPS. In contrast, in the pressure range of 1-750 Torr at 25 °C, HP-STM observed a decrease of nanocluster density by 4-5 times, consistent with the growth of the average nanocluster size from 2.3 ± 1.0 nm in 1 Torr CO to 4.6 ± 1.8 nm in 750 Torr. This uncovers a reactant pressure-driven coalescence of nanoclusters even at room temperature. Nanoclusters formed at 25 °C in 750 Torr CO require annealing to 100-130 °C to reach equilibrium size, indicating akinetic control of nanocluster growth at low preparation temperatures, such as room temperature. Our neural network potential (NNP) coupled with basin-hopping (BH) simulations determined the optimal CO coverage and configuration at various CO pressures and showed, in agreement with experiments, an optimum nanocluster size resulting from a competition between the size-dependent energy cost of nanocluster formation and the energy gain through CO adsorption. The formation of Pt nanoclusters, followed by their breakdown with increasing CO pressure from 2 × 10^-8 to 1 Torr and coalescence in CO pressure from 1 to 750 Torr highlights the significance of imaging catalyst nanoparticle surfaces in gas phase at a specific reactant pressure toward establishing a direct structure-catalytic performance correlation.

Accurate adsorption thermodynamics of reactive intermediates at electrified metal interfaces are central to predictive surface science, heterogeneous catalysis, and electrochemical modeling, yet remain challenging for standard density functional approximations and difficult to benchmark experimentally. Here we apply electrochemical-aware random phase approximation (RPA) methods that incorporate solvent dielectric screening and grand-canonical constant-potential control to establish a reference-quality description of hydroxyl (*OH) adsorption on Cu(100) in electrocatalytic conditions. At the potential of zero charge (pzc), we quantify the site dependence of *OH binding across terrace sites and representative defective motifs. Under applied potential, electrochemical-aware RPA reproduces the experimentally inferred *OH desorption fingerprint, predicting an *OH desorption potential of -0.54 V vs SHE, in excellent agreement with experimental value -0.56 V vs SHE at pH = 7, whereas widely used GGA functionals (PBE, RPBE) underestimate *OH stability and compress the stability window under reducing conditions. G₀W₀-RPA electronic structure analysis provides a mechanistic rationale for the discrepancy. Finally, we reassess the Cu(100) surface-state diagram with *OH and *CO coadsorption under electrochemical conditions, including the stability of metastable CuCO(OH)_n motifs, and show that many-body accuracy can qualitatively alter predicted interfacial speciation. Overall, our results establish electrochemical-aware RPA as a broadly applicable, systematically improvable many-body framework for quantitative adsorption thermodynamics at constant potential, enabling predictive surface-state maps for complex electrochemical interfaces.

Propane dehydrogenation is a major reaction in industry, as it transforms the abundant propane into propylene, which is a vital raw material for higher-value products. Although Pt-based catalysts have been extensively used for this process, challenges such as over-dehydrogenation and coking often pose obstacles to their effectiveness. Here, we show from first-principles calculations that single-atom alloys formed by dispersing more electropositive, earlier transition metals into Cu(111) could potentially enhance the reactivity and selectivity for propylene formation. Density functional theory (DFT) calculations show that CuIr1 possesses reactivity comparable to pure Pt and that it does not lead to over-dehydrogenation beyond propylene. An even higher propylene production rate, surpassing Pt(111) by 10-fold, is predicted using earlier Hf with CuHf1. This study demonstrates the depletion of anti-bonding orbitals and, hence, the stronger interaction between the rate-limiting transition state for propane activation and the earlier transition metals, an insight applicable to engineering other alloy catalysts.

Interrupted reactions, in which an intermediate is redirected from its conventional mechanistic pathway, offer a unique approach to the assembly of complex natural products. This study details the biosynthesis of a newly discovered family of alkaloids named the subrubines alongside the total synthesis of the penultimate member, pensubrubine, featuring distinct interrupted reaction pathways. These natural products, identified using high-resolution genome mining of an active site mutation, represent the only reported microbial diaza[3.3.3]-propellane pyrrolidinoindolines. We demonstrate through complete pathway reconstitution that the putatively annotated ene-reductase SubF functions as the propellane synthase that directs an enolate intermediate toward an intramolecular Mannich cyclization. Concurrently, a concise 7-step total synthesis of pensubrubine was developed, employing a diastereoselective interrupted Fischer indolization reaction to rapidly construct the diaza[3.3.3]-propellane core and establish the absolute configuration of pensubrubine. The reported bio- and total syntheses of subrubines showcase the value of interrupted pathways in assembling complex scaffolds.

Controlling the surface-adsorbates interactions is critical to advancing numerous chemical processes. Static scaling correlations between adsorption energies of chemically related surface species impose limits on selectivity in chemical processes, as exemplified by constraints in heterogeneous catalysis. Here we demonstrate that dynamic surface polarization under oscillating electric potentials can overcome this limitation in Pd-catalysed acetylene semi-hydrogenation. Unlike static polarization, which only imparts a minor improvement to ethylene selectivity, dynamic polarization drastically enhances selectivity without further sacrificing conversion, yielding a high ethylene productivity. Mechanistic insights from hydrogenation kinetics, in situ diffuse reflectance infrared Fourier transform spectroscopy, X-ray absorption spectroscopy and density functional theory reveal that time-dependent polarization dynamically modulates the Pd’s electronic structure and adsorption energetics. Alternating between strong-binding states with positive polarization during acetylene hydrogenation and weak-binding states with negative polarization during ethylene formation effectively suppresses over-hydrogenation while maintaining semi-hydrogenation activity. This work establishes dynamic electric surface modulation as a powerful strategy for decoupling adsorption-energy correlations to improve heterogeneous catalysis and other adsorption-mediated processes.

The threat posed by chemical warfare agents (CWAs) in the modern era necessitates increased innovation in understanding new mechanisms to neutralize their lethality. By identifying novel materials and chemical reaction pathways, better protection can be offered. Single metal atoms supported on TiO₂ represent a promising avenue of exploration in designing systems which can effectively capture and degrade the sulfur mustard agent. By modelling sulfur mustard and its simulant, 2-chloroethyl-ethylsulfide (2-CEES), this work provides a proof of concept for the facile decomposition pathways of sulfur-containing vesicant agents over Pt, Pd, and Ir single atoms on the anatase TiO₂(101) surface with and without the presence of water. Under ambient conditions, 2-CEES will favorably be transformed into ethyl-vinylsulfide (EVS) through a dehydrochlorination reaction involving C-H and C-Cl bond cleavages. Notably, the single atom cleaves the α-C-H bond with a low calculated barrier. The reaction energetics are most favorable on the Pd system with barriers passable at a temperature of 298 K with EVS desorption facilitated by adsorption and a reaction of additional reactant molecules, and with the produced H and Cl fragments stored on the titania support. The Pd single atom is proposed to be able to degrade 2-CEES and sulfur mustard through a mechanism combining C-H bond cleavage at the Pd-O center and sorption of the H and Cl fragments from 2-CEES or mustard on TiO₂, however with a larger reactivity for the removal of the second Cl of mustard than for dehydrochlorination of a second 2-CEES reactant. The reaction appears as a hybrid combination of catalytic steps evolving products in the gas phase with reactive sorption of the remaining fraction of products on the support.