A Simple and Efficient Synthesis of an Acid-Labile Polyphosphoramidate by Organobase-Catalyzed Ring-Opening Polymerization and Transformation to Polyphosphoester Ionomers by Acid Treatment

Abstract

The direct synthesis of an acid-labile polyphosphoramidate by organobase-catalyzed ring-opening polymerization and an overall two-step preparation of polyphosphodiester ionomers (PPEI) by acid-assisted cleavage of the phosphoramidate bonds along the backbone of the polyphosphoramidate were developed in this study. The ultrafast organobase-catalyzed ring-opening polymerization of a cyclic phospholane methoxyethyl amidate monomer initiated by benzyl alcohol allowed for the preparation of well-defined polyphosphoramidates (PPA) with predictable molecular weights, narrow molecular weight distributions (PDI<1.10), and well-defined chain ends. Cleavage of the acid-labile phosphoramidate bonds on the polyphosphoramidate repeat units was evaluated under acidic conditions over a pH range of 1–5, and the complete hydrolysis produced polyphosphodiesters. The thermal properties of the resulting polyphosphoester ionomer acid and polyphosphoester ionomer sodium salt exhibited significant thermal stability. The parent PPA and both forms of the PPEIs showed low cytotoxicities toward HeLa cells and RAW 264.7 mouse macrophage cells. The synthetic methodology developed here has enriched the family of water-soluble polymers prepared by rapid and convenient organobase-catalyzed ring-opening polymerizations and straightforward chemical medication reactions, which are designed to be hydrolytically degradable and have promise for numerous biomedical and other applications.

Reversible Bioconjugation: Biodegradable Poly(phosphate)‐Protein Conjugates

“…Phosphate monomers are easily accessible via the commercially available precursor COP (2‐chloro‐2‐oxo‐1,3,2‐dioxaphospholane), which can also be prepared in a straightforward manner following literature procedures . Simple condensation of a (functional) alcohol with COP yields the corresponding monomer in one step, as demonstrated in some elegant examples by other groups . In this way, we prepared phosphate monomer bearing a methoxy ethoxy (EEP) group (Scheme a), which produces water‐soluble polymers; the successful synthesis can be confirmed by 31 P NMR spectroscopy with the typical chemical shift of 16.8 ppm (for EEP) for strained cyclic phosphoesters.…”

Organophosphate-catalyzed bulk ring-opening polymerization as an environmentally benign route leading to block copolyesters, end-functionalized polyesters, and polyester-based polyurethane

“…In order to avoid metal contamination without any special purification steps, the organocatalytic approach has emerged as a powerful metal-free polymerization process in recent years. 7 Considerable effort has been directed toward the evaluation of various types of both organic acids/bases for the ROP of cyclic esters, 7-37 cyclic carbonates, [38][39][40][41][42][43] epoxides, [44][45][46][47] lactams, 48 cyclic (carbo)siloxanes, 49 cyclic phosphates, [50][51][52][53][54] etc. Regarding the ROP of cyclic esters, organic Brønsted acids, e.g., methane sulfonic acid (MSA) and triflimide, were found to be suited for the polymerization of lactones, [8][9][10][11][12][13][14][15][16][17][18][19] whereas organic bases, e.g., 1,8-diazadicyclo [5.4.0]undec-7-ene (DBU) and 4-dimethylaminopyridine (DMAP), were effective for the ROP of the lactide (LA).…”

Double hydrophilic polyphosphoester containing copolymers as efficient templating agents for calcium carbonate microparticles

“…Compared to other strategies reported for the synthesis of poly(phosphodiester)s, 68 the deprotection of the allyl group can be achieved under non acidic conditions, which prevents premature degradation of the poly(phosphate) chain. The general synthetic strategy (Scheme 1, route B) relies on the ROP of 2-(prop-2-en-1-yloxy)-1,3,2-dioxaphospholane 2-oxide 4, a cyclic phospholane monomer with an allyl moiety as side chain (AllP), followed by the nucleophilic deprotection of the allyl group of PEO-b-poly(allyl phospholane) 5.…”