Synthesis and characterization of a new family of cationic amino acid‐based poly(ester amide)s and their biological properties

Abstract

A new family of positively charged and water soluble amino acid-based poly(ester amide)s (PEAs) consisting of nontoxic L-arginine, diols, and aliphatic dicarboxylic acids building blocks was synthesized and characterized. The L-arginine based PEAs (Arg-PEAs) were prepared by a solution polycondensation of two monomers: tetra-p-toluenesulfonic acids salts or hydrochloride acid salts of bis-(L-arginine) a, x-alkylene diesters (monomer II), and di-p-nitrophenyl esters of saturated or unsaturated dicarboxylic acids (monomer I). Optimal reaction conditions were studied as functions of type of solvents and acid acceptors, concentrations of reactants. The molecular weights (M n and M w ) of Arg-PEAs measured by GPC ranged from 20,000 to 60,000 g mol À1 with a rather narrow molecular weight distribution below 1.5. The chemical structures were confirmed by IR and NMR spectra. ArgPEAs obtained were all amorphous materials with T g from 33 to 125 C, depending on the number and the type (saturated vs. unsaturated) of methylene groups in diols or diacids, and the type of counter-ions attached to the guanidine group of the Arg-based PEAs. The Arg-PEAs had a high solubility in all polar solvents, including water. Preliminary studies of cell morphology and DNA capture capability of Arg-PEAs indicated that this new family of cationic PEAs was nontoxic and more biocompatible than a commercial transfection agent (Superfect V R ), and can successfully capture plasma DNA. The strong positive charge of Arg-PEAs as well as their good water solubility could provide unique characteristics for potential gene transfection or other charge preferred biomedical applications.

Biodegradable nanocomplex from hyaluronic acid and arginine based poly(ester amide)s as the delivery vehicles for improved photodynamic therapy of multidrug resistant tumor cells: An in vitro study of the performance of chlorin e6 photosensitizer

“…We also reported a amine terminated phenylalanine based PEA from the same synthesis method . 1 H NMR spectrum was obtained to characterize the amine terminated Arg‐PEA, and typical chemical shifts were observed at 8.25 ppm ( NH CO  ), 4.23 ppm ( CH 2  O  CO  ) and 3.09 ppm (  NH  CO CH 2  ) The 1 H NMR result was consistent with our previous study . The molecular weight of the amine terminated Arg‐PEA was 6.5 kDa with PDI =1.36, as detected by GPC.…”

“…Snakeskin dialysis tubing (MWCO = 10 kDa) and NHS‐rhodamine were from Pierce (Rockford, IL). The monomer Arg‐4 (tetra‐ p ‐toluenesulfonic acid salt of bis‐ l ‐arginine butane‐1, 4‐diester) and NA (di‐ p ‐nitrophenyl adipate) were synthesized according to our previous studies …”

Poly(ester-amide)s Derived From Adipic Acid, 1,4-Butanediol and β-Alanine: Synthesis and Characterization

“…Various monomers and various synthetic strategies can be used for the preparation of PEAs exhibiting alternating (16), block (17) or random (18,19) structures. Alternating PEAs are synthesized by reacting diol or diacid derivatives with intermediate compounds, such as diamine-terminated diesters or diester-terminated diamides (20)(21)(22)(23)(24)(25)(26)(27) or by ring-opening polymerization of a cyclic morpholine-2,5-dione derived from natural a-amino acids and a-hydroxy acids (28)(29)(30)(31)(32).…”

Quasi‐alternating polyesteramides from ε‐caprolactone and α‐amino acids

“…Various approaches have been employed to synthesize amino acid‐based polyesteramides exhibiting block, random, or alternating structures. Block amino acid‐based polyesteramides are prepared by the ring‐opening polymerization of ɛ‐caprolactone initiated by amine‐terminated peptides or by the ring opening polymerization of α‐amino acid N‐carboxyanhydrides (NCAs) initiated by amine‐terminated polylactide or poly(ɛ‐caprolactone) .…”

“…On the other hand alternating amino acid‐based polyesteramides can be synthesized by reacting diol or diacid derivatives with intermediate compounds, such as diamine‐terminated diesters, prepared from α‐amino acids and diols or diester‐terminated diamides, prepared from α‐amino acid derivatives and dicarboxylic acids . For instance, diamine‐terminated diesters were first synthesized by 1/2 mol/mol solution reaction of a diol with an α‐amino acid in the presence of p‐toluenesulfonic acid and alternating amino acid‐based polyesteramides were then obtained either by interfacial polycondensation of these diesters with a diacid chloride or by solution polycondensation with an activated p‐nitrophenyl dicarboxylate .…”