Disaggregation and Anionic Activation of Nanodiamonds Mediated by Sodium Hydride—A New Route to Functional Aliphatic Polyester‐Based Nanodiamond Materials

Polylactide-modified nanodiamond particles (n-DP-g-PLA) are prepared by sodium-hydride-activated nanodiamond-initated anionic ring-opening polymerization. Activated nanodiamond particles repel each other, preventing agglomeration during the polymerization. This universal modification provides a platform for the functionalization of all types of nanoparticles containing hydroxyl groups. Functional nanoparticles have attracted great interest in the past few decades. In the limelight are currently nanoscale diamond particles (n-DP), although relatively unexplored until the 1990s. Their true potential was only realized when single-digit nanodiamond particles of 4–5 nm size were successfully synthesized1-3 and prepared as isolated nanoparticles in solution.4, 5 Nanoscale particles, due to their size, have a tremendous surface area, which increases the importance of the surface functionality. In addition to this, n-DP combine a unique set of properties including high rigidity, strong photo­stability, biocompatibility, good thermal conductivity, and low chemical reactivity.6-8 The pristine n-DP surface contains many functional groups, which can be formed by oxidation and reduction.9 Beyond the traditional polishing and grinding applications, nanodiamond particles are attractive for their applications in fluorescence labeling and imaging,10-13 drug delivery, and cancer treatment,14-16 biomolecules delivery,17-20 nanocomposites,21 and various types of cell proliferation and differentiation.22-24 Most commonly, the development of those applications has been based on flexible surface modification techniques including hydrogenation, hydroxylation, and carboxylation, which enable the functionality of n-DP to be modified for application in different fields.25-27 More recently, a broad range of surface reactions on n-DP has been applied, such as amination,28, 29 silanization,30 fluorination,31 partial bromination,32 chlorination,33 and alkylation.34 The introduction of n-DP into polymer science is an attractive idea not only due to increase in mechanical resistance of the polymer matrix, but also to enable, e.g., controlled drug delivery or labeling using the inherent luminescence of doped nanodiamonds. Even though nanocomposites have been well known for decades, very few reports on n-DP composites have been published. Currently, the most common way of forming n-DP/polymer composites is by direct blending21, 35-37 and extrusion.38, 39 In many cases, a good dispersion and reinforcement effect is obtained due to the high degree of interaction between the n-DP surface groups and the polymer matrix. However, when poor dispersion occurs with consequentially low interaction, a mechanical improvement of the composite is very limited. In addition, highly divergent interactions between n-DP and polymers can cause significant agglomeration when high amounts of n-DP are added. This means that for nanodiamond composites, an appropriate surface modification is very helpful in constructing a desired n-DP/polymer composite, such as the composites of carboxylated n-DP blended with hydrophilic poly (vinyl alcohol),37 amino-functionalized n-DP blended with polyurethanes,40 and octadecylamine-functionalized n-DP blended with polylactide (PLA).41 The functional groups at the diamond surface have also been applied for initiation of the synthesis of polyimide,42 poly(ether-ketone),43 N,O-carboxymethyl chitosan,44 polystyrene and poly(t-Bu methacrylate),45 and polyglycerol.46 However, carboxyl groups at the n-DP surface have commonly been used as the initiator, which may not be easy to handle and can eventually form inter-particle agglomerates by noncovalent bonding.21, 27 The issue of homogeneous n-DP disaggregation in organic solvent has not been fully addressed so far. An interesting, yet unexplored area is the embedding of n-DP in a matrix of, e.g., lactide or ε-caprolactone. The corresponding polyesters are easy to process, have good biocompatibility,47, 48 and have in some cases already been commercialized in various clinical products. The combination of n-DP grafted with different polyesters, for instance PLA, to produce versatile nanodiamond-based polyesters could benefit from the unique properties exhibited by both nanodiamond and poly­esters. Here, we describe the development of different pathways for grafting lactide from n-DP and compare them, with the aim of achieving a method which is useful for many types of nanoparticles and which improves the miscibility between n-DP and polyesters. Usually, these polyesters are synthesized by ring-opening polymerization using hydroxyl groups as the initiators and tin(II) 2-ethylhexanoate (Sn(Oct)2) as the catalyst.49 High amounts of hydroxyl groups at the surface of pristine n-DP were confirmed by Fourier transform infrared spectroscopy (FTIR, Figure S1, Supporting Information). Therefore, it was conceivable that hydroxyl groups at the n-DP surface could be used as an innovative choice of initiator. First, we assessed the efficiency of Sn(Oct)2-catalyzed grafting from Sn(Oct)2-initiated bulk polymerization (n-DP-PLA-SnB), and Sn(Oct)2-initiated solution polymerization (n-DP-PLA-SnS). The results are shown in Table 1. The bulk polymerization of n-DP-PLA-SnB yielded a solid product, which had very high molecular weight and low ĐM. However, the viscosity was high and a well-dispersed system was not obtained before the reaction. Certainly, all n-DP modification methods have the same basic prerequisite of homogeneity. The concern of homogeneous distribution in the composite is critical and depends on the level of particle agglomeration. For that reason, even though the bulk polymerization could reach very high molecular weights, this method was not suitable for the grafting of n-DP as particle aggregation represented an insurmountable obstacle. For better n-DP dispersion and reaction conditions, anhydrous tetrahydrofuran (THF) was added into the bulk system to process the reaction in solution (n-DP-PLA-SnS). The particle dispersion was improved using ultrasound but the lactide conversion was only 10% after 24 h. This result was probably due to the low reaction temperature, limited by the boiling temperature of THF, which has a significant effect on the rate of polymerization. Another solvent, like toluene, could be used in the Sn(Oct)2 initiated reaction for tolerating higher reaction temperatures, or even another catalyst system could be chosen at room temperature. However, in these solvents, the dispersion of n-DP is not possible without more complex surface modification. It has also been shown before that it is difficult to gain high yield when the hydroxyl groups at the surface of hydroxyapatite nanoparticle are used in combination with Sn(Oct)2 in a grafting-from reaction.50 Interestingly, however, the particle dispersion in PLA was improved.51 Therefore, we aimed at the dispersion of modified n-DP by a more efficient method. We assessed this by designing a new reaction scheme, i.e., surface grafting of PLA at the n-DP surface by anionic polymerization. Additionally, anionic polymerization initiated by anions might create repulsive forces at the active sites, allowing the use of n-DP to initiate the reaction and disperse n-DP even further at the same time. It would prevent the particle aggregation from the beginning and possibly reduce the size of already existing particle aggregates. Modifying the n-DPs with PLA would in turn facilitate subsequent solvent casting and the production of a polymer composite with much higher miscibility. Anionic polymerization is a good alternative as it can be used at low temperature in solution. In this reaction, sodium hydride (NaH), a strong base, was used as initiator in the solution polymerization (n-DP-PLA-NaH). Hydroxyl groups at the n-DP surface were used as co-initiators. From the result in Table 1, NaH induced a very efficient reaction, with high conversion of l-lactide (LLA) achieved after 15 min only in the presence of n-DPs. A high-molecular-weight product with high monomer conversion rate and low ĐM was synthesized and the detailed results are shown in Table 1. The schematic drawing and the formula of reactions are described in the text below (Scheme 1). In this system, NaH reacts first with the hydroxyl-functionalized initiators (here: hydroxyl groups on n-DP surfaces) as a strong base, to generate alkoxide anion initiators in the form of free ion pairs in the solvent THF (Scheme 1a). These alkoxide anions act as active sites on the surface of n-DP to start the polymerization by ring opening of the lactide. Propagation proceeds by further diffusion of LLA molecules towards the active hydroxyl end group and is terminated by accepting a proton, for example from ammonium chloride (NH4Cl) in this system (Scheme 1b,c). After polymerization, n-DP-g-PLA was analyzed by 1H NMR spectroscopy. The main side reaction was the reverse reaction of the active anionic group, which could cleave the acyl-oxygen chain and degrade the synthesized polymer. One major challenge of this method is the determination of the proper feeding ratio of NaH as the amount of hydroxyl groups at the pristine n-DP surface is very hard to quantify. By the available analytical methods, it was only possible to confirm of the existence of substantial amounts of hydroxyl groups on the surface of pristine n-DP. In addition, the number of hydroxyl groups at the surface is believed not to correspond to the number of grafted chains because a more activated surface is less prone towards further activation due to electrostatic repulsion and steric hindrance. Therefore, any unreacted NaH will form active anions when exposed to hydroxyl compounds and hence degrade the synthesized polymer. To quench these active anions and remove all unreacted NaH, nontoxic molecules with deactivating groups were needed. NH4Cl was chosen and added to destroy the unreacted NaH. NH4Cl provides a proton from the NH4+, which reacts with NaH to form hydrogen gas, ammonia, and sodium chloride (Scheme 1c). Furthermore, n-DP-g-PLA was solidified during the precipitation in heptane/methanol solution, and any degradation caused by excess NaH was thereby avoided. The salt residues of ammonium chloride and sodium chloride were removed by subsequent washing using deionized water. When the nanoparticles are used as initiators for anionic polymerization, the most unique and important advantage is the capacity to charge and further split the nanoclusters during initiation. NaH is not a nucleophilic base like n-butyllithium, which initiates ring-opening polymerization of LA directly. To substantiate that n-DP acted as an initiator, a control experiment of PLA-NaH without the addition of n-DP was performed. There was almost no reaction, nor could a product be collected through precipitation. As a consequence, when NaH is used together with hydroxyl groups from nanoparticles as coinitiators, it is ensured that the reaction starts at the nanoparticle surface. Since sodium salts exist as a solid crystal in the organic solvent and are very easy to remove by washing through water, the purification method for the resulting products does not require harmful solvents nor produces problematic waste. In the n-DP-PLA-NaH reaction, the ratio of initiator and monomer was chosen in order to drive the reaction to completion. It has to be mentioned that excess n-DP leads to poor and uneven grafting, which results in unstable n-DP dispersion. For a homogeneous grafting reaction, a proper ratio among monomer, initiator, and co-initiator needed to be determined. Based on the n-DP-PLA-NaH reaction, several polymerizations using different ratios of n-DP and NaH were designed (Table 2). The purified products were characterized by several methods including NMR, differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA). When the weight ratio of n-DP to NaH was 1:0.25 (in sample n-DP-PLA-NaH-2), the polymerization reached both high monomer conversion and molecular weight compared with other ratios. The ratio of 1:0.5 also resulted in a high monomer conversation, but a very low grafting rate of 31%. In n-DP-PLA-NaH-3, the weight ratio of 1:0.125 resulted in the lowest monomer conversion and grafting rate. As shown in Figure 1, n-DP-PLA-NaH-2 has the typical semicrystalline thermal behavior of PLA with a glass transition temperature (Tg) of about 55–60 °C and a Tm around 145 °C. Additionally, double-melting peaks were also recorded, which indicates that there are different types of crystalline structures existing in the product. This was considered to be the effect of n-DP on PLA crystal formation. The crystalline structure may have been influenced when the crystals formed close to n-DP rather than close to PLA chains, which could shift the Tm. Compared with n-DP-PLA-NaH-2, the other two reactions yielded much lower molecular weights. When excessive NaH was added in n-DP-PLA-NaH-1, the side reaction might dominate and degrade PLA rather than initiating the polymerization, thus resulting in the low grafting rate observed in this study. However, an insufficient amount of NaH in reaction n-DP-PLA-NaH-3 was not capable to fully initiate the reaction. In n-DP-PLA-NaH-3 (where a low ratio of NaH was used), the grafted PLA chains were too short to form crystallites, only one Tg at around 21 °C was measured. One reason for this could be that a part of the NaH would react with carboxyl groups, which may come from the n-DP surfaces or impurities, since these are more acidic compared with hydroxyl groups. The carboxylate ions could not initiate ring opening of lactide monomers, though. However, pristine n-DP has only few carbonyl groups, suggesting that a rather low amount of NaH is required for their deprotonation prior to the formation of alkoxides on the n-DP surface. The reaction activity of anionic polymerization depends on the temperature, the solvent polarity, and the solvation interaction. The side reactions are related to the excess of ion pairs created by NaH since they can break the acyl-oxygen bonds and degrade PLA grafts. Hence, it is necessary to analyze the effect of degradation in the reaction. Three different monomer/initiator ratios were therefore evaluated (Figure 2a) to compare to the previous results, and an n-DP:NaH weight ratio of 1:0.25 was also used in this experiment. Figure 2b shows that two of these polymerizations reached full conversion but n-DP-PLA-NaH-2–3 did not. This reaction had the lowest amount of NaH, and the monomer conversion of n-DP-PLA-NaH-2–3 was never higher than 85%. As shown in Figure 2d, a significant decrease in molecular weight was observed for n-DP-PLA-NaH-2–1 during the first 60 min, followed by a plateau at low . ĐM increased during the whole reaction (Figure 2c). This behavior indicates that there is a significant amount of side reactions, or degradation, during the reaction. This degrading effect was only seen for the n-DP-PLA-NaH-2–1 reaction, and was likely caused by residual NaH. In addition, due to incomplete polymerization, the n-DP-PLA-NaH-2–3 reaction had a lower molecular weight compared with n-DP-PLA-NaH-2–2, even though n-DP-PLA-NaH-2–3 had a higher amount of monomer in the feed. Thus, the n-DP-PLA-NaH-2–2 reaction gave the best results in all the experiments. Polylactide-grafted nanodiamond based on the n-DP-PLA-NaH-2–2 reaction was synthesized and characterized in detail. First, we determined the structure of the grafts by analyzing the molecular weight using different characterization methods. It is important to remember that ungrafted PLA chains, in addition to PLA-grafted nanodiamonds, might be formed during the reaction from active impurities and during a degradation process. Such undesirable reactions are however minimized in an anhydrous environment and by a proper monomer/initiator ratio. In addition to this, we included a supplementary purification step. Grafted and ungrafted PLA were separated by precipitation, n-DP-g-PLA suspension precipitated unreacted pristine n-DP and lactide monomer in The was removed the ungrafted After the collected was analyzed by of and 1H NMR together with to the molecular weight of the synthesized n-DP-g-PLA (Figure from Figure the presence of a grafting The by was very to the result obtained from 1H NMR the from was around to higher than the with which molecular weights, 1H NMR and were used to the of the chain This the PLA grafts are initiated from the n-DP. The thermal properties of n-DP-g-PLA were characterized using (Figure Supporting and (Figure Supporting Information). The results are shown in Figure together with the results from and The infrared of n-DP-g-PLA (Figure had the same as the for PLA, after the grafted PLA the whole particle surface. The particle size were by in (Figure and it was that the size from about nm very typical for diamond in less organic before grafting to about nm after grafting, which is the of the n-DP polymer The improved dispersion and particle size is a effect from the anionic polymerization in which nanodiamond particles were further as the result of by the repulsive of and the with the PLA For this of each other is very not only to agglomeration but also to the during the initiation. It be mentioned that the relatively size of about nm of the n-DP-g-PLA is in part due to the strong agglomeration of however, the is the of the n-DP with the The included n-DPs are of size as can be seen in Figure The of n-DP suspension from solid form is the most way to produce n-DP suspension and is used in both and From it is not possible to n-DP in organic solvents to any size than nm using a It has been that the n-DP break even without a system due to strong and noncovalent the of a and the properties of a diamond surface in THF, it is not that the size of n-DP in in organic solvents such as or THF is than n-DP in these solvents with size could be it would be possible to modified n-DP in much particle In Figure we compared dispersion of pristine n-DP with n-DP-g-PLA by various methods. After n-DP-g-PLA was in for 24 the pristine n-DP The n-DP-g-PLA suspension was for more than When it was the product solidified into a hard that could be and even after into It was (Figure that the n-DP-g-PLA to in the the pristine n-DP to in the From the scanning (Figure it was observed that the pristine n-DP had a very of the n-DP-g-PLA a that is most likely formed by PLA In Figure a structure was which could have been formed by grafted polymer of n-DP-g-PLA (Figure many particles with a surface In only surface was observed for pristine n-DP (Figure The particle size distribution of n-DP-g-PLA from that the particle size after grafting was about than pristine n-DP from the organic solution size, the and increased from about to about these confirmed a grafting process, in which the n-DP surface was n-DP with different the in The described anionic polymerization grafting method is not limited to nanodiamond particles but all types of nanoparticles could be modified using this they a amount of hydroxyl groups. Even though it was to be difficult to high-molecular-weight polymers with this method due to side reactions, we were to results of particle In many cases, nanoparticle modification is the is to the miscibility between the nanoparticle and another since many nanoparticles are used as or Another would be to the nanoparticle with groups and with other active These two may also be in many Therefore, during grafting, it is more important to the nanoparticles in the composite matrix than to high molecular weights. this, anionic polymerization suitable for particle In a versatile and method for grafting PLA to nanoparticles has been and nanodiamond particles were further separated and grafted with PLA by anionic polymerization. the reaction, the nanodiamond were and n-DP-g-PLA particles with a size of nm were It is possible to the n-DP-g-PLA composites and in THF or This method new to nanoparticles with polymer further and improved and a for new and nanodiamond was to a described using an and and from using of the resulting It was followed by to further reduce agglomeration of the particle solution after The hydrophilic surface was achieved by the amount of groups by the reaction during the The the presence of several groups and a very low of groups. confirmed the presence of significant amounts of hydroxyl groups in addition to water. n-DP obtained by the was before experiments. LLA was from for NaH was used as THF was and collected in a with molecular THF was into a containing 5 of n-DP to form a suspension of followed with in a for more than 5 to reduce agglomeration. THF was also used to the lactide monomer solution of An appropriate amount of n-DP solution was into a with NaH After an appropriate amount of LLA solution was NH4Cl was added to NaH at different reaction The n-DP-g-PLA suspension was precipitated using and in deionized water. The suspension was 15 for min, in a to the product. Sn(Oct)2 was used as the catalyst for PLA on n-DP by bulk and solution The Sn(Oct)2-initiated solution polymerization in anhydrous THF at °C in a The ratios of the different are shown in Table 1. were at 24 before spectroscopy was to and compare n-DP-g-PLA with n-DP. were in the range of for the with of each was on a system were prepared by n-DP or n-DP-g-PLA solution on a of was used for the study. The surface of pristine n-DP and n-DP-g-PLA were determined in using with a with of 5 and The particle size was by analysis was on the for particle size distribution of pristine n-DP and the n-DP after modification. the were prepared in solution with a of The particle size distribution was from of were obtained using a with a ion with a were in with an of and a of in was used as a matrix. The polymer were in THF at a of of polymer and matrix were in a ratio of the sample was on a and at room temperature before into the of For is for the and helpful This is by the and the number As a to and this provides by the Such are and may be for delivery, but are not or from than be addressed to the The is not for the or functionality of any by the than be to the corresponding for the