Polymeric Amines and Ampholytes Derived from Poly(acryloyl chloride): Synthesis, Influence on Silicic Acid Condensation and Interaction with Nucleic Acid

Abstract

Polymeric amines are intensively studied due to various valuable properties. This study describes the synthesis of new polymeric amines and ampholytes by the reaction of poly(acryloyl chloride) with trimethylene-based polyamines containing one secondary and several (1-3) tertiary amine groups. The polymers contain polyamine side chains and carboxylic groups when the polyamine was in deficiency. These polymers differ in structure of side groups, but they are identical in polymerization degree and polydispersity, which facilitates the study of composition-properties relationships. The structure of the obtained polymers was confirmed with 13 C nuclear magnetic resonance infrared spectroscopy, and acid-base properties were studied with potentiometry titration. Placement of the amine groups in the side chains influences their acid-base properties: protonation of the amine group exerts a larger impact on the amine in the same side chain than on the amines in the neighboring side chains. The obtained polymers are prone to aggregation in aqueous solutions tending to insolubility at definite pH values in the case of polyampholytes. Silicic acid condensation in the presence of new polymers results in soluble composite nanoparticles and composite materials which consist of ordered submicrometer particles according to dynamic light scattering and electron microscopy. Polymeric amines, ampholytes, and composite nanoparticles are capable of interacting with oligonucleotides, giving rise to complexes that hold promise for gene delivery applications.

Design of Oligonucleotide Carriers: Importance of Polyamine Chain Length

“…Oligo( N -methylazetidine) (LCPA, ZS-309 sample) was prepared from 1,3-dibromopropane and N , N -bis[3-(methylamino)propyl]methylamine according to earlier work from our group [32]. AKX-182 polymer was prepared according to the protocol described earlier [21]. PEI (M w = 30,000–40,000) was obtained from SERVA Fine Biochemica (Heidelberg, Germany).…”

“…Our work has two objectives with the first being estimation of L c for DNA oligonucleotides in the reaction with PEI and new polymeric amine poly( N -(3-((3(dimethylamino)propyl)(methyl)amino)propyl)Nmethylacrylamide) (AKX-182, Scheme 1) [21]. We have used the DNA oligonucleotides (TCAG) n , where n = 1–6, which contain equal amount of the each nucleotide and cannot form stable hairpins or self-dimers.…”

Design of the Oligonucleotide Carriers: Importance of Polyamine Chain Length

“…These oligomers as well as non-fractioned sample were involved in the reaction with activated polymer giving rise to the target polymers (Scheme 3, Table 2). Grafting degree of the LCPA chains is 1.8-3.4, Mw/Mn ratio is 1.16-1.24 for polymers with fractionated LCPA chains which is significantly lower than the values for polymers based on poly(acryloyl chloride) without fractionation (1.37-1.58 [13]).…”

“…Our work has two objectives with the first being estimation of Lc for DNA oligonucleotides in the reaction with PEI and new polymeric amine poly(N- (3-((3-(dimethylamino)propyl)(methyl)amino)propyl)Nmethylacrylamide) (AKX-182, Scheme 1) [13]. We have used the DNA oligonucleotides (TCAG)n, where n = 1-6, which contain equal amount of the each nucleotide and cannot form stable hairpins or self-dimers.…”

“…Oligo(N-methylazetidine) (LCPA, ZS-309 sample) was prepared from 1,3-dibromopropane and N,N-bis [3-(methylamino)propyl]methylamine according to earlier work from our group [24]. AKX-182 polymer was prepared according to the protocol described earlier [13]. PEI (Mw = 30000-40000) was obtained from SERVA Fine Biochemica (Heidelberg).…”