VIRTUAL STUDENT SCHOLARS SYMPOSIUM 2020 PRESENTATIONS

Chemistry - Poster Presentations

High School Division

Applying the Surface Plasmon Resonance of Gold Nanoparticles to Denature Proteins Characteristic of Alzheimer's Disease
Cooper J Hanley, Monarch High School

Beta-secretase (BACE), an enzyme responsible for the endoproteolysis of amyloid precursor protein to produce the hallmark amyloid-beta plaques of Alzheimer's pathology, has been of considerable interest to the medical community as a target for drug development. Yet, numerous small-molecule therapeutic candidates developed for BACE have faltered in clinical trials due to a lack of specificity, adverse side effects, or an inability to cross the blood-brain barrier, demonstrating the need for innovative alternatives. In contrast with the small-molecule approach, this experiment investigated whether the surface plasmon resonance induced oscillation of 800 nm near-infrared resonant gold nanorods, and their consequent ability to generate localized heat, could serve as a mechanism to denature BACE. To determine whether gold nanorod-mediated photothermal therapy successfully denatured the enzyme, tryptophan fluorescence analysis was utilized to track its structural changes. The results suggest that by conjugating gold nanorods with BACE via polyethylene glycol and anti-BACE antibodies, the denaturation of BACE was induced upon irradiation with near-infrared light. This novel tactic, which has never been translated from the cellular to the molecular level, indicates the potential of plasmonic nanogold in protein-specific therapeutics. These findings may serve as a platform for addressing the shortcomings of past drug development for Alzheimer’s disease, and for a diverse array of other therapeutic applications in protein-related illnesses.

Characterization of Cr-doped ε - LiVOPO4 as a Novel Cathode for Higher Energy Lithium-ion Batteries Using a First-Principles DFT Approach
Vedanth B Iyer, Sunset High School

Lithium-ion batteries power essentially all of the world’s technology and infrastructure however, the current Lithium-ion batteries are not able to provide sufficient energy needed for many rechargeable devices including smart-phones, electric-vehicles and active implantable medical devices (AIMDs). Additionally, with the development of next-generation technologies, there is an even higher demand for higher capacity batteries. To increase the capacity and efficiency of batteries, a higher-energy next-generation cathode must be produced to meet consumer demands and safety standards. Commercial cathodes such as LiCoO₂ have relatively low energy capacities and cathode efficiency so to solve the current cathode problems, a novel Cr-doped ε-LiVOPO₄ cathode was developed and characterized using First-Principles Density Functional Theory. Chromium is generally an uncommon dopant choice for electronic materials but in this specific framework, proves to significantly improve the electrochemical and structural performance. The delithiation behavior proves that Cr-LiVOPO₄ has a chemically reversible framework with full delithiation and the Li-insertion energies over multiple lithium intercalation are extremely low. Additionally, the bandstructure shows that Cr-LiVOPO₄ has extremely low bandgaps thus having a significantly higher electronic conductivity than conventional LiCoO₂. Nudge Elastic Band further shows the compatibility of Cr-LiVOPO₄ as a cathode material as the novel material displays optimal cathode behavior showing extremely favorable Li+ migration along the 1-D octahedral chains but not the 3-D pathways. Overall, Cr-LiVOPO₄ displays a theoretical energy capacity of 2.5x more than LiCoO₂ translating to over 500 mAh/g making Cr-doped ε-LiVOPO₄ an extremely promising candidate for higher energy, next generation Li-ion batteries.

Undergraduate Division

Discovery and Characterization of Novel Sedatives via High-Throughput Screening, Behavioral Profiling of Zebrafish, and Chemical Synthesis
Jung Ho Gong, Brown University

In 2017, the US Department of Health Services declared a public health emergency as opioid-overdose deaths accounted for more than 40% of drug overdose deaths. Co-prescription of opioids and benzodiazepines, prescription sedatives such as Valium and Xanax, which account for 30% of opioid overdose deaths, have contributed significantly to the public health crisis. To address the necessity of a new class of anesthetics, we have focused on the discovery of novel sedatives using zebrafish as a powerful drug discovery tool for small molecule screening so that physiology of consciousness and anesthesia can be better understood. Our collaborators at University of California, San Francisco (UCSF) screened 10,000 novel, structurally diverse compounds using high-throughput behavior-based drug profiling and identified an isoflavone compound. The top hit compound induces sedation through γ-aminobutyric acid type A receptor (GABAAR), whose key agonist, GABA, is the chief inhibitory neurotransmitter of central nervous system. We explored the chemical spaces in isoflavone and synthesized over 30 isoflavone analogs using a diversity-oriented synthesis approach. These isoflavone analogs were assessed at UCSF using the behavior-based drug profiling assay. We identified two compounds that further improved the sedative effect of the top hit compound from the high-throughput behavior-based drug profiling. Together, this multi-institutional study identified a structurally novel sedative and further improved its efficacy using the principles of structure-activity relationship. Further work is ongoing to identify these analogs’ binding site within GABAAR and understand their effects on zebrafish brain.

Antibacterial effects of organosulfur compounds against gram-negative bacteria
Zamiur Rahman, New York Institute of Technology

Antibiotic resistance is a growing concern and novel antibiotics with new mechanisms of action are needed. Hydrogen sulfide (H2S) is a biological signaling molecule, which has diverse functions in mammalian cells including pro- or anti-tumorigenic activity, and possibly antibacterial activities. Organosulfur compounds (OSC) may release H2S. We examined a group of OSCs produced by fermentation or by chemical synthesis for their chemical moieties for possible release of H2S. From these, Difurfuryl disulfide (DFFDS), 3-(Methylthio) Propyl Isothiocyanate (3MPITC), and Methyl 2-methyl 3-furyl disulfide (MMFD) were examined for antibacterial properties. Disk diffusion method was used to test gram negative bacteria Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa , using paper disks saturated with 30 μL OSC at various concentrations. In broth, the OD was measured with various concentrations of the compounds and growth curves were plotted. H2S release was measured in an in-vitro kinetic assay using methylene blue, with OSC or cysteine, followed by collection of the absorption spectra. Disc diffusion assays revealed that 3MPITC produces concentration dependent increases in the zone of inhibition on all three gram-negative bacteria. DFFDS showed no zones on any of the bacteria. We focused on 3MPITC for growth curve analysis, wherein Klebsiella showed a concentration dependent inhibition obacterial growth with an IC50 of approx 75 mM. DFFDS and 3MPITC exhibited evidence of H2S release, and further studies are needed to resolve solubility issues to compare the amount of H2S release. Our results show promise in this new category of H2S releasing antibacterial compounds.

Graduate Division

Divergence of Many-Body Perturbation Theory in Noncovalent Interactions
Brian D Nguyen, University of California, Irvine

Many-body perturbation theory (MBPT) has been the method of choice to predict
noncovalent interactions (NIs). The assumption that “weak” closed-shell interactions between
distant electron pairs are accurately captured by MBPT is implicit in many applications as well as theoretical approaches such as local correlation methods. How- ever, recent benchmark calculations for supramolecular complexes with 4 − 206 atoms revealed large errors in NI energies of supramolecular complexes obtained from MBPT. Noncovalent interactions (NIs) play a large role in structural biology and supramolec- ular chemistry. The prediction of NIs remains an outstanding computational challenge. Many-body perturbation theory (MBPT) has been the approach to predict NIs such as the efficient second-order Møller-Plesset perturbation theory (MP2) which is accu- rate for small complexes based on the S66 benchmark. However, recent reports re- vealed large errors in NI energies of supramolecular complexes obtained from MBPT. Prompted by these errors, we compare the performance of MP2, spin-scaled MP2, dispersion-corrected semilocal density functional approximations (DFAs), and the post- Kohn–Sham random phase approximation (RPA) for predicting binding energies of complexes within the S66, L7, and S30L benchmarks. Numerical results demonstrated that the accuracy of MP2 severely deteriorates as the system size grows with an er- ror rate of 0.1% per electron. Whereas, empirical dispersion-corrected DFAs and RPA errors remain virtually constant.
To analyze these results, the asymptotic adiabatic connection symmetry-adapted perturbation theory (AC-SAPT) is developed which uses monomers at full coupling whose ground-state density is constrained to the ground-state density of the complex. Taylor series expansion of AC-SAPT interaction energies with respect to the coupling strength integrand is shown to be convergent for nondegenerate monomers when RPA is used, while it spuriously diverges for second-order MBPT. Based on the analysis and numerical results, MBPT for NIs may safely be replaced with non-perturbative approaches such as RPA or coupled cluster methods.

VIRTUAL STUDENT SCHOLARS SYMPOSIUM 2020 PRESENTATIONS

Chemistry - Poster Presentations

High School Division

Undergraduate Division

Graduate Division

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