Chemistry and Biochemistry

James K. Harper

James Harper

Office: C363 BNSN
Office Phone: 801-422-5044
Email: jkharper@chem.byu.edu
Office Hours

Education:

Postdoctoral work, Montana State University

Ph.D.,  Analytical Chemistry, University of Utah

M.S., Physical Chemistry, Brigham Young University

B.S., Chemistry, Brigham Young University

Curriculum Vitae

Research:

The primary research goal in the Harper Lab 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 the Harper Lab's 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 C-13 and N-15 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 in 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. Harper researchers 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 the Harper 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 the Harper 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 Harper scientists 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.


Citations.
1. 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).
2. Kalakewich, K.; Iuliucci, R.; Harper, J. K. “Establishing accurate high resolution crystal structures in the absence of diffraction data and single crystals” Cryst. Growth Des., 2013, In press.
3. Harper, J. K.; Iuliucci, R.; Gruber, M.; Kalakewich, K. “Refining crystal structures with experimental  13 C NMR shift tensors and lattice-including electronic structure methods” CrystEngComm, 2013, DOI:10.1039c3ce40108a.
4. (a) 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.  (b)  Harper, J. K.; Ford, E. J.; Strobel, G. A.; Porco, J. A. Jr.; Tomer, D. P.; O’neill, K. L.; Heider, E. M.; Grant, D. M. “Pestacin: a 1,3-dihydro isobenzofuran from Pestalotiopsis microspora possessing antioxidant and antimicotic activities” Tetrahedron, 2003, 59, 2471.  (c) Strobel, G. A.; Ford, E.; Worapong, J.; Harper, J. K.; Arif, A. M.; Grant, D. M.; Fung, P. C. W.; Ming, W. C. R. “Isopestacin, an isobenzofuranone from Pestalotiopsis microspora possessing antifungal and antioxidant activity” Phytochem. 2002, 60, 179.

Publications:

(61 total and 3 patents in reverse chronological order)

All articles listed were published in peer-reviewed journals or books.  Those articles where I am the primary author are shown with my name underlined.  Asterisk’s indicate the corresponding author and bold denotes students from the University of Central Florida. 

Publications resulting from work performed at UCF, Department of Chemistry.

REFEREED JOURNAL ARTICLES

58. Newsome, W. J.; Ayad, S.; Cordova, J.; Reinheimer, E. W.; Campiglia, A. D.; Harper, J. K.; Hanson, K.*; Uribe-Romo, F. J.* J. Am. Chem. Soc. 2019, 141, 11298–11303.

57. Harper, J. K.*; Pope, G. M. “Recent developments in the use of one bond C-C couplings in structure determination” Annu. Rep. NMR Spectrosc. 2019, In press.

56. Liyanage, P. Y.; Graham, R. M.; Pandey, R. R.; Chusuei, C. C.; Mintz, K. J.; Zhou, Y.; Harper, J. K.; Wu, W.; Wikramanayake, A. H.; Vanni, S.; Leblanc, R. M.* “Carbon nitride dots: a selective bioimaging nanomaterial” Bioconjugate Chem. 2019, 30, 111–123.

55. Young, R. P.; Lewis, C. R.; Yang, C.; Wang, L.; Harper, J. K.; Mueller, L. J.* “TensorView: A software tool for displaying NMR tensors” Magn. Reson. Chem. 2019, 57, 211–223.

54. Vazquez-Molina, D. A.; Pope, G. M.; Ezazi, A. A.; Mendoza-Cortes, J. L.; Harper, J. K.; Uribe-Romo, F. J.* “Framework vs. side-chain amphidynamic behavior in oligo-(ethylene oxide) funcioalisation covalent-organic frameworks” Chem. Comm. 2018, 54, 6947–6950.

53. Maxwell,T.; Blair, R. G.; Wang, Y.; Kettring, A. H.; Moore, S. D.; Rex, M.; Harper, J. K.* “A solvent free approach for converting cellulose into volatile organic compounds with endophytic fungi” J. Fungi 2018, 4, 10.

52. Wang, Y.; Harper, J. K.* “Restoring waning production of volatile organic compounds in the endophytic fungus Hypoxylon sp. (BS15)” J. Fungi 2018, 4, 69.

51. Mohammad-Pour, G.; Ly, R.; Fairchild, D.; Burnstine-Townley, A.; Vazquez-Molina, D.; Trieu, K.; Campiglia, A.; Harper J.;* Uribe-Romo F.* “Modular design of highly fluorescent dibenzo- and naphtha- fluoranthenes: structural rearrangements and electronic properties” J. Org. Chem. 2018, 83, 8036–8053.

50. Pope, G. M.; Hung, I.; Gan, Z.; Mobarak, H.; Widmalm, G.; Harper, J. K.* “Exploiting 13C/14N solid-state NMR distance measurements to assign dihedral angles and locate neighboring molecules” Chem. Comm. 2018, 54, 6376–6379.

49. Wang, L.; Uribe-Romo, F. J.; Mueller L. J.; Harper, J. K.* “Predicting anisotropic thermal displacements for hydrogens from solid-state NMR: a study on hydrogen bonding in polymorphs of palmitic acid” Phys. Chem. Chem. Phys. 2018, 20, 8475–8487. (Cover)

48. Heider, E. C.;* Valenti, D.; Long, R. L.; Garbou, A.; Rex, M.; Harper J. K. “Quantifying sucralose in a water-treatment wetlands: service-learning in the analytical laboratory” J. Chem. Ed. 2018, 95, 535–542. (Cover)

47. Soss, S. E.; Flynn, P. F.; Iuliucci, R. J.; Young, R. P.; Mueller, L. J.; Hartman, J.; Beran, G. J O.; Harper, J. K.* “Measuring and modeling highly accurate 15N chemical shift tensors in a peptide” ChemPhysChem 2017, 18, 2225–2232.

46. Powell, J.; Valenti, D.; Bobnar, H.; Drain, E.; Elliot, B.; Frank, S.; McCullough, T.; Moore, S.; Kettring, A.; Iuliucci, R.; Harper, J. K.* “Evaluating the accuracy of theoretical one-bond 13C–13C scalar couplings and their ability to predict structure in a natural product” Magn. Reson. Chem. 2017, 55, 979–989.

45. Harper, J. K.; Heider, E. C.* “Data linearization activity for undergraduate analytical chemistry lectures” J. Chem. Ed. 2017, 94, 610 – 614.

44. Vazquez-Molina, D. A.; Mohammad-Pour, G. A.; Lee, C.; Logan, M. W.; Duan, X.; Harper, J. K.; Uribe-Romo, F. J.* “Mechanically shaped 2-dimensional covalent organic framewors reveal crystallographic alignment and fast Li-ion conductivity” J. Am. Chem. Soc. 2016, 138, 9767–9770.

43. Powell, J.; Heider, E. C.; Campiglia, A.; Harper, J. K.* “Predicting accurate fluorescent spectra for high molecular weight polycyclic aromatic hydrocarbons using density functional theory” J. Mol. Spectrosc. 2016, 328, 37–45.

42. Nash, D. J.; Restrepo, D. T.; Parra, N. S.; Giesler, K. E.; Penabad, R. A.; Aminpour, M.; Le, D.; Li, Z.; Farha, O.; Harper, J. K.; Rahman, T. S.; Blair, R. G.* ACS Omega, 2016, 1, 1343.

41. Powell, J.; Kalakewick, K.; Uribe-Romo, F.; Harper, J. K.* “Solid-state NMR and DFT predictions of differences in COOH hydrogen bonding in odd and even numbered n-alkyl fatty acids” Phys. Chem. Chem. Phys. 2016, 18, 12541.

40. Kalakewich, K.; Iuliucci, R.; Mueller, K. T.; Eloranta, H.; Harper, J. K.* “Monitoring the refinement of crystal structures with 15N solid-state NMR shift tensor data” J. Chem. Phys. 2015, 143, 194702.

39. Nigg, J.; Strobel, G.*; Knighton, W. B.; Hilmer, J.; Geary, B.; Riyaz-Ul-Hassan, S.; Harper, J. K.; Valenti, D.; Wang, Y. “Functionalized para-substituted benzenes as 1,8-cineole production modulators in an endophytic Nodulisporium species”  Microbiol. 2014, 160, 1772.

38. Kalakewich, K.; Iuliucci, R.; Harper, J. K.* “Establishing accurate high-resolution crystal structures in the absence of diffraction data and single crystals – an NMR approach” Cryst. Growth Des. 2013, 13, 5391.

37. Harper, J. K.*; Tishler, D.; Richardson, D.; Lokvam, J.; Pendrill, R.; Widmalm, G. “Solid-State NMR Characterization of the Molecular Conformation in Disordered Methyl α‑L‑Rhamnofuranoside” J. Phys. Chem. A 2013, 117, 5534.

36. Valenti, D. J.; Arif, A. M.; Strobel, G. A.; Harper, J. K.* “(6S*)-[(1S*,2R*)-1,2-Dihydroxypentyl]-4-methoxy-5,6-dihydropyran-2-one” Acta Crystallogr. 2013, E69, o1657.

35. 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, 15, 8693.

34. Harper, J. K.*; Strobel, G. A.; Arif, A. “3-Carbamoylquinoxalin-1-ium chloride” Acta Crystallogr., 2012, E68, o79.

 

REFEREED BOOK CHAPTERS

3. Harper, J. K.*; Iuliucci, R. 2014 “C-13 chemical shift tensors in organic materials” In Encyclopedia of Analytical Chemistry, Meyers, R. A., Ed.; Wiley: New York, pp. 1–37.

 

Articles published before my appointment at UCF, Department of Chemistry.

 

REFEREED JOURNAL ARTICLE

33. 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).

32. 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.

31. 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.

30. 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.

29. 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.

28. Heider, E. M.; Harper, J. K.; Grant, D. M.* “Structural characterization of an anhydrous polymorph of paclitaxel by solid-state NMR” Chem. Chem. Phys. 2007, 9, 1 (Cover).

27. 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” Magn. Reson. 2007, 189, 20.

26. 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” Phys. Chem. A, 2007, 111, 2020.

25. Harper, J. K.; Grant, D. M.* “Enhancing crystal structure prediction with NMR tensor data” Crystal Growth & Design, 2006, 6, 2315.

24. 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” Am. Chem. Soc. 2006, 128, 1547.

23. 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.

22. 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.

21. Strobel, G. A.*; Daisy, B.; Castillo, U. C.; Harper, J. K. “Natural products from endophytic microorganisms” Nat. Prod. 2004, 67, 257.

20. 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” Org. Chem. 2003, 68, 4609 (Cover).

19. 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.

18. Carter, D.; Harper, K. T.*; Shiffler, A. K.; Jolley, V. D.; Harper, J. K. “Relationship between soil extractable boron and tissue concentrations in rosaceae shrubs in Utah” Plant Nutr. 2003, 26, 297.

17. Harper, J. K.; Ford, E. J.; Strobel, G. A.; Porco, J. A. Jr.; Tomer, D. P.; O’neill, K. L.; Heider, E. M.; Grant, D. M.* “Pestacin: a 1,3-dihydro isobenzofuran from Pestalotiopsis microspora possessing antioxidant and antimicotic activities” Tetrahedron, 2003, 59, 2471.

16. Harper, J. K.; Facelli, J. C.; Barich, D. H.; McGeorge, G.; Mulgrew, A. E.; Grant, D. M.* “13C NMR investigation of solid-state polymorphism in 10-deacetyl baccatin III” Am. Chem. Soc. 2002, 124, 10589.

15. Strobel, G. A.*; Ford, E.; Worapong, J.; Harper, J. K.; Arif, A. M.; Grant, D. M.; Fung, P. C. W.; Ming, W. C. R. “Isopestacin, an isobenzofuranone from Pestalotiopsis microspora possessing antifungal and antioxidant activity” 2002, 60, 179.

14. Harper, J. K.; Mulgrew, A. E.; Li, J. Y.; Barich, D. H.; Strobel, G. A.; Grant, D. M.* “Characterization of stereochemistry and molecular conformation using solid-state NMR tensors” Am. Chem. Soc. 2001, 123, 9837.

13. Harper, J. K.; Dalley, N. K.; Mulgrew, A. E.; West F. G.; Grant, D. M.* “10-decetyl baccatin III dimethyl sulfoxide disolvate” Acta Crystallogr. 2001 C57, 64.

12. Li, J. Y.; Harper, J. K.; Grant, D. M.; Tombe, B. O.; Bashyal, B.; Hess, W. M.; Strobel, G.* “Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp.” Phytochem. 2001, 56, 463.

11. Harper, J. K.; Arif, A. M.; Li, J. Y.; Strobel, G.; Grant, D. M.* “Terrein” Acta Crystallogr. C . 2000, C56, e570.

10. Hu, J. Z.; Harper, J. K.; Taylor, C.; Pugmire, R. J.; Grant, D. M.* “Modified spectral editing methods for 13C CP/MAS experiments in solids” Magn. Reson. 2000, 142, 326.

9. Harper, J. K.; Arif A. M.; Grant D. M.* “cis-verbenol” Acta Crystallogr. C 2000, 56, 451.

8. Li, J. Y.; Strobel, G.*; Harper, J. K.; Lobkovsky E.; Clardy J. “Cryptocin, a potent tetramic acid antimycotic from the endophytic fungus Cytosporiopsis cf. quercina” Org. Lett. 2000, 2, 767.

7. Harper, J. K.; Grant, D. M.* “Solid-state 13C chemical shift tensors in terpenes. 3. Structural characterization of polymorphous verbenol” Am. Chem. Soc. 2000, 122, 3708.

6. Strobel, G.*; Li, J. Y.; Sugawara, F.; Koshino, H.; Harper, J. K.; Hess, W. M. “Oocydin A, a chlorinated macrocyclic lactone with potent anti-oomycete activity from Serratia marcescens” 1999, 145, 3557.

5. Harper, J. K.; McGeorge, G.; Grant, D. M.* “Solid-state 13C chemical shift tensors in terpenes. 2. NMR characterization of distinct molecules in the asymmetric unit and steric influences on shift in parthenolide” J. Am. Chem. Soc. 1999, 121, 6488.

4. Harper, J. K.; McGeorge G.; Grant, D. M.* “Solid-state 13C chemical shift tensors in terpenes. Part I. Spectroscopic methods and chemical shift structure correlations in caryophyllene oxide” Reson. Chem. 1998, 36, S135.

3. Harper, J. K.; Dunkel, R.; Grant, D. M.*; Owen, N. L.; Li, D.; Wood S. G.; Cates, R. G. “NMR characterization of obscurinervine and obscurinervidine using novel computerized analysis techniques” J. Chem. Soc., Perkin Trans. 2 1996, 91.

2. Harper, J. K.; Dalley, N. K.; Owen, N. L.*; Li, D.; Wood, S. G.; Cates, R. G. “X-ray structure and 13C NMR assignments of indole alkaloids from Aspidosperma cruenta” J. Crystallogr. Spectrosc. Res. 1993, 23, 1005.

1. Elmquist, T.*; Cates, R. G.; Harper J. K.; Gardfjell, H. “Flowering in males and females of a Utah willow, Salix rigida, and effects on growth, tannins, phenolic glycosides and sugars” Oikos 1991, 61, 65.

 

REFEREED BOOK CHAPTERS

2. Harper, J. K.* “Chemical shift anisotropy and asymmetry: Relationships to crystal structure” In NMR Crystallography, Harris, R. K., Wasylishen, R. E., Duer, M. J., Eds.; Wiley: Chichester, 2009, 119.

1. Harper, J. K.* “Natural products structural analysis enhancements” In Encyclopedia of NMR;  Grant, D. M., Harris, R. K., Eds.; Wiley: Chichester, 2002 Vol. 9, pp 589 – 597.

 

PATENTS

1. Strobel, G. A.; Castillo, U. F.; Harper, J. K.; Yaver, D. S. Microbicidal and anticancer endophytic streptomycetes from higher plants.  International Patent WO 2003085122 A2 20031016, 2003.

2. Ford, E.; Harper, J. K.; Strobel, G. A. Pestalotiopsis microspora isolates and compounds derived therefrom.  U.S. Patent 2,004,009,537 A1 20040115, 2004.

3. Harper, J. K.; Grant, G. M. Two novel trihydrates of paclitaxel. U.S. patent 8,633,240, 2014.

 

PRESENTATIONS (reverse chronological order).  Asterisk’s indicate the presenting author and bold denotes students from UCF.

 

International conferences

 

Regional conferences

 

Invited seminars