Zachary T. Ball

Associate Professor of Chemistry

My research focuses on new methodology, reaction design, and especially transition-metal catalysis. I am interested in bringing these tools to bear on problems within a variety of fields where sophisticated reaction design has the potential to serve as an enabling tool to produce unique insights into complex, interdisciplinary problems. We are interested in the design of synthetic methodologies that are simple addition reactions, combining readily available, air- and water-stable “feedstock” chemicals. Typically relying on transition-metal catalysis, these methods aspire to fulfill the goals of “green chemistry,” while at the same time affording new insights into the synthesis of complex molecules. The use of simple, stable precursors ameliorates the problems of functional-group compatibility often faced by synthetic chemists. As such, we are investigating hydrogenative, carbonylative, and related carbon-carbon bond-forming reactions. These reactions allow the investigation of catalyst structure for the design of diastereoselective and enantioselective processes. Nature uses transition-metal cofactors to perform a variety of enzymatic functions—nitrogen fixation, methane oxidation—that are almost certainly impossible without the aid of metal cofactors. The exquisite selectivity obtained by metalloenzymes is an inspiration to organometallic chemists, and is a tribute to the power of molecular evolution as a means of optimizing enzyme efficiency. Chemists have imitated metalloenzyme active sites in an attempt to better understand enzyme function, but in most cases small-molecule or oligopeptide enzyme mimics cannot compete with the efficiency of the native enzyme. However, a significant limitation for nature is that in an oxidative world where transition metals are scarce, only a few metals (Fe, Mn, Cu, Zn), in limited oxidation states, appear frequently in natural metalloenzymes. As chemists, we intend to merge the power of modular polypeptide “ligand” frameworks with the plethora of unique transition-metal catalysts developed by chemists to develop readily optimizable, wholly new metalloenzymes that display bio-orthogonal reactivity, and function in water on biomolecule substrates. This approach allows us to gain insight into important biochemical problems such as protein-protein interactions. We are pursuing new ways to produce functional polymers with control over polydispersity, end-group structure, and complex polymer architecture. Methods which allow the synthesis of exciting new electroactive polymers for organic electronics and photovoltaics are important targets of this investigation.

Publications

R. Kundu, Z. T. Ball A rhodium-catalyzed method for serum-stable cysteine modification.  Chem. Commun., ASAP 2013

Z. Chen, F. Vohidov, J. M. Coughlin, L. J. Stagg, S. T. Arnold, J. E. Ladbury, and Z. T. Ball Catalytic Protein Modiication with Dirhodium Metallopeptides: Specificity in Designed and Natural Systems.  J. Am. Chem. Soc., 134 2012: 10138-10145

Z. T. Ball Designing enzyme-like catalysts: a rhodium(II) metallopeptide case study.  Acc. Chem. Res., ASAP 2012

R. Sambasivan and Z. T. Ball Determination of orientational isomerism in rhodium(II) metallopeptides by pyrene fluorescence.  Org. Biomol. Chem., 10 2012: 8203-8206

R. Kundu, P. R. Cushing, B. V. Popp, Y. Zhao, D. R. Madden, and Z. T. Ball Hybrid Organic-Inorganic Inhibitors of a PDZ Interaction that REgulates the Endocytic Fate of CFTR.  Angew. Chem. Int. Ed., 51 2012: 7217-7220

R. Sambasivan and Z. T. Ball Screening Rhodium Metallopeptide Libraries 'On Bead': Asymmetric Cyclopropanation and a Solution to the Enantiomer Problem.  Angew. Chem. Int. Ed., 51 2012: 8568-8572

B. V. Popp, Z. Chen and Z. T. Ball Sequence-specific Inhibition of a Designed Metallopeptide Catalyst.  Chem. Commun., 48 2012: 7492-7494

R. Sambasivan, Z. T. Ball Studies of asymmetric styrene cyclopropanation with a rhodium(II) metallopeptide catalyst developed with a high-throughput screen.  Chirality 2012

A. N. Zaykov and Z. T. Ball A general synthesis of dirhodium metallopeptides as MDM2 ligands.  Chem. Commun., 47 2011: 10927-10929

A. N. Zaykov, Z. T. Ball Kinetic and stereoselectivity effects of phosphite ligands in dirhodium catalysts.  Tetrahedron, 67 2011: 4397-4401

B. V. Popp, Z. T. Ball Proximity-Driven Metallopeptide Catalysts: Remarkable Side-Chain Scope Enables Modification of the Fos bZip Domain.  Chem, Sci., 2 2011: 690-695

Z. Chen, B. Popp, C. L. Bovet, Z. T. Ball Site-specific protein modification with a dirhodium metallopeptide catalyst.  ACS Chem. Biol., 6 2011: 920-925

V. Russo, J. R. Herron, Z. T. Ball Allylcopper Intermediates with N-Heterocyclic Carbene Ligands: Synthesis, Structure, and Catalysis.  Org. Lett., 12 2010: 220-223

Kundu, R.; Ball, Z.T. Copper-Catalyzed Remote sp3 C–H Chlorination of Alkyl Hydroperoxides.  Org. Lett., 12 2010: 2460–2463

Zaykov, A.N.; Popp, B.V.; Ball, Z.T. Helix Induction by Dirhodium: Access to Biocompatible Metallopeptides with Defined Secondary Structure.  Chem.—Eur. J., 16 2010: 6651 - 6659

Sambasivan, R.; Ball, Z.T. Metallopeptides for Asymmetric Dirhodium Catalysis.  J. Amer. Chem Soc, 132 2010: 9289-9291

Popp, B.V.; Ball, Z.T. Structure-Selective Modification of Aromatic Side Chains with Dirhodium Metallopeptide Catalysts.  J. Amer. Chem Soc, 132 2010: 6660–6662

B. M. Trost, J. D. Sieber, W. Qian, R. Dhawan, Z. T. Ball Asymmetric Total Synthesis of Soraphen A: A Flexible Alkyne Strategy.  Angew. Chem. Int. Ed., 48 2009: 5478-5481

J. R. Herron, V. Russo, E. J. Valente, Z. T. Ball Catalytic Organocopper Chemistry from Organosiloxane Reagents.  Chem. Eur. J., 15 2009: 8713-8716

A. N. Zaykov, K. R. MacKenzie, Z. T. Ball Controlling Peptide Structure with Coordination Chemistry: Robust and Reversible Peptide-Dirhodium Ligation.  Chem. Eur. J., 15 2009: 8961-8965

V. Russo, J. Allen, Z. T. Ball Synthesis and isotopic labeling of a naturally occurring alkyl-thiadiamondoid.  Chem. Commun. 2009: 595-596

Jessica R. Herron and Zachary T. Ball Synthesis and Reactivity of Functionalized Arylcopper Compounds by Transmetalation of Organosilanes.  J. Amer. Chem. Soc., 130 2008: 16486-16487

Ball, Z.T. Hydrosilylation of Alkynes and Related Reactions. In Comprehensive Organometallic Chemistry III; Crabtree, R. H. and Mingos, D. M. P., Eds.; Elsevier: Oxford 2006; vol. 10; pp 789-814.