Cationic copolymers consisting of polycations linked to nonionic polymers are evaluated as non-viral gene delivery systems. These copolymers are known to produce soluble complexes with DNA, but only a few studies have characterized the transfection activity of these complexes. This work reports the synthesis and characterization of a series of cationic copolymers obtained by grafting the polyethyleneimine (PEI) with non-ionic polyethers, poly (ethylene oxide) (PEO) or Pluronic 123 (P123). The PEO-PEI conjugates differ in the molecular mass of PEI (2 kDa and 25 kDa) and the degree of modification of PEI with PEO. All of these conjugates form complexes upon mixing with plasmids, which are stable in aqueous dispersion for several days. The sizes of the particles formed in these systems vary from 70 to 200 nm depending on the composition of the complex. How-

This study for the first time demonstrates phenomenon of recognition of DNA tertiary structure by the synthetic polycationic molecules. Effects of DNA topology were evaluated using supercoiled and linearized forms of plasmid DNA (scDNA and lDNA). Recognition is achieved by using relatively simple chemical structures interacting with the DNA. Two polycations modified with water-soluble poly(ethylene glycol) (PEG) chains, PEG−block−poly(N-methyl-4-vinylpyridinium sulfate) (PEG−b−PVP) and PEG−graft−polyethyleneimine (PEG−g−PEI) were used. When added to the mixtures of lDNA and scDNA, PEO−b−PVP selectively bound to scDNA, while lDNA remained free. In contrast, PEO−g−PEI interacted with both forms of the DNA present in the mixture. Distinct behavior of two copolymers was attributed to the differences in their structure, particularly, charge density of the polycation blocks. Relatively small variation in the polycation ionization state can result in drastic changes in its behavior upon interaction with DNA. Particularly, the change of pH from 7.0 to 5.0, increasing the charge density of PEI block in PEO−g−PEI, was also accompanied by the appearance of recognition phenomena. These findings uncover possibilities for the control of the processes of DNA incorporation in the complexes with cationic species by altering the DNA topology, which may have practical significance in using these complexes for gene delivery.

Self-assembling complexes from nucleic acids and synthetic polymers are evaluated for plasmid and oligonucleotide (oligo) delivery. Polycations having linear, branched, dendritic. block- or graft copolymer architectures are used in these studies. All these molecules bind to nucleic acids due to formation of cooperative systems of salt bonds between the cationic groups of the polycation and phosphate groups of the DNA. To improve solubility of the DNA/polycation complexes, cationic block and graft copolymers containing segments from polycations and non-ionic soluble polymers, for example, poly(ethylene oxide) (PEO) were developed. Binding of these copolymers with short DNA chains, such as oligos, results in formation of species containing hydrophobic sites from neutralized DNA polycation complex and hydrophilic sites from PEO. These species spontaneously associate into polyion complex micelles with a hydrophobic core from neutralized polyions and a hydrophilic shell from PEO. Such complexes are very small (10-40 nm) and stable in solution despite complete neutralization of charge. They reveal significant activity with oligos in vitro and in vivo. Binding of cationic copolymers to plasmid DNA forms larger (70-200 nm) complexes. which are practically inactive in cell transfection studies. It is likely that PEO prevents binding of these complexes with the cell membranes ("stealth effect"). However attaching specific ligands to the PEO-corona can produce complexes, which are both stable in solution and bind to target cells. The most efficient complexes were obtained when PEO in the cationic copolymer was replaced with membrane-active PEO-b-poly(propylene oxide)-b-PEO molecules (Pluronic 123). Such complexes exhibited elevated levels of transgene expression in liver following systemic administration in mice. To increase stability of the complexes, NanoGel carriers were developed that represent small hydrogel particles synthesized by cross-linking of PEI with double end activated PEO using an emulsification/solvent evaporation technique. Oligos are immobilized by mixing with NanoGel suspension, which results in the formation of small particles (80 nm). Oligos incorporated in NanoGel are able to reach targets within the cell and suppress gene expression in a sequence-specific fashion. Further. loaded NanoGel particles cross-polarized monolayers of intestinal cells (Caco-2) suggesting potential usefulness of these systems for oral administration of oligos. In conclusion the approaches using polycations for gene delivery for the design of gene transfer complexes that exhibit a very broad range of physicochemical and biological properties, which is essential for design of a new generation of more effective non-viral gene delivery systems.

An azobenzene-containing zirconium metal-organic framework was demonstrated to be an effective heterogeneous catalyst for the direct amidation of benzoic acids in tetrahydrofuran at 70 °C. This finding was applied to the synthesis of several important, representative bioactive compounds.

This article systematically presented analysis results of factors affecting the preparation of nano‐ZIF‐8 in methanol for high yield. Samples were characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Brunauer‐Emmett‐Teller (BET) adsorption, and thermogravimetry‐differential thermal analysis (TG/DTA). Synthesized nano‐ZIF‐8 had advantages over commercial ZIF‐8 (Basolite® Z1200 from Sigma‐Aldrich) such as a higher surface area, consisting of not only micropores like Basolite® Z1200 but also subordinate mesopores, formed by an assembly of nano‐ZIF‐8 crystals, which was 30 nm. Specifically, for the first time, nano‐ZIF‐8 was prepared in methanol with the yield of 61.2 %.

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