58887-04-0Relevant academic research and scientific papers
Development of Fully Degradable Phosphonium-Functionalized Amphiphilic Diblock Copolymers for Nucleic Acids Delivery
Borguet, Yannick P.,Khan, Sarosh,Noel, Amandine,Gunsten, Sean P.,Brody, Steven L.,Elsabahy, Mahmoud,Wooley, Karen L.
, p. 1212 - 1222 (2018)
To expand the range of functional polymer materials to include fully hydrolytically degradable systems that bear bioinspired phosphorus-containing linkages both along the backbone and as cationic side chain moieties for packaging and delivery of nucleic acids, phosphonium-functionalized polyphosphoester-block-poly(l-lactide) copolymers of various compositions were synthesized, fully characterized, and their self-assembly into nanoparticles were studied. First, an alkyne-functionalized polyphosphoester-block-poly(l-lactide) copolymer was synthesized via a one pot sequential ring opening polymerization of an alkyne-functionalized phospholane monomer, followed by the addition of l-lactide to grow the second block. Second, the alkynyl side groups of the polyphosphoester block were functionalized via photoinitiated thiol-yne radical addition of a phosphonium-functionalized free thiol. The polymers of varying phosphonium substitution degrees were self-assembled in aqueous buffers to afford formation of well-defined core-shell assemblies with an average size ranging between 30 and 50 nm, as determined by dynamic light scattering. Intracellular delivery of the nanoparticles and their effects on cell viability and capability at enhancing transfection efficiency of nucleic acids (e.g., siRNA) were investigated. Cell viability assays demonstrated limited toxicity of the assembly to RAW 264.7 mouse macrophages, except at high polymer concentrations, where the polymer of high degree of phosphonium functionalization induced relatively higher cytotoxicity. Transfection efficiency was strongly affected by the phosphonium-to-phosphate (P+/P-) ratios of the polymers and siRNA, respectively. The AllStars Hs Cell Death siRNA complexed to the various copolymers at a P+/P- ratio of 10:1 induced comparable cell death to Lipofectamine. These fully degradable nanoparticles might provide biocompatible nanocarriers for therapeutic nucleic acid delivery.
Synthesis of Cyclic Carbonates from Epoxides and Carbon Dioxide by Using Bifunctional One-Component Phosphorus-Based Organocatalysts
Büttner, Hendrik,Steinbauer, Johannes,Werner, Thomas
, p. 2655 - 2669 (2015/09/02)
Numerous bifunctional organocatalysts were synthesized and tested for the atom-efficient addition of carbon dioxide and epoxides to produce cyclic carbonates. These catalysts are based on phosphonium salts containing an alcohol moiety in the side chain for substrate activation through hydrogen bonding. In the model reaction, converting 1,2-butylene oxide with CO2, 19 catalysts were tested to determine structure-activity relationships. In total, 28 epoxides were converted with CO2 to give the respective cyclic carbonates in yields of up to 99%. Even at 45C, the most active catalyst was able to produce cyclic carbonates selectively in high yields. The carbonates were generally obtained as analytically pure products after simple filtration over silica gel. This single-component catalyst system works under neat and mild reaction conditions and tolerates several useful moieties. Two heads are better than one! Bifunctional organocatalysts are synthesized and tested in the catalytic reaction of epoxides and carbon dioxide to give the respective cyclic carbonates. Product formation is significantly increased by hydrogen-bond donation from the bifunctional phosphonium catalyst.
Phosphorus-based bifunctional organocatalysts for the addition of carbon dioxide and epoxides
Werner, Thomas,Büttner, Hendrik
, p. 3268 - 3271 (2015/02/03)
Bifunctional phosphonium salts were synthesized and employed as organocatalysts for the atom efficient synthesis of cyclic carbonates from CO2 and epoxides for the first time. These catalysts were obtained in high yields by a modular, straightforward one-step synthesis. The hydrogen-bond donating alcohol function in the side chain leads to a synergistic effect accelerating the catalytic reaction. The desired cyclic carbonates are obtained in high yields and selectivity under solvent-free reaction conditions without the use of any co-catalyst. Under optimized reaction conditions various epoxides were converted to the corresponding cyclic carbonates in excellent yields. The products were obtained analytically pure after simple filtration over a silica gel pad. This protocol is even applicable for a multigram reaction scale. Moreover, the catalysts could be easily recovered and reused up to five times.
