A5056365473- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Metal-Organic Frameworks: Synthesis and Applications
- Supramolecular Chemistry and Complexes
- Medical Imaging Techniques and Applications
- Magnetism in coordination complexes
- Fluorine in Organic Chemistry
- Crystallography and molecular interactions
- Radiopharmaceutical Chemistry and Applications
- Lanthanide and Transition Metal Complexes
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Mesoporous Materials and Catalysis
- Molecular Sensors and Ion Detection
- Supramolecular Self-Assembly in Materials
- Advanced NMR Techniques and Applications
- Wnt/β-catenin signaling in development and cancer
- Iron oxide chemistry and applications
- Glioma Diagnosis and Treatment
- Alzheimer's disease research and treatments
- Metal complexes synthesis and properties
- Neuroinflammation and Neurodegeneration Mechanisms
- Protein Tyrosine Phosphatases
- Microtubule and mitosis dynamics
- Immune cells in cancer
University of Missouri
2010-2022
Robert Bosch (Germany)
2022
University of Michigan
2015-2021
Ann Arbor Center for Independent Living
2019-2020
Michigan United
2016-2018
South College
2011-2016
Columbia College - Missouri
2011-2013
A copper-mediated radiofluorination of aryl- and vinylboronic acids with K18F is described. This method exhibits high functional group tolerance effective for the a range electron-deficient, -neutral, -rich aryl-, heteroaryl-, acids. has been applied to synthesis [18F]FPEB, PET radiotracer quantifying metabotropic glutamate 5 receptors.
A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [18F]KF is described. This method fast, uses commercially available reagents, compatible both electron-rich electron-deficient arene substrates. has been applied to the manual synthesis a variety clinically relevant radiotracers including protected [18F]F-phenylalanine [18F]F-DOPA. In addition, an automated [18F]MPPF demonstrated that delivers validated dose 200 ± 20 mCi high specific activity 2400 900 Ci/mmol.
Thermodynamic versus kinetic control: Small-angle neutron scattering (SANS) and single-crystal X-ray diffraction data have been used to elucidate the effect of temperature, solvent, metal identity on formation dimeric or hexameric metal-seamed pyrogallol[4]arene capsules. Higher temperatures, methanol solution, use nickel favor dimer (see scheme). Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited typeset....
In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET radiochemistry landscape. These enabled wide range substrates, facilitating access to radiopharmaceuticals that were challenging synthesize using traditional fluorine-18 radiochemistry. However, process adapting these new for automated radiopharmaceutical production has revealed limitations in fitting them into confines systems. particular, presence bases (e.g. K
Nickel and cobalt seamed metal-organic capsules have been isolated studied using structural, magnetic computational approaches. Antiferromagnetic exchange in the Ni capsule results from coordination environments enforced by framework.
Copper seamed dimeric metal-organic pyrogallol[4]arene capsules have been synthesized and engineered into coordination polymer chains, either by direct or with additional bridging ligands. The formation of this copper capsule also demonstrates selective hexameric capsules.
A one-pot two-step synthesis of 6-[<sup>18</sup>F]fluoro-<sc>l</sc>-DOPA has been developed, involving Cu-mediated radiofluorination the corresponding pinacol boronate ester precursor, and validated for production doses human use.
[18F]AV-1451 is one of the most widely used radiotracers for positron emission tomography (PET) imaging tau protein aggregates in neurodegenerative disorders. While radiotracer binds with high affinity to neurofibrillary tangles, extensive clinical studies have simultaneously revealed off-target tracer accumulation areas low burden such as basal ganglia and choroid plexus. Though there are a number possible reasons this accumulation, it often attributed binding monoamine oxidase (MAO). In...
In this paper, we describe the use of Cu‐mediated [ 18 F]fluorodeboronation for automated production positron emission tomography radiotracers suitable clinical use. Two recurrent issues with method, low radiochemical conversion on automation and protoarene byproduct purification issues, have been successfully addressed. The new method was utilized to produce sterile injectable doses F]‐( ± )‐IPMICF17, a radiotracer tropomyosin receptor kinase B/C, using an synthesis module. product isolated...
Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was via a tandem trapping [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) synthesized followed by an intermolecular cycloaddition between [(11)C]isocyanate isothiocyanate form the 1,2,4-thiadiazolidine-3,5-dione...
Using structure-guided design, several cell based assays, and microdosed positron emission tomography (PET) imaging, we identified a series of highly potent, selective, brain-penetrant oxazole-4-carboxamide-based inhibitors glycogen synthase kinase-3 (GSK-3). An isotopologue our first-generation lead, [3H]PF-367, demonstrates selective specific target engagement in vitro, irrespective the activation state. We discovered substantial ubiquitous GSK-3-specific radioligand binding Tg2576...
The magnetic behavior of nickel-seamed C-propylpyrogallol[4]arene dimeric and hexameric nanocapsular assemblies has been investigated in the solid state using a SQUID magnetometer. These capsular entities show differentiation both terms moment per nanocapsule potential antiferromagnetic interactions within individual nanocapsules. weak observed at low temperatures indicates dipolar between neighboring nickel atoms; however, this effect is higher assembly. differences dimer versus hexamer can...
The differences in magnetic properties of metal-based nanometric assemblies are due to distinct contributions from host-guest interactions, structural integrity, and interactions. To disentangle these contributions, it is necessary control the self-assembly process that forms entities. Herein we study effect host-to-guest ratios identify remarkably different structural-magnetic C-methylpyrogallol[4]arene⊂ferrocene/(PgC1)2⊂Fc dimers vs (PgC1)3⊂Fc nanotubes. At low temperature, a weak...
Changes in expression and dysfunctional signaling of TrkA/B/C receptors oncogenic Trk fusion proteins are found neurological diseases cancers. Here, we describe the development a first 18F-labeled optimized lead suitable for vivo imaging Trk, [18F]TRACK, which is radiosynthesized with ease from nonactivated aryl precursor concurrently combining largely reduced P-gp liability improved brain kinetics compared to previous leads while displaying high on-target affinity human kinome selectivity.
Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R expressed on microglia macrophages. AZ683 has high affinity (Ki = 8 nM; IC50 6 nM) >250-fold selectivity over 95 other kinases. In this paper, we report radiosynthesis [11C]AZ683 initial evaluation its use PET. was synthesized by 11C-methylation desmethyl precursor with [11C]MeOTf 3.0% non-corrected...
Tubes versus spheres: A new inclusion complex of alkylpyrogallol[4]arene and ferrocene is described. Unlike the previously reported dimer, tubular motif shown not stable in methanolic solution dissociates into a dimer. Its formation thus likely due to high alkylpyrogallol[4]arene/ferrocene ratio coupled with shifting solvent conditions during evaporation. Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but copy-edited or...
Hollow cylinders: Gallium- and gallium–zinc-seamed pyrogallol[4]arene nanoassemblies were studied in the solution phase through various methods. The results reveal their rearrangement from spheres solid state to toroids (see, for example, PgC4GaZn) illustrating structural flexibility of gallium metal-seamed frameworks. Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available...
Computational methods were used as a proof of principle in the synthesis two-dimensional coordination polymer constructed from zinc-seamed pyrogallol[4]arene dimeric nanocapsules and 4,4′-bipyridine.
Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by the authors. Please note: The publisher is responsible for content functionality any supporting information supplied Any queries (other than missing content) should be directed corresponding author article.
A family of hydrogen-bonded supramolecular frameworks based on C-alkylresorcinol[4]arene (RsC) and 4,4′-bipyridine (bpy) type spacers are described in this article. The size shape the void space enclosed within these engineered by varying solvent (acetonitrile ethanol), spacer molecules (4,4′-bipyridine (bpy), trans-1,2-bis(4-pyridyl)ethylene (bpe), 1,2-bis(4-pyridyl)acetylene (bpa)), conformations and/or RsC bowl (boat vs cone or C-methylresorcin[4]arene/RsC1 C-propylresorcin[4]arene/RsC3)....
This report describes a Pd-mediated C-H radiofluorination of 8-methylquinoline derivatives with no-carrier-added Ag[18F]F. To achieve this transformation, new method was developed for the generation Ag[18F]F using sep-pak cartridge. The then optimized and applied to series substituted derivatives. Finally, fully automated radiochemistry synthesis module.
Metal-containing tubes: The structures of several iron-containing C-methylpyrogallol[4]arene (PgC1) nanoassemblies were studied in both the solid and solution phases. have a tubular architecture with iron as part framework (see picture; gray C, red O, turquoise/blue Fe), magnetic analysis suggests canted or spiral arrangement centers.
[18F]AV1451 is a commonly used radiotracer for imaging tau deposits in Alzheimer's disease (AD) and related non-AD tauopathies. Existing radiosyntheses of require complex purifications to provide doses suitable use clinical studies. To address this issue, we have modified the synthesis only 0.5 mg precursor, optimized Boc-deprotection step developed simplified method HPLC purification radiotracer. An using TRACERLab FXFN module led high radiochemical yield (202 ± 57 mCi per synthesis) with...
The proto-oncogenes NTRK1/2/3 encode the tropomyosin receptor kinases TrkA/B/C which play pivotal roles in neurobiology and cancer. We describe herein discovery of [11C]-(R)-3 ([11C]-(R)-IPMICF16), a first-in-class positron emission tomography (PET) TrkB/C-targeting radiolabeled kinase inhibitor lead. Relying on extensive human kinome vetting, we show that (R)-3 is most potent selective TrkB/C characterized to date. It demonstrated readily crosses blood-brain barrier (BBB) rodents...