35 research outputs found
PET Imaging of Soluble Yttrium-86-Labeled Carbon Nanotubes in Mice
The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 ((86)Y-CNT and (111)In-CNT, respectively) in a mouse model.The (86)Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting (111)In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intravenous or intraperitoneal injection.The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of (86)Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications
Strategic Vinyl Sulfone Nucleophile Substitution Significantly Impacts Selectivity in Vinylogous Darzens and Aza-Darzens Reactions
Correction to [2.2.2]- to [3.2.1]-Bicycle Skeletal Rearrangement Approach to the Gibberellin Family of Natural Products
[2.2.2]- to [3.2.1]-Bicycle Skeletal Rearrangement Approach to the Gibberellin Family of Natural Products
Synthetic studies toward the gibberellin
family of natural products
are reported. An oxidative dearomatization/Diels–Alder cascade
assembles the carbon skeleton as a [2.2.2]-bicycle, which is then
transformed to the [3.2.1]-bicyclic gibberellin core via a novel Lewis
acid catalyzed rearrangement. Strategic synthetic handles allow for
late-stage modification of the gibberellin skeleton and provides efficient
access to this important family of natural compounds
Double-Diels–Alder Approach to Maoecrystal V. Unexpected C–C Bond-Forming Fragmentations of the [2.2.2]-Bicyclic Core
Synthetic
studies toward maoecrystal V are reported. An oxidative
dearomatization/Diels–Alder cascade to assemble the natural
product carbocyclic core in one step is proposed. A facile electrocyclization
is shown to suppress the intramolecular allene Diels–Alder
pathway. This obstacle is alleviated via a stepwise approach with
an allene equivalent to access the key cyclopentadiene-fused [2.2.2]-bicyclic
core. Upon treatment with Lewis acid, the proposed intramolecular
hetero-Diels–Alder reaction is cleanly and unexpectedly diverted
either via C–C bond-forming fragmentation to the spiro-indene
product (when R = OMe) or via elimination (when R = H)
Dearomatization Approach to 2‑Trifluoromethylated Benzofuran and Dihydrobenzofuran Products
A mild dearomatization enabled <i>ortho</i>-selective
replacement of an aromatic C–H bond with a hexafluoroacetylacetone
(hfacac) substituent has been developed. This reaction is dependent
on a hypervalent iodine generated phenoxonium intermediate, a critical
choice of solvent, and reagent addition order. The fluorinated dihydrobenzofuran
product can be transformed into dihydrobenzofuran and benzofuran products
decorated with a 2-trifluoromethyl group. The 3-trifluoromethylacyl
substituted benzofurans rapidly form hydrates, which can be reduced
to the corresponding alcohols
Beyond C, H, O, and N! Analysis of the Elemental Composition of U.S. FDA Approved Drug Architectures
The
diversity of elements among U.S. Food and Drug Administration
(FDA) approved pharmaceuticals is analyzed and reported, with a focus
on atoms other than carbon, hydrogen, oxygen, and nitrogen. Our analysis
reveals that sulfur, chlorine, fluorine, and phosphorous represent
about 90% of elemental substitutions, with sulfur being the fifth
most used element followed closely by chlorine, then fluorine and
finally phosphorous in the eighth place. The remaining 10% of substitutions
are represented by 16 other elements of which bromine, iodine, and
iron occur most frequently. The most detailed parts of our analysis
are focused on chlorinated drugs as a function of approval date, disease
condition, chlorine attachment, and structure. To better aid our chlorine
drug analyses, a new poster showcasing the structures of chlorinated
pharmaceuticals was created specifically for this study. Phosphorus,
bromine, and iodine containing drugs are analyzed closely as well,
followed by a discussion about other elements