Chia-Hsin Chen

Emeline Gaillard

Frederic Mentink-Vigier

Kuizhi Chen

Zhehong Gan

Philippe Gaveau

Bertrand Rebière

Romain Berthelot

Pierre Florian

Christian Bonhomme

Frédéric Mentink-Vigier

Mark E Smith

Thomas-Xavier Métro

Bruno Alonso

Danielle Laurencin
email: danielle.laurencin@umontpellier.fr

Direct 17O-isotopic labeling of oxides using mechanochemistry

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Oxygen, as an element, is present in the majority of natural and synthetic materials. It is thus essential to have access to information about the local binding environment around this element to be able to rationalize structure -properties relationships in a variety of systems. Oxygen-17 NMR spectroscopy is one of the most promising spectroscopic techniques for this. [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] Indeed, thanks to the very wide range of variation of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR parameters, detailed insight into the bulk and surface structure of a variety of materials can be obtained. For example, recent studies have used [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR to elucidate the structure of porous materials like zeolites and metal organic frameworks, [START_REF] Huo | Solid-State MAS NMR Studies of Brønsted Acid Sites in Zeolite H-Mordenite[END_REF][START_REF] Bignami | Cost-effective 17 O enrichment and NMR spectroscopy of mixed-metal terephthalate metal-organic frameworks[END_REF][START_REF] Bignami | Synthesis, Isotopic Enrichment, and Solid-State NMR Characterization of Zeolites Derived from the Assembly, Disassembly, Organization, Reassembly Process[END_REF][START_REF] Heard | Fast room temperature lability of aluminosilicate zeolites[END_REF] of mixed metal oxides used as electrode materials, [START_REF] Reeves | Characterizing the Structure and Phase Transition of Li 2 RuO 3 Using Variable-Temperature 17 O and 7 Li NMR Spectroscopy[END_REF][START_REF] Geng | Monitoring the evolution of local oxygen environments during LiCoO 2 charging via ex situ 17 O NMR[END_REF] or of nanoparticle surfaces. [START_REF] Hope | Surface-selective direct 17 O DNP NMR of CeO 2 nanoparticles[END_REF][START_REF] Li | Distinguishing faceted oxide nanocrystals with 17 O solid-state NMR spectroscopy[END_REF][START_REF] Shen | 17 O Solid-State NMR Studies of ZrO 2 Nanoparticles[END_REF][START_REF] Chen | Polar surface structure of oxide nanocrystals revealed with solid-state NMR spectroscopy[END_REF] Natural abundance [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR unfortunately suffers from a very poor absolute signal sensitivity, due to the very low abundance of the NMR-active isotope (only 0.04%). This implies that enriching the compounds of interest in [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O is generally necessary to be able to perform high-resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR studies. Until recently, this has actually hampered the large-scale development of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR spectroscopy, due to the lack of cost-efficient and user-friendly enrichment protocols. Indeed, some of the early labeling schemes employed excessive amounts of expensive [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched precursors (H 2 [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O or [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O 2 ), and/or were experimentally constraining, due to the need to operate under inert atmosphere or at high temperatures, or because of the excessive experimental times (lasting hours or days). [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF][START_REF] Mackenzie | Multinuclear Solid-State Nuclear Magnetic Resonance of Inorganic Materials[END_REF] In the case of oxides, among the different labeling procedures proposed, those based on sol-gel chemistry have found some success for the preparation of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched phases. However, they rely on the availability of the metal alkoxide precursors, and also require optimizing not only the hydrolysis and condensation steps, but also the drying step, in order to remove the alcohol by-product from the reaction mixture and produce a dry gel which can be then converted into the metal oxide of interest. 12- 16 More recently, affordable and practical [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment protocols have been proposed, [START_REF] Bignami | Cost-effective 17 O enrichment and NMR spectroscopy of mixed-metal terephthalate metal-organic frameworks[END_REF][START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF][START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] either for the direct labeling of the inorganic or hybrid materials of interest, or for the labeling of the precursors which can then be used for preparing these materials. In both cases, mechanochemistry techniques like ball-milling (BM) have been shown to be particularly attractive. [START_REF] Geng | Monitoring the evolution of local oxygen environments during LiCoO 2 charging via ex situ 17 O NMR[END_REF][START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] In ball-milling, mechanical forces are applied to solid particles, in order to mix them efficiently, alter their size and shape, and make them react at their interfaces. [START_REF] James | Mechanochemistry: opportunities for new and cleaner synthesis[END_REF][START_REF] Friščić | Mechanochemistry for Synthesis[END_REF] The addition of small amounts of liquid during the milling process (typically in the order of 0.1 μL/mg of sample) can have a significant impact on the course of the reactions, such as accelerating their speed. [START_REF] Bowmaker | Solvent-assisted mechanochemistry[END_REF] This general approach, which is referred to as "liquid assisted grinding" (LAG), served as a basis of the development of new [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment schemes. Indeed, we showed that using [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water as a liquid-grinding assistant, it was possible to enrich in oxygen-17 a variety of organic and inorganic compounds of synthetic interest, including metal hydroxides like Mg(OH) 2 , Ca(OH) 2 and Al(OH) 3 . [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] These were then converted into the corresponding metal oxides by heat-treatment under inert atmosphere, leading to the formation of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled MgO, CaO and Al 2 O 3 (Scheme 1).

Scheme 1. Strategy previously proposed for the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeling of Mg-, Ca-and Al-oxides, starting from their hydroxides. [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] The possibility to easily produce [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched oxides is highly attractive, as these can then be engaged in a variety of reactions using previously established synthetic protocols, to prepare enriched ceramics, glasses, or hybrid organic-inorganic materials. However, in order to further broaden the scope of oxides which can be enriched in [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O using mechanochemistry, it appeared to us necessary to look into synthetic approaches which would not require starting from a hydroxide. Indeed, in contrast to Mg(OH) 2 , Ca(OH) 2 and Al(OH) 3 , a well-defined and stable form of the starting hydroxide may not be readily available, as is the case for titania and silica. Moreover, the initial labeling step of the hydroxide by LAG proceeds by equilibration in the presence of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water (scheme 1), which is not optimal in terms of enrichment yield, because the by-product formed after full isotopic scrambling will be partially-enriched H 2 *O (with the same [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeling level as the final labeled hydroxide). Using oxides as precursors instead of the hydroxides should allow both these issues to be addressed at the same time. Preliminary evidence that oxides could potentially be directly enriched in [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O using LAG was provided in a recent study, in which [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled alkali transition metal oxides like Li 2 MO 3 (M = Mn, Ru) were synthesized by performing an initial LAG step on non-enriched oxide precursors in the presence of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water, followed by a heat-treatment at high temperature. [START_REF] Geng | Monitoring the evolution of local oxygen environments during LiCoO 2 charging via ex situ 17 O NMR[END_REF] However, no detail regarding the mechanisms by which the isotopic labeling was occurring was proposed, making it difficult to determine at what moment of the reaction the enrichment had taken place, and how to adapt this strategy to other materials systems in order to achieve optimal labeling for high resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR.

In this article, we study the reactivity of a selection of oxides under LAG using [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled water, with the overall goal of producing [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched compounds of synthetic interest for the elaboration of advanced functional materials. First, an improved strategy for preparing Ca*O will be described, calcium oxide being of interest for the elaboration of bioceramics and bioglasses. Its extension to the synthesis of Li 2 *O is also presented, this precursor being important for preparing lithium-based batteries and ion-conducting glasses. Then, the direct labeling of four widely-used oxides of different composition and crystallinity (silica, alumina, titania and zirconia) will be discussed, providing insight into the isotopic enrichment process using high-resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR and DNP (Dynamic Nuclear Polarization) analyses. Besides the interest for direct and efficient [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] Olabeling, it will be shown how our approach offers new opportunities for understanding mechanochemical processes at the atomic level.

M(OH) x M(*OH) x M*O y

Equilibration

Results and discussion

1/ Improved LAG approach for the 17 O-labeling of s-block metal oxides

We first focused on improving the labeling strategy we had previously proposed for enriching calcium oxide. [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] More specifically, in order to avoid the initial equilibration step (scheme 1) and to achieve a better enrichment level of the intermediate hydroxide, we started from the non-labeled oxide

CaO, and hydrolyzed it by mechanochemistry to produce Ca(*OH) 2 (scheme 2). The idea here is that all the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] The BM conditions required to perform the hydrolysis step were initially tested using nonlabeled water, by analyzing the reaction medium by powder X-ray diffraction (PXRD). It was found that after 1 hour milling of CaO at 25 Hz in the presence of 1 equivalent of water, complete conversion into the hydroxide phase occurred. Using these synthetic conditions with [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water, [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] Olabeled Ca(*OH) 2 was then obtained, as shown by PXRD (Figure 1a) and [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O Magic Angle Spinning . These [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR spectra are in agreement with previous measurements at this magnetic field. [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] Heat-treatment Ar atm. Based on the above, it is clear that direct conversion of oxides like CaO into their hydroxides can be achieved by BM in the presence of stoichiometric amounts of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water, which is an improvement for the production of labeled hydroxides like Ca(*OH) 2 . [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] Using a similar approach, the labeling of other s-block oxides like Li 2 O could be achieved, which provide attractive alternatives in comparison to existing protocols, [START_REF] Leskes | Monitoring the Electrochemical Processes in the Lithium-Air Battery by Solid State NMR Spectroscopy[END_REF][START_REF] Abys | Preparation of O 17 -labelled glasses and glass precursers[END_REF] as discussed in supporting information S1. As detailed below, the extension of this type of approach to oxides of the p-and d-blocks was then studied, in order to expand the scope of precursors which could be enriched by this technique.

CaO

2/ 17 O-labeling of p and d-block oxides using LAG 2a/ Enrichment of SiO 2 , Al 2 O 3 , TiO 2 and ZrO 2 : structural analyses after 1 hour LAG

Silica, alumina, titania and zirconia were selected for the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O labeling tests on p-and d-block oxides, due to their numerous usages for the preparation of functional materials. For each of these phases, the starting materials were commercially available porous samples with relatively high surface areas (all above 80 m 2 /g), as this was expected to favor surface-reactions with the enriched water during BM. Based on scanning electron microscopy (SEM) and PXRD analyses, each precursor was initially composed of agglomerated nanoparticles of ~10 to 20 nm diameter, but with different crystallinity. Indeed, while the silica precursor was fully amorphous, the three others gave diffraction peaks in XRD, which could be assigned to the anatase phase for titania, to the monoclinic polymorph for zirconia, and to a mixture of γ and δ polymorphs for alumina (see Figure 2, inserts).

Each compound was milled in presence of stoichiometric amounts of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] After 1 hour of LAG, no new phase was observed by PXRD, and the diffractograms of all phases were essentially the same as the ones recorded before milling (Figure 2, inserts). In SEM, the presence of agglomerated nanoparticles could still be observed, without any significant change in particle size, except in the case of silica, for which nanoparticles appeared to have merged into forming larger entities. More striking differences were found in the nitrogen adsorption-desorption isotherms of all oxides before and after milling (Figures S2 to S5), due to changes in surface area and/or pore geometry. In the case of silica, a decrease in porosity was observed (the surface area being reduced by a factor of ~ 3), while in the case of alumina, the main change concerned the pore geometry (as the surface area remained essentially the same as before milling). For titania and zirconia, the differences in the isotherms revealed that both a reduction in surface area and a change in pore geometry had occurred, pointing to significant surface-reconstruction taking place during the milling. In order to understand the changes in texture of the different oxides, high-resolution NMR experiments were performed. S6a). All NMR acquisition conditions are provided in Supporting Information (Table S1).

All four materials were analyzed by [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O solid state NMR (Figure 2). The spectra obtained

show that in all cases the labeling was successful. Indeed, for each oxide, [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR resonances attesting of the formation of a significant proportion of *OM x environments (M = Si, Al, Ti, Zr) were observed. In the case of silica, the observed quadrupolar lineshape is consistent with enriched siloxanes (Si-*O-Si), as shown by the fit of the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS spectrum (Figure S7). [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF][START_REF] Merle | 17 O NMR Gives Unprecedented Insights into the Structure of Supported Catalysts and Their Interaction with the Silica Carrier[END_REF][START_REF] Freude | Survey of NMR Parameters for Quadrupolar Nuclei in Powder Materials[END_REF] Concerning alumina, two broad resonances are observed, the high-frequency contribution (centered at ~60 ppm at 14.1T) coming from various *OAl x environments (x = 3, 4), [START_REF] Mackenzie | Multinuclear Solid-State Nuclear Magnetic Resonance of Inorganic Materials[END_REF][START_REF] Freude | Survey of NMR Parameters for Quadrupolar Nuclei in Powder Materials[END_REF][START_REF] Walter | Magic angle spinning oxygen-17 NMR of aluminum oxides and hydroxides[END_REF] while the other originates from *OH groups, as further discussed below. In the case of titania, the main [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O resonance is centered at ~560 ppm, which corresponds to the *OTi 3 environments of anatase. [START_REF] Bastow | 17 O NMR in simple oxides[END_REF][START_REF] Sun | Solid-state NMR investigation of the 16/17 O isotope exchange of oxygen species in pure-anatase and mixed-phase TiO 2[END_REF] and *OZr 3 environments of the monoclinic form. [START_REF] Bastow | Characterisation of zirconia gels by 17 O nuclear magnetic resonance[END_REF][START_REF] Bastow | 17 O NMR in simple oxides[END_REF][START_REF] Pimentel | 17 O MAS NMR and first principles calculations of ZrO 2 polymorphs[END_REF] For the latter two phases, it is particularly noteworthy that the main [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR resonances detected are those of crystalline environments of titania (anatase form) and zirconia (monoclinic form). Hence, although XRD had not revealed any strong changes during the LAG step, [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR shows that a significant restructuring of the four oxides actually occurs, which leads to the breaking/formation of multiple M-O bonds, and eventually results in a significant proportion of enriched *OM x core-like environments.

The [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O solid state NMR data also reveals that the overall [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment level is high (see Figure S6b for comparison with natural-abundance data). More quantitative analyses were carried out on the silica and titania samples using surface ion mass spectrometry (SIMS), in order to determine the absolute enrichment after the LAG step. Measurements were performed on [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] O-enriched samples, which were prepared using a similar procedure as above, but with 97% O-LAG. After 1 hour LAG (followed by drying at room temperature under vacuum), the [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] O-enrichments determined by SIMS were of 27% for silica and 15% for titania. This demonstrates that the isotopic scrambling was indeed nearly complete for silica under the milling conditions used here, but that a higher enrichment level is potentially achievable for titania. From a more general perspective, considering that the natural abundance of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O is only 0.04%, these analyses confirm that high enrichment levels of oxides can be easily reached by LAG in just 1 hour, using stoichiometric amounts of enriched H 2 *O.

2b/ Insight into the labeling mechanisms: NMR analyses after different LAG times

Given that the source of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O is enriched water, it is reasonable to propose that part of the labeled *OM x sites have formed by condensation reactions involving intermediate M-*OH species (M = Si, Al, Ti, Zr). Additional multinuclear NMR analyses at different milling times were thus performed on each of the oxides to gain more insight into the enrichment mechanisms. The most complete studies were carried out on alumina and titania, as described below.

Alumina

Quantitative [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR analyses were performed on alumina phases recovered after different LAG times (between 5 minutes and 1 hour). In all cases, two main resonances were observed at 14.1T, which were centered at ~ 9 and 60 ppm. As mentioned above, the higher frequency signal corresponds to *OAl x environments, and its intensity was found to gradually increase with the milling time (see Figures 3a-b). This is all the more interesting that no significant changes could be observed for these samples in the X-ray diffraction patterns, nor in the [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al MAS and 27 Al{ 1 H} CPMAS NMR spectra (aside from the appearance of a very weak Al V signal after 1h BM, as shown in Figure S8). These observations confirm that [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR can provide unique insight into both structural and kinetic aspects of the bonding-rearrangements occurring at the atomic level during ball-milling for this system.

The broad low frequency signal (centered at ~9 ppm) is consistent with labeled *OH groups.

Given that both Al x -OH species and H 2 O molecules can potentially be found in this chemical shift range at 14.1 T, [START_REF] Freude | Survey of NMR Parameters for Quadrupolar Nuclei in Powder Materials[END_REF][START_REF] Walter | Magic angle spinning oxygen-17 NMR of aluminum oxides and hydroxides[END_REF][START_REF] Li | Probing the surface of γ-Al 2 O 3 by oxygen-17 dynamic nuclear polarization enhanced solid-state NMR spectroscopy[END_REF][START_REF] Oglesby | Oxygen sites in hydrous aluminosilicate glasses: the role of Al-O-Al and H 2 O. Geochim[END_REF][START_REF] Neuhoff | Effect of extraframework species on 17 O NMR chemical shifts in zeolite A. Micropor[END_REF] additional characterizations were performed at ultra-high magnetic field (35.2 T), to reduce the effect of second-order quadrupolar broadening [START_REF] Mackenzie | Multinuclear Solid-State Nuclear Magnetic Resonance of Inorganic Materials[END_REF] and discriminate better the *OH and H 2 *O species. When comparing the 1D MAS spectrum at 35.2T to data reported in the literature, [START_REF] Bignami | Synthesis, Isotopic Enrichment, and Solid-State NMR Characterization of Zeolites Derived from the Assembly, Disassembly, Organization, Reassembly Process[END_REF][START_REF] Freude | Survey of NMR Parameters for Quadrupolar Nuclei in Powder Materials[END_REF][START_REF] Oglesby | Oxygen sites in hydrous aluminosilicate glasses: the role of Al-O-Al and H 2 O. Geochim[END_REF][START_REF] Neuhoff | Effect of extraframework species on 17 O NMR chemical shifts in zeolite A. Micropor[END_REF] it appears that few [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water molecules are likely to be present, meaning that the majority of enriched *OH groups correspond to Al x -*OH species (Figure 3c). In order to achieve higher resolution, complementary analyses were performed, using the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O multiple quantum MAS (MQMAS) sequence. [START_REF] Frydman | Isotropic Spectra of Half-Integer Quadrupolar Spins from Bidimensional Magic-Angle Spinning NMR[END_REF] This allowed the Al x -*OH sites to be more clearly separated from the *OAl x ones (Figure 3d, dashed circles). Moreover, it revealed a significant distribution in the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] on the literature. [START_REF] Mackenzie | Multinuclear Solid-State Nuclear Magnetic Resonance of Inorganic Materials[END_REF][START_REF] Freude | Survey of NMR Parameters for Quadrupolar Nuclei in Powder Materials[END_REF][START_REF] Walter | Magic angle spinning oxygen-17 NMR of aluminum oxides and hydroxides[END_REF][START_REF] Oglesby | Oxygen sites in hydrous aluminosilicate glasses: the role of Al-O-Al and H 2 O. Geochim[END_REF][START_REF] Neuhoff | Effect of extraframework species on 17 O NMR chemical shifts in zeolite A. Micropor[END_REF] Acquisition conditions can be found in supporting information (Table S1). "*" symbols correspond to spinning sidebands.

The different types of protons present around the enriched oxygen sites were studied using fast MAS 1 H{ [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O} HMQC (Heteronuclear Multiple Quantum Coherence) experiments at high magnetic field (20.0 T), looking at through-bond connectivities (J-HMQC), as well as through-space proximities (D-HMQC). The main crosspeak observed on the 2D J-HMQC spectrum correlates the low frequency [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O resonance (Al x -*OH) to a 1 H resonance centered at ~ 3.8 ppm (Figure 4a). This 1 H chemical shift is consistent with a surface OH group acting as hydrogen-bond donor (denoted here μ-OH HBD ). [START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF] The significant linewidth of the 1 H resonance points to a distribution in μ-OH HBD …O bond distances and angles. [START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF][START_REF] Pourpoint | Calcium Phosphates and Hydroxyapatite: Solid-State NMR Experiments and First-Principles Calculations[END_REF] Complementary 2D D-HMQC experiments were carried out to further characterize these hydroxyl environments (Figure 4b). At short recoupling time (τ rec = 100 μs), the D-HMQC spectrum provides similar conclusions as the J-HMQC experiment, given that only correlations to the closest H atoms appear in these conditions, i.e. with hydrogen atoms which are directly bound to [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O. In contrast, at longer recoupling times (τ rec = 300 μs), an additional correlation is observed with *OAl x resonances. This points to the close proximity of some of the μ-OH HBD protons to *OAl x sites, possibly due to μ-OH HBD …*OAl x hydrogen bonds. It is worth noting that recent computational studies of γalumina surfaces suggest that μ-OH HBD …OAl x hydrogen bonds can indeed be present at the surface. [START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF] The diversity of H-bonding environments of surface hydroxyls can thus account, at least in part, for the distribution in oxygen environments around the Al x -*OH and *OAl x moieties mentioned above (Figure 3d). only from the number but also from the type of aluminum atoms attached to the oxygen (Al IV and/or Al VI ).

The lack of Al IV -*OH correlations in Figure 4c may seem surprising when considering the 1 H MAS NMR data (see Figures 4d andS10). Indeed, the 1D 1 H NMR spectrum (which was recorded using two different echo delays to achieve better resolution) shows sharp resonances, notably at ~ -0.2, 0.7 and 1.1 ppm. Based on the literature, these could correspond to terminal (μ 1 -OH) and bridging (μ 2 -OH) sites, [START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF][START_REF] Taoufik | Heteronuclear NMR Spectroscopy as a Surface-Selective Technique: A Unique Look at the Hydroxyl Groups of γ-Alumina[END_REF] located at the surfaces and edges of alumina particles. In particular, the signal at -0.2 ppm has recently been attributed to μ 1 -OH species present at the edges, [START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF] which are likely to be linked to tetrahedral Al IV sites. [START_REF] Taoufik | Heteronuclear NMR Spectroscopy as a Surface-Selective Technique: A Unique Look at the Hydroxyl Groups of γ-Alumina[END_REF] This would imply that while Al IV -OH species appear to be present in the sample, they could not be detected in [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR. Several explanations can be proposed to this. First, this observation could be consistent with the known difference in reactivity of the different surface hydroxyls. [START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF][START_REF] Digne | Atomic Scale Insights on Chlorinated γ-Alumina Surfaces[END_REF] Indeed, it is possible that upon exposure of the sample to air and hence ambient humidity (when recovering the sample after the LAG step or during the packing/unpacking of NMR rotors), some of the enriched Al-*OH groups back exchange with non-labeled hydroxyls. The fact that the samples are still porous after LAG would indeed be in favor of surface exchanges of reactive OH groups, which would be more likely to occur for the hydroxyls which are more reactive and/or less tightly bound, as would be the case for μ 1 -OH and μ 2 -OH groups with 1 H resonances below 3 ppm, which are not involved in strong H-bonds. [START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF] This exchange would also be consistent with the fact that on the 1 H{ 17 O} J-HMQC data, only the 1 H resonances of the hydrogen-bonded μ-OH groups at ~ 3.8 ppm correlate to the Al x -*OH resonance, but not those at ~ -0.2, 0.7 and 1.1 ppm (due to their backexchange). Second, from a purely NMR perspective, it is also possible that the small proportion of μ 1 -OH and μ 2 -OH resonances (shown by [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] H NMR), combined to a potentially smaller values of J couplings, renders them "invisible" in the [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al{ 17 O} 2D experiment (Figure 4c). All the above reasons could explain (at least in part), why no cross-peak correlating Al IV sites to OH groups could be observed on the [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al{ 17 O} J-HMQC spectrum.

The observation of the progressive formation of *OAl x sites (Figure 3b), and the potential back-exchange of some of the enriched hydroxyls, prompted us to use [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O DNP SENS (surface enhanced NMR spectroscopy) [START_REF] Rossini | Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy[END_REF][START_REF] Lesage | Surface Enhanced NMR Spectroscopy by Dynamic Nuclear Polarization[END_REF] to examine the nature of the oxygen environments present at the surface of the alumina particles. DNP analyses were performed on a sample recovered after 15 minutes milling, after impregnation by a biradical solution of TEKPol in deuterated tetrachloroethane.

Two types of NMR sequences were used, as a means to polarize differently the surface atoms oxygen during microwave irradiation: (i) direct-excitation [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR (preceded by a double-frequency sweep enhancement), in order to polarize the surface oxygen sites directly from the radical, and (ii) [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O{ 1 H} CPMAS, where [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O sites are detected based on their relative proximity to the protons polarized by the biradical (by varying the contact time used). In both situations, the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR signals of *OAl x and *OH groups were found to be enhanced upon microwave irradiation (Figure 5), suggesting that both of these [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O environments are present at the surface of the alumina particles. In particular, under [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O{ 1 H} DNP CPMAS conditions (Figure 5), both sites were enhanced by a factor ~ 4, meaning that protons located at the surface of the particles after LAG can transfer their polarization to neighboring Al-*OH (at short contact time) and *OAl x sites (at longer contact time). Although these DNP-SENS experiments did not allow any absolute quantification of the relative labeling of the bulk or surface of the material, they clearly suggest that some enriched oxygen sites are still present at the surface of the particles, despite possible partial [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O/ [START_REF] Babonneau | Advances in Characterisation Methods for Sol-Gel Derived Materials: High Resolution Solid State Nuclear Magnetic Resonance[END_REF] O back-exchanges upon exposure of the sample to ambient atmosphere.

Figure 5. [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O DNP experiments carried out at 14.1T on an Al 2 O 3 phase enriched in [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O by 15 minutes LAG (followed by drying the sample at room temperature), and impregnation by TEKPol/D 2 -TCE: (i) Direct-excitation [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O DNP NMR spectra (with a DFS enhancement), and (ii) 1 H{ [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O} CPMAS DNP NMR spectra recorded at 50 μs and 5 ms contact times (CT). Spectra recorded without (brown) and with (blue) microwave irradiation are compared (μw on / μw off). DNP acquisition conditions and enhancements are discussed in Supporting Information (S11), and comparisons to [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR data recorded at room temperature are reported in Figure S12.

In summary, although the overall structure of alumina appears to be maintained during the LAG step (according to X-ray diffraction and [START_REF] Bastow | 17 O NMR in simple oxides[END_REF]

Titania

Enriched titania phases were studied by [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR after different LAG times (1 min, 15 min and 1 hour). NMR spectra were recorded both on "fresh" samples, which were analyzed by NMR directly after milling, and on samples which had undergone an additional drying step at room temperature. In all cases, signals belonging to *OTi 3 environments were observed around 550 ppm.

The resonance characteristic of crystalline anatase was found to increase with the milling time (signal at 560 ppm, Figure 6a). Weaker underlying resonances, which span between 500 and 600 ppm (Figure 6b), were also observed at all milling times, and can be ascribed to more distorted/disordered *OTi 3 environments and surface defects. [START_REF] Li | Distinguishing faceted oxide nanocrystals with 17 O solid-state NMR spectroscopy[END_REF][START_REF] Sun | Solid-state NMR investigation of the 16/17 O isotope exchange of oxygen species in pure-anatase and mixed-phase TiO 2[END_REF][START_REF] Scolan | Surface and bulk characterisation of titanium-oxo clusters and nanosized titania particles through 17 O solid state NMR[END_REF] In the case of the "fresh" phases, residual [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O labeled water was detected at ~0 ppm. Its relative proportion was found to decrease as the milling time increased (Figure 6a). However, no clear evidence of Ti-*OH groups was observed. Based on the literature, Ti-*OH resonances were expected to be centered just above 200 ppm. 9, 40-41 Complementary 17 O DNP SENS analyses were thus carried out to try to detect more clearly the surface species (Figures 6c-d), and bring direct evidence of Ti-*OH groups (if any). First, it is worth noting that at low temperatures such as those used for DNP analyses (~100 K), a very weak signal could be detected at ~200 ppm, suggesting the presence of a small number of Ti-*OH species. Dynamics within the Ti-*OH moieties at room temperature may explain why they could not be detected by conventional NMR. This signal could then be enhanced by direct excitation [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-DNP (Figure 6c), and even more so using DNP [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O{ [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] H} CPMAS experiments at very short contact times (Figure 6d). Indeed, the main signal observed by DNP 17 O{ 1 H} CPMAS for 50 μs contact time was centered at ~200 ppm.

Based on previous experimental and computational studies reported in the literature, the extent of water dissociation on anatase surfaces is known to be highly dependent on several parameters, including the nature of the surface exposed and the extent of surface defects. [START_REF] Shi | Role of Surface Stress on the Reactivity of Anatase TiO 2 (001)[END_REF][START_REF] Aschauer | Influence of Subsurface Defects on the Surface Reactivity of TiO 2 : Water on Anatase (101)[END_REF] Hence, it is possible that the formation of Ti-*OH groups by dissociation of H 2 *O on anatase requires the creation of reactive surfaces by mechanochemistry. Moreover, given that very few Ti-*OH species could be detected at the surface of the materials (even for "fresh" phases), it is possible that these recondense quickly to form *OTi x sites under the reaction conditions used here. Overall, this would explain the evolution of the reaction medium shown in Figure 6a. on the different oxygen environments is expected to be of high interest for proposing realistic models of the anatase surface recovered after the milling step, by combining computational modeling to abinitio calculations of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR parameters, and comparing results to experimental [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR data, as previously proposed for other studies on titania surfaces. [START_REF] Li | Distinguishing faceted oxide nanocrystals with 17 O solid-state NMR spectroscopy[END_REF][START_REF] Tielens | Characterization of Phosphate Species on Hydrated Anatase TiO 2 Surfaces[END_REF] To sum up, although the overall structure of anatase appears to be maintained according to Xray diffraction, the texture of the material is affected by the milling process, and [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR further

shows that this phase reacts with labeled water to form enriched anatase-like *OTi 3 environments after only 1 minute of milling. However, in contrast to alumina, only a very small number of labeled *OH species were observed in the 1D [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR spectra (even when analyzing freshly recovered samples), and these could only be clearly detected using DNP-SENS analyses.

Silica and zirconia

Preliminary investigations were also performed at different milling times on silica and zirconia. For the former (Figure 7a), characterizations after only 1 minute milling suggested the presence of both silanols (Si-*OH) and siloxanes (Si-*O-Si). The significant proportion of siloxane bridges after 1 minute of milling is particularly noteworthy, because it demonstrates that the condensation reactions of intermediate Si-*OH groups proceeds quickly under the reaction conditions used here. In contrast, in the case of zirconia, it was found that the 17 O-enrichment using LAG is much more challenging to achieve. Indeed, the two resonances characteristic of the monoclinic form were barely visible after 15 minutes milling (Figure 7b). Moreover, no direct evidence of Zr-*OH groups could be detected by conventional [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR (these being expected around ~ 100 ppm). [START_REF] Shen | 17 O Solid-State NMR Studies of ZrO 2 Nanoparticles[END_REF] The underlying resonances observed as a shoulder around 400 ppm after 1 hour of milling may be due to more disordered *OZr x environments. Further investigations are currently in progress on these phases, both from the synthesis and NMR/DNP points of view, in order to better characterize and control the nature of enriched *OM x and M-*OH groups at different milling times, and to establish the optimal conditions for isotopic labeling. The silanol resonances could be more clearly resolved using 17 O{ 1 H} CPMAS analyses at short contact times (see Supporting Information, Figure S13), and their NMR signature is consistent with previous reports. [START_REF] Merle | 17 O NMR Gives Unprecedented Insights into the Structure of Supported Catalysts and Their Interaction with the Silica Carrier[END_REF][START_REF] Walter | Oxygen-17 cross-polarization nmr spectroscopy of inorganic solids[END_REF] b/ [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR analyses performed at 14.1T and 20 kHz MAS on a ZrO 2 phase enriched in [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O by LAG, after 15 min (black) and 1h (blue) milling. The "m" symbols indicate the two main resonances of monoclinic zirconia. * symbols correspond to spinning sidebands, and the ◊ symbol to the zirconia rotor background signal (see Figure S6).

3/ 17 O-labeling of mixtures of oxides: from liquid to solid oxygen-transfer reactions

Having demonstrated that it is possible to perform the direct [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment of simple oxides using LAG, the obvious next step was to see how mechanochemistry can be used to synthesize [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] These two approaches were tested on a TiO 2 /SiO 2 mixture, using the same oxide sources as mentioned previously (mesoporous anatase and amorphous silica), with the aim of comparing the media recovered just after the milling step, i.e. before any further heat treatment. On one hand, equimolar quantities of TiO 2 and SiO 2 were milled together by LAG using H 2 *O. On the other hand, a pre-enriched Ti*O 2 phase was dry-milled in presence of an equimolar quantity of non-labeled SiO 2 .

Both media were compared after 3 minutes BM. Although the XRD patterns were found to be the same (Figure 8b), their solid-state NMR spectra were completely different (Figure 8c).

In the LAG case, the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O signatures of enriched titania and silica were both visible, but with a significant discrepancy in their relative enrichment, the vast majority of the isotopic label having entered the silica phase (Figure 8c, black curve). Interestingly, in addition to the *OTi 3 and siloxane resonances, it is worth noting that a broad signal is also observed between ~ 450 and 100 ppm, i.e. in a zone which covers the range expected for *OTi 4 , Si-*O-Ti and Ti-*OH groups. [START_REF] Gervais | Detection, Quantification, and Magnetic Field Dependence of Solid-State 17 O NMR of X-O-Y (X,Y = Si,Ti) Linkages: Implications for Characterizing Amorphous Titania-Silica-Based Materials[END_REF][START_REF] Gervais | Solid State NMR Interaction Parameters of Oxygens Linking Titanium and Silicon in Crystalline Cyclic Titanodiphenylsiloxanes[END_REF] The more distinct contribution around ~200 ppm could be indicative of the formation of a small number of Ti-*OH groups under these synthetic conditions.

In the Ti*O 2 /SiO 2 "dry-milling" case, although the *OTi 3 anatase signal is still predominant, a broad signal is also detected between ~ 450 and 100 ppm, as well as a new resonance around ~30 ppm (Figure 8c, red curve). The latter resonance can be assigned to enriched Si-*O-Si bridges (see Figure S14 in supporting information, for an expansion into the siloxane region). Given that the silica precursor was initially non-labeled, this clearly points to the fact that the reactions occurring at the interface of Ti*O 2 and SiO 2 during the ball-milling eventually result in bonding rearrangements around the oxygen atoms, which lead to the enrichment of the silica phase. More importantly, such an "oxygen transfer" between the two oxides starts to occur after just 3 minutes, meaning that very short milling times are sufficient to mix the reagents intimately, so that they can start reacting at their interface. The comparison of the two [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeling approaches points to the major advantages of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR for studying the reactivity of inorganic oxides in BM and helps understand better the differences in reactivity of oxides during ball-milling. On one hand, it allows identifying the different oxygen environments present, thereby revealing oxygen bonding rearrangements which occur at the interfaces between the oxides. On the other hand, it can also bring clear evidence of discrepancies in oxygen isotopic distribution within samples. Moreover, the H 2 17 O-LAG approach used here could more generally help shed light on differences in reactivity of liquid grinding assistants like water with respect to the different components of a mixture, a feature which has not been looked into so far.

4/ Discussion

New 17 O-enrichment approaches for oxides

The enrichment strategies described above significantly broaden the scope of approaches available for producing [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched s-, p-and d-block oxides, and offer synthetic alternatives which are highly efficient, both in terms of cost and practicality. One of the reasons to this comes from the nature of the precursors involved: oxides and [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water. Oxides are indeed very interesting starting materials because they are either directly commercially available (as for TiO 2 , SiO 2 , Al 2 O 3 and ZrO 2 ), or because they can be easily produced by heat treatment of hydroxides (as illustrated here for CaO and Li 2 O) or even carbonates. Moreover, being able to perform the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeling on commercially available sources of titania, silica, alumina and zirconia, which can be stored and handled under ambient conditions for several months, is a key advantage in comparison to other procedures used so far for enriching these phases, in which more sensitive alkoxide or chloride precursors had been used. 12-15, 46, 48-51 Indeed, no safety hazard was involved here in the LAG step, which could be easily scaled up to produce gram quantities of labeled material, which contrasts with syntheses involving highly reactive and toxic reagents such as SiCl 4 and TiCl 4 . Although the maximum [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment is meant to be higher in the latter case (as the only source of oxygen is [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water), the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O content of the phases recovered after LAG was nevertheless sufficient for performing a wide range of high-resolution NMR experiments, as shown in the case of the 2D 1 H- [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O and [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al- [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR experiments performed on alumina (Figures 4a-c). Moreover, it is expected that further optimizations of the LAG step could lead to higher enrichments than those achieved so far, by increasing the amount of H 2 *O added, varying the texture/porosity of the oxide precursor used, and/or optimizing the ballmilling conditions. Indeed, a preliminary investigation on the 17 O-labeling of monoclinic zirconia phases of different initial crystallinity was performed, showing the importance of the choice of the precursor on the efficiency of the isotopic enrichment (see Supporting Information, Figure S15).

Using stoichiometric amounts of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water for the labeling-step is also much less hazardous and constraining than having to manipulate 17 O-enriched O 2 gas at high temperatures, as had been described in previous [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment protocols for oxides. 9-10, 12,52 Indeed, the labeling reactions were performed here under ambient temperature and pressure, and proceeded extremely quickly (less than 1 hour of milling). Moreover, in terms of cost, all syntheses were relatively cheap, amounting to less than ~ 40 euros for enriching ~ 50 mg of compound (when using 90% [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water in the syntheses). Overall, this implies that these protocols are expected to be accessible to both research and teaching laboratories, and to contribute to the development of advanced spectroscopic studies on various oxides (or oxide mixtures), which would require oxygen-17 (or oxygen-18) labeling.

Another very attractive feature of the protocols developed here is that the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched phases recovered after LAG can be used in multiple ways. First, they can be converted into related oxide phases by performing additional heat-treatments under inert conditions, as illustrated in Figure S16 for alumina and titania. Alternatively, they can directly serve as precursors for the synthesis of more complex mixed metal oxides, as illustrated in the previous section for the dry milling of Ti*O 2 with SiO 2 . Last but not least, given that one of the unique properties of the enriched p-and d-block oxides produced here is that they are still mesoporous after LAG, with some of the surface sites enriched in [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O (as suggested by DNP), they could be used as model systems for studying the surface reactivity of oxides by high-resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR. In particular, considering the wide range of applications of transitional aluminas like γ-and δ-Al 2 O 3 in heterogeneous catalysis, the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled alumina phases prepared by LAG could be of high interest to gain new insight into the surface reactivity of catalytic materials using high-resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR and DNP.

Atomic-level insight into reactions occurring during ball-milling

Beyond the production of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched materials, our results also show how high-resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR and DNP can help gain atomic-level information into LAG processes, and more generally reaction mechanisms in ball-milling. Mechanochemical reactions are indeed far from trivial, as they involve both physical steps (mixing of reagents, particle size reduction, creation of reactive surfaces, diffusion of atoms/molecules at the interfaces…) and chemical steps (chemical reactions), both of which are important for the system to evolve towards a given product. [START_REF] Boldyreva | Mechanochemistry of inorganic and organic systems: what is similar, what is different?[END_REF][START_REF] Hutchings | Feedback Kinetics in Mechanochemistry: The Importance of Cohesive States[END_REF] Despite numerous investigations, some of which include in situ measurements and/or innovative designs of the milling equipment, [START_REF] Hutchings | Feedback Kinetics in Mechanochemistry: The Importance of Cohesive States[END_REF][START_REF] Kulla | In Situ Investigations of Mechanochemical One-Pot Syntheses[END_REF][START_REF] Xu | A kinetic study of mechanochemical halogen bond formation by in situ 31 P solid-state NMR spectroscopy[END_REF][START_REF] Michalchuk | Challenges of Mechanochemistry: Is In Situ Real-Time Quantitative Phase Analysis Always Reliable? A Case Study of Organic Salt Formation[END_REF][START_REF] Užarević | Real-Time and In Situ Monitoring of Mechanochemical Reactions: A New Playground for All Chemists[END_REF][START_REF] Michalchuk | Ball size or ball masswhat matters in organic mechanochemical synthesis[END_REF] many blind spots remain regarding both the physics and chemistry of mechanochemical reactions. This is even more true when common techniques like X-ray diffraction are not informative, as observed here for the four p-and d-block oxides, as well as for the mixed SiO 2 /TiO 2 system.

In the case of titania, alumina, and silica, [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR and DNP measurements at different milling times were able to provide clear evidence of the presence of intermediate M-*OH species, which can then condense to form *OM x sites. One important point arising from these analyses was that the quantity of M-*OH sites detected differed significantly from one oxide to the other. In particular, at the shortest milling times, while Al-*OH and Si-*OH groups could be clearly observed, this was not the case for Ti-*OH species, for which DNP analyses were needed to bring evidence of their presence.

Given that several parameters can influence the formation of M-*OH groups (initial degree of covalency or ionicity of the M-O bonds within the oxide, texture and surface area of the material, and reactivity under the ball-milling conditions used), further investigations will be needed to determine the mechanism(s) by which enriched M-*OH groups form for each phase, i.e. whether it is by surface hydrolysis, dissociative adsorption of water, or exchange of labile M-OH groups initially present at the surface. From a more practical perspective, the differences in reactivity shown here demonstrate that milling conditions need to be optimized case by case for each oxide, in order to find how to achieve the highest [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment possible.

Based on the different high-resolution NMR experiments and the changes in porosity observed by N 2 volumetric analyses, it is reasonable to say that the initial formation of bulk-like *OM x environments by ball-milling under ambient conditions results from the condensation of (transient) M-*OH sites. Due to these surface-reconstruction processes, which lead to changes in some of the oxygen-bonds of the initial particles, some enriched oxygen sites which were located at the surface of the oxide particles may become more "core-like". Under a given set of milling conditions, the extent of formation of these *OM x sites and the depth of enrichment of the initial oxide particles depends on the nature and texture of the initial oxide, and the capacity of mechanochemistry to create "fresh" reactive surfaces to trigger these reactions. [START_REF] Boldyreva | Mechanochemistry of inorganic and organic systems: what is similar, what is different?[END_REF] This is illustrated when comparing the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR data and SIMS analyses of SiO 2 and TiO 2 , and even more so when considering the different [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR analyses of Al 2 O 3 , as detailed below.

Concerning alumina, solid state NMR analyses also enabled to shed light on additional features of ball-milling reactions. First, as shown in Figure 3b, it is interesting to note that no "induction time" in the formation of *OAl x species could be detected within the time scale investigated. Induction periods in ball-milling are generally made evident using X-ray diffraction techniques, [START_REF] Belenguer | Understanding the unexpected effect of frequency on the kinetics of a covalent reaction under ball-milling conditions[END_REF][START_REF] Gotor | Influence of the milling parameters on the mechanical work intensity in planetary mills[END_REF][START_REF] Kulla | The effect of the ball to reactant ratio on mechanochemical reaction times studied by in situ PXRD[END_REF] but such analyses would have led to an erroneous conclusion here, given that no change was observed in PXRD. Moreover, it is interesting to note that while an increase in the relative number of *OAl x environments with time was observed, it progressively slowed down after the first 15 minutes. Given that Al-*OH and *OAl x environments very easily formed during the milling (as they were detected after only 5 minutes of reaction), this suggests that other rate-limiting steps takeover after 15 minutes. It is possible that the enrichment of *OAl x sites then proceeds by other mechanisms, involving the gradual rearrangement of oxygen bonding environments within the intermediate oxy-hydroxy phase. Alternatively, changes in the texture and rheological properties of the medium (due to the progressive consumption of enriched water and/or modification of the mesoporosity of the material) may render the milling process less efficient in creating new reactive surfaces, thereby slowing down the speed of enrichment. To go one step further, additional highresolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR and DNP analyses will be needed to study the relative binding of oxygen atoms to Al IV and Al VI sites as a function of milling time, and the reactivity of the different surface *OH groups created by LAG. This should, in return, help rationalize the enrichment process at the atomic level, and better control the nature and proportion between the enriched sites.

Finally, the studies on the mixed SiO 2 /TiO 2 system show how [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR can be used for looking at reactions occurring at the interfaces between different oxides during ball-milling. Indeed, the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR characterization performed on the {SiO 2 + Ti*O 2 } system demonstrate that after only 3 minutes of reaction, a variety of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched oxygen environments are present, which include enriched oxygen atoms within the silica phase. Being able to provide such atomic-level insight at the very early stages of the reaction is important evaluate the efficiency of a given milling process to mix different solid particles (whether they are crystalline or amorphous, as is the case here), and to create contacts between them which will allow solid/solid reactions to occur. More generally, such analyses will certainly help understand better what chemical reactions occur during ball-milling when disordered or amorphous phases are involved, such reactions being intrinsically very complex to study.

Conclusion

In this manuscript, we have shown how the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeling of oxides using mechanochemistry can be used for two main purposes: (i) preparing [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched oxides, and (ii) understanding reaction mechanisms occurring during ball-milling. Concerning the first point, liquid assisted grinding in presence of [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched water was shown to be a highly attractive enrichment strategy for the fast and straightforward labeling of simple oxides of the s, p and d blocks, starting from the non-labeled oxide precursors. Regarding the second point, it was demonstrated how thanks to mechanochemistrymediated isotopic labeling, it becomes possible to address questions regarding the physical and chemical processes occurring at the atomic level during ball-milling, by performing advanced [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O solid state NMR analyses, including ultra-high-field NMR, DNP and fast-MAS measurements. In this context, one of the highlights of this work is to shed light on what chemical reactions start occurring at the interfaces between different oxide particles in the first few minutes of milling. Given that milling together inorganic precursors is frequently one of the first steps in the synthesis of functional mixedmetal oxides, performing similar high-resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR analyses on different mixtures of enriched oxide precursors and under different milling conditions could not only help optimize the milling process, but also help identify intermediate phases, which could in turn serve for the preparation of novel materials. operated at 25 Hz. The reactor was opened, and the solid powder was recovered by scraping the edges of the reactor and beads with a spatula (average mass of the crude material (n = 4): 45 mg). The recovered sample was white for short milling times, but very light grey beyond 15 minutes milling (see supporting information, Figure S3, for EDXS analyses). Depending on the sample, further treatments were performed, either under vacuum at room temperature, or at high temperature under Ar atmosphere (heating rate: 10°C / min; dwell-time at 900°C: 4 hsee Figure S16). LAG of TiO 2 . TiO 2 (50 mg, 0.63 mmol, 1.0 eq) was introduced in a grinding jar with [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled water (11 μL, 0.61 mmol, 1.0 eq) and one stainless steel ball (10 mm diameter). The jar was closed and subjected to grinding for milling times ranging from 1 minute to 1 hour in the mixer mill operated at 25 Hz. The reactor was opened, and the solid powder was recovered by scraping the edges of the reactor and beads with a spatula (average mass of the crude material (n = 4): 44 mg). The recovered sample was white for short milling times, but light grey/yellowish beyond 15 minutes milling (see supporting information, Figure S4, for EDXS analyses). Depending on the sample, further treatments were performed, either under vacuum at room temperature, or at high temperature under Ar atmosphere (heating rate: 10°C / min; dwell-time at 900°C: 4 h -See figure S16).

LAG of ZrO 2 . ZrO 2 (50 mg, 0.41 mmol, 1 eq) was introduced in a grinding jar with [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled water (7 μL, 0.39 mmol, 1 eq) and one stainless steel ball (10 mm diameter). The jar was closed and subjected to grinding for milling times ranging from 15 minutes to 1 hour in the mixer mill operated at 25 Hz. The reactor was opened, and the solid powder was recovered by scraping the edges of the reactor and beads with a spatula (average mass of the crude material (n = 4): 42 mg). The recovered sample was white for short milling times, but very light grey beyond 15 minutes milling (see supporting information, Figure S5, for EDXS analyses). Samples were then dried under vacuum at room temperature.

LAG of TiO 2 and SiO 2 . TiO 2 (28.3 mg, 0.35 mmol, 1 eq) and SiO 2 (21.5 mg, 0.35 mmol, 1 eq) were introduced in a grinding jar with [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled water (13 μL, 0.72 mmol, 2 eq) and one stainless steel ball (10 mm diameter). The jar was closed and subjected to grinding for 3 minutes in the mixer mill operated at 25 Hz. The reactor was opened, and the white powder was recovered by scraping the edges of the reactor and beads (m ~ 43 mg).

BM of Ti*O 2 with SiO 2.

Ti*O 2 was first synthesized as described above, by milling TiO 2 for 15 minutes, and then drying the sample under vacuum for 1 hour at room temperature. Then, labeled Ti*O 2 (28.6 mg, ~0.35 mmol, 1 eq) was introduced in a grinding jar with non-labeled SiO 2 (21.4 mg, 0.35 mmol, 1 eq) and one stainless steel ball (10 mm diameter). The jar was closed and subjected to grinding for 3 minutes in the mixer mill operated at 25 Hz. The reactor was opened, and the solid powder was recovered by scraping the edges of the reactor and beads (m = 42 mg). low-Al background zirconia rotors for these measurements. Single-pulse experiments were performed spinning at 18 kHz, using a [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al excitation pulse of 0.7 μs (π/18 tip angle), a recycle delay of 6s, and acquiring a total of 512 transients. [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al{ 1 H} CPMAS experiments were performed spinning at 18kHz, using a 1 H excitation pulse of 6 μs (π/2 tip angle), and a contact time of 0.5 ms. The recycle delay was set to 1s, and the number of scans acquired ranged from 8000 to 61700, depending on the sample. [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al chemical shifts were referenced externally to a 1 M aqueous solution of Al(NO 3 ) 3 .

1 H solid state NMR -1D experiments. Fast MAS 1 H solid state NMR spectra were recorded on a Bruker 850MHz (20.0 T) instrument, using a Bruker 1.3 mm probe spinning at 60 kHz. A Hahn echo sequence was used, with π/2 and π pulses of 2.05 and 4.1 μs, and a rotor-synchronized echo delay corresponding to 2 or 50 rotor periods (Figure 4d). [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] H chemical shifts were referenced to a dipeptide (Asp-Ala), used as a secondary reference, the low frequency signal being set to 1.1 ppm with respect to tetramethylsilane. Additional Hahn-echo 1 H NMR spectra were also recorded on a Varian VNMRS 600 MHz (14.1 T) NMR spectrometer using a Phoenix 1.2 mm MAS probe, in order to evaluate potential contributions of background 1 H signals from the rotor and caps (see Figure S10, supporting information).

27 Al{ 17 O} J-HMQC. A 27 Al{ 17 O} J-HMQC MAS NMR experiment was performed on a Bruker 850MHz (20.0 T) NMR spectrometer, using a 3.2 mm HXY probe, tuned to 1 H (850.29 MHz), [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al (221.56 MHz), and 17 O (115.27 MHz), and spinning at 24 kHz. DFS excitation pulses were first applied on [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al (1 ms pulse of 30 W, with a 600 to 150 kHz sweep). The π/2 and π pulses on [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al were set to 8.3 and 16.6 μs, respectively (~10 kHz RF). The evolution delay following the π/2 pulse on [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al was set to 2.5 ms. The π/2 pulses on [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O were set to 8.5 μs (~10 kHz RF). Spinal-64 [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] H decoupling (100 kHz RF) was applied throughout the sequence (except during the DFS). The recycle delay was set to 1s, and a total of 10000 scans were acquired for each of the 18 increments of the 2D. [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O and [START_REF] Bastow | 17 O NMR in simple oxides[END_REF] Al chemical shifts were referenced using respectively tap water (at 0 ppm) and a 1 mol.L -1 solution of aluminum-nitrate (at 0 ppm).

1 H{ 17 O} D-and J-HMQC. [START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] H{ 17 O} HMQC MAS NMR experiments were performed on a Bruker 850MHz (20.0 T) NMR spectrometer, using a 1.3 mm HX probe, tuned to 1 H (850.29 MHz) and 17 O (115.27 MHz), and spinning at 60 kHz. The π/2 and π pulses on 1 H were set to 2.05 and 4.1 μs, respectively. The π/2 pulses on [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O were set to 6.0 μs. For the J-HMQC experiment, the evolution delay following the π/2 pulse on 1 H was set to 600 μs. For the D-HMQC experiment, the recoupling time τ rec was set to 100 or 300 μs, during which an SR4 [START_REF] Huo | Solid-State MAS NMR Studies of Brønsted Acid Sites in Zeolite H-Mordenite[END_REF] 1 pulse was applied on 1 H (120 kHz RF) and a WURST pulse was applied on 17 O (at an offset of 120 kHz). [START_REF] Brinkmann | Proton-Selective 17 O-1 H Distance Measurements in Fast Magic-Angle-Spinning Solid-State NMR Spectroscopy for the Determination of Hydrogen Bond Lengths[END_REF] The recycle delay was set to 0.5s. The number of scans and duration of each experiment can be found in supporting information (Table S1). [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O and 1 H chemical shifts were referenced using respectively tap water (at 0 ppm) and a dipeptide (Asp-Ala), for which the low frequency signal was set to 1.1 ppm with respect to tetramethylsilane.

O MQMAS.

A [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MQMAS experiment was performed on an enriched alumina phase on the SCHinstrument in Tallahassee, 64 using a 3.2 mm single-channel MAS probe, and spinning at 16 kHz. [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O excitation and conversion pulses were respectively set to 4 and 1.4 μs (600W power), and followed by a 4.4 μs pulse (36W power). The recycle delay was set to 0.2s, and a total of 240 scans were acquired for each of the increments of the 2D. [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O chemical shifts were referenced externally to D 2 O at -2.7 ppm (which was measured to be equivalent to tap-water at 0 ppm). 17 O DNP. The MAS-DNP experiments were carried out on the 600 MHz/395 GHz setup installed at the National High Magnetic Field Laboratory in Tallahassee. The magnetic field was set at 14.094 T, the gyrotron generates a microwave power of 12 W at the probe base and a frequency of 395.166 GHz.

The sample was packed in a 3.2 mm thin wall ZrO 2 rotor and spun at 13 kHz. The temperature for VT/Bearing/Drive were 91.6/98/110 K, leading to a sample temperature under microwave irradiation of ~ 100K, and ~94K in absence of it. [START_REF] Rossini | Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy[END_REF] The higher drive temperature allowed achieving 13 kHz spinning frequency while reducing the pressure needed. The sample was pre-spun at room temperature with a benchtop spinner (home-built) and the EPR measurement was carried out prior to the MAS-DNP experiment. Finally, 3 freeze-thaw were applied to the sample before insertion into the probe.

The powder was impregnated with a 16 mM solution of TEKPol (purchased from Cortecnet) in D 2 -tetrachloroethane (Cortecnet) for Al 2 O 3 , or tetrabromoethane (Sigma-Aldrich) for TiO 2 . For the experiments, ~30 mg of powder was impregnated with ~30 µL of solution leading to tooth-pasty texture. The NMR acquisition parameters used for each spectrum are reported in Table S1, for the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O{ 1 H} CPMAS and DFS-echo experiments performed with or without microwaves.

(

  MAS) solid state NMR (Figure 1b, top). This phase could then be transformed into enriched Ca*O by heat treatment under an inert atmosphere (Figure 1b, bottom).

Figure 1 .

 1 Figure 1. a/ PXRD analyses before and after LAG: CaO precursor obtained after heat-treatment of commercial Ca(OH) 2 (top), and enriched phase recovered after LAG in the presence of H 2 *O (bottom). "■" and "○" symbols correspond to the diffraction peaks expected for CaO (ICSD # 163628) and Ca(OH) 2 (ICSD #15471), respectively; b/ 17 O solid state NMR

Figure 3 .

 3 Figure 3. a/ Quantitative single pulse 17 O MAS NMR spectra, recorded at 14.1 T for Al 2 O 3 phases obtained after different milling times in the presence of H 2 17 O, followed by drying under vacuum at room temperature (all spectra were acquired over 18 h, using a π/12 excitation pulse and a recycle delay of 16s). b/ Evolution of the relative proportion of *OAl x sites as a function of milling time, as determined by quantifying the relative intensity of the *OAl x signal to that of the naturalabundance zirconia rotor peak (spectra shown in a/), and normalizing for the mass of sample introduced in the rotor (see supporting information, Figure S9). c/ 17 O MAS NMR spectrum recorded at 35.2 T for an Al 2 O 3 phase enriched in 17 O by LAG, after 15 minutes grinding, followed by drying the sample at room temperature (this spectrum was recorded using a much shorter recycle delay and different excitation scheme than the one in Figure 3a); d/ 17 O MQMAS NMR spectrum recorded at 35.2 T, in which the *OAl x (dashed green circle) and Al x *OH sites (dashed brown circle) are resolved. Colored bars above the spectra in Figures 3c and 3d correspond to the shift ranges expected for different oxygen environments, based

Figure 4 .

 4 Figure 4. a/ 1 H{ 17 O} J-HMQC NMR spectrum recorded at 20.0 T and 60 kHz MAS on an Al 2 O 3 phase enriched in[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O by LAG after 15 minutes grinding, followed by drying the sample at room temperature; the projection corresponds to the DFS-1pulse signal for this phase; b/ 1 H{ 17 O} D-HMQC NMR spectra recorded at 20.0 T and 60 kHz MAS on the same phase, using 2 different recoupling times (100 and 300 μs); c/ 27 Al{ 17 O} J-HMQC spectrum recorded at 20.0 T for an Al 2 O 3 phase enriched in[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O by LAG (15 min BM), after drying under vacuum at room temperature (the total acquisition time was ~50 h for this spectrum). Projections correspond to Hahn-echo spectra recorded for the sample at this magnetic field; d/ 1 H Hahn echo NMR spectra recorded at 20.0 T and 60 kHz MAS, using echo delays of 2 (black) and 50 (brown) rotor periods (see FigureS10in Supporting Information for comparison to the background 1 H NMR spectrum).[START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] H resonances are assigned based on recent literature (HBD = hydrogen bond donor).[START_REF] Batista | Beyond γ-Al 2 O 3 crystallite surfaces: The hidden features of edges revealed by solid-state 1 H NMR and DFT calculations[END_REF]

  Al NMR), part of this phase actually undergoes several reactions in the presence of H 2 *O, leading to a change in texture of the material, and to the formation of Al x -*OH and *OAl x species. The fact that *OAl x environments were detected after only 5 minutes of milling underscores that the condensation of Al x -*OH groups proceeds very quickly under the reaction conditions used here. For both Al x -*OH and *OAl x species, high resolution NMR experiments were able to shed light on the diversity of oxygen local environments, due to the presence of hydrogen bonds and differences in the nature and number of Al-sites to which they are bound.

Moreover, 17 O

 17 DNP-SENS experiments were performed, suggesting that some of the enriched Al x -*OH and *OAl x sites are located at the surface of the particles.

Figure 6 .

 6 Figure 6. a/ 17 O MAS NMR spectra recorded at 14.1T on "fresh" TiO 2 phases enriched in 17 O by LAG (for 1 min, 15 min and 1 hour milling times); b/ 17 O MAS NMR spectrum recorded at 35.2T on a TiO 2 phase enriched in 17 O by LAG (15 min BM), after drying under vacuum at room temperature; c/ 17 O DNP NMR spectrum of a TiO 2 phase enriched in 17 O by LAG (15 min BM), after drying under vacuum at room temperature, and impregnation by a 16 mM solution of TEKPol in TBE(spectra recorded at ~100 K, with and without microwave irradiation); d/ 17 O{ 1 H} DNP-CPMAS spectra recorded at 50 μs and 3 ms contact times, in comparison to the DFS-enhanced echo spectrum recorded at ~100K. All acquisition parameters can be found in TableS1(supporting information). * symbols correspond to spinning sidebands, and ◊ symbols to the zirconia rotor background signal.

Figure 7 .

 7 Figure7. a/[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR analysis performed at 20.0T and 60 kHz MAS on a SiO 2 phase enriched in[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O by LAG (1 min BM), after drying under vacuum at room temperature. The fit (dashed red line) was performed considering siloxanes (green) and silanols (purple). The silanol resonances could be more clearly resolved using[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O{[START_REF] Ashbrook | Solid state 17 O NMR-an introduction to the background principles and applications to inorganic materials[END_REF] H} CPMAS analyses at short contact times (see Supporting Information, FigureS13), and their NMR signature is consistent with previous reports.[START_REF] Merle | 17 O NMR Gives Unprecedented Insights into the Structure of Supported Catalysts and Their Interaction with the Silica Carrier[END_REF][START_REF] Walter | Oxygen-17 cross-polarization nmr spectroscopy of inorganic solids[END_REF] b/[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR analyses performed at 14.1T and 20 kHz MAS on a ZrO 2 phase enriched in[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O by LAG, after 15 min (black) and 1h (blue) milling. The "m" symbols indicate the two main resonances of monoclinic zirconia. * symbols correspond to spinning sidebands, and the ◊ symbol to the zirconia rotor background signal (see FigureS6).

  Olabeled mixed oxides. Two mechanochemical approaches were considered to introduce the[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-label (Figure8a): (i) milling the non-labeled oxide precursors together with H 2 *O, or (ii) pre-enriching separately oxide precursors, before 'dry'-milling them together. While the former strategy was recently used for enriching the lithium-ion battery electrode materials like Li 2 RuO 3 , 7 no[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR analysis of the milling medium just after the LAG step was reported. Moreover, comparing the two strategies may actually shed light on how oxides react with each other in the solid state during mechanochemical reactions.

Figure 8 .

 8 Figure 8. a/ Schematic representation of the two synthetic approaches tested for enriching mixtures of SiO 2 and TiO 2 in 17 O using mechanochemistry (shades of red are used to reflect the average relative 17 O-labeling of the oxides after milling); b/ and c/ Characterizations of 17 O-enriched SiO 2 /TiO 2 mixtures using PXRD and 17 O MAS solid state NMR at 20T. Top: Drymilling of non-labeled SiO 2 with enriched Ti*O 2 for 3 minutes (blue curves). Bottom: LAG of a mixture of TiO 2 and SiO 2 for 3 minutes in presence of H 2 *O (black curves). "∆" symbols correspond to the diffraction peaks of anatase in PXRD (ICSD #7206075), and "*" symbols correspond to spinning sidebands in 17 O NMR. The shaded regions on the 17 O MAS NMR

  O label introduced as H 2 *O during the LAG step reacts with CaO to form the 17 O-enriched hydroxide.

Scheme 2. Alternative strategy proposed here for the

[START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF]

O-labeling of Ca oxide.

OAl x OH SiOSi OTi 3 OZr 3 OZr 4

	SiO 2			Counts (a.u.)	800 200 400 600			1h BM no BM	Al 2 O 3		Counts (a.u.)	2000 4000 6000 8000	1h BM no BM
						20	2 θ/ 30	40	50					20	30	2 θ/ 40	50	60
	150	100	50	0	-50	-100					200	100	0	-100	-200
			δ( 17 O) /ppm									δ( 17 O)/ ppm
	TiO 2				Counts (a.u.)	2000 3000 1000			1h BM no BM	ZrO 2		Counts (a.u.)	1000 2000 3000	1h BM no BM
						20	30	40	50					20	30	40	50
							2 θ/							2 θ/
	*		◊	*	*				* *	◊		* * * *
	800	600	400	200		0				600	500	400	300	200	100	0	-100
			δ( 17 O)/ ppm								δ( 17 O)/ ppm
														Regarding zirconia, two
	sharp resonances are observed, which are centered at 325 and 403 ppm, and correspond to the *OZr 4

17 O MAS NMR of SiO 2 (20.0T, room temp) b/ 17 O MAS NMR of ZrO 2 (14.1T, room temp)

	1 min BM	a/ Si-*O-Si					15 min vs 1h BM	m	m
			*O-H
							*	*	◊		*	*	* *
	120	80	40	0	-40	-80	600	500	400	300	200	100	0	-100
			δ( 17 O) /ppm							δ( 17 O) /ppm

Acknowledgements

This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 772204; 2017 ERC-COG, MISOTOP project). A portion of this work was performed at the National High Magnetic Field Laboratory, which is supported by the National Science Foundation Cooperative Agreement No. DMR-1644779, the State of Florida and the United States Department of Energy. The MAS-DNP system at the NHMFL is funded in part by NIH S10 OD018519 and P41 GM122698. Financial support from the IR-RMN-THC Fr3050 CNRS for conducting part of the high-field NMR experiments is gratefully acknowledged. The UK 850 MHz solid-state NMR Facility used in this research was funded by EPSRC and BBSRC, as well as the University of Warwick including via part funding through Birmingham Science City Advanced Materials Projects 1 and 2 supported by Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF). Dr Franck Fayon (CEMHTI, CNRS) and Dr Dinu Iuga (University of Warwick) are acknowledged for discussions, and

Anastasia Kuznetsova for the BM-enrichment of some of the alumina phases studied here.

Experimental section

Synthesis of 17 O-labeled phases

Reagents and milling equipment. Calcium hydroxide (Ca(OH) 2 , Sigma-Aldrich, ≥ 96%) and lithium hydroxide monohydrate (LiOH.H 2 O, Prolabo Normapur, Analytical Reagent, ≥ 99.0%) were used as received, and served as precursors for the synthesis of CaO and Li 2 O. Silica (SiO 2 , Aerosil 200, Degussa, 180 m 2 /g), alumina (Al 2 O 3 , "aluminoxid C", Degussa, mixture of γ-and δforms, 100 m 2 /g), titania (TiO 2 , St-Gobain Norpro, anatase phase, 150 m 2 /g), and zirconia (ZrO 2 St-Gobain Norpro, monoclinic form, 85 m 2 /g) were dried under vacuum for 3 to 4 hours at room temperature prior to use. [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-labeled water (with 40% or 90% [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment) was purchased from CortecNet. [START_REF] Métro | Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry[END_REF] O-labeled water (with 97% 18 O-enrichment) was purchased from Eurisotop. For DNP experiments, TEKPol [START_REF] Zagdoun | Large Molecular Weight Nitroxide Biradicals Providing Efficient Dynamic Nuclear Polarization at Temperatures up to 200 K[END_REF] was purchased from Cortecnet.

All milling treatments were carried out at ~ 22°C (± 3 °C) in a Retsch Mixer Mill 400 apparatus, using 10 mL stainless steel grinding jars with screw top or push-fit lids. Unless otherwise noted, the protocols were first tested in triplicate using non-labeled water, before performing the experiments with [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O (or 18 O) -enriched H 2 O.

Synthesis of Ca(*OH) 2 and Ca*O.

Non-labeled Ca(OH) 2 was first heat-treated to 950°C in a tubular furnace under Ar atmosphere (heating rate: 10°C / min; dwell-time at 950°C: 4 h) to produce CaO.

The freshly prepared CaO phase (50 mg, 0.9 mmol, 1 eq) was introduced in the grinding jar together with 16μL of 40%-enriched H 2 17 O (0.9 mmol, 1 eq) with two stainless steel balls (10 mm diameter).

The jar was closed and subjected to grinding for 1 hour in the mixer mill operated at 25Hz. The reactor was opened and the white powder, which progressively dries upon contact with air, was recovered by scraping the edges of the reactor and beads with a spatula, and characterized by XRD and [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O solid state NMR, showing the formation of Ca(*OH) 2 . (Average yield (n = 4): 54 mg, 82%). [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enriched CaO was then synthesized by heat-treating the labeled hydroxide for 4 h at 950°C in a tubular furnace under Ar atmosphere, using the same conditions as above.

LAG of SiO 2 . SiO 2 (50 mg, 0.84 mmol, 1.0 eq) was introduced in a screw top grinding jar with [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] Olabeled water (15 μL, 0.83 mmol, 1.0 eq) and two stainless steel balls (10 mm diameter). The jar was closed and subjected to grinding for milling times ranging from 1 minute to 1 hour, in the mixer mill operated at 25 Hz. The reactor was opened, and the sample was recovered by scraping the edges of the reactor and beads with a spatula (average mass of the crude material (n = 4): 60 mg). The recovered sample was white for short milling times, but light grey beyond 15 minutes milling (see supporting information, Figure S2, for EDXS analyses). Samples were then dried under vacuum at room temperature.

LAG of Al

Supporting information

Preliminary study on the synthesis of 17 O-enriched Li 2 *O (including Fig. S1); SEM, N 2 adsorption/desorption isotherms and EDXS analyses of SiO 2 (Fig. S2), Al 2 O 3 (Fig. S3), TiO 2 (Fig. S4)

and ZrO 2 (Fig. S5); [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR spectra of enriched Zr*O 2 and of the empty zirconia rotor (Fig. S6a), and [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O MAS NMR spectrum of a non-labeled Al 2 O 3 phase (Fig. S6b); Fit of the [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] S1).

For Table of contents only

The direct [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O-enrichment of s-, p-and d-block metal oxides is achieved with high efficiency using mechanochemistry. Atomic-level insight into the enrichment process is obtained using high-resolution [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O solid state NMR and DNP analyses, which demonstrate that enriched oxygen sites are present both at the surface and within the oxide particles. Moreover, it is demonstrated how these labeling schemes allow studying unique aspects of mechanochemical reactions between oxides by [START_REF] Griffin | Ionothermal 17 O enrichment of oxides using microlitre quantities of labelled water[END_REF] O NMR.