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. 2020 Oct 20;9(10):1417-1422.
doi: 10.1021/acsmacrolett.0c00401. Epub 2020 Sep 15.

Degradable Polyphosphoramidate via Ring-Opening Metathesis Polymerization

Yifei Liang  1 , Hao Sun  1   2 , Wei Cao  1   2 , Matthew P Thompson  1   2 , Nathan C Gianneschi  1   2
Affiliations

Degradable Polyphosphoramidate via Ring-Opening Metathesis Polymerization

Yifei Liang et al. ACS Macro Lett. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
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.
Figure 2.
Synthesis of PPTDOs by ROMP in accordance with Table 2. (A) Plot of Mn and Đ vs monomer conversion, obtained by a combination of SEC-MALS and 1H NMR analysis. The dotted line represents the theoretical Mn. (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.
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.
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.
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