Site‐Selective, Multistep Functionalizations of CO2‐Based Hyperbranched Poly(alkynoate)s toward Functional Polymetric Materials

Abstract Hyperbranched polymers constructed from CO2 possess unique architectures and properties; however, they are difficult to prepare. In this work, CO2‐based, hyperbranched poly(alkynoate)s (hb‐PAs) with high molecular weights and degrees of branching are facilely prepared under atmospheric pressure in only 3 h. Because hb‐PAs possess two types of ethynyl groups with different reactivities, they can undergo site‐selective, three‐step functionalizations with nearly 100% conversion in each step. Taking advantage of this unique feature, functional hb‐PAs with versatile properties are constructed that could be selectively tailored to contain hydrophilic oligo(ethylene glycol) chains in their branched chains, on their periphery, or both via tandem polymerizations. Hyperbranched polyprodrug amphiphiles with high drug loading content (44.3 wt%) are also generated, along with an artificial light‐harvesting system with high energy transfer efficiency (up to 92%) and white‐light‐emitting polymers. This work not only provides an efficient pathway to convert CO2 into hyperbranched polymers, but also offers an effective platform for site‐selective multistep functionalizations toward functional polymeric materials.


Materials and instruments S3
Preparation of monomer 3b S4 Optimization of polymerization conditions S5 Typical procedures for polymerization of CO 2 , 1 and 2 S6 Characterization data for hyperbranched poly(alkynoate)s S7 GPC curves for hyperbranched poly(alkynoate)s S8 TGA curves of hyperbranched poly(alkynoate)s S9

Preparation of model compounds S9
FT-IR and NMR spectra of monomers and polymers S11 Degree of Branching S17 Photophysical properties S18 Procedures of site-selective three-step functionalizations of hb-P1 S19 Procedures of site-selective tandem polymerization S21 Synthesis of hyperbranched polyprodrug amphiphiles S23

Preparation of hyperbranched polyprodrug NPs S25
In vitro drug release S26

CLSM study S27
In vitro anti-cancer efficacy S27 S4 analyzer under a nitrogen atmosphere at a heating rate of 20 K/min. UV−vis absorption spectra were recorded on a SHIMADZU UV-2600 spectrophotometer. Fluorescence spectra were recorded on a Horiba Fluoromax-4 fluorescence spectrophotometer. Absolute fluorescence quantum yields and CIE chromaticity coordinates were measured using a Hamamatsu absolute PL quantum yield spectrometer C11347 Quantaurus QY. pH values were measured via METTLER TOLEDO FiveEasy FE20. Confocal laser scanning microscope (CLSM) characterization was conducted with a confocal laser scanning biological microscope (LSM 710,Zeiss,Germany). The absorbance for MTT analysis was recorded on a microplate reader (Thermo Fisher, USA) at a wavelength of 570 nm. Size measurements were conducted on Dynamic Light Scattering (ZSE, Malvern, UK). Transmission electron microscope was carried on JEM-2100F (JEOL, Japan).

Preparation of monomer 3b
The monomer 3b was synthesized in two steps, and the synthetic routes are show in Scheme S2.
The organic phases were combined and washed with water and brine and then dried over MgSO 4 for 1 h.
After filtration and solvent evaporation, the crude product was purified by a silica gel column chromatography using PE/DCM

S6
The yield of the product was calculated via following equation: where m t is the theoretical mass of polymers we could obtain, m a is actual mass of polymers we got.

Preparation of model compounds
Model compounds 5-7 was synthesized by three-component reaction of 1, 1-bromooctane and CO 2 .
Typically, into a 10 mL dried Schlenk tube equipped with magnetic stirrer was placed with 1 (158.7 mg, 0.5 mmol), 1-bromooctane (193.1 mg, 1 mmol), Ag 2 WO 4 (34.8 mg, 0.075 mmol), and Cs 2 CO 3 (977.5 mg, 3 mmol) under CO 2 (balloon). Dried DMAc (3 mL) were injected into the tube by a syringe. The resultant mixture was stirred at 80 o C under atmospheric CO 2 for 3 h. Then the reaction mixture was cooled to room temperature and extracted with dichloromethane (DCM) (60 mL × 3). The organic layer was washed by water (100 mL × 3) and dried over Na 2 SO 4 . After filtration, the filtrate was concentrated and purified by silica gel column chromatography using petroleum ether (PE)/DCM mixture as the eluent, a yellow solid of compounds 5-7 (293.1 mg) was obtained.

S18
where A 1 , A 2 and A 3 represent the integrals of the areas of resonance peaks 1, 2 and 3, respectively, as labelled in Figure S14F. The values can be determined from the 1 H NMR spectral data, from which the following equations are deduced: From the above equations, f D , f L and f T were calculated to be: According to the definition, DB is expressed as: Inset: photographs of hb-P2 in pure THF and a THF/water mixture with 90% water fraction.

Synthesis of hyperbranched polyprodrug amphiphiles
Into a 10 mL dried Schlenk tube equipped with magnetic stirrer were placed with 1 (63.5 mg, 0.2 mmol),

In vitro drug release
The drug release from NPs was studied using PBS (pH 7.4 and 5.0). Briefly, hb-P1-8(1) NPs (5 mL, containing 300 μg DOX) were placed in a dialysis bag (MWCO 3500 Da), which was immersed in 45 mL of the release medium. The release study was performed at 37 °C under gentle shaking (100 rpm).
At pre-determined time intervals, 4 mL of the release medium was withdrawn and replaced with equal S27 amount of fresh release medium. The DOX amount in the release medium was determined by UV-vis spectrophotometry.

Statistical analysis
Experiments were repeated for at least three times and results were expressed as means ± SD. Statistical significances were analyzed using the Student's t-test, and differences between the test and control groups were judged to be significant at *p < 0.05. The Student's t-test was carried out using Origin9 Software.

Construction of artificial light-harvesting system
Into 10 mL dried Schlenk tubes equipped with magnetic stirrer were placed with 1 (63.5 mg, 0.2 mmol), Scheme S5. Construction of artificial light-harvesting system via a "one-pot" tandem reaction strategy.

Preparation of fluorophores C343-Br
The