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Center for Advanced Scientific Computing and Modeling
Department of Chemistry
University of North Texas
1155 Union Circle #305070
Denton, Texas 76203-5017

Phone: (940) 565-4372
Fax: (940) 565-4318

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The chemistry building at the University of North Texas. CASCaM Instituted at UNT   [ Official UNT News Story ]
The University of North Texas is the home of the Center for Advanced Scientific Computing and Modeling (CASCaM), whose central mission involves research, education, training and outreach in all facets of advanced scientific computing and modeling. The CASCaM facility, supported by the United States Department of Education, the United States Department of Energy, and the United States Air Force Research Laboratory, affords excellent opportunities for collaboration with UNT computational chemists for students and faculty mentors in Texas and the surrounding states. You can download the official brochure here (PDF format).

Chemistry student receives Honorable Mention for NSF Graduate Research Fellowship Program
Emmett Leddin, a graduate student in Dr. Andrés Cisneros' lab, has received a Honorable Mention for the National Science Foundation Graduate Research Fellowship Program. There are many perks and much prestige for receiving an Honorable Mention. According to the letter received by Mr. Leddin, he will receive "enhanced access to cyberinfrastructure resources, including supercomputing time, in support of research toward completion of the graduate program of study." Mr. Leddin will also be able to request access to the XSEDE resources and services..

You can read the UNT Chemistry article here.

You can learn more about the fellowship here.

You can learn more about the XSEDE resources and services here.

Chemistry students present during the ACS National Meeting and Exposition
Several Chemistry students (listed below) working with Drs. Andrés Cisneros and Thomas Cundari presented research talks during the Annual ACS National Meeting and Exposition in Orlando, FL, March 31-April 4, 2019.

  • Yavus Ceylan presented a poster entitled "Theoretical study on hydrolysis of β-lactam antibiotics and their structures with β-lactamases"
    • Abstract: Density functional theory (DFT), quantum mechanical/molecular mechanical (QM/MM), and molecular dynamics (MD) calculations were applied in studying the reaction of seven different β-lactam ruthenocenyl-ADBA (ADBA = aminodesacetoxybetalactamic acid) antibiotics with the CTX-M enzyme. The mechanism was studied in the gas phase and water solvent, and is summarized as follows: the antibiotic (β-lactam) forms an adduct with the enzyme (protein binding protein, PBP), PBP-OH, then the hydroxyl group of the serine forms a covalent acyl linkage with the β-lactam carbonyl group; serine β-lactamases made by PBPOH hydrolyze the covalent acyl-enzyme linkage, regenerating the enzyme, thus degrading the antibiotics. The catalytic process was characterized by two distinct free energy barriers: the formation of the covalent acyl linkage with β-lactam carbonyl group and its breaking to serine β-lactamases and inactivated drug. Based on kinetic and thermodynamic parameters, the rate-determining step of the process is associated with the second transition state and carbapanem was found as best inhibitory candidate. In order to better establish the interactions between the enzyme and the drug, the catalytical and binding residue of the enzyme was evaluated via QM/MM calculations. The serine 70 residue was found as the preferred catalytic site for the inhibitor by having quite strong nucleophilic oxygen. Also the site is adjacent to more residues, which result in more hydrogen bonds with the inhibitors. The level of inhibition and antibacterial properties of optimized transition state structures were evaluated. Molecular dynamics calculations gave insight about structure-activity relationships (SARs) that connect the computed energy diagrams of β-lactam hydrolysis with reported IC50 (μM) measurements. Our findings demonstrate how metallocenyl groups can be utilized to enhance the interactions between β-lactam compounds and the target bacterial enzymes.
  • Emmett Leddin presented two posters:
    • Computational investigation of single nucleotide polymorphisms in human DNA polymerase κ: DNA polymerase κ (pol κ) is a member of the Y-family DNA polymerases that perform translesion synthesis. Single nucleotide polymorphisms in pol κ have been implicated in several different cancers. The primer extension activity and single-nucleotide incorporation kinetics of nine variants of pol κ were investigated experimentally with DNA containing correct base pairs at the primer terminus and mismatches. These variants were grouped into having either more, similar, or less activity to the wild-type (WT) protein. The WT and five variants, spanning across those three categories, were then simulated using molecular dynamics (MD) with either the correctly- or incorrectly-matched incoming nucleotide triphosphate. Several notable changes are seen between the systems, and structural differences show a similar pattern to those found experimentally. Most notably, mutants that were identified as less active with the correct incoming nucleotide shared structural characteristics with the WT structure with the incorrect incoming nucleotide. These results suggest that there may be different conformations for pol κ activity that are codependent on protein variant and DNA adduct identity.
    • Computational investigation of TET2 activity on RNA-containing substrates: TET2 is a protein implicated in several myeloproliferative disorders, including acute myeloid leukemia. TET2 catalyzes a stepwise oxidation from 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to 5-formylcytosine (5fC) to 5-carboxylcytosine (5caC). Experimental investigation of TET2 activity with various DNA, RNA and DNA-RNA substrates indicate that all-DNA strands were preferred over either dsDNA or ssDNA with a corresponding ribo-5mC target base, which showed a significant reduction in activity. Molecular dynamics (MD) simulations have been performed to investigate the impact that RNA's 2' hydroxyl at the target position of the DNA strand complexed with TET2 in both single-stranded and double-stranded contexts. These analyses reveal significant structural and dynamical changes between the DNA-only backbone and the mixed DNA-RNA backbone, which may impact the oxidation of 5mC, and provide an explanation for the differences in stalling behavior seen experimentally.
  • Catherine Moulder presented a poster entitled "DFT survey of the effects of d-electron count and metal identity on the activation and functionalization of C-H bonds for mid to late transition metals"
    • Abstract: The contribution of metal identity to the activation and functionalization of methane by a series of three-coordinate imide complexes is evaluated in silico for a 3-by-3 block of metals from Fe to Pt. Three mechanisms were studied: oxidative addition (OA) to the metal; hydrogen atom abstraction (HAA) by the imide nitrogen; and, 2+2 addition across the metal-imide bond. In no studied case, was a 2+2 mechanism preferred, perhaps suggesting this mechanism is largely (entirely?) the domain of d0 imides. There is a diagonal relationship within the nonet of metals studied in that OA is preferred for earlier, heavier (5d) members of the series, transitioning to an HAA mechanism for later, lighter (3d) imides. DFT indicates that important parameters in partitioning between HAA and OA mechanisms include the strength of the metal-imide π-bond, the ability of larger metals to accommodate increases in formal oxidation state and coordination number, and the soft acid/base compatibility of larger transition metals with soft hydride and methyl ligands.
  • Ahmad Najafian presented a poster titled "DFT modeling of the complete catalytic cycle of methane-to-methanol via Earth-abundant late 3d bimetallic complexes"
    • Abstract: In methanotrophic bacteria, methane monooxygenase enzymes (MMOs) are responsible for directly and selectively oxidizing methane to methanol; the active site of the enzyme contains a diiron(IV) bis-μ-oxo species. In the present work, inspired by the nature, different bimetallic-oxo complexes were modeled with density functional theory to calculate complete catalytic cycles of methane conversion to methanol (C-H activation and oxy-insertion reactions). We focused our attention on mid – late, Earth-abundant 3d transition metals using N,O- (oxypiridinate) supporting ligands to elucidate important trends. To explore the potential of various bimetallic catalyst candidates, two series of bimetallic complexes were investigated: (1) CoMb, where Mb = Fe, Co or Ni, and (2) MaCo, where Ma = Fe, Co or Ni. Per previous research on M-M complexes, the B3LYP-D3/6-311+G(d,p)/SMD-acetone level of theory was selected for the calculations. The plausible pathways for the reactions were surveyed by computing the barriers and thermodynamics of the reactions. Two possibilities for C-H bond scission by M-M-oxo complexes were calculated: (1) hydrogen atom abstraction (HAA) -radical rebound (RR), and (2) [2 + 2] addition in which the C-H bond is cleaved by the active metal-oxo, via a kite-shaped, four-centered TS. This reaction is followed by formation of a methane adduct and subsequent formation of methanol. Pyridine-N-oxide (PyO) was used as a model oxygen atom transfer reagent to generate the bimetallic-oxo complexes to close the catalytic loop. In general, the thermodynamics of the reactions were calculated to be very exergonic with reasonable barrier free energies in which the HAA pathway was found to be more plausible as compared to the [2+2] mechanism. Also, all complex models are more stable in their high spin multiplicities.
  • Azadeh Nazemi presented a poster titled "Computational analysis of proton-coupled electron transfer in molecular electrocatalysts containing tris(triazolyl)borate ligand"
    • Abstract: The design of electrocatalysts for the evolution of H2, the reduction of O2, N2, and CO2, as well as the splitting of water into protons, electrons, and O2 is essential for the development of the alternative energy sources. Typically, the catalytic cycle for the electrocatalysts is controlled by key proton-coupled electron transfer (PCET) processes including sequential or concerted electron transfer (ET) and proton transfer (PT) steps. Studying the thermodynamics and kinetics of PCET processes can give insights into which pathway is dominant, sequential (ET-PT/PT-ET) or concerted (EPT), in order to design more effective electrocatalysts. Herein, the focus is on complexes with the scorpionate ligand hydrotris(1,2,4-triazole-1-yl)borate (Ttz), [M(Ttz)(CO)3], which have been less studied as electrocatalysts. To the best of our knowledge, a systematic study of PCET reactions for mid – late 3d, 4d-transition metals complexes of Ttz has not been reported. Preliminary results indicate in the sequential process the preferred mechanism is ET-PT over PT-ET for most of the studied 3d and 4d metals.
  • Riffat Parveen presented a poster titled "Computational study for understanding the action of nickle acireductone dioxygenase (Ni-ARD) through a biomimietic structural modeling"
    • Abstract: Computational study for the biomimetic reactivity of the structural analogue for the resting state of the active site of the nickel acireductone dioxygenase (Ni-ARD) is presented. A series of complexes with the n4o motif mimics the contribution of the glutamate and histidine enzymatic residue. Various substrate including acireductone and related compounds are used to assess the enzyme substrate interaction with dioxygen. Computational calculations are performed using BP86 functional and 631+G(d) basis set. IRC calculations were used to confirm that transition states lead to desired intermediate. We have proposed a mechanism for oxygen insertion and C-C bond cleavage and results are presented here.
  • Daniel Sun presented a poster and talk.
    • Design of earth-abundant nitridyl catalysts for C-H functionalization (talk): Highly reactive transition metal nitrides have received attention as key intermediates in nitrogen fixation, C-H bond activation and other catalytically relevant processes. Motivated by reports by Atienza et al. of a possible cobalt-nitride intermediate for benzylic C-H amination, we initiated a modeling study of methane functionalization by 3d metal nitrides. We utilized density functional (DFT) and MCSCF methods to study the electronic structure and reactivity of metal-nitridyl complexes supported by two NNN pincer-type ligands: monoanionic CztBu(PyriPr)2- and neutral 2,6-(PhN=CMe)2C5H3N. Calculations indicated that a low- to intermediate-spin metal-nitridyl intermediate with significant radical character on the nitridyl nitrogen can aminate aliphatic C-H bonds; the process is most energetically and kinetically favorable for cobalt and nickel complexes. These predictions were supported by independent experiments from the Thomson and Lee groups. A collaborative project with the Lee group led to an unprecedented example of double intramolecular C-H activation, which computations suggest occurs via a Ni-nitridyl intermediate.
    • Intramolecular C-H functionalization followed by a [2σ+2π]-addition via an intermediate nickel-nitridyl complex: Irradiation of the azide complex [CztBu(PyriPr)2NiN3] supported by NNN pincer ligand, CztBu(PyriPr)2-, revealed an unprecedented nickel complex, [CztBu(PyriPr)(NH2-PyriPr)] that was generated by double intramolecular C-H activation from a putative nickel nitridyl intermediate, [CztBu(PyriPr)2Ni…N]. C-H amination at the methine (Csp3-H) of an isopropyl substituent is followed by "rollover" C-H activation of the other PyriPr arm yielding [CztBu(PyriPr)(NH2-PyriPr)]. Experiments and calculations (DFT and MCSCF) support the generation of an intermediate with significant nitridyl radical character after loss of N2, which in turn undergoes tandem C-H activations leading to functionalized intermediates and products. According to the calculation, the putative Ni nitridyl CztBu(PyriPr)2NiN is closer to disphenoidal than square planar due to the nature of the monoanionic NNN pincer ligand, while most characterized transition metal nitrides adopt either tetrahedral or square planar geometry. Complex [CztBu(PyriPr)(NH2-PyriPr)] is also observed from the reaction of Ni(I) precursor CztBu(PyriPr)2Ni and Me3SiN3, suggesting a unique thermal route towards a "masked" nickel nitridyl intermediate.
  • Erik Vazquez Montelongo presented a talk titled "Development of AMOEBA parameters for ionic liquids from density-based energy decomposition analysis (DEDA)"
    • Abstract: Room temperature ionic liquids (RTILs) are molten salts composed of (usually) organic cations and inorganic or organic anions. RTILs have several desirable properties such as relatively low viscosity, low vapor pressure, high thermal conductivity, to name a few. These systems have been use in a wide range of applications, such as electrochemistry (non-aqueous electrolyte), synthetic chemistry and as an alternative for organic solvents. The experimental determination of properties for these systems can become an expensive and time-consuming process due to the very large number of cation/anion combinations, thus computational simulations provide a complementary approach. The reliability of the property predictions from these simulations depends on the accuracy of the underlying model. Polarizable force fields (PFFs) such as AMOEBA have been shown to provide accurate thermodynamic and transport properties for RTILs. This work will describe a method to fit the non-bonded terms (electrostatic, polarization and van der Waals terms) for the multipolar/polarizable AMOEBA potential using the Density-based decomposition analysis (DEDA), and provide initial results for the calculation of properties using these parameters for several IL pairs.

New Publication: Active control of coherent dynamics in hybrid plasmonic MoS2 monolayers with dressed phonons
Dr. Yuri Rostovtsev (Physics), and others, recently published "Active control of coherent dynamics in hybrid plasmonic MoS2 monolayers with dressed phonons" in the journal ACS Photonics.

Abstract: The near-field interaction due to a strong electromagnetic field induced by resonant localized plasmons can result in a strong coupling of excitonic states or the formation of hybrid exciton-plasmon modes in quantum confined structures. The strength of this coupling can be increased by designing a system with its vibronic states resonant to the energy of the driving field induced by the localized plasmon excitation. Silver (Ag) nanoparticles (NPs) nucleated on molybdenum disulfide (MoS2) is an ideal platform for such interaction. The influence of localized plasmons (LSP) on the formation and dissociation of excitons due to resonant and off-resonant optical excitation of carriers to excitonic states is studied using ultrafast optical spectroscopy. The presence of Ag-NPs generates a local field that enhances the magnitude of the Raman modes in MoS2 under the resonant plasmon excitation. An ultrashort pulsed optical excitation at ~ 2.3 eV resonantly excites the LSP modes and the optical near-field resonantly drives the phonon modes, which leads to a coherent coupling of the A and B excitons in MoS2 with the plasmon modes. The localized near-field optical driving source induces dressed vibronic states. The resonant excitation of the LSP modes modulates the optical absorption of the probe field. The optical excitation at ~ 3.0 eV, which is resonant to the C excitonic state but off-resonant to the LSP modes, increases the electrostatic screening in the presence of excess carriers from Ag-NPs. It results in a faster dissociation of optically generated C excitons into free carriers that eventually increases the population of A and B excitonic states. The coherent interaction in the hybrid nano-plasmonic system is described using a density matrix theory.

You can view the article here.

New Publications: Two Publications by CASCaM Professor
Dr. Andrés Cisneros (Chemistry), and others, recently published three papers:
  • Unfolding Pathways of Hen Egg White Lysozyme in Ethanol, Journal pf Physical Chemistry B. The article can be found here.
    • Abstract: The aggregation of amyloid fibrils can lead to various diseases including Alzheimer's, Parkinson's disease, and transmissible spongiform encephalopathy. Amyloid fibrils can develop from a variety of proteins in the body as they misfold into a primarily β sheet structure and aggregate. Human lysozyme has been shown to have far reaching effects in human health—a homologous enzyme, hen egg white lysozyme (HEWL), has been shown to denature to a primarily β sheet structure at low pH and high alcohol content solution. We have studied these systems in atomic-level detail with a combination of constant pH and μ-second long molecular dynamics sim-ulations in explicit solvent, which cumulatively total over 10 &mus of simulation time. These studies have allowed us to determine two potential unfolding pathways depending on the protonation state of a key glutamic acid residue, as well as the effect of solution dynamics and pH on the unfolding process.
  • LICHEM 1.1: Recent Improvements and New Capabilities, Journal of Chemical Theory and Computation. The article can be found here.
    • Abstract: The QM/MM method has become a useful tool to investigate various properties of complex systems. We previously introduced the Layered Interacting Chemical Models (LICHEM) package to enable QM/MM simulations with advanced potentials by combining various (unmodified) QM and MM codes (JCC, 27, 1019). LICHEM provides several capabilities such as the ability to use polarizable force fields, such as AMOEBA, for the MM environment. Here, we describe an updated version of LICHEM (v1.1), which includes several new functionalities including a new method to account for long-range electrostatic effects in QM/mm (QM/MM-LREC), a new implementation for QM/MM with the Gaussian Electrostatic Model (GEM), and new capabilities for path optimizations using the quadratic string model (QSM) coupled with restrained MM environment optimization.

Chemistry Professor Emeritus to present invited lectures in April & May 2019
Dr. Wes Borden, Chemistry Professor Emeritus, will be speaking at a Symposium at Ohio State University in April 2019, honoring his friend and collaborator, Professor Matthew Platz. Professor Platz was not only Chair of Chemistry at Ohio State University, but, subsequently, he became Dean of the Faculty of Arts and Sciences. Professor Platz also served as the Director of the Chemistry Division of NSF. In May, Dr. Borden will be giving two lectures at the University of Zurich in Switzerland.

Recent CASCaM graduate joins Michigan State University
Quan Jiang, a Fall 2018 Chemistry graduate that worked with Dr. Cundari, has joined the research group of Dr. Kenneth Merz at Michigan State University as Research Associate/Post-Doctoral Fellow.

New Version of QM/MM Code Published
Dr. Andrés Cisneros (Chemistry)and his research group have published a new version of their QM/MM code LICHEM on github: This new version of LICHEM comprises several new capabilities including a hybrid--parallel implementation of the quadratic string method coupled with restrained MM environment optimization, point-charge and multipolar long--range electrostatic corrections via QM/MM--LREC, a new implementation of QM/GEM and several minor improvements.

For a full description of the new capabilities, please see the article currently posted on ChemRxiV.

New Publications: Three Publications by CASCaM Professor
Dr. Andrés Cisneros (Chemistry), and others, recently published three papers:
  • Selectivity and Promiscuity in TET-Mediated Oxidation of 5-Methylcytosine in DNA and RNA, Biochemistry. The article can be found here.
    • Abstract: Enzymes of the ten-eleven translocation (TET) family add diversity to the repertoire of nucleobase modifications by catalyzing the oxidation of 5-methylcytosine (5mC). TET enzymes were initially found to oxidize 5-methyl-2'-deoxycytidine in genomic DNA, yielding products that contribute to epigenetic regulation in mammalian cells, but have since been found to also oxidize 5-methylcytidine in RNA. Considering the different configurations of single-stranded (ss) and double-stranded (ds) DNA and RNA that coexist in a cell, defining the scope of TET's preferred activity and the mechanisms of substrate selectivity is critical to better understand the enzymes' biological functions. To this end, we have systematically examined the activity of human TET2 on DNA, RNA, and hybrid substrates in vitro. We found that, while ssDNA and ssRNA are well tolerated, TET2 is most proficient at dsDNA oxidation and discriminates strongly against dsRNA. Chimeric and hybrid substrates containing mixed DNA and RNA character helped reveal two main features by which the enzyme discriminates between substrates. First, the identity of the target nucleotide alone is the strongest reactivity determinant, with a preference for 5-methyldeoxycytidine, while both DNA or RNA are relatively tolerated on the rest of the target strand. Second, while a complementary strand is not required for activity, DNA is the preferred partner, and complementary RNA diminishes reactivity. Our biochemical analysis, complemented by molecular dynamics simulations, provides support for an active site optimally configured for dsDNA reactivity but permissive for various nucleic acid configurations, suggesting a broad range of plausible roles for TET-mediated 5mC oxidation in cells.
  • Insight into wild-type and T1372E TET2-mediated 5hmC oxidation using ab initio QM/MM calculations, Chemical Science. The article can be found here.
    • Abstract: Ten-eleven translocation 2 (TET2) is an Fe/α-ketoglutarate (α-KG) dependent enzyme that dealkylates 5-methylcytosine (5mC). The reaction mechanism involves a series of three sequential oxidations that convert 5mC to 5-hydroxy-methylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Our previous biochemical and computational studies uncovered an active site scaffold that is required for wild-type (WT) stepwise oxidation (Nat. Chem. Bio., 13, 181). We showed that the mutation of a single residue, T1372 to some amino acids, such as Glu, can impact the iterative oxidation steps and stop the oxidation of 5hmC to 5fC/caC. However, the source of the stalling at the first oxidation step by some mutant TET proteins still remains unclear. Here, we studied the catalytic mechanism of oxidation of 5hmC to 5fC by WT and T1372E TET2 using an ab initio quantum mechanical/molecular mechanical (QM/MM) approach. Our results suggest that the rate limiting step for WT TET2 involves a hydrogen atom abstraction from the hydroxyl group of 5hmC by the ferryl moiety in the WT. By contrast, our calculations for the T1372E mutant indicate that the rate limiting step for this variant corresponds to a second proton abstraction and the calculated barrier is almost twice as large as for WT TET2. Our results suggest that the large barrier for the 5hmC to 5fC oxidation in this mutant is due (at least in part) to the unfavorable orientation of the substrate in the active site. Combined electron localization function (ELF) and non-covalent interaction (NCI) analyses provide a qualitative description of the evolution of the electronic structure of the active site along the reaction path. Energy decomposition analysis (EDA) has been performed on the WT to investigate the impact of each MM residue on catalytic activity.
  • Reduced structural flexibility for an exonuclease deficient DNA polymerase III mutant, Physical Chemistry Chemical Physics. The journal can be found here.
    • Abstract: DNA synthesis, carried out by DNA polymerases, requires balancing speed and accuracy for faithful replication of the genome. High fidelity DNA polymerases contain a 3'-5' exonuclease domain that can remove misincorporated nucleotides on the 3' end of the primer strand, a process called proofreading. The E. coli replicative polymerase, DNA polymerase III, has spatially separated (~55 Å apart) polymerase and exonuclease subunits. Here, we report on the dynamics of E. coli DNA polymerase III proofreading in the presence of its processivity factor, the β2-sliding clamp, at varying base pair termini using single-molecule FRET. We find that the binding kinetics do not depend on the base identity at the termini, indicating a tolerance for DNA mismatches. Further, our single-molecule data and MD simulations show two previously unobserved features: (1) DNA Polymerase III is a highly dynamic protein that adopts multiple conformational states while bound to DNA with matched or mismatched ends, and (2) an exonuclease-deficient DNA polymerase III has reduced conformational flexibility. Overall, our single-molecule experiments provide high time-resolution insight into a mechanism that ensures high fidelity DNA replication to maintain genome integrity.

New Publication: Polarizable ab initio QM/MM Study of the Reaction Mechanism of N-tert-Butyloxycarbonylation of Aniline in [EMIm][BF4]
Dr. Andrés Cisneros (Chemistry), and others, recently published "Polarizable ab initio QM/MM Study of the Reaction Mechanism of N-tert-Butyloxycarbonylation of Aniline in [EMIm][BF4]" in the journal Molecules.

Abstract: N-tert-butoxycarbonylation of amines in solution (water, organic solvents, or ionic liquids) is a common reaction for the preparation of drug molecules. To understand the reaction mechanism and the role of the solvent, quantum mechanical/molecular mechanical simulations using a polarizable multipolar force field with long–range electrostatic corrections were used to optimize the minimum energy paths (MEPs) associated with various possible reaction mechanisms employing the nudged elastic band (NEB) and the quadratic string method (QSM). The calculated reaction energies and energy barriers were compared with the corresponding gas-phase and dichloromethane results. Complementary Electron Localization Function (ELF)/NCI analyses provide insights on the critical structures along the MEP. The calculated results suggest the most likely path involves a sequential mechanism with the rate–limiting step corresponding to the nucleophilic attack of the aniline, followed by proton transfer and the release of CO2 without the direct involvement of imidazolium cations as catalysts.

You can view the article here.

CASCaM professor receives UNT Research Leadership Award
Dr. Jincheng Du, Materials Science & Engineering, has received the UNT Research Leadership Award. According to the UNT Faculty Success website, the award "is given to a full-time University faculty member whose research excellence and leadership at UNT has made substantial contribution to their respective discipline and achieved national and/or international recognition." He will be presented with the award at the UNT Salute to Faculty Excellence Awards Dinner & Ceremony in the Emerald Ballroom (University Union) on Friday, October 5, 2018. (Click on the picture to see a larger version, courtesy of UNT Libraries)

More information about the award can be found here.

A list of the other UNT Faculty Excellence award winners can be found here.

Chemistry student presented during the Fall 2018 ACS National Meeting
Azadeh Nazemi, graduate student working with Dr. Thomas Cundari, presented a talk titled "DFT Study of Hydroaminoalkylation of Alkenes with Amidate Tantalum Complexes" at the Fall 2018 ACS National Meeting & Expo in Boston, MA, August 2018. The focus of the talk was about studying the nature of hydrogen, proton or hydrogen radical, during hydrogen transfer in the rate determining step and see how pKa is important in the reaction mechanism of hydroaminoalkylation.

CORRECTIONS: New Publications: Three Publications by CASCaM Professor
Dr. Andrés Cisneros (Chemistry), and others, recently published three papers:

  • DNArCdb: A Database of Cancer Biomarkers in DNA Repair Genes that Includes Variants Related to Multiple Cancer Phenotypes, DNA Repair. The article can be found here.
    • Abstract: Functioning DNA repair capabilities are vital for organisms to ensure that the biological information is preserved and correctly propagated. Disruptions in DNA repair pathways can result in the accumulation of DNA mutations, which may lead to onset of complex disease such as cancer. The discovery and characterization of cancer-related biomarkers may allow early diagnosis and targeted treatment, which could significantly contribute to the survival rates of cancer patients. To this end, we have applied a hypothesis driven bioinformatics approach to identify biomarkers related to 25 different DNA repair enzymes, in combination with structural analysis of six selected missense mutations of newly discovered SNPs that are associated with cancer phenotypes. Our search on 8 distinct cancer databases uncovered 43 missense SNPs that statistically significantly associated at least one phenotype. Moreover, nine of these missense SNPs are statistically significantly associated with two or more cancers. In addition, we have performed classical molecular dynamics to characterize the impact of rs10018786 on POLN, which results in the M310 L Pol ν variant, and rs3218784 on POLI, which results in the I236 M Pol ι. Our results suggest that both of these cancer-associated variants result in noticeable structural and dynamical changes compared with their respective wild-type proteins.
  • Corrected Article Link: Characterization of Nine Cancer-Associated Variants in Human DNA Polymerase κ, Chemical Research in Toxicology. The article can be found here.
    • Abstract: Specialized DNA damage-bypass Y-family DNA polymerases contribute to cancer prevention by providing cellular tolerance to DNA damage that can lead to mutations and contribute to cancer progression by increasing genomic instability. Y-family polymerases can also bypass DNA adducts caused by chemotherapy agents. One of the four human Y-family DNA polymerases, DNA polymerase (pol) κ, has been shown to be specific for bypass of minor groove adducts and inhibited by major groove adducts. In addition, mutations in the gene encoding pol κ are associated with different types of cancers as well as with chemotherapy responses. We characterized nine variants of pol κ whose identity was inferred from cancer-associated single nucleotide polymorphisms for polymerization activity on undamaged and damaged DNA, their abilities to extend from mismatched or damaged base pairs at primer termini, and overall stability and dynamics. We find that these pol κ variants generally fall into three categories: similar activity to wild-type (WT) pol κ (L21F, I39T, P169T, F192C, and E292K), more active than WT pol κ (S423R), and less active than pol κ (R219I, R298H, and Y432S). Of these, only pol κ variants R298H and Y432S had markedly reduced thermal stability. Molecular dynamics (MD) simulations with undamaged DNA revealed that the active variant F192C and more active variant S423R with either correct or incorrect incoming nucleotide mimic WT pol κ with the correct incoming nucleotide, whereas the less active variants R219I, R298H, and Y432S with the correct incoming nucleotide mimic WT pol κ with the incorrect incoming nucleotide. Thus, the observations from MD simulations suggest a possible explanation for the observed experimental results that pol κ adopts specific active and inactive conformations that depend on both the protein variant and the identity of the DNA adduct.
  • Corrected Article Title, Journal and Link: Characterizing Hydrogen-Bond Interactions in Pyrazinetetracarboxamide Complexes: Insights from Experimental and Quantum Topological Analyses, Inorganic Chemistry. The journal can be found here.
    • Abstract: Experimental and topological analyses of dipalladium(II) complexes with pyrazinetetracarboxamide ligands containing tetraethyl (1), tetrahexyl (2), and tetrakis(2-hydroxyethyl) ethyl ether (3) are described. The presence of two very short O---O distances between adjacent amide carbonyl groups in the pincer complexes revealed two protons, which necessitated two additional anions to satisfy charge requirements. The results of the crystal structures indicate carbonyl O---O separations approaching that of low barrier hydrogen bonds, ranging from 2.413(5) to 2.430(3) Å. Solution studies and quantum topological analyses, the latter including electron localization function, noncovalent interaction, and Bader’s quantum theory of atoms in molecules, were carried out to probe the nature of the short hydrogen bonds and the influence of the ligand environment on their strength. Findings indicated that the ligand field, and, in particular, the counterion at the fourth coordination site, may play a subtle role in determining the degree of covalent association of the bridging protons with one or the other carbonyl groups.
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