Degradable Polyphosphoramidate via Ring-Opening Metathesis Polymerization

Abstract

We report the synthesis of a degradable polyphosphoramidate via ring-opening metathesis polymerization (ROMP) with the Grubbs initiator (IMesH₂)(C₅H₅N)₂(Cl)₂Ru═CHPh. Controlled ROMP of a low ring strain diazaphosphepine-based cyclic olefin was achieved at low temperatures to afford well-defined polymers that readily undergo degradation in acidic conditions via the cleavage of the acid-labile phosphoramidate linkages. The diazaphosphepine monomer was compatible in random and block copolymerizations with phenyl and oligo(ethylene glycol) bearing norbornenes. This approach introduced partial or complete degradability into the polymer backbones. With this chemistry, we accessed amphiphilic poly(diazaphosphepine-norbornene) copolymers that could be used to prepare micellar nanoparticles.

Figure 1.

Synthesis and ring-opening metathesis polymerization of 2-phenoxy-1,3,4,7-tetrahydro-1,3,2-diazaphosphepine 2-oxide (PTDO) to afford polymers bearing phosphoramidate linkages.

Figure 2.

Synthesis of PPTDOs by ROMP in accordance with Table 2. (A) Plot of M_n and Đ vs monomer conversion, obtained by a combination of SEC-MALS and ¹H NMR analysis. The dotted line represents the theoretical M_n. (B) SEC traces (normalized RI) of PPTDOs quenched at different reaction times (correlated to Table 2, entries 1–5). (C) SEC traces (normalized RI) of PPTDOs of different molecular weights (correlated to Table 2, entry 5: PTDO₅₅; entry 6: PTDO₉₄; entry 7: PTDO₂₁₆).

Figure 3.

Degradation of PTDO and PPTDO (DP = 94) in 0.25 M HCl in DMSO-d₆ at room temperature. ³¹P NMR spectra of (A) PTDO degradation and (B) PPTDO degradation at different times. (C) SEC traces of PPTDO before and after 240 h acid treatment. Note: ³¹P NMR spectroscopy of phenylphosphoric acid was measured to give a signal at −6.23 ppm.

Figure 4.

Synthesis and degradation of NB-PTDO copolymers. Synthetic scheme for the preparation of (A) random copolymers, and (B) block copolymers of NB and PTDO. SEC traces (normalized RI) of random copolymers with (C) NBPh, and (D) NBOEG before and after acid treatment. SEC traces (normalized RI) of block copolymers with (E) NBPh, and (F) NBOEG before and after acid treatment. Degradation condition: 0.5 M HCl in DMSO for 24 h at room temperature.