Sn oct 2

Methoxy poly(ethylene glycol) (MPEG) (Sigma-Aldrich, number-average molecular weight (M_n = 750)), and Sn(Oct)₂ (Sigma-Aldrich, Yongin, Korea) were used as received. l-lactide (LA; Boehringer Ingelheim, Blanquefort, France) was recrystallized in ethyl acetate twice. ε-Caprolactone (CL; Sigma-Aldrich) was distilled over CaH₂ under reduced pressure. Dex and Dex(p) were purchased from Tokyo Chemical Industry Co., Ltd. (TCI; Fukaya City, Japan). Hexafluoro-2-propanol (HFIP), IR-780, and IR-783 were purchased from Sigma-Aldrich.

TMC was purchased from Daigang Biomaterial Co., Ltd. (Jinan, Shandong, China), recrystallized twice in ethyl acetate and vacuumed dried at 37 °C for 24 h before polymerization. ε-caprolactone (99%) was purchased from Sigma-Aldrich (St Louis, MO, USA), freshly distilled over CaH₂ under reduced pressure before use. Sn(Oct)₂ (95%) was purchased from Sigma-Aldrich and used as received. All other solvents and reagents were analytical grades and purified by standard methods.

Chalcone MB was synthesized and characterized by the Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy/CIIMAR research group, as previously described [27 (link)]. Methoxy PEG 2000, Methoxy PEG 5000, ε-caprolactone, and Sn(oct)₂ were acquired from Sigma-Aldrich Co. (Sintra, Portugal) and methanol (HPLC grade) from VWR chemicals. IR spectra were obtained in a KBr microplate in an FTIR spectrometer Nicolet iS 10 from Thermo Scientific with the Smart OMNI-Transmission accessory (Software OMNIC 8.3, Thermo Scientific, Madison, WI, USA). ¹H and ¹³C NMR spectra were recorded in the Department of Chemistry at the University of Aveiro, Portugal, on a Bruker Avance 300 instrument (Bruker Biosciences Corporation, Billerica, MA, USA) (¹H: 300.13 MHz; ¹³C: 75.47 MHz). ¹³C NMR assignments were made in bidimensional HSQC and HMBC experiments (long-range C, H coupling constants were optimized to 7 and 1 Hz). Chemical shifts are expressed in ppm values relative to tetramethylsilane (TMS) as an internal reference and coupling constants are reported in hertz (Hz). HPLC was performed on a Dionex Ultimate 3000 (Thermo Scientific, Darmstadt, Germany).

Dehydrated tetrahydrofuran (Kanto Chemical, Tokyo, Japan) was further purified by distillation from Na-benzophenone under nitrogen prior to use. Toluene was purified by distillation from sodium-benzophenone. Each solvent was stored over sodium. Chloroform was dried over CaH₂ overnight and then distilled. Methanol (Kanto Chemical) and PhCH₂OH (Wako Pure Chemical, Tokyo, Japan) was distilled, and stored over activated molecular sieves (3A). LA and PL were purchased from Tokyo Chemical Industry (Tokyo, Japan). LA was sublimated under nitrogen before use. PL and TfOH (Sigma-Aldrich Japan, Tokyo, Japan) were distilled under reduced pressure before use. Sn(Oct)₂ was purchased from Sigma-Aldrich and used without further purification. SmMe(C₅Me₅)₂(THF) (Sm-1) was synthesized according to Reference [47 (link)].

An mPEG-PCL di-block copolymer was synthesized by ring-opening polymerization of CL (Sigma-Aldrich) and poly (ethylene glycol) methyl ether (mPEG; M_n = 750, Sigma-Aldrich) in the presence of tin (II) 2-ethylhexanoate [Sn (Oct)₂, Sigma-Aldrich] as the catalyst [49 (link)]. Briefly, mPEG (10 mmol) and distilled CL (150 mmol) were prepared in a 3-necked round-bottom flask under a nitrogen atmosphere. The mixture was heated up to 140 °C and then allowed to react with Sn(Oct)₂ (0.2 mmol) for 1.5 h. The product was dissolved in dichloromethane and precipitated with cold diethyl ether, followed by vacuum drying for 24 h to obtain mPEG-PCL.