Professor Smith joined the Department of Chemistry and Biochemistry at Notre Dame in 1991. He teaches organic chemistry at the undergraduate & graduate levels. His research interests encompass the areas of Supramolecular & Bioorganic Chemistry. Personal Information: Born 1961, Melbourne Australia, married with two daughters. B.Sc., 1983, University of Melbourne; Ph. D., 1988, Pennsylvania State University; Postdoctoral, 1989, Oxford University; Postdoctoral, 1990, Columbia Univeristy.

The work in this laboratory is multidisciplinary and encompasses organic synthesis, molecular design, biophysical methods, fluorescence microscopy, and animal imaging. As a result, the students receive broad training and the individual research topics are quite varied. Shown below is a sampling of some recent projects: Fundamental Studies Synthavidin technology is a synthetic mimic of streptavidin and biotin binding which results in a very stable host guest complex. High affinity (Kd ~1 nM) and controllable threading kinetics between a squaraine dye and a macrocycle make them an ideal synthavidin pair with the added benefit of near-infrared fluorescence. Synthavidin pre-assembly technology takes advantage of the high affinity and slow threading kinetics to produce a library of kinetically stably complexes as fluorescent probes for molecular imaging, whereas synthavidin in situ capture technology relies on rapid in-situ capture by macrocycle coated bead for enzyme activity detection with high sensitivity of fluorescent response. Disease Diagnostics One way to diagnose disease is by monitoring the enzyme activity associated with that disease. Synthavidin in situ capture technology provides a conceptually new type of enzymatic cleavage assay that utilizes in situ capture of the fluorescent product. The enzyme assay can be conducted in aqueous solution where dramatic colorimetric and fluorescence changes are easily observed by the naked eye. Alternatively, affinity capture beads coated with macrocycle can be used to immobilize the liberated squaraine and enable a range of heterogeneous analysis options. With further optimization, this new type of neuraminidase assay may be useful in a point of care clinic to rapidly diagnose influenza infection and also determine which of the approved antiviral inhibitor drugs is likely to be the most effective treatment for an individual patient. Drug Delivery Targeted delivery and imaging systems would be an important achievement in medicine. Synthavidin was used to rapidly functionalize the surface of nanoparticles without perturbing the membrane integrity or causing leakage of the aqueous contents. The two‐step method involves spontaneous insertion of a cholesterol anchored dye into the outer leaflet of pre‐formed liposomes, followed by squaraine threading with a macrocycle that has appended targeting ligands. Functionalized liposomes were able to selectively target bacteria in the presence of human cells for fluorescence imaging.

Croconaine Rotaxane for Acid Activated Photothermal Heating and Ratiometric Photoacoustic Imaging of Acidic pH. Guha, S.; Shaw, G. K.; Mitcham, T. M.; Bouchard, R. R.; Smith, B. D. Chem. Commun. 2016, 52, 120-123. Phenoxide-bridged Zinc(II)-Bis(dipicolylamine) Probes for Molecular Imaging of Cell Death. Clear, K. L.; Harmatys, Rice, D. R.; Wolter, W. R.; Suckow M. A.; Wang, Y.; Rusckowski, M.; Smith, B. D. Bioconjugate Chem. 2016, 27, 363-75. Using Membrane Composition to Fine-Tune the pKa of an Optical Liposome pH Sensor. Clear, K. J.; Virga, K.; Gray, L.; Smith, B. D. J. Mat. Chem. C 2016, 4, 2925 – 2930. Zinc(II)-Dipicolylamine Coordination Complexes as Targeting and Chemotherapeutic Agents for Leishmania Major. Rice, D. R.; Vacchina, P.; Morales, M. A.; Smith, B. D. Antimicrobial Agents and Chemotherapy, 2016, 60, 2932 – 2940. Biomolecule Recognition using Transition Metal Ions and Hydrogen Bonding. Plaunt, A. J.; Betancourt-Mendiola, M. de L.; Smith, B. D. in Comprehensive Supramolecular Chemistry II, Atwood, J. Ed.; Elsevier: Kidlington, 2016 Pre-assembly of Near-infrared Fluorescent Multivalent Molecular Probes for Biological Imaging. Peck, E. M.; Battles, P. M.; Rice, D. R.; Roland, F. M.; Norquest, K. A.; Smith, B. D. Bioconjugate Chem. 2016, 27, 1400 – 1410. Imaging and Therapeutic Applications of Zinc(II)-dipicolylamine Molecular Probes for Anionic Biomembranes. Rice, D. R.; Clear, K. J.; Smith, B. D. Chem. Common. 2016, 52, 8787-8801. Small Molecule Additive Enhances Cell Uptake of 5-Aminolevulinic Acid and Conversion to Protoporphyrin IX. Harmatys, K. M., Musso, A. J., Clear, K. J., Smith, B. D. Photochem. and Photobiol. Sci. IX, 2016, 15, 1408-1416. Preassembled Fluorescent Multivalent Probes for the Imaging of Anionic Membranes. Roland, F. M.; Peck, E. M.; Rice, D. R.; Bradley D. Smith, B. D. Bioconjugate Chem.2017, 28, 1093-1101. Synthetic Mimics of Biotin/(strept)avidin. Liu, W.; Samanta, S. K.; Smith, B. D.; Isaacs, L. Chem Soc. Rev. 2017, 46, 2391-2403. Fluorescent Neuraminidase Assay Based on Supramolecular Dye Capture After Enzymatic Cleavage. Liu, W.; Gomez-Duran, C. F. A.; Smith, B. D. J. Am. Chem. Soc.2017, 139, 6390-6395. Antiplasmodial Activity of Targeted Zinc(II)-dipicolylamine Complexes. Rice, D. R.; de Lourdes Betancourt Mendiola, M.; Murillo-Solano, C.; Checkley, L. A.; Ferdig, M. T.; Pizarro; J. C.; Smith, B. D.Bioorg. Med. Chem.2017, 25, 2754-2760. Synthesis and Structure of 3,3-Dimethylindoline Squaraine Rotaxanes. Jarvis, T. S.; Collins, C. G.; Dempsey, J. M.; Oliver, A. G.; Smith, B. D. J. Org. Chem.2017, 82, 5819–5825. Selective Photothermal Inactivation of Cells Labeled with Near-infrared Croconaine Dye. Harmatys, K. M.; Battles, P. M.; Peck, E. M.; Spence, G. T.; Roland, F. M.; Smith, B. D. Chem. Commun.2017, 53, 9906-9909. Structural Control of Kinetics for Macrocycle Threading by Fluorescent Squaraine Dye in Water. Gómez-Durán, C. F. A.; Liu, W.; Betancourt-Mendiola, M. L.; Smith, B. D. J. Org. Chem.2017, 82, 8334–8341. Non-Covalent Assembly Method that Simultaneously Endows a Liposome Surface with Targeting Ligands, Protective PEG Chains, and Deep-Red Fluorescence Reporter Groups. Shaw, S. K.; Liu, W.; Brennan, S. P.; Betancourt-Mendiola M. L.; Smith, B. D. Chem. Eur. J.2017, 51, 12646-12654. Guest Back-Folding: a Molecular Design Strategy that Produces a Deep-red Fluorescent Host/guest Pair with Picomolar Affinity in Water. Liu, W.; Johnson, A.; Smith, B. D. J. Am. Chem. Soc. 2018, 140, 3361-3370. High Expression of Integrin αvβ3 Enables Uptake of Targeted Fluorescent Probes into Ovarian Cancer Cells and Tumors. Shaw, S. K.; Schreiber, C. L.; Roland, F. M.; Battles, P. M.; Brennan, S. P.; Padanilam, S. J.; Smith, B. D. Bioorg. Med. Chem. 2018, 26, 2085-2091. Cyclodextrin Rotaxane with Switchable Pirouetting. Zhang, Q.; Zajíček, J.; Smith, B. D. Org. Lett. 2018, 20, 2096-2099. Macrocyclic Receptor for Precious Gold, Platinum, or Palladium Co-ordination Complexes. Liu, W.; Oliver, A. G.; Smith, B. D. J. Am. Chem. Soc. 2018, 140, 6810-6813.