Catalytic oxidative transformation of betulin to its valuable oxo-derivatives over gold supported catalysts: Effect of support nature

Article abstract of DOI:10.1016/j.cattod.2020.07.051

Liquid-phase oxidation of betulin extracted from birch bark was studied over gold catalysts supported on a range of supports (hydrotalcite, ZrO₂, ZnO, MgO, CeO₂, La₂O₃, HMS and various alumina) with different morphology and properties. Gold catalysts as well as the corresponding supports were characterized by XRD, BET, ICP-OES, XPS and TEM. It was found that the nature of the support plays a decisive role in betulin oxidation over gold-based catalysts, expressed in the influence on the average size and distribution of gold nanoparticles and, thereby, on their catalytic performance (activity and selectivity) in betulin oxidation. Moreover, it was revealed that betulin oxidation catalyzed by gold is a structure sensitive reaction, requiring an optimal size of gold nanoparticles of ca. 3.3 nm. The most suitable support for gold was found to be alumina. Kinetic studies allowed determination of reaction orders and conditions favorable for selective formation of a particular oxo-derivative of betulin (betulone, betulinic and betulonic aldehydes, betulinic acid).

Full text of DOI:10.1016/j.cattod.2020.07.051

Journal Pre-proof
Catalytic oxidative transformation of betulin to its valuable oxo-derivatives
over gold supported catalysts: Effect of support nature
¨
E. Kolobova (Investigation) (Writing - original draft), P. Maki-Arvela
(Writing - review and editing) (Conceptualization) (Supervision), A.
Grigoreva (Investigation), E. Pakrieva (Investigation), S.A.C.
Carabineiro (Investigation) (Supervision), J. Peltonen (Investigation),
S. Kazantsev (Investigation), N. Bogdanchikova (Investigation), A.
Pestryakov (Conceptualization) (Funding acquisition), D. Yu Murzin
(Writing - review and editing) (Conceptualization) (Supervision)
PII:
S0920-5861(20)30524-1
DOI:
https://doi.org/10.1016/j.cattod.2020.07.051
CATTOD 13056
Reference:
To appear in:
Catalysis Today
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Revised Date:
Accepted Date:
15 December 2019
27 April 2020
13 July 2020
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Catalytic oxidative transformation of betulin to its valuable oxo-derivatives over gold supported
catalysts: Effect of support nature
E. Kolobovaa,*, P. Mäki-Arvelab, A. Grigorevaa, E. Pakrievaa, S.A.C. Carabineiroc, J. Peltonend, S.
Kazantseve, N. Bogdanchikovaf, A. Pestryakova, D. Yu. Murzinb,*
aResearch School of Chemistry & Applied Biomedical Sciences, Tomsk Polytechnic University, Lenin
Avenue 30, 634050 Tomsk, Russia
bJohan Gadolin Process Chemistry Centre, Abo Akademi University, FI-20500 Turku, Finland
cCentro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais,
1049-001 Lisboa, Portugal
dLaboratory of Industrial Physics, University of Turku, 20014 Turku, Finland
eInstitute of Strength Physics and Materials Science of Siberian Branch of Russian Academy of
Sciences, (ISPMS SB RAS) pr. Akademicheskii 2/4, 634055 Tomsk, Russia
fCentro de Nanociencias y Nanotecnología, UNAM Post box 14, 22860 Ensenada, Mexico
*Corresponding authors: dmurzin@abo.fi (D. Yu. Murzin), ekaterina_kolobova@mail.ru (E.
Kolobova)
Graphical abstract
Highlights
1

 Betulin can be transformed into its oxo-derivatives by liquid-phase oxidation over gold-based
catalysts under mild conditions
 Gold catalyzed betulin oxidation is a structure sensitive reaction
 An optimum gold particle size of 3.3 nm gave the highest TOF in betulin oxidation
 Alumina materials are suitable supports for gold nanoparticles
 A certain oxo-derivative of betulin be preferentially formed by adjusting the experimental
conditions
ABSTRACT
Liquid-phase oxidation of betulin extracted from birch bark was studied over gold catalysts supported
on a range of supports (hydrotalcite, ZrO2, ZnO, MgO, CeO2, La2O3, HMS and various alumina) with
different morphology and properties. Gold catalysts as well as the corresponding supports were
characterized by XRD, BET, ICP-OES, XPS and TEM. It was found that the nature of the support
plays a decisive role in betulin oxidation over gold-based catalysts, expressed in the influence on the
average size and distribution of gold nanoparticles and, thereby, on their catalytic performance
(activity and selectivity) in betulin oxidation. Moreover, it was revealed that betulin oxidation
catalyzed by gold is a structure sensitive reaction, requiring an optimal size of gold nanoparticles of ca.
3.3 nm. The most suitable support for gold was found to be alumina. Kinetic studies allowed
determination of reaction orders and conditions favorable for selective formation of a particular oxo-
derivative of betulin (betulone, betulinic and betulonic aldehydes, betulinic acid).
Keywords: Gold catalyst, betulin oxidation, support nature, structure sensitivity
1. Introduction
Medical drugs obtained by chemical transformations of natural compounds have several
advantages over synthetic analogues. They show low toxicity, provide a multilateral effect on the
2

organism, rarely cause side effects. It is especially valuable that many promising objects of chemical
transformations can be obtained in almost unlimited quantities from the waste of the forest and wood
processing industry. One such example is birch bark, a large-tonnage waste product from birch
processing with a share is 15-17% from the total harvested wood volume. The outer part of the birch
bark is a source of a number of valuable organic substances. The birch extracts are dominated by
cyclic triterpenoids of the lupane series, the main of which is betulin - (lup-20 (29)-ene-3, 28-diol,
C30H50O2, CAS: 473-98-3) [1]. Betulin is produced from birch bark of various species [2]. The content
of betulin in the outer part of the bark varies (10-35 %) depending on the species of birch, the place
and conditions of its growth, the age of the tree and other factors [3]. Betulin is easily and almost
completely extracted from birch bark by such extracting agents as aliphatic hydrocarbons, alcohols C1
– C4 or acetone [1, 2, 4-8], and, therefore, is considered as an available feedstock.
Betulin, and especially its oxo-derivatives (betulone, betulinic and betulonic aldehydes, betulinic
and betulonic acids, as well as their derivatives) exhibit a broad-spectrum biological activity per se
(immunostimulatory, antioxidant, hepatoprotective, anti-inflammatory, antiviral, etc.) and, moreover,
can serve as building blocks for the creation of new generation of drugs, thereby representing an
exceptional interest for the pharmaceutical, cosmetic and food industries [2, 9-24]. The main method
for the synthesis of betulin oxo-derivatives is its oxidation. Complexity of betulin oxidation is due to
several reasons: presence of three reaction centers in the molecule, namely a primary hydroxyl group
at C-28, a secondary alcohol group at C-3 and a multiple bond at the C-20 - C-29 position; difficulty of
regulating selectivity to a specific product, lability of the betulin structure and its solubility [2]. The
most commonly used oxidizing agents are Cr(VI) compounds, for example, the Jones reagent,
pyridinium dichromate, pyridinium chlorochromate, pyridinedichromate complex with acetic
anhydride, etc. [2, 25-30]. However, despite numerous studies aimed at modifying the method of
betulin oxidation by chromium compounds, the synthesis of oxo-derivatives is a quite complex process
characterized by low yields of the target products, low temperature and long reaction times, low
selectivity leading to a mixture of products, as well as complexity of toxic Cr(III) disposal and
3

handling of very toxic residual Cr(VI). Subsequently, product isolation requires complex purification,
the use of a large number of different types of organic solvents and different techniques for removing
Cr(III). There are also several approaches in which betulin oxo-derivatives are synthesized using
mixtures: TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) - NaClO2-NaOCl; butyl acetate, phosphate
buffer, 4-acetamido-TEMPO and Bu4NBr×H2O in an aqueous solution of NaClO2 and NaOCl [31]. In
addition, methods of biological transformation by microorganisms are used to obtain betulin oxo-
derivatives, in particular, this is the main way to obtain betulone, due to the fact that during chemical
transformation it is very difficult to keep other groups intact. However, despite a possibility to obtain
the target products with a high degree of regio- and stereoselectivity using biocatalysts, this approach
is characterized by an even larger set of disadvantages than chemical transformation methods
(complex nutrient media, long duration, low substrate concentrations, etc.) [12, 32-35].
Earlier in a series of articles [36-39], some of the authors of this work demonstrated that a more
environmentally and economically viable alternative to existing stoichiometric methods for producing
betulin oxo-derivatives can be heterogeneous catalytic oxidation of betulin with synthetic air over
catalysts based on Pd, Ru, Ag and Au nanoparticles deposited on various carbon and oxide supports.
The best results were achieved over gold catalysts supported on modified titania [39]. Gold catalysts
have been shown to be more stable and less sensitive to changes in reaction conditions and the
inhibitory effect of water. A more detailed comparative analysis of the catalysts (Pd, Ag, and Au)
previously studied in betulin oxidation is given in [39].
It should be noted that, gold-based nanosized catalysts due to their unique properties are one of the
most studied systems for aerobic oxidation of all types of alcohols [40-42], as well as others substrates
and reactions [43-49].
The aim of this work is to further explore the liquid phase betulin oxidation with synthetic air over
supported nanogold catalysts, with a focus on assessing the effect of oxide support nature on the
catalytic behavior of supported gold catalysts.
4

2. Materials and methods
2.1. Catalysts preparation
Hydrotalcite (HT, Merck), ZrO2 (Alfa Aesar), ZnO (Merck), MgO (Merck), CeO2 (Merck), La2O3
(Merck), Al2O3_V (Versal gamma alumina (VGL-25), UOP), AlOOH_L (pseudoboehmite (LaRoche
V-280), LaRoche Chemicals), AlOOH_C (boehmite (Catapal B), Sasol), AlOOH_S (silica-alumina
hydrate (Siral 5), Sasol), AlOOH and HMS (hexagonal mesoporous silica) were used as supports.
AlOOH was obtained by water oxidation of Al nanopowder obtained by electric explosion of Al wire
in an atmosphere of nitrogen (or argon), according to the procedure previously described [50]. 1.0 g of
the powder was placed in a thermally insulated vessel containing 100 ml of distilled water and heated
to 60 ⁰ C under stirring. The oxidation reaction was performed for 1 hour. Thereafter, the resulting
suspension was filtered, followed by washing the precipitate was washed with distilled water and
drying at 120 ®C for 2 hours. HMS was synthesized by a neutral S0I0 templating route (S0: neutral
primary amine surfactant; I0: neutral inorganic precursor), according to the procedure previously
described [51]. Dodecylamine was employed as a surfactant, tetraethyl orthosilicate as an inorganic
precursor and mesitylene as a swelling organic agent. The reaction mixture was aged at ambient
temperature for 18 hours. This was followed by filtration of the reaction products, washing with
distilled water, and drying at room temperature for 24 h and at 100 ⁰ C for 2 h. The template was then
removed by calcination at 550 ⁰ C for 3.5 h in air.
Gold catalysts (denoted as Au/HT, Au/ZrO2, Au/ZnO, Au/MgO, Au/CeO2, Au/La2O3, Au/HMS,
Au/Al2O3_V, Au/AlOOH_L, Au/AlOOH_S, AlOOH_C and Au/AlOOH) were prepared by
deposition–precipitation with urea, according to the procedure previously described [52-55]. The
nominal gold content in all catalysts was 4 wt%. The gold precursor (HAuCl4×3H2O, Merck) and urea
(Merck) were dissolved in distilled water, and thereafter the support was added to the solution. The
resulting mixture was heated to 80 ⁰ C and kept at constant temperature for 16 h, with stirring.
Thereafter, the catalysts were pretreated at 300 ⁰ C for 1 hour under H2 atmosphere.
5

2.2. Catalysts characterization
The phase composition of ZnO, ZrO2, MgO, HT and Al2O3_V supports was studied by the step-
scanning procedure (step size: 0.02⁰ ; 0.5 s) with a Philips XPert PRO diffractometer, using CuKα
radiation (λ = 0.15406 nm) and a Ni-filter. The measured diffractograms were analyzed with the
ICDD-2013 powder diffraction database. For other studied materials, structural characterization was
carried out by X-ray powder diffraction (XRD) in a PAN’alytical X’Pert MPD equipped with a
X’Celerator detector and secondary monochromator (Cu Kα λ = 0.154 nm, 50 kV, 40 mA; data
recorded at a 0.017⁰ step size, 100 s/step). The collected spectra were analyzed by the Rietveld
refinements using the Highscore Plus 4.8 program (from PANalytical), allowing determination of the
crystallite size by means of the Williamson-Hall plot. To determine the amount of each phase,
refinements were performed using the Highscore Plus 4.8 program (from PANalytical), except
Au/HMS, when amorphous phases were present. In the latter case, a more appropriate PowderCell
software was used.
The samples texture was analyzed using an ASAP 2060 (Micromeritics) apparatus. Materials were
previously degassed in vacuum, at 300 ⁰ C for 5 hours. The surface area was determined using the
Brunauer-Emmett-Teller (BET) equation applied for the adsorption isotherm at the relative pressures
between 0.005 to 0.25. The pore size distribution was determined by the Barrett-Joyner-Halenda (BJH)
method (desorption branch).
The metal loading of the catalysts was determined by inductively coupled plasma optical emission
spectrometry (ICP-OES) using a Horiba JobinYvon (France) Ultima apparatus. The solids were treated
by aqua regia, digested in microwave oven, diluted to 100 mL and analyzed in the spectrometer.
The surface composition and the chemical state of each element were determined by X-ray
photoelectron spectroscopy (XPS), performed on a VG Scientific ESCALAB 200A spectrometer using
Al Kα radiation (1486.6 eV) in CEMUP. The charge effect was corrected using the C1s peak as a
reference (binding energy of 285 eV). The CASA XPS software (http://www.casaxps.com/) was used
for data analysis.
6

The size of gold nanoparticles was investigated by high resolution transmission electron
microscopy (HRTEM) using JEM-2100F instrument. The samples were ground to a fine powder and
sonicated in hexane at room temperature. Then a part of the suspension was placed on a lacey carbon-
coated Cu grid. For each sample, at least 150 particles were counted.
2.3. Catalytic testing
Betulin (90–94%) was extracted from birch bark with a non-polar solvent and recrystallized from
2-propanol according to the procedure, previously reported [5]. Typically oxidation of betulin was
carried out using 200 mg of betulin in 100 ml of mesitylene (the initial betulin concentration was 4.5
mmol/l) and 200 mg of Au catalyst (betulin to gold molar ratio was 11:1) under atmospheric pressure
with synthetic air (AGA, 20% oxygen, 80% nitrogen) as an oxidant at 140 ⁰ C. The gas phase was
bubbled through the liquid with an inlet for the gas (flow rate: 50 ml/min) located at the bottom of the
reactor to enhance the gas–liquid mass transfer. Moreover, a metallic sinter was applied to diminish
the size of air bubbles. The reaction started when the desired temperature was reached via turning on
stirring (500 rpm). Small catalyst particles (<63 μm) and a high stirring rate of 500 rpm were used to
suppress the internal and external mass transfer limitations. To confirm reliability of the results of
catalytic studies, the tests were performed twice for each studied catalyst. Kinetic experiments were
performed in the temperature range of 80 - 140 ⁰ C using 0.05 – 0.4 g catalyst and the initial betulin
concentration varied from 1.13 mmol/l – 9.04 mmol/l. In addition, the oxygen content in the gas
atmosphere was changed from 0% to 100% by adjusting the oxygen level with nitrogen (Table 1).
The samples for analysis were withdrawn from the reactor at regular intervals. Prior to GC-
analysis, the samples (150 μL) were silylated by adding 150 μL of the mixture of pyridine (VWR
International, Fontenay-sous-Bois, France), N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA,
Supelco Analytical, Bellefonte, PA, USA), and trimethylsilyl chloride (TMCS, Merck KGaA,
Darmstadt, Germany) with the 1:4:1 volume ratio followed by heating of a mixture was heated in an
oven at 70 ⁰ C for 45 min. GC analysis was performed on a Crystallux-4000M Meta-chrome gas
7

chromatograph using an Agilent HP-1 capillary column, 25 m (L) × 0.2 mm (ID), film thickness: 0.11
mm. Hydrogen was used as a carrier gas, with a flow rate of 30 ml/min. Betulinic aldehyde, betulonic
acid and betulinic acid (90% purity), used as standards, were purchased from MedChem Express and
Merck, respectively. The products were confirmed by GC-MS. The conditions of betulin oxidation and
the analytical procedure were previously published [36-39].
The TOF values were calculated as the number of converted moles of betulin per mole of exposed
catalytic site per unit time, during the first 5 min, taking into account the metal dispersion:
푛
퐵푒푡푢푙푖푛
푇푂퐹 =
(1)
푛
푀푒푡푎푙
퐷푡
where nBetulin is the number of converted moles of betulin, nMetal is the number of moles of the metal in
the catalyst, D is dispersion and t is time [39]. The metal dispersion was calculated knowing the
average gold particle size measured by transmission electron microscopy (TEM), according to the
following equation:
6푀
퐷 =
(2)
휌푑 푁 푐푠
퐴푢
퐴
where 푑퐴푢 - average gold particle size, and cs its bulk density and cross-section, NA is the

Avogadro number.
For determination of the activation energy of betulone formation from the Arrhenius equation the
initial rate of this reaction was calculated as moles of formed betulone in 30 min divided by that time.
3. Results and discussion
3.1. Betulin oxidation over gold supported on various oxide supports
3.1.1. Catalyst characterization results
Table 2 summarizes the textural and structural data of supports and catalysts, Au content and the
average gold particle size. Analysis of X-ray powder diffraction data of the studied supports and the
8

corresponding catalysts showed that the deposition of gold leads to a change in the support structure
and composition in only three cases, namely transformations of MgO to Mg(OH)2, La2O3 to (La(OH)3
and La2(CO3)2(OH)2) and Al2O3 to (Al2O3 and AlO(OH)) (Supporting Information, Fig. S1, S4). Such
changes can be explained by the chemical properties of these supports, manifested by interactions with
water and urea hydrolysis products (Eq. 3) during the catalyst preparation [52,56,57].
+
CO(NH2)2 + 3H2O = 2NH4 + CO2(g) + 2OH-
(3)
At the same time, the average crystal sizes dc of the supports decreased after gold deposition for
almost all samples. It can be hypothesized that interactions of a support with the gold precursor and
urea hydrolysis products during the catalyst preparation lead to deagglomeration depending on the
surface charge density of particles and repulsion forces between them [58,59].
Au was detected by XRD in all catalysts except Au/La2O3 and Au/CeO2 (Table 2). The reasons for
a lack of diffraction peaks of gold in XRD patterns of Au/La2O3 and Au/CeO2 were previously
discussed in [60], namely, that the size of gold nanoparticles is lower than 3–4 nm (i.e. sensitivity of
XRD) or that they are X-ray amorphous. The gold loading in the studied catalysts determined by XRD
was in good agreement with elemental analysis by ICP (Table 2), as well as very close to the nominal
value of 4 wt.%. The average gold particle size determined by HRTEM for almost all studied catalysts
is more than 3 nm and varies from 3.6 (for Au/La2O3) to 18.2 nm (for Au/HMS). For Au/CeO2 and
Au/Al2O3_V, the size is 2.6 and 3.1 nm, respectively (Table 2, Supporting Information Fig.S2). It
should be noted that the average particle size of gold is not directly related to the specific surface area
(SBET) of the support. For example, for HMS with SBET is 478 m2/g, the average Au particle size is 18.2
nm; while for ZnO these values are 5 m2/g and 7.4 nm, respectively. It was demonstrated in [52] that
the average size of gold nanoparticles depends on the point of zero charge (PZC) of the support
surface, determining the efficiency of interactions of gold precursor with the support surface during the
catalyst preparation. According to the mechanism of interactions of the gold precursor, urea and the
support during catalyst preparation by DP with urea proposed in [52]: during the initial time (up to 1
9

hour) the pH of media ~ 3. Under these conditions the surface of such supports as TiO2 (PZC ~ 6),
Al2O3 (PZC ~ 7.5) and CeO2 (PZC ~ 6) is positively charged, and gold species in the solution are
[AuCl4]- or [Au(OH)Cl3]-. Subsequently, there are initially electrostatic interactions between the
support and these gold species, followed by growth of the gold precipitate on the support surface.
Formation of this gold precipitate occurs fast within the first hour of the preparation. Thereafter, with
increasing pH due to urea hydrolysis, there is a change in the surface charge density of the gold
precipitate particles, which leads to fragmentation, and then to a decrease in the size of the gold
particles with increasing deposition time. As a result it was possible to obtain gold particles in the
range of 2.3 - 5 nm for these supports. The largest gold particles were obtained on the silica surface
[52], which has the lowest zero charge point (PZC ~ 2), thereby complicating adsorption of gold
species [AuCl4]- or [Au(OH)Cl3]- on the negatively charged silica surface. It should be noted that in the
case of magnesia, the introduction of MgO into the aqueous media leads to its rapid hydration to
Mg(OH)2 and a rapid increase of pH to 9-10, due to its high solubility [57]. As shown in [61,62], the
adsorption rate of the gold precursor is linearly proportional to the difference between the pH of media
and the point of zero charge of the support (PZC), which is about 12 in the case of magnesia. With
such a small difference, the adsorption of the gold precursor is very slow, leading to the formation of
gold(I) polynuclearhydroxo complexes in the solution along with gold(III) polynuclearhydroxo
complexes, resulting in a broad particle size distribution with a predominance of particles larger than 5
nm on the magnesia surface (Supporting Information, Fig.S2).
It should be noted that because the size of gold nanoparticles depends on the point of zero charge
of a particular support and pH of deposition [63], in general regulation of the deposition pH can
optimize dispersion of gold on the supports, which are otherwise less active when the same preparation
method is applied. Understanding of the influence of preparation and pretreatment methods, as well as
gold loading on the catalytic behavior, clearly requires a stand-alone comprehensive study, going
beyond the scope of the current work aiming at elucidation of selectivity in catalytic transformations of
betulin. Moreover, differences between the pzc and the pH during metal deposition are certainly not
10

the only criterium for formation of gold clusters with an optimum dispersion. A suitable method for
obtaining gold catalysts for a particular support should take, into account not only its chemical nature
and pH during introduction of the metal onto a support, but also textural and structural features of the
latter, including potential phase transformations.
It is worth mentioning that Au addition led to a significant change in the specific surface area only
for Au/HT, Au/MgO and Au/HMS, while for other supports it remained practically unaffected.
Herewith, for Au/HT and Au/HMS, the surface area decreases by 4.3 and 2.9 fold, even increasing for
Au/MgO 2.2 fold after gold deposition. For the latter case, an increase in the specific surface area after
gold addition is probably due to changes in the structure and composition of the support, namely,
transformations of an oxide to a hydroxide and/or decrease in the crystallite size, resulting from
reasons described above. For Au/HT and Au/HMS, the reason for a decrease in the specific surface
area is most likely pore plugging by gold nanoparticles [51].
To study the electronic state of gold on the surface of different oxide supports, the catalysts were
analyzed by XPS (Supporting Information, Fig. S3 and Table S1). Analysis of XPS results shows that
most of gold (50 - 100%) on the surface of the studied catalysts is in a metallic state with BE (Au 4f7/2)
in the range of 84.0 - 84.2 eV [39, 60,64,65]. Gold is only in the metallic (Au0) state on the surface of
ZrO2, MgO and HMS. For Au/HT and Au/ZnO, Au 4f7/2 BE is lower than the standard of metallic Au
(84.0 - 84.2 eV), namely, 83.7 eV. In these cases, sometimes it is assumed that there is a donation of
electrons from the support to gold with generation of Auδ- [66-68], although most authors attribute this
value of BE to metallic gold [69-76]. It should be noted that in the XPS spectra of Au/HT, Au/ZnO
and Au/MgO catalysts, there was an overlapping of the Au4f peak with the Mg2s, Zn3p and Mg2s
peaks, respectively, leading to challenges in interpretation of these peaks. At the same time, because
the Au4f7/2 line is clearly visible, it can be assumed that the states are defined correctly. In the XPS
spectra of Au/CeO2 (21 %), Au/La2O3 (12 %) and Au/Al2O3_V (13 %) another state of Au appears
with BE (Au 4f7/2) in the range 85.0 - 85.3 eV related to single charged ions (Au+) [39, 60, 69, 76-79].
11

As previously reported [60], Au/CeO2 (22 %) and Au/La2O3 (38 %) are characterized by the presence
of Auδ- state with BE (Au 4f7/2) within the range of 83.3 - 83.5 eV.
3.1.2. Catalytic results
It was found that the support nature plays a crucial role in the betulin oxidation over gold
supported catalysts. From the results presented in Table 3 it can be seen that for most of the studied
materials, betulin conversion does not exceed 8% (i.e., for 6 out of 8 samples), including Au/HT,
Au/ZrO2, Au/ZnO and Au/HMS, for which betulin conversion is less than 2%, despite different
textural and structural properties (Table 2), as well as the average size of gold nanoparticles and their
distribution. At the same time, for all these catalysts, the gold particle size exceeds 3 nm displaying a
wide distribution, with a significant fraction of gold particles being larger than 10 nm (Supporting
Information, Fig. S2). This is probably the reason for low activity of such catalysts in betulin
oxidation.
For Au/CeO2 with gold particles of 2.6 nm, betulin conversion after 6 h was 27% with selectivity
to betulone (B), betulonic (D) and betulinic aldehydes (C) of 43, 18 and 39 %, respectively (Fig. 1,
Table 3). For Au/Al2O3_V with gold particles of 3.1 nm, betulin conversion reaches already 71% in 30
minutes, being 97% after 6 h with selectivity to betulone (B), betulonic aldehyde (D) and betulinic acid
(E) of 29, 64 and 7 %, respectively. Even if the particle size of gold in Au/Al2O3_V is 1.2 fold larger
than in Au/CeO2, betulin conversion is 3.6 fold higher, meaning that, the size of gold particles is not
only factor determining catalytic behaviour. The textural and structural properties of supports should
be also taken into account. Ceria has large pores exhibiting the specific surface area of 38 m2/g.
Alumina is characterized by a better developed porous structure and a higher specific surface area of
277 m2/g.
12

For deeper understanding of the reasons for the observed catalytic behavior of Au/Al2O3, a series
of materials based on gold nanoparticles supported on alumina with different morphology and
modification was prepared, characterized and tested in betulin oxidation (Section 3.2.).
3.2. Betulin oxidation over gold on various types of alumina supports
3.2.1. Catalyst characterization results
Structural characteristics of bare alumina supports and catalysts containing gold were determined
by X-ray diffraction (Supporting Information, Fig. S4). Table 4 shows the phases detected for each
alumina support, their crystallite sizes, and some other characterization data. Four out of five aluminas
are in the boehmite phase with an orthorhombic framework. For Al2O3_V, γ or η-alumina with a cubic
framework was found. The average crystal size for the bare supports varies slightly from 4 nm (for
Al2O3_V) to 6.4 nm (for AlOOH_C). Gold deposition leads to a change in the structure and
composition of the support only in the case of Al2O3_V, for which, along with the main phase of γ or
η-alumina (89%), also the boehmite phase was present (7%), resulting from a change in the support
during the catalyst preparation [56]. Au phase was detected by XRD for all Au/alumina materials. The
gold loading determined by the Rietveld refinements is in good agreement with elemental analysis data
(Table 4). For three out of five studied samples, the average crystal size of gold obtained from XRD
data is close to the average particle size of gold determined by HRTEM (Table 4). For Au/Al2O3_V
and Au/AlOOH_L, the values obtained from XRD are slightly higher than those determined by
HRTEM (Table 4). It is well known that lower particles are not detected by XRD, therefore it is
possible that XRD gives an overestimation of the average size. Fig. 2 shows Au particle size
distribution and HRTEM images of Au/alumina materials. Gold on AlOOH_S shows the broadest
nanoparticle size distribution (2 - 19 nm) with the largest average nanoparticle size of 4.2 nm. A broad
distribution of Au particles (1 - 14 nm) was also observed for Au/AlOOH_L, while the average Au
size was 3.2 nm. Gold on AlOOH shows the large average nanoparticle size (3.7 nm), not exhibiting
13

such a wide distribution (1–11 nm). Smaller Au nanoparticles are found on the surface of AlOOH_C
and Al2O3_V with average sizes of 2.9 and 3.1 nm, and with the narrowest distributions, i.e., 2 - 5 and
2 - 11 nm, respectively.
Table 4 also shows the BET surface area, pore size and pore volume of the bare supports and
Au/alumina materials. After deposition of Au, specific surface area for almost all studied catalysts
noticeably decreased, except Au/Al2O3_V, for which it remained practically unchanged. A decrease in
the specific surface area probably originated from an increase in the average crystal size of aluminas
after gold deposition, as well as a decrease in the accessible pores. All studied materials exhibited a
mesoporous structure. For supports, pores size vary from 5.7 (for AlOOH_S) to 11.7 nm (for
Al2O3_V). For the corresponding catalysts, these values are slightly lower, which can be caused by
partial blocking of the pores by gold [80].
Au/alumina materials were further investigated by XPS (Fig. 3). The chemical state of Au found
on the alumina supports and their relative atomic concentrations are listed in Table 5. On the surface of
Au/AlOOH_S and Au/AlOOH_L, gold is only in the metallic (Au0) state with BE (Au 4f7/2) in the
range of 84.0 - 84.2 eV [39, 60,64,65], while for Au/Al2O3_V (13%), Au/AlOOH (10%) and
Au/AlOOH_C (19%) an additional state of gold with BE (Au 4f7/2) in the range 85.0 - 85.3 eV [39, 60,
69, 77-79] related to Au+ ions was found.
A special focus is given to surface oxygen species (Fig. 3), since, as repeatedly noted in the
literature, they play a special role in different type of reactions [81-89], namely, chemisorbed oxygen
species are affirmed as the most reactive oxygen species for phenol photocatalytic degradation,
oxidative coupling of alcohol and amine, phenol wet oxidation, NO oxidation, low-temperature CO
oxidation, etc. For all studied catalysts, the O 1s peak can be deconvoluted into three bands associated
14

with the lattice oxygen at 530 – 531 eV (marked as OI), the low coordination oxygen species, surface
defects/vacancies, and hydroxyl groups at 531 - 532 eV (marked as OII), carbonate species and/or
adsorbed water at 532 – 534 eV (marked as OIII) [85-94]. The relative contribution of each oxygen
species is presented in Table 5. According to this Table, the main contribution is from OII species, with
their surface concentration varying from 46% (for Au/AlOOH) to 72% (for Au/AlOOH_C) in good
agreement with the structural data. In Table 2, four out of five materials are present in the boehmite
phase. Moreover, for Al2O3_V after gold deposition this phase is also observed, which means the
presence of a large amount of OH specie on the surface. The contribution of lattice oxygen (OI) is
higher for Au/AlOOH, almost the same value is observed for Au/Al2O3_V and Au/AlOOH_L, while
for Au/AlOOH_S and Au/AlOOH_C this value is almost 1.5 and 2 folds lower than for the previous
ones. The amount of OIII species does not exceed 7%.
3.2.2. Catalytic results
Catalytic data for a series of catalysts bearing gold nanoparticles on several alumina supports with
different texture and morphology in betulin oxidation are presented in Table 6 and Fig. 4.
The highest betulin conversion of 97% in 6 h was achieved on Au/Al2O3_V and Au/AlOOH_L,
giving mainly betulonic aldehyde (D), followed by betulone (B) and betulinic acid (E) (Table 6, entries
1 and 5). Despite high conversion, the mass balance closure (GCLPA - the sum of the reactant and
product masses in GC analysis (%)) was far from complete (ca. 60%). For Au/AlOOH betulin
conversion was lower, while the product yield was almost the same (62%) due to better GCPLA – 72%
(Table 6, entry 2). For the catalysts mentioned above, the distribution of products was rather similar.
For Au/AlOOH_S and Au/AlOOH_C, betulin conversion was significantly lower than for other
catalysts (Table 6, entries 3 and 4). At the same time, for Au/AlOOH_C, the total product yield was
the highest (69%) among the studied catalysts with the highest GCLPA (91%) (Table 6, entry 4). In
both latter cases, the main product was betulone (B), followed by betulonic aldehyde (D) and betulinic
acid (E).
15

It should be noted that in the reaction products, betulinic aldehyde (С) was observed only in the
initial period of reaction contrary to a previous study [39], when for the most active Au/La2O3/TiO2, the
selectivity to betulin aldehyde (C) was 27%. It can be assumed that in current case it was very quickly
transformed into betulonic aldehyde (D) or betulinic acid (E) (Fig. 1). It should be taken into account that
for Au/Al2O3_V, Au/AlOOH_L and Au/AlOOH, the concentration of betulinic acid (E) in the reaction
media increased only up to betulin conversion level of 80%, followed by a decrease (Fig. 4). This may be
explained by further transformations of betulinic acid (E), giving higher molecular weight products, not
detectable by GC, thereby giving lower values of GCPLA for these catalysts. Similar trends for the
discrepancy between the total yield of products and conversion were previously observed in our recent
work [39] (Table 6, entry 6). This was ascribed to an incomplete mass balance caused by side reactions of
oligomerization/polymerization occurring with the participation of strong acid sites on the catalyst
surface. Most likely, in the case of Au/alumina materials, similar centers are responsible for side
reactions. It is difficult, however, to have an unequivocal conclusion because of difficulties in an adequate
determination of the acidic properties of used aluminas. The following reasons can be mentioned. When
using the Hammett indicator method, water cannot be considered inert as upon its adsorption on the
Lewis centers, additional Brønsted acid centers are created, being absent in the initial catalyst [95].
Surface layers of alumina in an aqueous media can be transformed by surface dissociation, deprotonation
and dimerization via a hydroxyl bridge into various types of ions and multinuclear cations [96,97].
According to temperature-programmed desorption of ammonia (TPD of NH3), boehmite structure
contains ca. 20% of weakly and strongly bound water giving an overestimation of acidity, while at
elevated temperature boehmite starts to be transformed into γ-alumina [98,99], not present in the catalysts
studied here.
Analyzing the kinetic plots and the yields of the main products at the same conversion level of
70% (Table 6 and Fig. 4), it is interesting to note that for three of the five studied catalysts
16

(Au/Al2O3_V, Au/AlOOH_L and Au/AlOOH) the product yields are very close. For Au/AlOOH_S
and Au/AlOOH_C, the yields of the main products differ significantly from other materials. Namely,
for Au/AlOOH_S, the yield of betulone (B) was 39%, otherwise not exceeding 27%. For
Au/AlOOH_C, the yield of betulonic aldehyde (D) was 20%, while for other catalysts it was below
9%. A possible explanation may be the involvement of active oxygen species (OII) on the catalyst
surface. Such species can promote betulin oxidation, in line with their maximum concentration on the
surface of Au/AlOOH_S and Au/AlOOH_C (Table 5). For the latter materials, the largest yields of
betulone (B) and betulonic aldehyde (D) were observed (Table 6, entries 3 and 4) at 70% conversion of
betulin. Confirmation that these species are involved in betulin oxidation comes from an experiment
carried out under neat nitrogen, with all other conditions being the same. In such experiment, betulin
conversion was 69% in 6 h (Table 7, entry 8) compared to 77% obtained using synthetic air (Table 6,
entry 4). It is also worth noting that the betulin conversion on bare supports did not exceed 5% in 6 h.
Table 6 also shows the TOF values calculated after 5 min. The highest TOF values among the
studied catalysts were obtained for Au/Al2O3_V and Au/AlOOH_L, followed by Au/AlOOH and
Au/AlOOH_C, and finally Au/AlOOH_S. For comparison, Table 6 also contains the TOF value for the
most active Au/La2O3/TiO2 from the previous study [39], which is significantly lower than the TOF
values calculated for Au/alumina materials. Visualization of TOF dependence on the average particle
size of gold is given in Fig. 5 (including data for Au/La2O3/TiO2) showing a volcano type behaviour.
Previously [100], structure sensitivity of the same type was observed for the gold catalyzed aerobic
selective oxidation of lignan hydroxymatairesinol (HMR) into oxomatairesinol (oxoMAT).
In [100] noncompetitive adsorption of the reactant and molecular oxygen on different sites was
assumed and the rate expression was simplified considering the zero order in oxygen and a fractional
reaction order in HMR. Similar kinetic regularities have been observed in the current work as will be
discussed in section 3.2.3, thus leading to the following expression for TOF:
훼휒/푑
푐푙푢푠푡푒푟
푘푒
퐾 퐶
퐵
퐵
푇푂퐹 =
(4)
휒
/푑
퐵
푐푙푢푠푡푒푟
1+ 퐾 푒
퐶
퐵
퐵
17

where 훼 is the Polanyi parameter, χ - reflects differences in the Gibbs energy of betulin adsorption on
edges and terraces, k and K correspond to the rate constant of betulin transformations and its
adsorption constant on terraces, respectively.
While in [100] a modified version of eq. (4) was used to describe a maximum in the rates per mass
of catalyst, eq. (4) per se can also be applied to describe an optimum in TOF dependence as a function
of the cluster size as demonstrated for decarboxylation of stearic acid [101].
In the present study, the same mathematical model as in [100] was applied, and a similar trend of
the dependence of TOF on Au cluster size was obtained. As can be seen from Fig. 5, the applied model
adequately describes the experimental data for TOF dependence on the average particle size of gold.
Thus, it can be concluded that the oxidation of betulin is also a structure sensitive reaction, requiring
an optimum of ca. 3.3 nm.
It should be noted, that while TOF dependence on the average gold particle size has a very clear
trend, not only the cluster size, but the nature of the support should be also taken into account. In the
case of Au/La2O3, deposition of gold on the surface of lanthana led to a change in the phase
composition as mentioned in section 3.1.1. Presence of La2(CO3)2(OH)2 also affects catalytic activity
of Au/La2O3 in betulin oxidation in a unique way, therefore not only the average size of gold particles
determines catalytic behavior.
3.2.3. Kinetic regularities in betulin oxidation over Au/AlOOH_C
The effect of the catalyst mass on betulin concentration as a function of normalized time (i.e., time
multiplied by catalyst mass) is shown in Fig. 6. The curves should overlap with each other if there is
no deactivation or influence of gas/liquid mass transfer [102]. In the current case, betulin concentration
after 6 h was higher with a lower amount of catalyst, indicating presence of catalyst deactivation due to
strong adsorption of the reactant. The corresponding conversion levels for different masses of catalysts
are shown in Table 7 (entries 1-4).
18

3.2.3.1. Reaction rates, conversion levels and liquid phase mass balance closure in betulin oxidation
over Au/AlOOH_C
The initial rates calculated from formation of the products between 0 to 5 min are shown in Fig.7,
as a function of the oxygen content, initial betulin concentration and temperature.
The effect of temperature on the initial reaction rate, calculated from formed products increased
from 80 to 140 oC (Table 7, entries 3, 5-7, Fig. 7c). The mass balance closure in the liquid phase was
under these conditions (C0,bet.=4.5 mmol/l, 0.2 g catalyst, 20% oxygen), above 90% in the whole
studied temperature range (Table 7, entries 3, 6, 7) except entry 5 (GCLPA = 82%).
Effect of oxygen amount in the reaction atmosphere in betulin oxidation showed that the initial
reaction rate was rather independent on the reaction atmosphere (Fig. 7a). Moreover, the initial
reaction rate, in the case of pure nitrogen was the same as when using 20% oxygen in nitrogen (Table
7, entries 3 and 8). The highest liquid phase mass balance closure was observed in nitrogen
atmosphere, being 94%, while in the presence of 12%, 48% and 100% oxygen, the GCLPA varied in
the range of 70-78 %. Interestingly, high GCLPA was obtained when using 20% oxygen, being 91%.
Betulin conversion was slightly lower in a neat nitrogen atmosphere, being 69% after 6 h, while with
oxygen, the conversion levels were in the range of 77 - 82%.
The initial rates calculated from formed products between 0 - 5 min increased with increasing
initial betulin concentration (Fig. 7b), indicating that the reaction order was higher than zero. Nearly
complete conversion of betulin was observed for the two lowest initial betulin concentrations, (Table
7, entries 12, 13). The liquid phase mass balance closure, GCLPA, was very small for these
experiments because of large available specific surface area, compared to the amount of betulin or
products.
3.2.3.2. Product distribution in betulin oxidation over Au/AlOOH_C
The concentration profiles of betulin and the main products, betulone and betulonic aldehyde as a
function of time, are shown in Fig. 8, varying the initial concentration of betulin, at different reaction
19

temperatures, in Fig. 9, and with different oxygen contents, in Fig. 10, while the concentration profiles
of the minor products. betulinic aldehyde and betulinic acid are shown in Fig. S5-S7 (Supporting
information). In all experiments the yield of the final product, betulonic acid was very low (Table 7).
The two primary products in betulin oxidation are betulone and betulinic aldehyde (Fig. 1). The
highest concentrations of betulone were obtained under 20% oxygen with 4.52 mmol/l initial betulin
concentration at 140 oC (Fig. 8b, Table 7, entry 3), while betulinic aldehyde formation is favored with
the highest initial betulin concentration (Fig. S5a, Table 7, entry 14). The selectivity to betulone was
also plotted as a function of conversion, showing that slightly lower betulone selectivity was obtained
with the highest initial betuline concentration, while with the initial betulin concentration varying in
the range of 1.13 mmol/l – 4.52 mmol/l, the difference in betulone selectivity was minor (Fig. 11).
The effect of temperature can be clearly seen for betulone formation, which increased with
increasing temperature (Fig. 9b, Table 7, entries 3, 5-7). This can also be clearly seen when plotting
betulinic aldehyde concentration vs betulone concentration at different temperatures (Fig. 12c).
Oxidation of C3 hydroxyl group and formation of betulone was favored at high temperature (Fig. 9c,
12c), indicating that betulone formation has a higher activation energy than competing routes. The
activation energy for betulone formation was calculated to be 38 kJ/mol. This value is in agreement
with the upper limit for activation energy for transformation of adsorbed benzyl carboxylate to benzoic
acid, over a Pd/C catalyst, in benzyl alcohol oxidation, with oxygen, being below 40 kJ/mol [103].
In nitrogen atmosphere a low conversion of betulin was obtained due to its rapid reaction to
betulonic aldehyde (Fig. 10, Table 7, entry 8). A low yield of betulone was obtained also in nitrogen
atmosphere (Table 7, entry 8) due to a fast formation of betulonic aldehyde under nitrogen (Fig. 10a,
c). In addition to an optimum oxygen amount, also an optimum initial concentration of betulin and the
highest studied reaction temperature were favorable for the formation of betulone (Fig. 10b, Table 7,
entry 3), while the lowest betulone concentrations being observed both with low and high initial
betulin concentrations.
20

The highest concentrations of betulinic aldehyde, when oxidation of betulin is occurring at C27
hydroxyl group, were observed at a high initial betulin concentration and at intermediate temperature
100 - 120 oC (Fig. S6a), when the adsorption through this hydroxyl group seems to be is favored.
According to the reaction scheme (Fig. 1), the consecutive reaction from betulinic aldehyde and
betulone is the formation of betulonic aldehyde, which was most prominent under nitrogen atmosphere
at 140 oC with 0.2 g catalyst and 4.52 mmol/l initial betulin concentration. At low initial betulin
concentrations, betulinic aldehyde reacted further, giving a maximum of betulonic aldehyde
concentration at 30 min. Nearly the same concentrations and yields of betulonic aldehyde were
observed in the temperature range of 100 - 140 oC, while, at 80 oC, betulonic aldehyde formation was
very small (Fig. S6b, Table 7, entries 3, 5 - 7). This result can be explained by the slow rates of both
reactions. A sharp decrease in the concentration of betulinic aldehyde after 30 minutes when using
20% oxygen (Table 7, entry 3, Fig. S7a) can be noted and explained by rapid transformations of
betulinic aldehyde preferentially into betulinic acid. Such transformations are becoming more apparent
when analyzing the effect of oxygen content on the changes in the concentration of betulinic aldehyde
(Fig. S7a) and betulinic acid (Fig. S7b) with time. A sharp increase in the concentration of betulinic
acid occurs simultaneously with a sharp decrease in the concentration of betulinic aldehyde.
Betulinic acid is only formed by oxidation of betulinic aldehyde, which has an aliphatic aldehyde
group attached to a cyclic group. It is known from literature that benzyl alcohol oxidation via
benzaldehyde to benzylic acid is favored at high temperatures, i.e., at 100 oC, in air, over a Pt/C
catalyst, in 7 h [104]. In the current case, the highest yield of betulinic acid by betulinic aldehyde
oxidation was obtained at 4.52 mmol/l initial betulin concentration, at 140 oC, with 12 and 20%
oxygen (Figs 8e, S6c), while with higher oxygen concentration and in the absence of oxygen, nearly
no betulinic acid was formed (Table 7, entry 8, Fig. S7b).
Formation of the final product, betulonic acid, under the studied reaction conditions was minor
(Table 7), due to catalyst deactivation, which is caused by strong reactant/product adsorption on the
21

catalyst surface as well as by poisoning water, which is formed in stoichiometric amounts, blocking
the active sites.
4. Conclusions
The current work is a continuation of the study of the liquid phase oxidation of betulin over
supported gold catalysts. Gold was deposited on oxide supports characterized by different textural,
structural and chemical properties (hydrotalcite, ZrO2, ZnO, MgO, CeO2, La2O3, HMS, various types
of alumina). It was found, that the support nature determines the uniformity of gold particle
distribution and their mean size, and as a result, the catalytic behavior of supported gold catalysts in
betulin oxidation. Such supports as hydrotalcite, ZrO2, ZnO, MgO, La2O3, HMS were characterized by
a wide distribution of gold nanoparticles with a significant fraction of particles being larger than 10
nm, and as a consequence, resulting in a very poor activity in betulin oxidation. Alumina materials
proved to be more suitable supports for gold nanoparticles. Gold catalysts based on them were
characterized by a narrower distribution of gold nanoparticles (1 - 11 nm), and the highest catalytic
activity in betulin oxidation among studied materials. The highest betulin conversion of ca. 100% in 6
h was achieved on Au/Al2O3_V and Au/AlOOH_L having almost the same mean size of gold
nanoparticles, exhibiting, however, different phases, namely, boehmite and γ-alumina. Similar to the
recently studied gold supported on a modified titania, Au/alumina materials also gave side reactions,
leading to a discrepancy between the observed conversion and the products yield, as well as an activity
decrease due to strong adsorption of reactant and products. As a result, the highest products yield of
69% was achieved on Au/AlOOH_C, having a lower level of betulin conversion of 77%, but the
highest mass balance closure among studied Au/alumina catalysts. In the latter case, the main product
was betulone (47 %), followed by betulonic aldehyde (34%) and betulinic acid (17%). It should be
noted that among all catalysts studied by the authors in betulin oxidation, appearance of betulinic acid
in the reaction products was observed only for Au/alumina catalysts. In addition, in the present study,
it was revealed that betulin oxidation is a structure sensitive reaction. The highest turnover frequency
for betulin oxidation was found for an optimum gold particle size of 3.3 nm.
22

Kinetics of betulin oxidation over Au/AlOOH_C catalyst was investigated with different initial
betulin concentrations, oxygen amounts and temperatures in mesitylene as a solvent. The reaction
order in the substrate was higher than zero, being zero toward oxygen. The conditions favorable for
obtaining a specific oxo-derivative of betulin with higher selectivity were determined. In the case of
betulone, these conditions are a low initial concentration of betulin, a high temperature and a high
catalyst loading, while the oxygen content had practically no effect. For betulinic aldehyde, a low
initial concentration of betulin and catalyst loading, an intermediate temperature (100 – 120 ⁰ C) and
neat oxygen were favorable. The amount of betulonic aldehyde in the reaction products increased with
an increase in the initial concentration of betulin and temperature and lower catalyst loading. The
oxygen content did not affect the amount of betulonic aldehyde; at the same time, its highest
concentration was obtained in neat nitrogen. Betulinic acid was formed only in the case of initial
betulin concentration of 4.52 mmol/l, 140 ⁰ C and a low oxygen content of 12 – 20%. Regardless of
the reaction conditions, the amount of betulonic acid did not exceed 2%.
E. Kolobova: Investigation; Writing -Original draft, P. Mäki-Arvel: Writing- review and editing,
Conceptualization; Supervision; A. Grigoreva: Investigation, E. Pakrieva: Investigation; S.A.C.
Carabineiro; : Investigation; Supervision; J. Peltonen: Investigation; S. Kazantsev: Investigation, N.
Bogdanchikova: : Investigation; A. Pestryakov: Conceptualization; Funding acquisition; D. Yu.
Murzin : Writing- review and editing, Conceptualization; Supervision
Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
Acknowledgements
The research is funded from the Russian Science Foundation project No. 18-73-00019 and Tomsk
Polytechnic University Competitiveness Enhancement Program, project VIU-ISHBMT-65/2019
(Russia). This work was partially supported by Fundação para a Ciência e a Tecnologia, Portugal
(2020-2023 multiannual funding to Centro de Química Estrutural). Authors thank Dr. Carlos Sá
23

(CEMUP) for the assistance with XPS analyses and Prof. Pedro Tavares (UTAD) for assistance with
XRD analyses.
24

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