Physical Chemistry; Electronic Structure Calculations; Conventional and Unconventional Hydrogen-Bonded Systems; Bioenergetics; Reactions at Silica Surfaces; Decomposition of Nitramine Propellants
BS, Rider College, 1971
MS, Carnegie Mellon University, 1972
PhD, Princeton University, 1976
Professor, University of Missouri, 2013-present
Associate Professor, University of Missouri, 2003-2013
Professor, Eastern Illinois University, 1994-2003
Associate Professor, Eastern Illinois University, 1990-1994
Contractor, Hanscom Air Force Base (through Wentworth Institute of Technology), 1986-1990
Air Force Geophysics Scholar, Hanscom Air Force Base, 1984-1986
Assistant Professor, College of the Holy Cross, 1978-1984
Postdoctoral Fellow, University of Southern California, 1976-1978
Honors and Awards:
Andrew J. Rider Scholar Award, 1971
Manufacturing Chemists Association Award, 1971
Air Force Geophysics Scholar Fellowship, 1984-1986
Presidential Merit Award, Eastern Illinois University, 1991
Faculty Excellence Award in Research, Eastern Illinois University, 1992
Faculty Excellence Award in Teaching, Eastern Illinois University, 1995
COS Teacher-Scholar Award, Eastern Illinois University, 2001
American Chemical Society:
Secretary, Central Massachusetts Local Section, 1981-1983
Chair, University of Missouri Local Section, 2005
Midwest Theoretical Chemistry Conference, co-Coordinator, 2005
Graduate Program Coordinator, Eastern Illinois University, 2000-2001
Expanding Your Horizons through Math and Science, Advisory Board, 1996-1997
Alpha Chi Sigma, Professional Chemistry Fraternity
My group’s current investigations in the areas of nanocapsular materials and radiopharmaceuticals build on our long-term interest in characterizing weak intermolecular interactions, especially hydrogen bonding. We are investigating the cation-π, C-HLO, and conventional hydrogen-bonding interactions that stabilize these systems. In particular, our recent collaborative studies have used computational techniques to elucidate and predict the structures, properties and behavior of pyrogallolarene-based host-guest nanoassemblies and metal-cyclized somatostatin peptide analogs, thereby directing more efficient synthesis of species with desired properties. The thermodynamic data provided by our quantum chemical calculations has provided insight into the stabilities, conformational preferences and mechanisms of formation of these species.
In our work on the pyrogallolarene-based nanoassemblies, we are tackling important topics in supramolecular chemistry: molecular recognition, templation, self-assembly, and molecular communication. This work is a collaborative effort between the Deakyne (electronic structure calculations), Adams (molecular dynamics) and Atwood (experimental) groups in the MU Chemistry department. Our focuses have been threefold: (1) the practical exploitation of the ability of macrocyclic compounds both to recognize and selectively bind guest species; (2) the attractive prospect of assembling these compounds into superstructures with unique physical properties; and (3) the synergistic interplay of theory and experiment in elucidating these properties and optimizing the research strategy.
An important advantage of the metal-seamed C-alkyl- and C-arylpyrogallolarene nanocapsules under investigation (Fig. 1) is that their relatively small interior volume provides an excellent opportunity to probe host-guest interactions and the properties and behavior of the guest in “tight” or confined space. The results of encapsulation will serve as a model for host-guest interactions in larger cavities by providing an upper limit on the strength of the interaction, on the amount of guest contortion, and on the changes in guest molecular properties. Thus, we are identifying and quantifying the through-space interactions and the importance of the orientation and restricted motion of the guest to the host-guest communication process in the Zn-containing systems of initial interest.
|Fig. 1. Calculated structures for the stripped A) neat Zn capsule, B) carbon protonated capsule and C) protonated MeOH-capsule. complex (R = H).|
In our work on the metal-cyclized somatostatin peptide analogs, we are using computational techniques to help develop a more directed experimental strategy for structural modification of Re-cyclized octreotides. This work is a collaborative project between the Deakyne, Adams, Jurisson and Lewis (experimental) groups in the Chemistry and Veterinary Medicine and Surgery departments. The goal of my group in this project is to determine conformational preferences and Re binding properties that are important for stability and receptor affinity of the analogues. The overall goal of the project is to determine structure-activity relationships of non-radioactive Re- and 99mTc-cyclized analogues by computational chemistry analyses, 3-D structure calculations, IC50 measurements, and 99mTc stability studies. These 99mTc analogues have potential application in imaging and staging of somatostatin receptor positive cancers.
Nearly all work reported to date with radiometal-labeled somatostatin analogues has involved the “bifunctional chelate” approach, in which a chelating group is appended to the peptide sequence. However, the therapeutic utility of these analogues has been limited by relatively poor tumor retention of radioactivity, requiring administration of extremely large therapeutic doses of radiolabeled drug to patients. We are investigating direct incorporation of 99mTc, for imaging, or 188Re, for targeted radiotherapy, into the disulfide bond of octreotides.
One component of this project is the examination of model Re(V) oxo compounds of the type ReOXnY4-n and ReOXnY4-n –, where X, Y = NH2–, NH3, and SH– (Fig. 2, lhs), and those with a Re environment more relevant to that in octreotides (Fig. 2, rhs). We are interested in evaluating the effect of the metal-coordinating atoms and chelating ring size on binding affinities and in deriving force field parameters for Re. A series of relaxed scans has been started in which each unique ligand is separated from the complex. In the component involving calculations on disulfide-bridged octreotide systems, we have begun by optimizing structures for which all of the R groups (except Cys2,7) have been substituted by methyl groups. This approach should allow us to locate a set of reasonable starting configurations for the backbone and to evaluate the effect of the R-groups on those configurations. It should also allow us to determine important steric interactions between the R groups that affect their orientations. Our calculations reproduce both the b-turn-like and a-helix-like structures identified experimentally and indicate that side-chain interactions indeed affect the shape of the peptide backbone and may explain the reduced receptor binding affinity of some analogues.
Fig. 2. Model compounds; Re: aqua, O: red, N: blue, S: yellow, C: gray, H: white.
A. M. Drachnik, H. Kumari, C. L. Barnes, C. A. Deakyne and J. L. Atwood, “Encapsulation of Cobalt and Manganese Complexes within Resorcinarene Dimers,” CrystEngComm. 2014, 16, 7172-7175.
A. V. Mossine, C. M. Mayhan, D. A. Fowler, S. J. Teat, C. A. Deakyne and J. L. Atwood, “Zinc-Seamed Pyrogallolarene Dimers as Structural Components in a Two-Dimensional MOF,” Chem. Sci. 2014, 5, 2297-2303.
C. M. Mayhan, H. Kumari, E. M. McClure, J. F. Liebman and C. A. Deakyne, “Proton Affinity and Gas-phase Basicity of Hydroxyquinol: A Computational Study,” J. Chem. Thermodyn. 2014, 73, 171-177.
H. Kumari, S. R. Kline, D. A. Fowler, A. V. Mossine, C. A. Deakyne and J. L. Atwood, “Solution Superstructures: Truncated Cubeoctahedron Structures of Pyrogallolarene Nanoassemblies,” Chem. Comm. 2014, 50, 109-111.
C. M. Mayhan, T. J. Szabo, J. E. Adams and C. A. Deakyne, “Mononuclear and Polynuclear 5-Coordinate Zinc(II) Model Complexes: A Quantum Chemical Calibration Study of Their Structure and Energy,” Structural Chem. 2013, 24, 2089-2099.
H. Kumari, L. Erra, A. C. Webb, P. Bhatt, C. L. Barnes, C. A. Deakyne, J. E. Adams, L. J. Barbour and J. L. Atwood, “Pyrogallolarenes as Frustrated Organic Solids,” J. Am. Chem. Soc. 2013, 135, 16963-16967.
H. Kumari, P. Jin, C. A. Deakyne and J. L. Atwood, “Metal Ion Transport across Metal-organic Nanocapsules”, Curr. Org. Chem. 2013, 17, 1481-1488. (Invited review article for a special issue on Nanoreactors and Molecular Prisons.)
H. Kumari, C. L. Dennis, A. V. Mossine, C. A. Deakyne, and J. L. Atwood, “Magnetic Differentiation of Pyrogallolarene Tubular and Capsular Frameworks”, J. Am. Chem. Soc. 2013, 135, 7110-7113.
D. W. Demoin, Y. Li, S. S. Jurisson and C. A. Deakyne, “Method and Basis Set Analysis of Oxorhenium(V) Complexes for Theoretical Calculations”, Comput. Theor. Chem. 2012, 997, 34-41.
H. Kumari, S. R. Kline, C. L. Dennis, A. V. Mossine, R. L. Paul, C. A. Deakyne, and J. L. Atwood, “Solution-phase and Magnetic Approach towards Understanding Iron Gall Ink-like Nanoassemblies”, Angew. Chem. Int. Ed. 2012, 51, 9263-9266.
H. Kumari, S. R. Kline, W. G. Wycoff, R. L. Paul, A. V. Mossine, C. A. Deakyne, and J. L. Atwood, “Solution-phase Structures of Gallium-containing Pyrogallolarene Scaffolds”, Angew. Chem Int. Ed. 2012, 51, 5086-5091.
C. A. Deakyne, D. A. Fowler, and J. L. Atwood, “Molecular Capsules Based on Metal Complexes with Resorcinarenes and Pyrogallolarenes”, In The Chemistry of Metal Phenolates (Ed. J. Zabicky), Wiley, Chichester, 2012, available on-line at http://onlinelibrary.wiley.com/book/10.1002/9780470682531.