College of Sciences
Permanent URI for this communityhttps://hdl.handle.net/20.500.12588/256
Browse
Browsing College of Sciences by Department "Chemistry"
Now showing 1 - 20 of 43
- Results Per Page
- Sort Options
Item A Computational Approach to Explore the Interaction of Semisynthetic Nitrogenous Heterocyclic Compounds with the SARS-CoV-2 Main Protease(2020-12-27) Llanes, Alejandro; Cruz, Héctor; Nguyen, Viet D.; Larionov, Oleg V.; Fernández, Patricia L.In the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic, numerous attempts have been made to discover new potential antiviral molecules against its causative agent, SARS-CoV-2, many of which focus on its main protease (Mpro). We hereby used two approaches based on molecular docking simulation to explore the interaction of four libraries of semisynthetic nitrogenous heterocyclic compounds with Mpro. Libraries L1 and L2 contain 52 synthetic derivatives of the natural compound 2-propylquinoline, whereas libraries L3 and L4 contain 65 compounds synthesized using the natural compound physostigmine as a precursor. Validation through redocking suggested that the rigid receptor and flexible receptor approaches used for docking were suitable to model the interaction of this type of compounds with the target protein, although the flexible approach seemed to provide a more realistic representation of interactions within the active site. Using empirical energy score thresholds, we selected 58 compounds from the four libraries with the most favorable energy estimates. Globally, favorable estimates were obtained for molecules with two or more substituents, putatively accommodating in three or more subsites within the Mpro active site. Our results pave the way for further experimental evaluation of the selected compounds as potential antiviral agents against SARS-CoV-2.Item Algorithmic Design of Geometric Data for Molecular Potential Energy Surfaces(2022-12-21) Cruz, Ahyssa R.; Ermler, Walter C.A code MolecGeom, based on algorithms for stepwise distortions of bond lengths, bond angles and dihedral angles of polyatomic molecules, is presented. Potential energy surfaces (PESs) are curated in terms of the energy for each molecular geometry. PESs based on the Born–Oppenheimer approximation, by which the atomic nuclei within a molecule are assumed stationary with respect to the motion of its electrons, are calculated. Applications requiring PESs involve the effects of nuclear motion on molecular properties. These include determining equilibrium geometries corresponding to stationary and saddle point energies, calculating reaction rates and predicting vibrational spectra. This multi-objective study focuses on the development of a new method for the calculation of PESs and the analysis of the molecular geometry components in terms of incremental changes that provide comprehensive sampling while preserving the precision of PES points. MolecGeom is applied to generate geometric data to calculate PESs for theoretical calculations of vibrational-rotational spectra of water and formaldehyde. An ab initio PES comprising 525 and 2160 intramolecular nuclear configurations results in vibrational frequencies in agreement with experiment, having errors less than 0.08% and 0.8%, respectively. Vinyl alcohol, with a total of 14 internal coordinates, generates a PES of 1458 unique geometries. Ascorbic acid, with 54 internal coordinates, generates a 1,899,776 point PES.Item Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2(2018-03-16) De la Guardia, Carolina; Stephens, David E.; Dang, Hang T.; Quijada, Mario; Larionov, Oleg V.; Lleonart, RicardoDengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.Item Attempted Synthesis of Casbene by Intramolecular Cyclopropanation(ARKAT USA, 2002-11-14) Doyle, Michael; Yan, MingThe antifungal diterpene casbene has been prepared in low yield by intramolecular cyclopropanation of the vinyldiazomethane reactant formed from geranylgeraniol. Careful analysis of the reaction mixture revealed relatively unselective addition catalyzed by dirhodium(II) and copper(I) catalysts.Item Challenges and Strategies of Successful Mentoring: The Perspective of LEADS Scholars and Mentors from Minority Serving Institutions(2021-06-07) Talbert, Patricia Y.; Perry, George; Ricks-Santi, Luisel; Soto de Laurido, Lourdes E.; Shaheen, Magda; Seto, Todd; Kumar, Deepak; Quarshie, Alexander; Thakar, Maya; Rubio, Doris M.Mentoring continues to be a salient conversation in academia among junior and senior faculty and administrators. Mentors provide guidance and structure to junior faculty so that they can meet their academic and professional goals. Mentors also convey skills in balancing life and academic pursuits. Therefore, the purpose of this descriptive study was to provide additional insight from a training program called Leading Emerging and Diverse Scientists to Success (LEADS) regarding successful strategies and challenges of mentoring relating to lessons learned from the scholars and mentees’ perspective. The LEADS program provided multiple training platforms to increase skills and knowledge regarding research to promote expertise in grant writing and submission for funding opportunities among diverse scientists. These findings reinforce the knowledge about the value of a mentor in helping define the research pathway of their mentee and underscoring the importance of mentoring.Item Challenges in the Highly Selective [3 + 1]-Cycloaddition of an Enoldiazoacetamide to Form a Donor–Acceptor Cis-Cyclobutenecarboxamide(2021-06-09) Joyasawal, Sipak; Ma, Donghui; Doyle, Michael P.A substituted donor–acceptor cyclobutenecarboxamide is synthesized with modest enantiocontrol through a chiral copper(I) complex catalyzed [3 + 1]-cycloaddition reaction of α-acyl diphenylsulfur ylides with 3-siloxy-2-diazo-3-butenamides. With a methyl substituent on the 4- position of the 3-butenamide, the cis-vicinal-3,4-disubstituted cyclobutenecarboxamide is formed with >20:1 diastereocontrol. Donor-acceptor 3-methyl-2-siloxycyclopropenecarboxamide is rapidly formed from the reactant enoldiazoamide and undergoes catalytic ring opening to give only the Z-γ-substituted metallo-enolcarbene. Elimination from 3-siloxy-2-diazo-3-pentenamide to form the conjugated 3-siloxy-2,4-pentadienamide is competitive but minimized at low temperature.Item Challenges in the Highly Selective [3+1]-Cycloaddition of an Enoldiazoacetamide to Form a Donor–Acceptor cis-Cyclobutenecarboxamide(MDPI, 2021-06-09) Joyasawal, Sipak; Doyle, Michael; Ma, DonghuiA substituted donor–acceptor cyclobutenecarboxamide is synthesized with modest enan tiocontrol through a chiral copper(I) complex catalyzed [3 + 1]-cycloaddition reaction of α-acyl diphenylsulfur ylides with 3-siloxy-2-diazo-3-butenamides. With a methyl substituent on the 4-position of the 3-butenamide, the cis-vicinal-3,4-disubstituted cyclobutenecarboxamide is formed with >20:1 diastereocontrol. Donor-acceptor 3-methyl-2-siloxycyclopropenecarboxamide is rapidly formed from the reactant enoldiazoamide and undergoes catalytic ring opening to give only the Z-γ-substituted metallo-enolcarbene. Elimination from 3-siloxy-2-diazo-3-pentenamide to form the conjugated 3-siloxy-2,4-pentadienamide is competitive but minimized at low temperature.Item Chemoselectivity in Dirhodium(II) Catalyzed Reactions of Diazoacetoacetates Prepared from α,β-Unsaturated Ketones(ARKAT USA, 2010-01-01) Doyle, Michael; Zhang, Yuα-Diazo β-keto esters from zinc triflate catalyzed Mukaiyama-Michael reactions between α,β unsaturated ketones and α silyloxyvinyldiazoacetates are valuable synthons for the synthesis of compounds that can be accessed through catalytic diazo decomposition. Two sets of examples involving C-H insertion and aromatic substitution demonstrate the versatility of this methodology.Item Chiral donor−acceptor azetines as powerful reactants for synthesis of amino acid derivatives(Nature, 2019-11-22) Doyle, Michael; Marichev, Kostiantyn; Dong, Kuiyong; Massey, Lynée; Deng, Yongming; De Angelis, Luca; Wang, Kan; Arman, HadiCoupling reactions of amines and alcohols are of central importance for applications in chemistry and biology. These transformations typically involve the use of a reagent, activated as an electrophile, onto which nucleophile coupling results in the formation of a carbon-nitrogen or a carbon–oxygen bond. Several promising reagents and procedures have been developed to achieve these bond forming processes in high yields with excellent stereo-control, but few offer direct coupling without the intervention of a catalyst. Herein, we report the synthesis of chiral donor–acceptor azetines by highly enantioselective [3 + 1]-cycloaddition of enoldiazoacetates with aza-ylides and their selective coupling with nitrogen and oxygen nucleophiles via 3-azetidinones to form amino acid derivatives, including those of peptides and natural products. The overall process is general for a broad spectrum of nucleophiles, has a high degree of electronic and steric selectivity, and retains the enantio-purity of the original azetine.Item Community Engagement Practices at Research Centers in U.S. Minority Institutions: Priority Populations and Innovative Approaches to Advancing Health Disparities Research(2021-06-21) Henry Akintobi, Tabia; Sheikhattari, Payam; Shaffer, Emma; Evans, Christina L.; Braun, Kathryn L.; Sy, Angela U.; Mancera, Bibiana; Campa, Adriana; Miller, Stephania T.; Sarpong, Daniel; Holliday, Rhonda; Jimenez-Chavez, Julio; Khan, Shafiq; Hinton, Cimona; Sellars-Bates, Kimberly; Ajewole, Veronica; Teufel-Shone, Nicolette I.; McMullin, Juliet; Suther, Sandra; Kimbro, K. Sean; Taylor, Lorraine; Velez Vega, Carmen M.; Williams, Carla; Perry, George; Zuchner, Stephan; Marzan Rodriguez, Melissa; Tchounwou, Paul B.This paper details U.S. Research Centers in Minority Institutions (RCMI) Community Engagement Cores (CECs): (1) unique and cross-cutting components, focus areas, specific aims, and target populations; and (2) approaches utilized to build or sustain trust towards community participation in research. A mixed-method data collection approach was employed for this cross-sectional study of current or previously funded RCMIs. A total of 18 of the 25 institutions spanning 13 U.S. states and territories participated. CEC specific aims were to support community engaged research (94%); to translate and disseminate research findings (88%); to develop partnerships (82%); and to build capacity around community research (71%). Four open-ended questions, qualitative analysis, and comparison of the categories led to the emergence of two supporting themes: (1) establishing trust between the community-academic collaborators and within the community and (2) building collaborative relationships. An overarching theme, building community together through trust and meaningful collaborations, emerged from the supporting themes and subthemes. The RCMI institutions and their CECs serve as models to circumvent the historical and current challenges to research in communities disproportionately affected by health disparities. Lessons learned from these cores may help other institutions who want to build community trust in and capacities for research that addresses community-related health concerns.Item Correlated Oxidative Stress and Mitochondrial Abnormalities in Aging are Discontinuous with Alzheimer’s Disease(Office of the Vice President for Research, 2018) Nguyen, Richard Q.; Bach, Stephan H.; Phelix, Clyde F.; Perry, GeorgeOxidative stress and mitochondrial damage precede Alzheimer’s disease (AD) hallmark pathologies, neurofibrillarytangles (NFT), and senile plaques.Mitochondria’s exact role in oxidation of pyruvate and NADH play a critical role in oxidative damage. We conducted this study to identify the relationship of oxidized RNA, 8--OHG biomarker, and mtDNA accumulation in AD and aging individuals. Abnormalities were examined by using densitometry of hippocampal pyramidal neurons: mtDNA accumulation as a marker of mitophagy and oxidative damage by 8-OHG. Among aging individuals, 8-OHG and mtDNA accumulation were highly correlated (R2=0.87,p=0.0007). While both 8-OHG and mtDNA were at higher levels in AD individuals, they were uncorrelated (R2=0.4418,p=0.07).In AD individuals, 8-OHG was inversely correlated with amyloid-β, while in aging, there was no significant correlation. These results suggest the discontinuity of similarities between aging and AD. These findings also indicate that the onset of AD is marked by a pleotrophic change in oxidative stress, one characterized by a change from mitochondria degeneration to amyloid-β independency.Item Cycloaddition reactions of enoldiazo compounds(Royal Society of Chemistry, 2017-07-20) Doyle, Michael; Cheng, Qing-Qing; Deng, Yongming; Lankelma, MarianneEnoldiazo esters and amides have proven to be versatile reagents for cycloaddition reactions that allow highly efficient construction of various carbocycles and heterocycles. Their versatility is exemplified by (1) [2+n]-cycloadditions (n = 3, 4) by the enol silyl ether units of enoldiazo compounds with retention of the diazo functionality to furnish α-cyclic-α-diazo compounds that are themselves subject to further transformations of the diazo functional group; (2) [3+n]-cycloadditions (n = 1–5) by metallo-enolcarbenes formed by catalytic dinitrogen extrusion from enoldiazo compounds; (3) [2+n]-cycloadditions (n = 3, 4) by donor–acceptor cyclopropenes generated in situ from enoldiazo compounds that produce cyclopropane-fused ring systems. The role of dirhodium(II) and the emergence of copper(I) catalysts are described, as are the different outcomes of reactions initiated with these catalysts. This comprehensive review on cycloaddition reactions of enoldiazo compounds, with emphasis on methodology development, mechanistic insight, and catalyst-controlled chemodivergence, aims to provide inspiration for future discoveries in the field and to catalyze the application of enoldiazo reagents by the wider synthetic community.Item Discussion Addendum for: Allylic Oxidation Catalyzed by Dirhodium(II) Tetrakis[e-caprolactamate] of tert-Butyldimethylsilyl-protected trans-Dehydroandrosterone(Organic Syntheses, Inc., 2012) Doyle, Michael; De Angelis, Luca; Su, Yong-LiangItem Electrophilic Metal Carbenes as Reaction Intermediates in Catalytic Reactions(American Chemical Society, 1986-11-01) Doyle, MichaelItem Enantioselectivity for Catalytic Cyclopropanation with Diazomalonates(ARKAT USA, 2003-03-24) Doyle, Michael; Hu, WenhaoThe use of chiral azetidinone-ligated dirhodium(II) catalysts activates dinitrogen extrusion from diazomalonates and provides access to cyclopropanation products with selectivities as high as 40-50% ee.Item Forces Governing the Transport of Pathogenic and Nonpathogenic Escherichia coli in Nitrogen and Magnesium Doped Biochar Amended Sand Columns(2023-02-07) Quinn, Katherine; Mood, Sohrab Haghighi; Cervantes, Elizabeth; Perez, Manuel Garcia; Abu-Lail, Nehal I.Background: Access to safe drinking water remains a global issue with fecal indicator bacteria being major pollutants. Biochars offer low-cost adsorbents for bacterial pathogens. A fundamental understanding of how biochars interact with bacterial pathogens is essential to designing effective biofilters. Methods: Water-saturated sand columns amended with Magnesium and Nitrogen-doped biochars produced by pyrolysis at 400, 500, 600, and 700 ◦C were used to Quantify the transport of pathogenic Escherichia coli O157:H7 and nonpathogenic E. coli k12 strains in porous media. Measured data were modeled using DLVO theory of colloidal stability. were explored. Results: (1) Biochar is hydrophobic while sand and bacteria are hydrophilic; (2) all Gibbs free energy values quantified between E. coli O157:H7 and biochar were negative except for biochar produced at 700 ◦C; (3) all types of forces investigated (van der Waals, electrostatic, and acid-base interactions) played a role in governing the interactions between bacteria and biochar. Conclusions: (1) Adding doped biochar to sand at a 2% weight ratio enhanced the retention of bacterial cells in the sand/biochar columns; (2) bacterial transport is strain-dependent and mediated by various types of forces resulting from interactions between the various functional groups displayed on bacteria and biochar/sand. Our findings emphasize the importance of monitoring biochar’s functionality to eliminate bacterial pollutants from contaminated water.Item Formal [4+4]-, [4+3]-, and [4+2]-Cycloaddition Reactions of Donor-Acceptor Cyclobutenes, Cyclopropenes and Siloxyalkynes Induced by Brønsted Acid Catalysis(Royal Society of Chemistry, 2021-02-18) Doyle, Michael; Zheng, Haifeng; Wang, Rui; Wang, Kan; Wherritt, Daniel J.; Arman, HadiBrønsted acid catalyzed formal [4 + 4]-, [4 + 3]-, and [4 + 2]-cycloadditions of donor–acceptor cyclobutenes, cyclopropenes, and siloxyalkynes with benzopyrylium ions are reported. [4 + 2]-cyclization/deMayo-type ring-extension cascade processes produce highly functionalized benzocyclooctatrienes, benzocycloheptatrienes, and 2-naphthols in good to excellent yields and selectivities. Moreover, the optical purity of reactant donor–acceptor cyclobutenes is fully retained during the cascade. The 1,3-dicarbonyl product framework of the reaction products provides opportunities for salen-type ligand syntheses and the construction of fused pyrazoles and isoxazoles that reveal a novel rotamer-diastereoisomerism.Item Fourier Transform Mass Spectrometry: The Transformation of Modern Environmental Analyses(2016-01-14) Lim, Lucy; Yan, Fangzhi; Bach, Stephen; Pihakari, Katianna; Klein, DavidUnknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS) has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and complex environmental analyses. Two features of FTMS are responsible for changing the face of how complex analyses are accomplished. First is the ability to quickly and with high mass accuracy determine the presence of unknown chemical residues in samples. For years, the field has been limited by mass spectrometric methods that were based on knowing what compounds of interest were. Secondly, by utilizing the high resolution capabilities coupled with the low detection limits of FTMS, analysts also could dilute the sample sufficiently to minimize the ionization changes from varied matrices.Item Heme Binding to HupZ with a C-Terminal Tag from Group A Streptococcus(2021-01-21) Traore, Ephrahime S.; Li, Jiasong; Chiura, Tapiwa; Geng, Jiafeng; Sachla, Ankita J.; Yoshimoto, Francis; Eichenbaum, Zehava; Davis, Ian; Mak, Piotr J.; Liu, AiminHupZ is an expected heme degrading enzyme in the heme acquisition and utilization pathway in Group A Streptococcus. The isolated HupZ protein containing a C-terminal V5-His6 tag exhibits a weak heme degradation activity. Here, we revisited and characterized the HupZ-V5-His6 protein via biochemical, mutagenesis, protein quaternary structure, UV–vis, EPR, and resonance Raman spectroscopies. The results show that the ferric heme-protein complex did not display an expected ferric EPR signal and that heme binding to HupZ triggered the formation of higher oligomeric states. We found that heme binding to HupZ was an O2-dependent process. The single histidine residue in the HupZ sequence, His111, did not bind to the ferric heme, nor was it involved with the weak heme-degradation activity. Our results do not favor the heme oxygenase assignment because of the slow binding of heme and the newly discovered association of the weak heme degradation activity with the His6 -tag. Altogether, the data suggest that the protein binds heme by its His6 -tag, resulting in a heme-induced higher-order oligomeric structure and heme stacking. This work emphasizes the importance of considering exogenous tags when interpreting experimental observations during the study of heme utilization proteins.Item Highly Efficient Olefin Isomerization Catalyzed by Metal Hydrides Derived from Dirhodium(II) Carboxylates and Catecholborane(De Gruyter Open, 1994-07-01) Doyle, Michael; Devora, GeneDirhodium(ll) tetraacetate in combination with catecholborane catalyzes the isomerization of alkenes and dienes. Effective isomerization occurs at 80-135°C with the use of only 0.1 mol % rhodium acetate. With 2-methyl-1,5-hexadiene the disubstituted double bond is preferentially isomerized. In addition, hydrogen transfer hydrogenation occurs with 1,4-cyclohexadienes. The mechanism of these reactions is proposed to involve organoborane addition across a Rh-0 bond which activates the catalyst for isomerization and hydrogenation.
- «
- 1 (current)
- 2
- 3
- »