Monday, August 20, 2012

PolyMPC-Doxorubicin Prodrugs

The authors prepared poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) linked to Dox via a hydrazone linkage using a one-pot ATRP/click reaction. They then test the pro-drug for solubility and stability at physiological conditions and in vitro uptake. They also examine the acid-assisted cleavage of the hydrazone for Dox release.

Branched Acid-Degradable, Biocompatible Polyether Copolymers via Anionic Ring-Opening Polymerization Using an Epoxide Inimer
Christine Tonhauser, Christoph Schüll, Carsten Dingels, and Holger Fre

This group synthesized epoxide monomers containing acid-cleavable inimer units. They used these monomers to make hyperbranched co-polymers through anionic ring polymerization with ethylene oxide or glycidol.The polymers did not degrade to any significant extent in pH 7 D20 at room temperature. However, at pH 4, the polymers did degrade and kinetics of degradation depended on the % of acetal groups present in the polymer.

Brush Polymers Containing Semiconducting Polyene Backbones: Graft-Through Synthesis via Cyclopolymerization and Conformational Analysis on the Coil-to-Rod Transition

Eun-Hye Kang, In-Hwan Lee, and Tae-Lim Choi

Conjugated backbone brush polymers were synthesized by first using a 1,6-heptadiyne with an alcohol group as an initiator to polymerize L-lactide or E-caprolactone by ring opening polymerization. These macromonomers were polymerized to brushes through cyclopolymerization with the Grubbs-Hoveyda catalyst. The resulting brushes were semiconducting with a bandgap of less than 2.0 eV as determined from UV-vis spectra. Time-dependent Mark-Houwink-Sakurada plots from SEC-viscometry suggested the brushes tend to extend over time. They also characterized their polymers through GPC-MALS, differential scanning calorimetry, and AFM.

pH-triggered blooming of "nano-flowers" for tumor intracellular drug delivery

Chemical Communications

The authors synthesized an octadecyl-PEG (biotin)-ocatadecyl ester type polymer, a benzoic-imine bond is used between the biotin and octadecyl ester, and an octadecyl-PEG-doxorubicin, hydrazone bond used to conjugate the dox to PEG, drug loaded polymer; both polymers bend at the PEG domain when introduced to water.  They use the term "nano-flower" for the polymers morphology and the blooming process that takes place when its introduced to different levels of pH.  The benzoic-imine bond hydrolyzes at pH <6.8 and the hydrazone hydrolyzes at pH >5.5; this allows the micelle to expose the biotin outside of the tumor cell and release the doxorubicin once the micelle has penetrated the cell membrane.

Cyclopolymerization To Synthesize Conjugated Polymers Containing Meldrum's Acid as a Precursor for Ketene Functionality

Jeongeun Kim, Eun-Hye Kang, and Tae-Lim Cho

A 1,6-heptadiyne monomer containing a Meldrum acid (ketene precursor) functional group was copolymerized with monomers 1 or 2 (see figure)  to afford solubility using cyclopolymerization with the third generation Grubbs catalyst. Studies from AFM, NMR, and DLS suggested these polymers self-assembled into core-shell type nanoparticles with the insoluble Meldrum's acid facing toward the center. Upon heating to 200 C, Meldrum's acid releases CO2 and acetone and generates a ketene. The formation of ketene was tested through thermal gravimetric analysis, in which a drop in the weight was observed; and infrared spectroscopy. Also upon heating to 240 C for ten minutes, IR signal suggested the ketenes started to react through [2+2] cycloaddition to give cyclobutanedione, which permanently crosslinked the cores.

Exploiting a dimeric silver transmetallating reagent to synthesize macrocyclic tetracarbene complexes

Zheng Lu, S. Alan Cramer and David M. Jenkins

The researchers synthesized a dimeric tetradente-NHC silver complex, as shown in the figure below. This metal complex was used as a transmetallation agent to make  monomeric tetradente-NHC metal complexes with platinum, palladium, nickel, chromium, gold, iron, cobalt, rhodium, and ruthenium. These metal complexes were studied with single crystal X-ray diffraction, ESI-MS, and other spectroscopic techniques where applicable.

“Black Swan Events” in Organic Synthesis

William A. Nugent

In this Angewandte essay, William Nugent discusses ten examples in organic chemistry that were thought to be "conventional wisdom" 35 years ago, but have now been proved incorrect through experimental research. Some examples brought up include:
  • "Gold compounds are simply too unreactive to be useful as homogeneous catalysts"
  • "Palladium-catalyzed cross-coupling is suitable for formation of C-C bonds but not for C-N bonds"
  • "Olefin metathesis is an ill-defined reaction of olefinic hydrocarbons and unlikely to find use in organic synthesis"
The following is one of his reflections:
"The third and final point I will direct toward younger scientists. On a couple of occasions, I have encountered chemists who feel overwhelmed by the sheer volume of the current chemical literature. They report that they approach the literature in a reactive fashion—they utilize search engines like SciFinder or Beilstein to address specific research problems to the exclusion of browsing current journals. I strongly disagree with this approach. It is by systematically reading current publications that we become aware of deficiencies in existing technologies, innovative solutions, research trends, and results from entirely different fields that could potentially impact our own interests. But I hope it is evident from the examples we have discussed that reading the literature over the last 40 years has been something more. It has, quite frankly, been an adventure. In such history one finds overarching themes, tales of dogged persistence, brilliant flashes of insight, and remarkable plot twists. One can only imagine what extraordinary developments those of you currently beginning your careers in chemistry will witness in the next 35 or 40 years. In this regard, I envy you."

Fluorescent Magnetic Nanoparticles for Magnetically Enhanced Cancer Imaging and Targeting in Living Subjects

ACS Nano

The authors describe a way to accumulate single superparamagnetic iron oxide (SPIO) nanoparticles (NP) at tumor sites.  Silanization coating chemistry was performed on the SPIO which increased the NP size from 8 nm to 87 nm and also left mercapto and amino groups on the surface.  Next, they attached fluorophores and RGD on the surface for imaging and tumor angiogenesis marker targeting.  They were able to target tumor tissue by placing a Ni wire mesh over the tumor area and using a magnet to attract the SPIO NP to the tumor site.  The half-life of tumor signal decay in vivo decreased from 6 days to .9 days when no magnetic targeting and magnetic targeting were compared, respectively. 

Stimuli-Responsive Y-Shaped Polymer Brushes Based on Junction-Point-Reactive Block Copolymers

Advanced Materials
A general concept for the preparation of junction-point-reactive, amphiphilic Y-shaped block copolymer brushes for ultrathin polymer films is demonstrated.

Thumbnail image of graphical abstract

Thiol-Selective Fluorogenic Probes for Labeling and Release

Vu Hong, Alexander A. Kislukhin, and M. G. Finn Journal of the American Chemical Society 2009 131 (29), 9986-9994

This article outlines a technique that utilizes thiol-ene chemistry to link peptides and other molecules together. When the thiol reacts with the oxonorbornadiene moiety, it activates a fluorescent dye that is attached. These adducts decompose readily via reverse Diels-Alder.

A General Route to Efficient Functionalization of Silicon Quantum Dots for High-Performance Fluorescent Probes

A General Route to Efficient Functionalization of Silicon Quantum Dots for High-Performance Fluorescent Probes 
Jing Wang, Yuexian Liu, Fei Peng, Chunying Chen, Yonghong He, Hui Ma, Lixin Cao, and Shuqing Sun* 

In this paper, functionalization of hydrogen-terminated silicon quantum dots via hydrosilylation of alkenes is presented.  The reactions are microwave-assisted (not UV-driven), carried out in the neat ligand or ethanol (depending on the functional group on the opposite end of the olefin) and are complete within 15 min at a frequency of 2450 MHz (temperature not reported).  The resulting silicon QDs were dispersible in hexane or water (depending on terminal functionality), and the water-dispersible carboxylic acid-terminal ones were internalized in HeLa cells, with a cytoplasmic distribution.

Temperature responsive hydrogel with reactive nanoparticles

Xiao, L., Isner, A. B., Hilt, J. Z. and Bhattacharyya, D. (2012), Temperature responsive hydrogel with reactive nanoparticles. J. Appl. Polym. Sci.. doi: 10.1002/app.38335
Here a hydrogel is used to imobilize Fe and Fe/Pd nanoparticles to be used in antifouling systems (dechlorination). NIPAM hydrogels are copolymerized with acrylic acid so as to capture metal centers. Once metal centers are incorporated by ion echange, the gel is cross linked using a UV initiator and the metal centers are reduced with NaBH4. The swelling characteristics and tricholorethylene reduction of these gels are probed at 30 and 34 °C. According to their results, the gels seem to be more effective at dechlorination at higher temperatures, perhaps due to enhanced TCE-metal center interactions when the NIPAm gel collapses.

Surface Charge Switchable Nanoparticles Based on Zwitterionic Polymer for Enhanced Drug Delivery to Tumor

Advanced Materials

 A zwitterionic polymer-based nanoparticle with response to tumor acidity is developed for enhanced drug delivery to tumors. The nanoparticles are neutrally charged at physiological conditions and show prolonged circulation time; after leaking into tumor sites, in the acidic extracellular tumor environment, nanoparticles are activated and become positively charged and are therefore efficiently taken up by tumor cells, leading to enhanced therapeutic effects in cancer treatment.