Harper, James - University of Central Florida

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Harper, James Assistant Professor 收藏完善纠错
University of Central Florida Department of Chemistry
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个人简介

EDUCATION Postdoctoral work, Montana State University Advisor: Gary A. Strobel (Professor of Plant Pathology) Ph.D., Analytical Chemistry, University of Utah Thesis advisor: David M. Grant (Distinguished Professor of Chemistry) Dissertation: Analysis of Tensors in Solid-state Terpenes by Magic Angle Turning Nuclear Magnetic Resonance Methods M. S., Physical Chemistry, Brigham Young University Thesis advisor: Noel Owen (Professor of Chemistry) Thesis: Isolation and Structure Elucidation of Indole Alkaloids from Aspidosperma Cruenta B. S., Chemistry, Brigham Young University. EMPLOYMENT Associate Research Scientist, University of Utah, Department of Chemistry, D.M. Grant NMR Center (2002-2011) Development of techniques for analyzing crystalline and amorphous biomaterials that defy traditional analysis. This work combines solid-state NMR techniques with ab initio computations, synchrotron data and chemical shift tensor analysis, and relies on traditional separation and crystallization methods to purify and prepare samples. Visiting Scientist, Yale University, Department of Molecular Biophysics and Biochemistry (2006) My time at Yale was a fast-paced tutorial in molecular biology. This work focused on learning RNA expression, purification, and modern nucleic acid analysis methods with specific emphasis on structural characterization of the guanosine riboswitch. Postdoctoral work, Montana State University Department of Plant Pathology (2000-2002) In Dr. Gary Strobel’s research laboratory, the emphasis was on diversifying my chemistry expertise by learning microbial growth techniques, isotopic labeling methods, natural products production and isolation. Two patents and eight publication resulted from this productive collaboration. Graduate studies at the University of Utah, Department of Chemistry (1993-2000) Graduate research with Dr. David Grant focused on developing methods for analyzing the structure of solids that are not suitable for study by traditional X-ray diffraction methods. Compounds that are amorphous or do not form suitable crystals or contain multiple crystalline forms are traditionally difficult to characterize. My work developed NMR methods to treat these challenging materials.

研究领域

The primary research goal in our laboratory is the NMR characterization of structure in solids that are difficult or impossible to examine by more conventional techniques. The relevance of our methods is, perhaps, best demonstrated by our recent characterization of the complete crystal structure of (+)-catechin, a ubiquitous and extensively studied antioxidant that had defied characterization for nearly a century.1 This NMR work emphasizes 13C and 15N shift tensor measurements and relies on computational chemistry methods to tie these results to structure. A secondary area of emphasis involves the search for novel bioactive fungal products with a special focus on identifying unusual antioxidants. Work is each of these areas is described below. 1) NMR crystallography – prediction of complete crystal structures for intractable materials. Conventional crystallographic techniques are often unable to provide structure in materials. The typical limitation lies in difficulty in growing suitable crystals. We have recently demonstrated that accurate crystal structure can often be established without single crystals or even diffraction data if a combination of solid-state NMR and a theoretically crystal structure prediction process are used.2 Remarkably, the structures now being solved in our lab with this methodology and powdered solids rival or surpass the accuracy of single crystal diffraction data.3 This approach promises to open new areas of structural analysis in challenging materials and studies are underway with the goal of characterizing high profile pharmaceuticals that have long defied traditional analysis. 2) Design of superior free radical scavengers. Some effort in our lab involves searching for bioactive fungi within higher plants (i.e. endophytic fungi). These “bioprospecting” studies have now identified several fungal products that have superb antioxidant activity.4 Some of these molecules have unique modes of action as indicated by mechanistic studies involving computational modeling. Presently the products we have examined are unsuited for pharmaceutical use, but it appears that the structural features creating the activity can be reproduced in more favorable products. Computational testing is now underway on a wide variety of candidate antioxidants with the goal of identifying superior radical scavengers with more favorable biocompatibility

近期论文

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Valenti, D. J.; Arif, A. M.; Strobel, G. A.; Harper, J. K.* “6S*-(1'S*,2'R*-dihydroxypentyl)-4-methoxy-5,6-dihydropyran-2-one” Acta Crystallogr. 2013, In press. Kalakewich, K.; Iuliucci, R. J.; Harper, J. K.* “Establishing accurate high-resolution crystal structures in the absence of diffraction structures and single crystals – an NMR approach” Cryst. Growth Des. 2013, In press. Harper, J. K.*; Tishler, D.; Richardson, D.; Lokvam, J.; Pendrill, R.; Widmalm, G. “Solid-state NMR characterization of the molecular conformation in disordered methyl--L-rhamnofuranoside” J. Phys. Chem. A 2013, 117, 5534. Harper, J. K.*; Iuliucci, R. J.; Grueber, M.; Kalakewich, K. “Refining crystal structures with experimental 13C NMR shift tensors and lattice-including electronic structure methods.” CrystEngComm, 2013, DOI: 10.1039/c3ce40108a. Harper, J. K.*; Strobel, G. A.; Arif, A. “3-Carbamoylquinoxalin-1-ium chloride” Acta Crystallogr., 2012, E68, o79. Harper, J. K.; Doebbler, J. A.; Jacques, E.; Grant, D. M.*; Von Dreele, R. “A combined solid-state NMR and synchrotron x-ray diffraction powder study on the structure of the antioxidant (+)-catechin 4.5 hydrate” J. Am. Chem. Soc. 2010, 132, 2928 (Cover). Jiang, Y. J.*; Harper, J. K. “An explanation of magic angle spinning NMR experiments in the time domain” Concepts in Magn. Reson. A, 2009, 34A, 249. Iuliucci, R.*; Hoop, C. L.; Arif, A. M.; Harper, J. K.; Pugmire, R. J.; Grant, D. M. “Redetermination of 1,4-dimethoxybenzene” Acta Crystallogr., 2009, E65, o251. Kharwar, R. N.; Verma, V. C.; Kumar, A.; Gond, S. K.; Harper, J. K.; Hess, W. M.; Lobkovosky, E.; Ma, C.; Ren, Y.; Strobel, G. A.* “Javinicin, an antibacterial naphthaquinone from an endophytic fungus of Neem, Chloridium sp.” Curr. Microbiol. 2008, 58, 233. Hoffman, A. M.*; Mayer, S. G.; Strobel, G. A.; Hess, W. M.; Sovocool, G. W.; Grange, A. H.; Harper, J. K.; Arif, A. M.; Grant, D. M. “Purification, identification and activity of phomodione, a furandione from an endophytic Phoma species” Phytochem. 2008, 69, 1049. Heider, E. M.; Harper, J. K.; Grant, D. M.* “Structural characterization of an anhydrous polymorph of paclitaxel by solid-state NMR” Phys. Chem. Chem. Phys. 2007, 9, 1 (Cover). Harper, J. K.; Strohmeier, M.; Grant, D. M.* “Pursuing structure in microcrystalline solids with independent molecules in the unit cell using 1H-13C correlation data” J. Magn. Reson. 2007, 189, 20. Ma, Z.; Halling, M. D.; Solum, M. S.; Harper, J. K.; Orendt, A. M.; Facelli, J. C.; Pugmire, R. J.; Grant, D. M.*; Amick, A. W.; Scott, L. T. “Ring current effects in crystals. Evidence from 13C chemical shift tensors for intermolecular shielding in 4,7-di-t-butylacenaphthene versus 4,7-di-t-butylnaphthylene” J. Phys. Chem. A, 2007, 111, 2020. Harper, J. K.; Grant, D. M.* “Enhancing crystal structure prediction with NMR tensor data” Crystal Growth & Design, 2006, 6, 2315. Harper, J. K.; Grant, D. M.*; Zhang, Y.; Lee, P. L.; Von Dreele, R. B.* “Characterizing challenging microcrystalline solids with solid-state NMR shift tensor and synchrotron x-ray powder diffraction data: structural analysis of ambuic acid” J. Am. Chem. Soc. 2006, 128, 1547. Heider, E. M.; Harper, J. K.; Grant, D. M.*; Hoffman, A.; Dugan, F.; Tomer, D. P.; O’Neill, K. L. “Exploring unusual antioxidant activity in a benzoic acid derivative: a proposed mechanism for citrinin” Tetrahedron, 2006, 62, 1199. Harper, J. K.; Barich, D. H.; Heider, E. M.; Grant, D. M.*; Franke, R. R.; Johnson, J. H.; Zhang, Y.; Lee, P. L.; Von Dreele, R. B.*; Scott, B.; Williams, D.; Ansell, G. B. “A combined solid-state NMR and x-ray powder diffraction study of a stable polymorph of paclitaxel” Crystal Growth & Design, 2005, 5, 1737. Strobel, G. A.*; Daisy, B.; Castillo, U. C.; Harper, J. K. “Natural products from endophytic microorganisms” J. Nat. Prod. 2004, 67, 257. Harper, J. K.; Barich, D. H.; Hu, J. Z.; Strobel, G. A.; Grant, D. M.* “Stereochemical analysis by solid-state NMR: structural predictions in ambuic acid” J. Org. Chem. 2003, 68, 4609 (Cover). Castillo, U.; Harper, J. K.; Strobel, G. A.*; Sears, J.; Alesi, K.; Ford, E.; Sugawara, F.; Lin, J.; Hunter, M.; Yaver, D.; Jensen, J. B.; Porter, H.; Robison, R.; Hess, W. M.; Condron, M.; Teplow, D. “Kakadumycins, novel antibiotics from Streptomyces sp. NRRL 30566, an endophyte from grevillea pteridifolia” FEMS Micro. Lett. 2003, 224, 183.

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