Novel Synthesis of Macromonomers by Mechanochemical Reaction for the Application to Polymeric Micelles

Abstract

We have presented the first example of the synthesis of macromonomers by mechanochemical reaction of polymethylmethacrylate (PMMA) and maleic anhydride (MA). The mechanochemical reaction of PMMA and MA was carried out by vibratory ball milling under anaerobic condition. The ESR spectrum of the fractured sample of PMMA and MA showed a broad singlet, which was apparently different from the spectrum of PMMA mechanoradical. Therefore, PMMA mechanoradical would react with MA. We underwent the UV-labeling of the fractured samples of PMMA and MA to confirm the formation of macromonomers. The gel permeation chromatograms of UV-labeled compounds derived from this fractured sample showed a broad peak in a polymer region with refractive index detector and UV detector, which indicates that macromonomers bounding MA would be produced. This method seems to be applicable for a wide variety of polymers to synthesize macromonomers possessing MA.

Synthesis of Amphiphilic Blockcopolymer Using Mechanically Produced Macromonomers Possessing Anhydrate as a Terminal Group and Its Application to Polymeric Micelles

“…Although the ESR spectrum of the fractured sample of PBzMA with MA at 30-min vibratory milling showed a broad singlet, the spectral feature at 60-min vibratory milling showed the overlapped spectrum of broad singlet and nine-line spectrum ascribed to PBzMA mechanoradicals (Figure 1). The similar results were obtained in the case of the mechanochemical reaction of poly(methyl methacrylate) and MA as previously reported [14]. Figure 2 shows the progressive changes in radical concentrations in the course of vibratory ball milling of PBzMA with or without MA.…”

“…In the previous paper, we reported the first example of the synthesis of macromonomers in the solid-state by the mechanochemical reaction of poly(methyl methacrylate) (PMMA) and maleic anhydride (MA) [14]. In this method the PMMA mechanoradicals, which are produced by mechanical fracture of polymer due to the polymer main-chain scission, can react with MA in the solid-state.…”

Characterization of a novel polymeric prodrug of an antibacterial agent synthesized by mechanochemical solid‐state polymerization

“…The spectral features remained unchanged at various stages of the mechanochemical processing, which are most characterized by five major lines with four shoulders (“nine‐line spectrum”). Virtually identical spectra have been observed for the mechanochemical polymerization of several methacryloyl‐monomers containing active pharmaceutical ingredients and the mechanolysis of poly(methyl methacrylate) (PMMA) at the various mechanical energies as shown in Figure 6b (Kondo, Tsukamoto, Sasai, Yamauchi, & Kuzuya, 2011). As reported previously, the radical in the ESR spectra can be unambiguously assigned to a single end‐chain radical (equivalent to a propagating radical; structure of radicals formed in mechanolysis of PMMA was shown in Figure 6b) of methacrylic polymers (Kuzuya, Noguchi, et al, 1991).…”

Drug Release Profile and Cellular Uptake of Polymeric Prodrugs Synthesized from Amphiphilic Blockcopolymer Using Mechanically Produced Macromonomers Possessing Anhydrate as a Terminal Group

“…We have reported the synthesis of macromonomers in the solid-state by the mechanochemical reaction of maleic anhydride (MA) and synthetic polymer, such as poly(methyl methacrylate) and poly(benzyl methacrylate) (PBzMA) [14,15]. In this method the mechanoradicals, which are produced by mechanical fracture of polymer due to the polymer main-chain scission, can react with MA in the solid-state.…”