Overview
Early Transition Radiometal Chemistry
Increasing availability of high energy, biomedical cyclotrons provides access to radiometals with properties suitable for PET imaging and radiotherapy. We are interested in exploring the the aqueous, radioactive coordination chemistry of early transition metals/pseudolanthanides, specifically Ti(IV), Zr(IV), Sc(III) and Y(III), and applying this chemistry to the imaging and treatment of cancer. We employ a palette of spectroscopic, physical inorganic chemistry methods to characterize the to-date understudied, aqueous coordination chemistry of these Lewis acids. Most recently, we have begun to explore reactivity and chemical transformations on tracer scale. Funding: NIH R01, DOE
Representative publications:
D. Śmiłowicz, S. Eisenberg, R. LaForest, J.N. Whetter, A. Harriharan, J. Bordenca, C.J. Johnson, E. Boros. “Metal-Mediated, Autolytic Amide Bond Cleavage: A Strategy for the Selective, Metal Complexation-Catalyzed, Controlled Release of Metallodrugs” J. Am. Che. Soc., 2023, in press.
D. Śmiłowicz, S. Eisenberg, S. H. Ahn, A. J. Koller, P. P. Lampkin, E. Boros. “Radiometallation and photo-triggered release of ready-to-inject radiopharmaceuticals from the solid phase” Chem. Sci., 2023, 14, 5038-5055
A. J. Koller, S. Saini, I.F. Chaple, M.A. Joaqui-Joaqui, B. M. Paterson, M. T. Ma, P. J. Blower, V. C. Pierre, J. R. Robinson, S. E. Lapi, E. Boros. A General Design Strategy Enabling the Synthesis of Hydrolysis-Resistant, Water-Stable Titanium(IV) Complexes. Angew. Chem. Int. Ed. 2022, in press. Also highlighted in ChemistryViews
J. N. Whetter, B. A. Vaughn, A. J. Koller, E. Boros An Unusual Pair: Facile Formation and In Vivo Validation of Robust Sc-18F Ternary Complexes for Molecular Imaging. Angew. Chem. Int. Ed. 2022 in press Hot Paper, highlighted in C&EN News.
B. A. Vaughn, S. H. Ahn, E. Aluicio-Sarduy, J. Devaraj, A. P Olson, J. W. Engle and E. Boros. Chelation with a Twist: A Bifunctional Chelator to Enable Room Temperature Radiolabeling and Targeted PET Imaging with Scandium-44. Chem. Sci. 2020. 11, 333-342
Lanthanide-based Imaging Probes
The prognosis and survival of patients with aggressive cancers depends on the presence of positive tumor margins (defined as the presence of tumor cells in the surrounding area) post surgical resection. Combining radioactive and luminescent reporters in a targeted molecular probe has the potential to provide pre-operative nuclear imaging, real-time luminescence-guided surgery followed by ex vivo imaging with one single probe. We are interested in employing luminescent lanthanides for in vivo optical imaging, a thus far insurmountable challenge due to the lanthanides’ need for short wave excitation. We have recently bypassed the need for short-wave, external excitation sources by carrying out in situ excitation of lanthanide luminescence with Cherenkov radiation emissive radioisotopes. Following extensive in vitro validation, we currently work on demonstrating that lanthanides are suitable for the in vivo optical imaging of cancer. Funding: NSF Career, NIH R21, Sloan
Representative publications:
A. G. Cosby, J. J. Woods, P. Nawrocki, T. J. Sorensen, J. J. Wilson, E. Boros. Accessing Lanthanide-based, In Situ Illuminated Optical Turn-On Probes by Modulation of the Antenna Triplet State Energy. Chem. Sci. 2021, 12, 9442-9451
K. E. Martin, A. G. Cosby, E. Boros. Multiplex and In Vivo Optical Imaging of Discrete Luminescent Lanthanide Complexes Enabled by In Situ Cherenkov Radiation Mediated Energy Transfer. J. Am. Chem. Soc. 2021, 143, 9206–9214
A. G. Cosby, S. H. Ahn, E. Boros. Cherenkov Radiation Mediated In Situ Excitation of Discrete Luminescent Lanthanide Complexes. Angew. Chem. Int. Ed. 2018, 57, 15496-15499.
A. G. Cosby, G. Quevedo, and E. Boros. A High-Throughput Method To Measure Relative Quantum Yield of Lanthanide Complexes for Bioimaging. Inorg. Chem. 2019, 58, 10611-10615
Imaging and Treatment of Bacterial Infections with Siderophores
Antibiotic resistance is an imminent global health threat. Accelerated diagnosis and new life-saving treatments are needed to overcome resistance. Most pathogens have developed sophisticated mechanisms to sequester the essential metal ion Fe(III) from their host. This process involves Fe(III) chelators called siderophores. Naturally occurring and synthetic siderophores can act as Trojan horses to deliver antibiotics to the site of infection. These conjugates are referred to as sideromycins. We are exploring sideromycins as new therapeutic tools for the treatment of bacterial infections in combination with non-redox active metal ions that mimic Fe(III), but can further enhance bacteriotoxicity, such as Ga(III). We also employ radioactive gallium isotopes to characterize stability, bacterial uptake and in vivo pharmacokinetics of our constructs, providing unprecedented access to predicting bicompatibility and efficacy. Funding: NIH R35, Dreyfus
Representative publications:
A. Pandey, M. Cao, E. Boros. Tracking Uptake and Metabolism of Xenometallomycins Using a Multi-Isotope Tagging Strategy. ACS Inf. Dis. 2022, in press.
A. Pandey, D. Śmiłowicz, E. Boros. Galbofloxacin: A Xenometal-Antibiotic with Potent in vitro and in vivo Efficacy Against S. aureus. Chem Sci. 2021, 12, 14546 - 14556. Also read about this work in C&EN News and Chemistry World.
A. Pandey, C. Savino, S. H. Ahn, Z. Yang, S. G. Van Lanen, E. Boros. Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency. J. Med. Chem. 2019, 62, 9947-9960.