Honors & Awards
Accel Leadership Fellowship, Stanford Technology Ventures Program (2020-2021)
DARE Doctoral Fellowship, Stanford University (2020-2022)
Excellence in Advocacy Award, Stanford University (2019)
Community Partnership Award, Stanford Office of Government and Community Relations (2019)
EDGE-STEM Doctoral Fellowship, Stanford University (2015)
Outreach Excellence Award, Stanford Department of Chemistry (2018)
Phenolate-bonded bis(μ-oxido)-bis-copper(III) intermediates: hydroxylation and dehalogenation reactivities.
Exogenous phenolate ortho-hydroxylation by copper oxidants formed from dioxygen is generally thought to occur through one of two limiting mechanisms defined by the structure of the active oxidant: an electrophilic μ-η2:η2-peroxo-bis-copper(II) species as found in the oxygenated form of the binuclear copper enzyme tyrosinase (oxyTyr), or an isomeric bis(μ-oxido)-bis-copper(III) species (O) with ligated phenolate(s) as evidenced by most synthetic systems. The characterization of the latter is limited due to their limited thermal stability. This study expands the scope of an O species with ligated phenolate(s) using N,N'-di-tert-butyl-1,3-propanediamine (DBPD), a flexible secondary diamine ligand. Oxygenation of the [(DBPD)Cu(I)]1+ complex at low temperatures (e.g., 153 K) forms a spectroscopically and structurally faithful model to oxyTyr, a side-on peroxide intermediate, which reacts with added phenolates to form a bis(μ-oxido)-bis-copper(III) species with ligated phenolates, designated as an A species. The proposed stoichiometry of A is best understood as possessing 2 rather than 1 bonded phenolate. Thermal decomposition of A results in regiospecific phenolate ortho-hydroxylation with the ortho-substituent as either a C-H or C-X (Cl, Br) group, though the halogen displacement is significantly slower. DFT and experimental studies support an electrophilic attack of an oxide ligand into the π-system of a ligated phenolate. This study supports a hydroxylation mechanism in which O-O bond cleavage of the initially formed peroxide by phenolate ligation, which precedes phenolate aromatic hydroxylation.
View details for DOI 10.1039/d1fd00071c
View details for PubMedID 35156114
Curiosity-Based Biophysics Projects in a High School Setting with Graduate Student Mentorship
2021; 2 (1): 6-11
View details for DOI 10.35459/tbp.2019.000136
Development of Decreased-Gluten Wheat Enabled by Determination of the Genetic Basis of lys3a Barley
2019; 179 (4): 1692–1703
Celiac disease is the most common food-induced enteropathy in humans, with a prevalence of approximately 1% worldwide. It is induced by digestion-resistant, proline- and glutamine-rich seed storage proteins, collectively referred to as gluten, found in wheat (Triticum aestivum). Related prolamins are present in barley (Hordeum vulgare) and rye (Secale cereale). The incidence of both celiac disease and a related condition called nonceliac gluten sensitivity is increasing. This has prompted efforts to identify methods of lowering gluten in wheat, one of the most important cereal crops. Here, we used bulked segregant RNA sequencing and map-based cloning to identify the genetic lesion underlying a recessive, low-prolamin mutation (lys3a) in diploid barley. We confirmed the mutant identity by complementing the lys3a mutant with a transgenic copy of the wild-type barley gene and then used targeting-induced local lesions in genomes to identify induced single-nucleotide polymorphisms in the three homeologs of the corresponding wheat gene. Combining inactivating mutations in the three subgenomes of hexaploid bread wheat in a single wheat line lowered gliadin and low-molecular-weight glutenin accumulation by 50% to 60% and increased free and protein-bound lysine by 33%.
View details for DOI 10.1104/pp.18.00771
View details for Web of Science ID 000462993100042
View details for PubMedID 30696748
View details for PubMedCentralID PMC6446766
Selective Oxidation of Exogenous Substrates by a Bis-Cu(III) Bis-Oxide Complex: Mechanism and Scope.
Inorganica chimica acta
2019; 486: 782-792
Cu(III)2(μ-O)2 bis-oxides (O) form spontaneously by direct oxygenation of nitrogen-chelated Cu(I) species and constitute a diverse class of versatile 2e-/2H+ oxidants, but while these species have attracted attention as biomimetic models for dinuclear Cu enzymes, reactivity is typically limited to intramolecular ligand oxidation, and systems exhibiting synthetically useful reactivity with exogenous substrates are limited. O tmpd (TMPD = N 1 , N 1 , N 3 , N 3 -tetramethylpropane-1,3-diamine) presents an exception, readily oxidizing a diverse array of exogenous substrates, including primary alcohols and amines selectively over their secondary counterparts in good yields. Mechanistic and DFT analyses suggest substrate oxidation proceeds through initial axial coordination, followed by rate limiting rotation to position the substrate in the Cu(III) equatorial plane, whereupon rapid deprotonation and oxidation by net hydride transfer occurs. Together, the results suggest the selectivity and broad substrate scope unique to O tmpd are best attributed to the combination of ligand flexibility, limited steric demands, and ligand oxidative stability. In keeping with the absence of rate limiting C-H scission, O tmpd exhibits a marked insensitivity to the strength of the substrate Cα-H bond, readily oxidizing benzyl alcohol and 1 octanol at near identical rates.
View details for DOI 10.1016/j.ica.2018.11.027
View details for PubMedID 31485082
View details for PubMedCentralID PMC6724545
Exclusive imidazole ligation to CuO2 and CuIIICuO2 cores.
Chemical communications (Cambridge, England)
We disclose herein the synthesis and characterization of L2Cu(iii)2O2 and L3Cu(iii)Cu(ii)2O2 complexes with nitrogen ligation exclusively from imidazoles for the first time. Their accessibility by direct oxygenation of a L-Cu(i) precursor and the resulting Cu(iii) formation inform on the kinetic accessibility and thermodynamic superiority of imidazole in stabilizing Cu(iii).
View details for DOI 10.1039/c9cc02982f
View details for PubMedID 31173011
A realistic in silico model for structure/function studies of molybdenum-copper CO dehydrogenase
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
2016; 21 (4): 491-499
CO dehydrogenase (CODH) is an environmentally crucial bacterial enzyme that oxidizes CO to CO2 at a Mo-Cu active site. Despite the close to atomic resolution structure (1.1 Å), significant uncertainties have remained with regard to the protonation state of the water-derived equatorial ligand coordinated at the Mo-center, as well as the nature of intermediates formed during the catalytic cycle. To address the protonation state of the equatorial ligand, we have developed a realistic in silico QM model (~179 atoms) containing structurally essential residues surrounding the active site. Using our QM model, we examined each plausible combination of redox states (Mo(VI)-Cu(I), Mo(V)-Cu(II), Mo(V)-Cu(I), and Mo(IV)-Cu(I)) and Mo-coordinated equatorial ligands (O(2-), OH(-), H2O), as well as the effects of second-sphere residues surrounding the active site. Herein, we present a refined computational model for the Mo(VI) state in which Glu763 acts as an active site base, leading to a MoO2-like core and a protonated Glu763. Calculated structural and spectroscopic data (hyperfine couplings) are in support of a MoO2-like core in agreement with XRD data. The calculated two-electron reduction potential (E = -467 mV vs. SHE) is in reasonable agreement with the experimental value (E = -558 mV vs. SHE) for the redox couple comprising an equatorial oxo ligand and protonated Glu763 in the Mo(VI)-Cu(I) state and an equatorial water in the Mo(IV)-Cu(I) state. We also suggest a potential role of second-sphere residues (e.g., Glu763, Phe390) based on geometric changes observed upon exclusion of these residues in the most plausible oxidized states.
View details for DOI 10.1007/s00775-016-1359-6
View details for Web of Science ID 000378819300006
View details for PubMedID 27229512