6 research outputs found
Design, Synthesis, Biological Evaluation, and StructureāActivity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4
International audienc
Enhanced Luminescent Iridium(III) Complexes Bearing Aryltriazole Cyclometallated Ligands
Herein we report the synthesis of 4-aryl-1-benzyl-1<i>H</i>-1,2,3-triazoles (atl), made via āClick chemistryā and their incorporation as cyclometallating ligands into new heteroleptic iridium(III) complexes containing diimine (N<sup>ā§</sup>N) ancillary ligands 2,2ā²-bipyridine (bpy) and 4,4ā²-di-<i>tert</i>-butyl-2,2ā²-bipyridine (dtBubpy). Depending on decoration, these complexes emit from the yellow to sky blue in acetonitrile (ACN) solution at room temperature (RT). Their emission energies are slightly blue-shifted and their photoluminescent quantum efficiencies are markedly higher (between 25 and 80%) than analogous (C<sup>ā§</sup>N)<sub>2</sub>Ir(N<sup>ā§</sup>N)<sup>+</sup> type complexes, where C<sup>ā§</sup>N is a decorated 2-phenylpyridinato ligand. This increased brilliance is in part due to the presence of the benzyl groups, which act to sterically shield the iridium metal center. X-ray crystallographic analyses of two of the atl complexes corroborate this assertion. Their electrochemistry is reversible, thus making these complexes amenable for inclusion in light-emitting electrochemical cells (LEECs). A parallel computational investigation supports the experimental findings and demonstrates that for all complexes included in this study, the highest occupied molecular orbital (HOMO) is located on both the aryl fragment of the atl ligands and the iridium metal while the lowest unoccupied molecular orbital (LUMO) is located essentially exclusively on the ancillary ligand
Activation of Phenyl 4ā(2-Oxo-3-alkylimidazolidin-1-yl)benzenesulfonates Prodrugs by CYP1A1 as New Antimitotics Targeting Breast Cancer Cells
Prodrug-mediated utilization of the
cytochrome P450 (CYP) 1A1 to
obtain the selective release of potent anticancer products within
cancer tissues is a promising approach in chemotherapy. We herein
report the rationale, preparation, biological evaluation, and mechanism
of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)Ābenzenesulfonates
(PAIB-SOs) that are antimicrotubule prodrugs activated by CYP1A1.
Although PAIB-SOs are inert in most cells tested, they are highly
cytocidal toward several human breast cancer cells, including hormone-independent
and chemoresistant types. PAIB-SOs are <i>N</i>-dealkylated
into cytotoxic phenyl 4-(2-oxo-3-imidazolidin-1-yl)Ābenzenesulfonates
(PIB-SOs) in CYP1A1-positive cancer cells, both in vitro and in vivo.
In conclusion, PAIB-SOs are novel chemotherapeutic prodrugs with no
equivalent among current antineoplastics and whose selective action
toward breast cancer is tailored to the characteristic pattern of
CYP1A1 expression observed in a large percentage of human breast tumors
Design, Synthesis, Biological Evaluation, and StructureāActivity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4
Sixty-one phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) and 13 of their tetrahydro-2-oxopyrimidin-1(2<i>H</i>)-yl analogues (PPB-SOs) were prepared and biologically evaluated. The antiproliferative activities of PIB-SOs on 16 cancer cell lines are in the nanomolar range and unaffected in cancer cells resistant to colchicine, paclitaxel, and vinblastine or overexpressing the P-glycoprotein. None of the PPB-SOs exhibit significant antiproliferative activity. PIB-SOs block the cell cycle progression in the G<sub>2</sub>/M phase and bind to the colchicine-binding site on Ī²-tubulin leading to cytoskeleton disruption and cell death. Chick chorioallantoic membrane tumor assays show that compounds <b>36</b>, <b>44</b>, and <b>45</b> efficiently block angiogenesis and tumor growth at least at similar levels as combretastatin A-4 (CA-4) and exhibit low to very low toxicity on the chick embryos. PIB-SOs were subjected to CoMFA and CoMSIA analyses to establish quantitative structureāactivity relationships
GoldāManganese Oxide CoreāShell Nanoparticles Produced by Pulsed Laser Ablation in Water
A single-step procedure for the preparation
of AuāMnO<sub><i>x</i></sub> NPs was achieved through
pulsed laser ablation
of a goldāmanganese metal target made of a pressed metal powder
mixture. First, a 248 nm nanosecond laser at 66.7 J cm<sup>ā2</sup> was used to synthesize AuāMnO<sub><i>x</i></sub> NPs from a goldāmanganese metal target immersed in an aqueous
solution at pH 11 (NaOH). It is demonstrated that the AuāMnO<sub><i>x</i></sub> NPs are made of a small Au core (around
5 nm in diameter) surrounded by a very thin manganese oxide layer
(0.3ā1.3 nm) as characterized by TEM, HAADF HR-STEM, and EELS.
The superficial MnO<sub><i>x</i></sub> layer has a local
structure that bears a close resemblance to that of Mn<sub>2</sub>O<sub>3</sub> and MnO<sub>2</sub> as revealed by EXAFS and XANES
measurements. Comparative studies were also performed with a 1064
nm nanosecond laser at 1.4 J cm<sup>ā2</sup>. In that case,
the resulting colloids are mainly made of a mixture of Au NPs and
MnO<sub><i>x</i></sub> NPs, with few AuāMnO<sub><i>x</i></sub> NPs, thereby suggesting the impact of the laser
wavelength and fluence on the synthesis process. The mechanisms responsible
for the production of AuāMnO<sub><i>x</i></sub> coreāshell
NPs are discussed
Characterizing Nanoparticle Mass Distributions Using Charge-Independent Nanoresonator Mass Spectrometry
Due to their unique size-dependent properties, nanoparticles
(NPs)
have many industrial and biomedical applications. Although NPs are
generally characterized based on the size or morphological analysis,
the mass of whole particles can be of interest as it represents the
total amount of material in the particle regardless of shape, density,
or elemental composition. In addition, the shape of nonspherical NPs
presents a conceptual challenge, making them difficult to characterize
in terms of size or morphological characteristics. Here, we used a
novel nano-electro-mechanical sensor mass spectrometry (NEMS-MS) technology
to characterize the mass distributions of various NPs. For standard
spherical gold NPs, mass distributions covered the range from ā¼5
to 250 MDa (8 to ā¼415 attograms). Applying the density of gold
(19.3 g/cm3) and assuming perfect sphericity, these mass
measurements were used to compute the equivalent diameters of the
NPs. The sizes determined agreed well with the transmission electron
microscopy (TEM) imaging data, with deviations of ā¼1.4%. Subsequently,
we analyzed the mass distribution of ā¼50 nm synthetic silicon
dioxide particles, having determined their size by electron microscopy
(SEM and TEM). Their estimated density was in line with the literature
values derived from differential mobility analyzer and aerosol particle
mass analyzer data. Finally, we examined the intact gold nanotetrapods
and obtained a mass distribution revealing their controlled polydispersity.
The presence of polyethylene glycol coating was also quantified and
corroborated nuclear magnetic resonance observations. Our results
demonstrate the potential of NEMS-MS-based measurements as an effective
means to characterize NPs, whatever their composition, shape or density