# Graphene Oxide as a Self-Carbocatalyst to Facilitate the Ring-Opening Polymerization of Glycidol for Efficient Polyglycerol Grafting

Yajuan Zou, Kentaro Ohkura, Israel Ortiz-Anaya, Ryota Kimura, Alberto Bianco, Yuta Nishina

► To cite this version:

Yajuan Zou, Kentaro Ohkura, Israel Ortiz-Anaya, Ryota Kimura, Alberto Bianco, et al., Graphene Oxide as a Self-Carbocatalyst to Facilitate the Ring-Opening Polymerization of Glycidol for Efficient Polyglycerol Grafting. Chemistry - A European Journal, 2025, 31 (14), pp.e202404400. 10.1002/chem.202404400. hal-04891759

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Distributed under a Creative Commons Attribution 4.0 International License
Graphene oxide as a self-carbocatalyst to facilitate the ring-opening polymerization of glycidol for efficient polyglycerol grafting

Yajuan Zou,* Kentaro Ohkura, Israel Ortiz-Anaya, Ryota Kimura, Alberto Bianco,* Yuta Nishina*

Dr. Y. Zou, Israel Ortiz-Anaya, Dr. A. Bianco, Prof. Y. Nishina

Research Institute for Interdisciplinary Science, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan

Kentaro Ohkura, Ryota Kimura, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama, Okayama 700-8530, Japan

Dr. A. Bianco, CNRS, Immunology, Immunopathology and Therapeutic Chemistry, UPR3572, University of Strasbourg, ISIS, Strasbourg, 67000, France

E-mail: [YajuanZou@okayama-u.ac.jp](mailto:YajuanZou@okayama-u.ac.jp) (Y.Z.);

[a.bianco@ibmc-cnrs.unistra.fr](mailto:a.bianco@ibmc-cnrs.unistra.fr) (A.B.);

[nisina-y@cc.okayama-u.ac.jp](mailto:nisina-y@cc.okayama-u.ac.jp) (N.Y.).

Dedicated to the memory of Professor Luis Moroder

**Keywords:** Carbon nanomaterials; epoxide ring-opening; catalysis; polyglycerol functionalization
**Abstract**

Grafting carbon-based nanomaterials (CNMs) with polyglycerol (PG) improves their application potentials in biomedicine and electronics. Although "grafting from" method offers advantages over "grafting to" one in terms of operability and versatility, little is known about the reaction process of glycidol with the surface groups onto CNMs. By using graphene oxide (GO) as a multi-functional model material, we examined the reactivity of the surface groups on GO toward glycidol molecules via a set of model reactions. We reveal that carboxyl groups spontaneously react with the epoxide ring with no need of catalyst, while GO catalyzes the reactions of hydroxyl groups with the epoxide of glycidol. In addition, the hydroxyl group of glycidol can open the epoxide in the basal plane of GO. The subsequent polymerization of PG is supposed to propagate at the primary and/or the secondary hydroxyl groups, generating a ramified PG macromolecule with random branch-on-branch topology. In addition, ketones, benzyl esters and aromatic ethers are found not to react with glycidol even in the presence of GO, while the aldehydes are easily oxidized into carboxyl groups under ambient condition, behaving then as the carboxyl groups. Our findings pose the foundation for understanding the polymerization mechanism of PG on CNMs.
# 1. Introduction

Polyglycerol (PG) functionalization has been gradually recognized as one of the most promising modification approaches for improving the applications of carbon-based nanomaterials (CNMs) in biology and biomedicine,[1] electronics,[2] and environmental science.[3] For instance, in the preparation of drug delivery systems, large amounts of hydroxyl groups presenting within the interior and at the periphery of the hyperbranched PG impart CNMs with a high dispersibility in physiological environment[4] and prevent their non-specific interactions with plasma proteins and immune cells from reticuloendothelial system,[5] increasing the amounts of CNMs reaching target organs *in vivo*.[6] Additionally, the abundant hydroxyl groups also serve as versatile scaffolds for further modification with various biological functionalities such as targeting ligands and anticancer drugs for efficient tumor eradication.[7] On the other hand, the hydroxyl groups in PG can be made more hydrophobic by alkyl functionalities to increase the dispersibility of CNMs in organic solvents, rendering them effective for applications of tribology, lubrication, and abrasion.[8]

For the applications mentioned above, a PG layer was mainly immobilized on the surface of CNMs via covalent bonding, prepared through either “grafting to” or “grafting from” methods. In one example of “grafting to” approach, amine-PG was grafted onto dichlorotriazine-functionalized fullerene through nucleophilic reactions.[9] By substituting the first chlorine atom in triazine-functionalized graphene oxide (GO) with propargylamine,[10] azido-PG and amine-PG allowed to be sequentially conjugated through Click and nucleophilic reactions, respectively. Although practical, this method requires the pretreatment of CNMs with nitrene [2+1] cycloaddition reaction and the introduction of specific functional groups in preformed PG units to tailor their reactivity. In addition, it may only applicable for a small portion of CNMs such as fullerene and GO that are compatible with cycloaddition reactions. In contrast to “grafting to” method, the “grafting from” one has attracted much more attention owning to its versatility. In this approach, the PG are grafted on CNMs by simply reacting them with glycidol in one pot with no need of solvent or catalysts. Since the first report of “grafting from” method for PG functionalization of nanodiamonds (NDs) in 2011,[11] this method has been extended to a wide range of CNMs including GO,[12] carbon nanotubes (CNTs)[13] and carbon dots.[14] Furthermore, the PG content in the products of “grafting from” method can be precisely controlled by tuning the reaction temperatures,[5] which, in turn, permits a controllable thickness of PG layer and the amounts of functional moieties per CNM particle, and consequently enhancing the performance of the resulting materials. Despite all these remarkable advantages, little is known about the polymerization mechanism of glycidol on CNMs, and the
reaction process of glycidol occurring on the surface groups of CNMs. Since hydroxyl and carboxyl groups are reported to promote the formation of free PG,[15] these oxygenated functional groups on the surface of CNMs are frequently considered as the initiating sites for the grafting of PG. However, there is lack of experimental proof for such assumption. In addition, little attention has been paid to epoxide rings, ketones, esters, and other functional groups that also exist on the surface of CNMs.

In order to provide a comprehensive understanding on the polymerization of glycidol on CNMs, we decided to initially investigate the reactions of glycidol with four types of CNMs including GO, partially reduced GO (rGO), single-walled CNTs (SWCNTs) and NDs under mild reaction conditions. We found that GO yielded the highest weight gain of PG in the reaction system. Together with its abundant oxygen-containing groups and acidic nature, GO was then selected as a model material to study the polymerization mechanism of glycidol on CNMs. For this purpose, a set of model reactions were performed to examine the reactivity of the surface groups onto GO toward glycidol molecules (Scheme 1). Our results demonstrated that the carboxyl groups spontaneously reacted with the epoxide moiety of glycidol, while GO catalyzed the reactions of hydroxyl groups of GO with the epoxide of glycidol in addition to the reactions of the GO epoxides with the hydroxyl group of glycidol. Other oxygenated functionalities including ketones, esters and ethers could not react with glycidol even in the presence of GO, while the aldehydes were easily oxidized into carboxyl groups under ambient condition, then followed the same reaction route as that of carboxyl groups. These results provide in-depth understandings on the polymerization mechanism of PG on CNMs.

<figure><img src="image_2.png" /><figcaption>**Scheme 1.** Schematic representation of the possible reactions between GO and glycidol.</figcaption></figure>

(a) Chemical structures of GO and glycidol. (b) Functional groups present onto the surface of GO selected to test the reactivity toward glycidol. (i) Carboxyl and hydroxyl groups of GO
toward the epoxide moiety of glycidol; (ii) Epoxides of GO toward the hydroxyl group of glycidol; (iii) Ketones, esters, ethers, and aldehydes of GO toward the hydroxyl group of glycidol.

## 2. Results and Discussion

### 2.1 Ring-opening polymerization of glycidol on CNMs

In order to elucidate the polymerization mechanism of glycidol in the "grafting from" method, we initially investigated the reactions of glycidol with four types of most widely used CNMs, including GO, rGO (obtained from the same GO), SWCNTs, and NDs. The morphology and surface chemistry of CNMs were fully characterized before use. In the images of scanning electron microscopy (SEM), GO nanosheets with an average lateral size of 500 nm were in a well-dispersed state (Figure 1a), while the sheets of rGO tended to aggregate and sometimes stacked upon each other (Figure 1b). The tubular structure of SWCNTs (around 10 nm in diameter) was clearly observed by scanning transmission electron microscopy (STEM, Figure 1c), and most of the tubes were bundled and randomly oriented. According to transmission electron microscopy (TEM) observation (Figure 1d), the diameter of NDs was determined to be around 50 nm. In the Raman spectra (Figure S1), all the CNMs showed typical D band (~1340 cm⁻¹) and G band (~1600 cm⁻¹), corresponding to disordered carbon and to the in-plane vibration of sp²-bonded carbon atoms, respectively. The similar intensity ratios of D and G band (ID/IG) in GO (1.12) and rGO (1.06) suggests that the degrees of disordered carbon in these two materials were almost the same. This is also in good agreement with rGO (1.07-1.13) prepared from GO (1.17) via solvothermal reduction methods.[16] Concerning SWCNTs, due to high degree of graphitization,[17] G band became narrow and intense while the intensity of D band decreased. In addition, the 2D band (first overtone of D band), which reflects the defect-free sp² carbons, is clearly present at ~2630 cm⁻¹. In the amorphous NDs, in contrast, a sharp peak arising from the vibration of sp³ hybridization appeared at 1322 cm⁻¹,[18] and the G band became relatively broader and weaker.
<figure><img src="image_3.png" /><figcaption>**Figure 1.** Morphology characterization of the different CNMs. SEM images of (a) GO and (b) rGO, STEM image of SWCNTs (c), and TEM image of NDs (d).</figcaption></figure>

All the reactions of CNMs with glycidol were performed at 75 °C under ambient condition for 20 h. The relatively low temperature was set to maintain the starting oxidation state of GO. Indeed, it has been extensively reported that GO can undergo a reduction/dehydration process when heated above 80 °C.[19] Once the reaction was completed, the weight gain of PG in each CNM was quantified by scale weight (see details in Material and Methods). As summarized in Table 1, the normalized weight gain of PG (defined as weight of PG per weight of CNM, expressed as mg·mg⁻¹), follows the order of GO (7.64) > rGO (4.76) > NDs (0.90) > SWCNTs (0.87), demonstrating that GO has the highest reactivity in promoting the polymerization of glycidol. The extremely low weight gain of PG in the case of SWCNTs should be attributed to its relatively low content of oxygen-containing groups to afford limited reaction sites with glycidol. Based on X-ray photoelectron spectroscopy (XPS, Figure 2 and S2, and Table S1) and thermogravimetric analyses (TGA, Figure S3), the contents of surface oxygen and total oxygen-containing groups in SWCNTs were determined to be only 11.7% and 0.9% of those in GO, respectively. Similarly, the comparable low weight gain of PG on NDs can be attributed to the
limited number of oxygen-containing groups available for initiating PG polymerization. Although a moderate oxygen content was detected on ND surface (13.7%, Figure 2d and Table S1), the content of total oxygen-containing groups in NDs was only ~1.7 wt% (Figure S3). Taking into account of the relatively low specific surface area of NDs (32 m²·g⁻¹)[5] as compared to that of GO (corresponding to 1555 m²·g⁻¹ based on a methylene blue-based adsorption method recently developed by our group),[20] the absolute number of oxygen-containing groups on ND surface should be very low when calculated in a weight-based manner. In the case of rGO, on the other hand, the weight gain of PG was around 5.0-fold higher than those of SWCNTs and NDs, presumably due to the higher amounts of oxygen-containing groups on its surface (Figure 2b), effectively promoting the polymerization of glycidol. However, due to the loss of oxygen-containing groups during the reduction process (Figure 2a and 2b) and the layer stacking (indicated by yellow circles in Figure 1b), the amounts of surface groups per specific surface area in rGO was lower than that of GO, thereby affording a lower weight gain of PG. In addition, the almost neutral states of rGO, NDs, and SWCNTs (pH values of 6.43, 7.01 and 6.47, respectively, at the concentration of 0.1 mg·mL⁻¹) is likely unfavorable for the opening of epoxide ring in glycidol.[15] Taken together, the high weight gain of PG, abundant surface groups, and the acidic nature of GO (pH 4.25 at the concentration of 0.1 mg mL⁻¹) make it as a suitable model material for the study of the polymerization mechanism of glycidol.

<figure><img src="image_4.png" /><figcaption>(b)</figcaption></figure>

<figure><img src="image_5.png" /><figcaption>(c)</figcaption></figure>

<figure><img src="image_6.png" /><figcaption>(d)</figcaption></figure>

<figure><img src="image_7.png" /></figure>
**Figure 2.** High resolution XPS C 1s spectra of the different CNMs. (a) GO, (b) rGO, (c) SWCNTs, and (d) NDs.

<table><caption>**Table 1.** Oxygen content and PG weight gain in the reaction of each CNM with glycidol.</caption><thead><tr><th>Entry</th><th>CNMs</th><th>Surface oxygen (at%)<sup>a)</sup></th><th>Total oxygen (wt%)<sup>b)</sup></th><th>Glycidol</th><th>PG/CNMs (mg·mg<sup>-1</sup>)</th></tr></thead><tbody><tr><td>1</td><td>GO</td><td>31.5</td><td>43.9</td><td>OH</td><td>7.64</td></tr><tr><td>2</td><td>rGO</td><td>22.7</td><td>30.9</td><td>OH</td><td>4.76</td></tr><tr><td>3</td><td>SWCNTs</td><td>3.7</td><td>0.4</td><td>OH</td><td>0.87</td></tr><tr><td>4</td><td>NDs</td><td>13.7</td><td>1.7</td><td>OH</td><td>0.90</td></tr></tbody></table>

## 2.2 Reactions of epoxides with carboxyl and hydroxyl groups in the presence or absence of GO

The typical reaction process of the polymerization of glycidol includes: 1) the initial reaction of the epoxide ring in glycidol with surface groups on GO, followed by 2) the successive addition of the glycidol molecules through their further reaction with the hydroxyl groups in the growing PG. For these reactions, the efficient opening of the epoxide ring in glycidol is a prerequisite. Therefore, we first selected benzoic acid, cyclohexanol and phenol as model molecules mimicking the oxygenated functionalities present on GO to test the reactivity of carboxyl and hydroxyl groups toward the epoxide ring (Entries 1, 2 and 4, Table 2). 1,2-Epoxyhexane was employed to mimic the epoxide ring in glycidol leading to easily characterize products (e.g., no possibility of self-polymerization). Benzoic acid is representative of the carboxyl groups at the edges of GO, while the cyclohexanol and phenol stand for hydroxyl groups located at the basal plane and at the edges of GO, respectively. In addition to these trials, the possibility of epoxide ring from the basal plane of GO to be attacked by hydroxyl group of glycidol was also tested by performing the reaction of 1,2-epoxycyclohexane with ethanol (Entry 6, Table 2). The different reaction mixtures were stirred under conditions identical to that of CNMs with glycidol (Table 1), and the reaction products were analyzed by gas chromatography mass spectrometry (GC-MS). Among all the above reactions, a new compound was detected only in the reaction of 1,2-epoxyhexane with benzoic acid (Figure S4a). In

<footnote>a) From XPS; b) From TGA (at 550 °C). All the reactions were performed at 75 °C for 20 h in ambient condition.</footnote>
addition, the newly detected compound was confirmed to be the mixture of the two regioisomers 2-hydroxyhexyl benzoate and 1-hydroxyhexan-2-yl benzoate, by comparing the GC-MS (Figure S4b) and the proton nuclear magnetic resonance (¹H-NMR, Figure S4c) spectra with those of the same compounds prepared in accordance with a procedure described in the literature in the presence of a catalyst.[21] These results imply that the carboxyl groups at the edges of GO are likely able to spontaneously react with the epoxide in glycidol to initiate the ring-opening reaction, although not reaching completion. On the contrary, only the starting reagents were detected for the Entries 2, 4, and 6 of Table 2 (Figure S5a, S6a, and S7a), indicating no conversion to the expected reaction products or almost no reactivity of the hydroxyl groups toward the epoxide moiety in our conditions.

Considering the high weight gain of PG in the reaction of GO with glycidol (Entry 1, Table 1) and the enhanced reactivity of epoxide ring toward a wide range of alcohols in the presence of GO[22] and other carbon allotrope such as mesoporous activated carbon,[23] it is reasonable to hypothesize that GO might promote the nucleophilic attack of alcohol to epoxide for efficient polymerization of glycidol. To test this hypothesis, the reactions illustrated in Entries 2, 4, and 6 (Table 2) were performed in the presence of GO (6 mg, ~2 wt% of epoxides and ~1 wt% of total reagents), corresponding to Entries 3, 5 and 7 (Table 2), respectively. The amount of GO was optimized based on a previous report,[22] in which small amount of GO (~1 wt% of epoxide), rather than large amount (>10 wt% of epoxide), was found to effectively promote the opening of epoxides. The GC-MS analyses demonstrated that the three reactions proceed smoothly with the addition of GO to afford new products (Figure S5b, S6b, and S7b). By using combined characterization techniques (e.g., GC-MS and ¹H NMR) similar to that applied to identify Entry 1 products, a part of the products from Entries 5 and 7 were confirmed to be the expected isomeric products 2-phenoxyhexan-1-ol and 1-phenoxyhexan-2-ol (Figure S6c and S6d) and racemic 2-ethoxycyclohexan-1-ol (Figure S7c and S7d), respectively. Since the structure of (cyclohexyloxy)hexanol isomers (desired products of Entry 3, Table 2) has not been reported yet, we tried to identify these new compounds by comparing the GC-MS spectrum with that of the same compound prepared adding *p*-toluenesulfonic acid as catalyst (Figure S5c). The structure of as-prepared products was analyzed by the combination of ¹H NMR (Figure S5d) and carbon NMR (¹³C NMR, Figure S5e), Fourier transform infrared spectrophotometer (FT-IR, Figure S5f), and high-resolution mass spectroscopy (HR-MS, Figure S5g). The mixture of two products in a 6:1 ratio correspond to 1-(cyclohexyloxy)hexan-2-ol and 2-(cyclohexyloxy)hexan-1-ol, although the relative structure of the two regioisomers was not assigned. The formation of the target products corresponding to Entries 3, 5 and 7
(Table 2) demonstrates that GO facilitates the ring-opening of epoxides leading to an efficient polymerization of glycidol. Since the ring-opening of epoxides by alcohols is known to be promoted under either acidic or basic conditions,[15] the enhanced reactivity of epoxides toward hydroxyl groups in the presence of GO is likely enabled by the acidic nature of GO (vide infra).

<table><caption>**Table 2** Reaction progress of the reactive functions onto GO against glycidol model compounds, in the presence or absence of GO.</caption><thead><tr><th>Entry</th><th>Epoxide</th><th>Carboxyl / hydroxyl</th><th>GO (mg)</th><th>Reaction progress</th><th>Product structures</th></tr></thead><tbody><tr><td>1</td><td>Δ</td><td>Δ</td><td>---</td><td>Yes</td><td>Δ</td></tr><tr><td>2</td><td>Δ</td><td>Δ</td><td>---</td><td>No</td><td>Δ</td></tr><tr><td>3</td><td>Δ</td><td>Δ</td><td>6.0</td><td>Yes</td><td>Δ</td></tr><tr><td>4</td><td>Δ</td><td>Δ</td><td>---</td><td>No</td><td>Δ</td></tr><tr><td>5</td><td>Δ</td><td>Δ</td><td>6.0</td><td>Yes</td><td>Δ</td></tr><tr><td>6</td><td>Δ</td><td>Δ</td><td>---</td><td>No</td><td>Δ</td></tr><tr><td>7</td><td>Δ</td><td>Δ</td><td>6.0</td><td>Yes</td><td>Δ</td></tr></tbody></table>

All the reactions were conducted at 75 °C for 20 hours under ambient conditions, with a 1:1 ratio of epoxide to carboxyl or hydroxyl.
## 2.3 Reactions of other oxygenated functionalities with epoxides in the presence or absence of GO

After demonstrating the efficiency of GO in promoting the reactions of epoxides with alcohols, efforts were also directed toward exploring the catalytic potential of this carbon material in the polymerization reactions of other possible functional groups including ketones, benzyl esters, aldehydes and aromatic ethers. Indeed, graphene-based materials are well-known carbocatalysts to promote relevant organic transformations [24]. To this end, we performed the reactions of benzophenone, phenyl benzoate and tetrahydropyran (Entries 1, 3 and 5, Table 3) with ethanol, a model compound to mimic the hydroxyl group in glycidol. The GC and GC-MS results indicated that none of above reaction proceeded under neat conditions, as only starting reagents were detected in the reaction systems (Figure S8a, S9a, and S10a). However, in the investigation of these reactions in the presence of GO (Entries 2, 4 and 6, Table 3), no new products were observed (Figure S8b, S9b, and S10b), implying that GO has no catalytic effect on these inert groups. Only the reactions with benzaldehyde corresponding to Entry 7 and 8 proceed to benzoic acid (Figure S11a and S11b). Subsequently, benzoic acid reacts with 1,2-epoxyhenxane (Figure S11c) to afford the same products described for the model reaction corresponding to Entry 1 of Table 2 (Figure S4a).
<table><caption>**Table 3** Reaction progress of other functional groups present on GO with ethanol.</caption><thead><tr><th>Entry</th><th>Substrate</th><th>Alcohol</th><th>GO (mg)</th><th>Reaction progress</th></tr></thead><tbody><tr><td>1</td><td><img src="image_0_0.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_1.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>---</td><td>No</td></tr><tr><td>2</td><td><img src="image_0_2.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_3.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>6.0</td><td>No</td></tr><tr><td>3</td><td><img src="image_0_4.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_5.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>---</td><td>No</td></tr><tr><td>4</td><td><img src="image_0_6.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_7.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>6.0</td><td>No</td></tr><tr><td>5</td><td><img src="image_0_8.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_9.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>---</td><td>No</td></tr><tr><td>6</td><td><img src="image_0_10.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_11.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>6.0</td><td>No</td></tr><tr><td>7</td><td><img src="image_0_12.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_13.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>---</td><td>Oxidized to carboxylic acid</td></tr><tr><td>8</td><td><img src="image_0_14.png" alt="Chemical structure of 4-tert-butylstyrene"></td><td><img src="image_0_15.png" alt="Chemical structure of 4-hydroxy-3-tert-butylphenol"></td><td>6.0</td><td>Oxidized to carboxylic acid</td></tr></tbody></table>

All the reactions were conducted at 75 °C for 20 hours under ambient conditions, with a 1:1 ratio of substrate to ethanol.
## 2.4 Mechanism of ring-opening polymerization of glycidol on GO

Based on our experimental results we propose the mechanisms of the ring-opening reactions of epoxide that can follow two types of routes: 1) a spontaneous reaction of epoxides with the carboxylic groups of GO (Entry 1, Table 2), and 2) a GO catalyzed reaction of the epoxides with the hydroxyl groups (Entries 3, 5 and 7, Table 2). In the case of the type 1 reaction (Scheme 2a), from the model reaction, the proton of benzoic acid transfers to 1,2-epoxyhexane to activate the oxirane ring. Subsequently, the negatively charged benzoate attacks the carbon atoms in the protonated epoxide to break the C-O bond, leading to the formation of the two regioisomers 2-hydroxyhexyl benzoate (i) and 1-hydroxyhexan-2-yl benzoate (ii) through a SN₂ reaction.[25] Due to the steric hindrance, the nucleophilic attack prefers the carbon atom at 1 position of the epoxide,[26] and therefore the production of isomer (i) is more favored (Scheme 2a). This is supported by the ¹H NMR characterization in Figure S4c, as the ratio of (i)/(ii) was determined to be 3/1, in accordance with hydroxyhexyl benzoate regioisomers prepared with metal-based Lewis acids (ratios of (i)/(ii): 2.0-2.8).[27] In the case of the type 2 reaction, the epoxide oxygen atom acquires first a proton from GO. The acidity of GO is considered to stem from its acidic surface functionalities such as carboxyl/hydroxyl groups (Brønsted acidity).[28] Then, the nucleophilic hydroxyl groups at the edges of either the aromatic ring or cyclohexane attack the cationic oxirane to break the weak C-O bonds leading to the expected products (iii-vi) via the transfer of a proton to GO. In the ring-opening reaction of 1,2-epoxyhexane, the nucleophilic attack at the carbon in position 2 leading to the formation of products (iii) and (v) happens more frequently than that to position 1,[29] because the carbon at 2-position is more electrophilic than that at 1-position (Scheme 2a). Actually, the ratio of (v)/(vi) was determined to be around 6 (0.85/0.15) in the ¹H-NMR spectrum (Figure S5d). Since the epoxide in 1,2-epoxycyclohexane is symmetric,[30] the reaction of this molecule with ethanol affords a racemic mixture of 2-ethoxycyclohexan-1-ol (vii).

Based on the above mechanisms, the possible polymerization process of glycidol onto GO is proposed in Scheme 2b. Initially, the carboxyl and hydroxyl groups react with the epoxide ring of glycidol through a ring-opening reaction introducing two hydroxyl groups. Subsequently, these newly generated hydroxyl groups further react with the epoxides of glycidol through GO catalyzed ring-opening reaction to increase glycerol units exponentially. Different from the carboxyl and hydroxyl groups, when the epoxides from the basal plane of GO are opened by the hydroxyl group of glycidol, an epoxide ring and a hydroxyl group are generated at the same time. Therefore, both the epoxide and hydroxyl groups are present as active propagation sites for the successive addition of glycidol molecules. If the secondary
hydroxyl group propagates, a glycerol unit is attached to the polymer chain forming a linear 1,3-unit ($L_{1,3}$) (Scheme 2b). A linear 1,4-unit ($L_{1,4}$) is formed, when the propagation takes place at the primary hydroxyl group (Scheme 2b). Since glycidol is a latent AB₂-type monomer[31] containing a highly strained three membered oxirane ring that generates a branching point upon ring-opening in the course of polymerization, the dendritic structure of PG is produced if both secondary and primary hydroxyl groups react with the monomer. Moreover, during the polymerization process, due to a fast proton exchange among the propagating hydroxyl groups, the simultaneous growth of different chains results in a random branching structure. For example, the degree of branching of PG on NDs was determined to be 0.5-0.6.[29] If a monomer unit is deactivated by a proton exchange, a terminal unit (T) with two hydroxyl end groups is formed (Scheme 2b). Consequently, the ring-opening polymerization of glycidol on GO initiates from the carboxyl and hydroxyl groups, as well as the epoxides, and further propagates with the hydroxyl groups and epoxides in the growing PG. The structure of PG onto GO is assumed to be a ramified macromolecule with a random branch-on-branch topology (Scheme 2c).
a Type 1 reaction

<figure><img src="image_8.png" /></figure>

Type 2 reaction

<figure><img src="image_9.png" /></figure>

b Type 1 reaction

<figure><img src="image_10.png" /></figure>

Type 2 reaction

<figure><img src="image_11.png" /></figure>

c

<figure><img src="image_12.png" /></figure>
**Scheme 2.** Mechanisms leading to the polymerization of glycidol onto GO. (a) Epoxide ring-opening by carboxyl and hydroxyl groups based on the model reactions illustrated in **Table 2**. (b) Proposed mechanism of ring-opening reactions of glycidol with carboxyl, hydroxyl, and epoxy groups on the surface of GO. The hydroxyl groups from the basal plane behave like those at the edges. (c) Schematic representation of the reaction of GO with glycidol to form GO-PG. [Note: if present, aldehydes on GO are readily oxidized into carboxyl groups and serve as starting sites for PG functionalization].

**3. Conclusion**

In summary, the mechanisms of ring-opening polymerization of glycidol onto CNMs was elucidated by using GO as a multi-functional model material. The initial reactions of glycidol with GO proceed either through a spontaneous reaction of the carboxyl groups with the epoxides of glycidol or through a GO catalyzed epoxide ring-opening by the hydroxyl groups. The subsequent polymerization propagates at the primary and/or the secondary hydroxyl groups, generating a dendritic PG macromolecule with a random branch-on-branch topology. As GO is frequently used as the precursors of graphene-like materials, and ubiquitously exists on the surface of NDs, the findings of this study attempt to provide deep insights into the “grafting from” reactions of glycidol with a variety of CNMs.

**4. Material and Methods**

**4.1 Materials and Characterization Methods**

All the chemicals were purchased from Fujiwako, TCI and Sigma, and used as received. GO was prepared by a modified Hummers' method,[32] and the GO sheets were collected by ultracentrifugation (6700 g, 60 min) and freeze-dried prior to use. rGO was prepared by treating GO with hydrazine, according to our previous protocol.[33] NDs and SWCNTs (SG 101) were supplied by ZZDM Superabrasives (China) and Zeno Nano Technology (Japan), respectively.

Morphology of GO, rGO and SWCNTs was observed on a Hitachi SU9000 field emission microscope in SEM and STEM modes, respectively, while NDs were analyzed by a field emission TEM (JEM-2200FS, JEOL). Raman spectra were recorded on a Jasco NRS-3100 spectroscopy within the range of 800-4000 cm⁻¹ using a laser of 532 nm. Surface chemistry of CNMs was analyzed by XPS (JPS-9030, JEOL). TGA was run from room temperature to 800 °C at a heating rate of 10 °C/min under nitrogen atmosphere on a Shimazu DTG-60AH analyzer. Column chromatography was performed on silica gel 60 (40-100 µm). GC and GC-
MS analyses were performed on a Shimadzu GC-2014 and GC/MS-QP 2010, respectively. ¹H- and ¹³C-NMR spectra were recorded in CDCl₃ on a JEOL JNM-ECZ600R spectrometer operating at 600 MHz. Chemical shifts are reported in ppm with the solvent resonance as the internal standard. The mass-to-charge ratio was measured on a Bruker micrOTOF II HR-MS in ESI/MS model. Infrared spectra were recorded with a Shimadzu IRTracer-100 FT-IR in the wavenumber range of 4000 to 500 cm⁻¹.

## 4.2 Reaction of CNMs with glycidol and determination of PG weight gain

GO, rGO, NDs and SWCNTs were individually mixed with glycidol at a ratio of 10 mg CNM per 1 mL glycidol, and sonicated at room temperature (RT) for 30 min. Then, the mixtures were heated at 75 °C for 20 h under stirring. The products of each reaction system were dialyzed against MilliQ® water using membrane with molecular weight cut off of 12-14 kDa (changing four times water over 72 h). The weight of resulting materials was determined after freeze drying. The weight difference of resulting materials and CNM in each reaction system was defined as the weight gain of PG.

## 4.3 General procedures for the model reactions in the presence or the absence of GO

In a typical ring-opening reaction, different epoxide-containing molecules (vide infra) were mixed with molecules bearing alcohols or carboxylic acids (in equimolar ratio at a 3 mmol scale) in the presence or the absence of GO (6 mg) under ambient condition. The mixtures were sonicated at RT for 30 min to obtain heterogenous suspensions and further heated at 75 °C for 20 h under vigorous stirring. After cooling to room temperature, an aliquot of each product was diluted with ethyl acetate (EtOAc), filtered through a short column of silica gel, and analyzed with GC-MS. The reactivity of esters, ketones, aldehydes and ethers toward ethanol was tested using similar procedures, and the products were characterized by GC or GC-MS.

## 4.4 Preparation and purification of standard samples

### 4.4.1 Hydroxyhexyl benzoate regioisomers

Hydroxyhexyl benzoate regioisomers were prepared by reacting benzoic acid (3 mmol, 366 mg) with 1,2-epoxyhexane (3 mmol, 300 mg) at 75 °C using 1-butyl-3-methylimidazolium bromide ([bmim]Br) as catalyst. [bmim]Br was synthesized by reacting bromobutane (31 mol, 4.2 g) and 1-methylimidizole (36 mmol, 3.0 g) at 70 °C for 48 h in neat condition, according to a procedure reported by Dharaskar et al.[34] Since the reaction was completed after 20 h, the mixture of 2-hydroxyhexyl benzoate and 1-hydroxyhexan-2-yl benzoate was dried under vacuum, identified with ¹H NMR (Figure S4c) and compared to reported data.[21] ¹H-NMR (600 MHz, CDCl₃, δ) 8.05-8.04 (m, 2H), 7.55-7.41 (m, 3H), 5.17-5.13 (m, 0.25H), 4.39-4.36 (m,
0.75H), 4.23-4.21 (m, 0.75H), 3.99-3.96 (m, 0.75H), 3.83-3.80 (m, 0.25H), 3.77-3.74 (m, 0.25H), 1.58-1.33 (m, 6H), 0.92-0.88 (m, 3H).

### 4.4.2 Cyclohexyloxy-hexanol regioisomers

1,2-Epoxyhexane (10 mmol, 1 g) was added to a mixture of cyclohexanol (10 mmol, 1 g) and *p*-toluenesulfonic acid (22 mg) in the glass vial. The reaction was proceeded at 140 °C for 3 h to avoid the generation of copolymer. The product was purified by column chromatography on silica gel with hexane/EtOAc (9/1) as eluant. Evaporation of the solvent followed by vacuum dry gave the mixture of 1-(cyclohexyloxy)hexan-2-ol and 2-(cyclohexyloxy)hexan-1-ol as colorless liquid. Their structures were identified by ¹H- and ¹³C-NMR (Figure S5d and 5e), FT-IR (Figure S5f) and HR-MS (Figure S5g). ¹H-NMR (600 MHz, CDCl₃, δ) 3.73-3.69 (m, 0.85H), 3.61-3.59 (m, 0.15H), 3.50-3.48 (m, 1H), 3.26-3.22 (m, 2H), 2.45 (s, 1H), 1.88-1.87 (s, 2H), 1.72-1.69 (m, 2H), 1.6-1.2 (m, 12H), 0.90-0.87 (m, 3H). ¹³C-NMR (600 MHz, CDCl₃, δ) 78.0, 72.3, 70.6, 64.8, 32.9, 32.4, 32.2, 27.8, 25.8, 24.1, 22.9, 14.1. FT-IR: stretching of O-H, C-H and C-O-C at 3400, 2900 and 1090 cm⁻¹, respectively. HR-MS (ESI) *m/z*: C₁₂H₂₄O₂[Na⁺] calcd 223.1669; found, 223.1664.

### 4.4.3 Phenoxy-hexanol regioisomers

A mixture of phenol (3 mmol, 282 mg), 1,2-epoxyhexane (3 mmol, 300 mg) and KOH (7.5 mg) was stirred at 75 °C for 20 h in neat condition. Base catalyst KOH was chosen because the acidic one could not well promote the reaction of phenol with 1,2-epoxyhexane. The product was extracted with EtOAc (10 mL) from H₂O (30 mL). The organic layer was further washed with NaOH (1 N) three times and dried with MgSO₄. The solvent was removed by evaporation and the product was dried under vacuum to give the mixture of 1-phenoxyhexan-2-ol and 2-phenoxyhexan-1-ol as white solid. The structure of the product was identified with ¹H NMR (Figure S6d) and compared with reported data.[³⁵] ¹H-NMR (600 MHz, CDCl₃, δ) 7.31-7.26 (m, 2H), 6.98-6.91 (m, 3H), 4.01-3.97 (m, 2H), 3.85-3.82 (m, 1H), 1.60-1.51 (m, 2H), 1.40-1.37 (m, 4H), 0.95-0.88 (t, 3H).

### 4.4.4 2-Ethoxycyclohexan-1-ol

1,2-Epoxycyclohexane (5 mmol, 490 mg) was added to an ethanol dispersion (50 mL) of (NH₄)₂Ce(NO₃)₆ (0.5 mmol, 274 mg), and the mixture was stirred at RT for 15 min. After this time, the solvent was evaporated, and the product was purified by column chromatography on silica gel with hexane/diethyl ether (9/1) as eluant. Evaporation of the solvent followed by drying in vacuum gave 2-ethoxycyclohexan-1-ol as a colorless liquid. The structure of the product was identified by ¹H-NMR (Figure S7d) and compared with reported data.[³⁶] ¹H-NMR
(600 MHz, CDCl3, δ) 3.71-3.66 (m, 1H), 3.41-3.39 (m, 2H), 3.01-2.87 (m, 1H), 2.74 (s, 1H), 2.07-1.97 (m, 2H), 1.68-1.67 (m, 2H), 1.24-1.18 (t, 7H).

**Supporting Information**

Supporting Information is available from the Wiley Online Library or from the author.

**Acknowledgements**

We thank Dr. Masato Komoda (Okayama University) for his help with STEM measurement and Ms. Tsugumi Shiokawa (Okayama University) for her help with HR-MS analysis. We gratefully acknowledge the Centre National de la Recherche Scientifique (CNRS) through the International Research Project MULTIDIM between I2CT Unit and Okayama University and the financial support from JSPS KAKENHI (JP22H04548 and JP23K17213) and JST CREST (JPMJCR20H3). This work was partly supported by the Interdisciplinary Thematic Institute SysChem, via the IdEx Unistra (ANR-10-IDEX-0002) within the French Investments for the Future Program. A.B. wishes to acknowledge the Centre National de la Recherche Scientifique and thank the Jean-Marie Lehn Foundation. Y.Z. and K.O. contributed equally to this work.
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