Marco Ciclosi

Chiara Dinoi

Luca Gonsalvi

Maurizio Peruzzini

Eric Manoury

Rinaldo Poli
email: poli@lcc-toulouse.fr

Oxidation of Thiophene Derivatives with H 2 O 2 in Acetonitrile Catalyzed by [Cp* 2 M 2 O 5 ] (M = Mo, W): A Kinetic Study

Keywords: Oxidation catalysis, hydrogen peroxide, benzothiophene, dibenzothiophene, 4, 6dimethyldibenzothiophene

come

Introduction

Sulfur contaminants in transportation fuels represent a major source of atmospheric SOx, which contribute to air pollution and acid rain, as well as having a poisoning effect on car exhaust catalysts. In order to minimize the sulfur oxide emissions, the desulfurization of crude oil has long been a topic of interest, deep desulfurization being even more critical for the production of fuel-cell grade fuel. Currently, the majority of sulfur is removed by hydrodesulfurization (HDS) technologies, [1][2][3][4][5] which require high temperatures and high H2 pressures in the presence of a Mo-based catalyst. Few sulfur compounds, however, are highly resistant to this process and can only be desulfurized slowly under extreme conditions, which raises the cost of the process. Particularly challenging compounds are fused-ring thiophenes, such as benzothiophene (BT), dibenzothiophene (DBT), and their derivatives. 4,6-Dimethyldibenzothiophene (DMDBT), in particular, is one of the most refractory compounds, the steric hindrance generated by the substituents limiting the access to the sulfur atom.

Although other techniques have been considered, including selective adsorption [6][7][8][9] and extraction with ionic liquids, 10 oxidative desulfurization (ODS) combined with extraction is considered as the most promising solution. [11][12][13][14] Concerning the choice of oxidant, H2O2 appears as the best compromise, being more affordable and more environmentally compatible than O3, NO2, tert-butylhydroperoxide (TBHP) or peracids, and in general more reactive than dioxygen.

Many efficient catalytic systems have been investigated over the last few years and compounds BT, DBT and DMDBT have often been chosen as the model compounds for the activity studies. For obvious reasons of catalyst recovery and recycling, the greatest emphasis is placed on heterogeneous or heterogenized catalysts [15][16][17][18][19][20][21][22][23][24] and on biphasic approaches using ionic liquids, 25 water emulsions 11,[26][27][28][29][30][31] or other polar media. 32 Nevertheless, useful insights on the reaction may be derived from studies carried out under homogeneous conditions. Studies of this type require a solvent that is capable of dissolving simultaneously the highly hydrophobic substrates and the oxidant. This has been accomplished with MeCN-H2O or tBuOH-H2O mixtures 29,33 or with neat MeCN 34 when performing oxidations with aqueous H2O2, or with CHCl3, CH2Cl2, or toluene when using TBHP. 35 The investigated homogeneous catalysts include methyltrioxorhenium (MTO), 33 a variety of oxorhenium(V) derivatives, 35 an iron system with a tetraamidomacrocyclic ligand, 29 and a few Ru(II) bis(phenantroline)-type complexes. 34 Some of us have recently carried out extensive studies on the aqueous chemistry of compounds [Cp*2M2O5] (M = Mo, 1; W, 2), [START_REF] Collange | Results and perspectives of high oxidation state organomolybdenum chemistry in water[END_REF][START_REF] Poli | [END_REF] which include an improved and simplified synthetic procedure, 38 a detailed speciation study for the Mo system, 39,40 and the application of 1 to the catalytic cyclooctene epoxidation in CHCl3 and water. 41 We have now extended our catalytic investigations to the oxidation of the thiophene derivatives BT, DBT and DMDBT with H2O2 in MeCN and report here the results of these studies.

Results

The oxidation of benzothiophene (BT), dibenzothiophene (DBT) and 4,6dimethyldibenzothiophene (DMDBT) with H2O2 was studied in MeCN at various temperatures by use of 1% molar amount of the bimetallic catalyst (i.e. thiophene/metal = 50).

In most catalytic runs, a H2O2/thiophene ratio of 4 was used. The oxidations did not take place to any measurable extent in the absence of catalyst. The gas-chromatographic monitoring in the presence of an internal standard revealed the consumption of the substrates, the formation and then disappearance of the intermediate sulfoxides, and the final formation of the corresponding sulfones as the terminal products. Although different by-products deriving from Diels-Alder cycloadditions may be obtained from simpler thiophene substrates, 33 in the case of BT, DBT and DMDBT no additional peaks from other products were visible from the GC traces, indicating that the reactions are selective and quantitative.

The results of two typical runs, one for BT and the other one for DBT, are shown in Figure 1 for the catalyst 2. Figures for all other kinetic runs are given as Supporting Information. The reactions took place at a convenient rate for GC monitoring in the 45-75°C range for BT and 15-45°C range for DBT when using the W catalyst. As 1 is much less active than 2, only one run was carried out with the former for each substrate, at the highest temperature used for the W analogue. For DMDBT oxidation, the low solubility of the sulfone hampered a careful kinetics study, especially at the lower temperatures. Even if the reaction was too fast to be monitored by GC at higher temperatures in the presence of 2, several attempts were made to obtain reliable data using this catalyst in order to compare the relative reactivity of DMDBT and DBT. The best compromise was reached using higher temperature (65°C) and a lower catalyst loading (0.2%, i.e. substrate/metal = 250). Even under these conditions, the sulfone started to precipitate after ca. 50% conversion. However, the data collected up to this conversion were sufficient to extract accurate kinetic information.

Observed rate constants were obtained by monitoring the decay of the sulfides (k1obs) or sulfoxides (k2obs) on the basis of two consecutive first order reactions, as indicated in Scheme

1. The values of the observed rate constants are collected in Table 1. -4 ). This experiment proves that compound 1 is not the catalytically active species but merely a pre-catalyst, which undergoes a rapid chemical transformation with H2O2 to afford the catalytically active species. The latter, however, appears to be stable under the conditions of the catalysis, even in the absence of substrate.

S S H 2 O 2 k 1obs O S O O H 2 O H 2 O 2 k 2obs H 2 O S S R R R R H 2 O 2 k 1obs O S R R O O H 2 O H 2 O 2 k 2obs H 2 O R = H, DBT R =
The nature of this catalytically active species will be the subject of further investigations, to be reported in due course.

Another question of stability concerns the oxidant, which is always used in slight excess. Hydrogen peroxide is known to be susceptible to disproportionation with oxygen evolution and some metal complexes are known to catalyze this process. Therefore, it is important to know whether the oxido derivatives used here induce partial oxidant loss during the catalytic run. However, another experiment carried out under the same conditions of that decribed in the previous paragraph (same conditions as run 8 without substrate), with aliquots periodically withdrawn and titrated iodometrically, reveals a negligible loss of H2O2 (ca. 0.5%) over 100 min, i.e. a time frame in which the catalyzed oxidation is complete (a plot of the data is shown in the Supporting Information).

The more active W system was investigated at several temperatures for both BT and DBT, allowing the determination of the activation parameters through an Eyring analysis, after conversion of the kobs to the true second order rate constants by dividing kobs by the catalyst concentration (graphs provided as Supporting Information). The resulting parameters are collected in Table 2. The activation enthalpy for the first oxidation process (thiophene to sulfoxide) is almost 4 kcal mol -1 higher for BT than for DBT, whereas the large negative activation entropies (around -30 e.u.) are consistent with an associative mechanism and a very high level of ordering in the transition state relative to the reactants. The second oxidation (sulfoxide to sulfone) affords similar activation enthalpies for both substrates, similar to the first activation enthalpy of the BT system. The activation entropies are again negative, although not as large in absolute value as those determined for the first oxidation step (around -25 e.u.) and again indicate a relatively ordered transition state. For the DBT system, H ‡ 2 is greater than H ‡ 1 by nearly 3 kcal mol -1 . However, the rates k1 and k2 are nearly the same in the studied temperature range, thanks to the less negative activation entropy (S ‡ 2 > S ‡ 1).

Discussion

The current investigation shows that the organometallic compounds [Cp*2M2O5] (M = Mo, 1; W, 2) are efficient catalysts for the oxidation of the some of the most resistant sulfurcontaining contaminants of crude oil under homogeneous conditions. The tungsten compound 2 shows a much greater activity, ca. 100 times higher than that of the Mo counterpart 1 under the same conditions. The greater activity of tungsten compounds relative to the Mo analogues in oxidation catalysis has been noted earlier, especially with respect to epoxidation reactions, 42 but also in a few instances with specific reference to the oxidation of thiophene derivatives. 28,43 The current contribution, however, appears to be the first one to quantitatively assess this difference using homogenous conditions for the oxidation of thiophene derivatives.

The relative reactivity of the three substrates investigated in this study is DBT > DMDBT >> BT, as already reported earlier by use of other catalysts. 15,18,28,29,33,43 However, other trends have been also described. For instance, DMDBT is more reactive than DBT with the metal-free HCOOH/H2O2 13,43 and isobutyraldehyde/O2 44 oxidation systems and also in other metal-catalyzed oxidations. 32 The faster oxidation of DBT relative to DMDBT is consistent with a more important contribution of the steric hindrance of the two methyl substituents located in the 4,6 positions of DMDBT, as these substituents should favour the reaction for electronic reasons where no prior coordination of the substrate is needed. Indeed, the oxidation mechanism is generally considered to involve the addition of the nucleophilic sulfur atom onto the oxygen atom in an activated hydroperoxo (M-O-O-H) or peroxo (M(O2))

intermediate, thus an electron-richer sulfur atom should be more reactive.

The oxidation of BT, DBT and DMDBT occurs with the formation of the corresponding sulfoxides as observable intermediates, as already reported in previous studies, 33 whereas dialkyl and alkyl-aryl sulfides undergo a first oxidation step (sulfide to sulfoxide) which is much faster than the second one (sulfoxide to sulfone), so that effectively no sulfone is obtained. 45 One of the most interesting observation of this study is the rate constant trend on going from the first oxidation step (thiophene to sulfoxide, k1) to the second one (sulfoxide to sulfone, k2). To the best of our knowledge, there is only one study making such comparison, by use of the Re VII MTO catalyst 33 for the oxidation of various thiophene derivatives, including BT and DBT.

As can be appreciated in Table 3 where these rate constants are summarized for both catalysts, the k1(DBT)/k1(BT) and k2(DBT)/k2(BT) ratios are very similar. In particular, their values indicate a greater reactivity of DBT relative to BT (ca. 10 times), whereas the corresponding sulfoxides have approximately the same reactivity. The similarity of these ratios suggests that the two catalysts operate by the same mechanism(s), although the mechanism of the transformation from thiophene to thiophene oxide may be different than that of the second oxidation process. 33 On the other hand, the k1/k2 ratios for the same substrate are very different when using a different catalyst. For BT, k1 << k2 when using the W catalyst whereas the two constants are nearly equal when using the Re catalyst, whereas DBT shows nearly equal rates for the two steps with the W catalyst but k1 >> k2 with the Re catalyst. In summary, on going from the W to the Re catalyst, the rate of the first oxidation is increased relative to that of the second oxidation by approximately the same factor for the two substrates. In other words, the Re compound performs better than the W compound as a catalyst for the thiophene to sulfoxide step, whereas the two catalysts perform with similar efficiencies in the sulfoxide to sulfone step. 1 by the catalyst concentration. b Rate constants for the [(CH3)ReO3]catalyzed process are from ref. 33. c The rates for the BT oxidation at 25°C are obtained by extrapolation using the H ‡ and S ‡ values from Table 2.

A question that merits consideration is: why is k1(DBT) > k1(BT), whereas k2(DBT)  k2(BT)?

In the case of DMDBT, both k1 and k2 remain close to those of DBT (slightly smaller, both by approximately the same ratio, probably for steric reasons). This comparison is not available for the MTO catalyst, but similar observations have qualitatively been presented (restricted to k1) for other catalysts. 15,18,28,29,43 A common interpretation is that the rate increase with an increase of benzannulation parallels the increase of nucleophilicity of the sulfur atom.

However, the addition of a fused benzene ring should not significantly affect the electron density at the sulfur atom, nor the energy of the orbital that is susceptible to electrophilic attack. These propositions seem to be supported by the results of DFT calculations. The computed Mulliken charge on the sulfur atom is positive (in agreement with the low reactivity of these compounds toward electrophilic reagents) and similar for the two compounds (0.23 for BT and 0.21 for DBT). The orbital diagram for the two compounds, Figure 2, shows an only marginally higher energy for the HOMO, which is the higher-energy Hückel-type orbital with a significant contribution from the sulfur atom, in the case of DBT. The -type lone pair of the sulfur atom is located below the highest Huckel-type bonding orbitals (no. 31 for BT, no. 43 for DBT), with an identical orbital energy for both compounds, and is therefore not susceptible to attack by the oxidant. These results are in close agreement with those of previous theoretical studies, which were carried out in relation to the catalyzed hydrodesulfurization process. [46][47][48] Thus, if the reactivity difference cannot be explained by a ground state effect, it may be explained by a transition state effect. This effect is most easily examined by looking at the thermodynamics of the reaction. From first principles, it may be expected that the sulfur oxidation removes completely the aromaticity of the thiophene ring, because the sulfur  lone pair is more accessible than the  lone pair (vide supra). Thus, the sulfur atom can no longer contribute two electrons to  delocalization in the oxidation product. The thiophene ring provides a greater contribution to the aromaticity of the less benzannulated system, thus the thermodynamic gain of the oxidation should be less for BT than for DBT. All these predictions are confirmed by the calculations. As shown in Figure 3, the sulfoxide compounds feature an S-O bond pointing away from the plane that contains the rest of the molecule. The O-S-CNT angle (CNT = thiophene ring centroid) is 127.5° for BTO and 124.8° for DBTO.

There is a greater energy gain for the oxidation of DBT relative to BT (by 4 kcal mol -1 ). This The calculated thermodynamic gains of the BTO and DBTO oxidations are essentially identical. In addition, the two sulfoxide compounds have sulfur atoms in essentially identical chemical environments and are no longer involved in a delocalized  system. According to the DFT calculations, the Hückel-type bonding orbitals shown in Figure 2 for BT (no. 32-35) and for DBT (no. 44-48) are slightly modified in energy and shape, because of the removal of the sulfur contribution (see details in the Supporting Information). The sulfur  lone pair (no.

31 for BT and no. 43 for DBT in Figure 2), on the other hand, is raised in energy by the rehybridization process and becomes the HOMO for each sulfoxide compound, with approximately the same orbital energy, see oxidations. These values will be a reference for future computational investigations of the mechanism of the catalytic cycle, the knowledge of which will in turn aid the tailoring of more efficient catalysts.

Experimental section

Materials and instrumentation. The substrates BT (Aldrich), DBT (Aldrich) and DMDBT (Acros), the internal standard 1,3,5-tribromobenzene (Acros) and the oxidant (30% H2O2, Fluka) were used as received. The catalysts, [Cp*2M2O5] (M = Mo, W), were prepared as described in the literature. 38 MeCN (SDS, synthesis grade) was used as received. The gaschromatographic analyses were carried out with a Fisons 8000 Series instrument equipped with a SPB-5 capillary column.

General procedure for the catalytic runs. The reactions were carried out in a Schlenk tube with magnetic stirring, held at the chosen temperature by immersion in a thermostated oil bath. The typical experiment was run by charging the tube with 15 mL of MeCN, followed by 1.2 mmol of the substrate (BT: ca. 161 mg; DBT: ca. 221 mg; DMDBT: ca. 255 mg), the internal standard (1,3,5-tribromobenzene ca. 132 mg, 0.42 mmol) and the catalyst (1.2•10 -2 mmol). The solution was then warmed to the chosen temperature and the aqueous H2O2 solution (0.55 mL; 4.8 mmol) was added dropwise. The reaction progress was monitored by gas-chromatographic analysis of periodically withdrawn samples, after quenching the excess H2O2 with MnO2 and filtration. This allowed the independent measurement, for each substrate, of the final sulfone product, the intermediate sulfoxide, and the residual thiophene.

Calibration curves could be constructed for the starting thiophenes and for the final sulfones, which were available as commercial products, but not for the sulfoxides. However, the absolute amounts of the sulfoxide intermediate were deduced from the measured gaschromatographic peak integrals using an arbitrary parameter, which was held constant for all data in any given run. This parameter was optimized, together with the rate constants, during the kinetic fit as two consecutive first order reactions, Scheme 1 (see details in the Supporting Information). The good quality of the fit obtained in each case attested to the suitability of this procedure.

Computational details. All geometry optimizations were performed using the B3LYP three-parameter hybrid density functional method of Becke, 49 as implemented in the Gaussian03 suite of programs. 50 The basis functions consisted of the standard 6-31G** for all atoms. All geometry optimizations were carried out without any symmetry constraint and all final geometries were characterized as local minima of the potential energy surface (PES) by verifying that all second derivatives of the energy were positive. All energies were corrected for zero point vibrational energy and for thermal energy to obtain the reaction enthalpies at 298 K. The standard approximations for estimating these corrections were used (ideal gas, rigid rotor and harmonic oscillator) as implemented into Gaussian03.

Acknowledgement

Table of Contents

Figure 1 .

 1 Figure 1. Time dependence of the molar fraction of substrate (diamonds), sulfoxide (triangles) and sulfone (squares) for the oxidation of BT (a) and DBT (b) catalyzed by 2 using H2O2 in MeCN at 45°C. The lines are the corresponding fits (see text).

Figure 2 .

 2 Figure 2. Orbital diagrams for BT (a) and DBT (b).

Figure 3 .

 3 Figure 3. Enthalpy diagrams for the oxidation of BT and DBT to the corresponding sulfoxides and sulfones by H2O2. The reported values are the calculated gasphase reaction enthalpies in kcal mol -1 for the reaction with H2O2, leading to the formation of H2O.

Figure 4 .

 4 Therefore, the two compounds are expected to display a very similar reactivity toward oxidation, in agreement with the observed approximately identical rate constants with either catalyst. -0.225 eV -0.223 eV

Figure 4 .

 4 Figure 4. Shape and energy (eV) of the HOMO for BTO and DBTO.

  *2M2O5] (M = Mo, W) catalyze the oxidation of thiophene derivatives to the corresponding sulfoxides and sulfones by H2O2 in MeCN. The W system is ca. 100 times more active than the Mo system. Activation parameters for both oxidation steps have been obtained for benzothiophene and dibenzothiophene with the W catalyst.

Table 1 .

 1 Pseudo

	BT	BTO	BTO 2
	Me, DMDBT	R = H, DBTO R = Me, DMDBTO	R = H, DBTO 2 R = Me, DMDBTO 2
	Scheme 1. Stepwise oxidation of BT, DBT and DMBT.
		-1 st order rate constants for the two-step oxidation of BT, DBT, and
	DMDBT with H2O2 in MeCN catalyzed by [Cp*2M2O5] (M = Mo,

1; W, 2).

  From an overview of the kinetic data the following trends are observed: (i) catalyst 2 is more active than 1 by a factor of ca. 10 2 (cf. runs 1 and 2 for BT at 75°C, or runs 6 and 7 for DBT at 45°C); (ii) DBT is oxidized ca. 10 times faster than BT in the presence of 2 at 45 °C (cf. runs 5 and 7); (iii) for BT, the rate of oxidation of the sulfoxide intermediate, k2obs, is much greater than that of the thiophene precursor, k1obs, by a factor of ca. 20 with both catalysts (runs 1-5); (iv) conversely, for DBT the two rates are very similar, once again independent on catalyst (runs 6-13); (v) the DMDBT oxidation is slower than that of DBT, by a factor of ca. 2 for both steps (cf. runs 13 and 14). Thus, DMDBT shows, like DBT and unlike BT, similar rates for the two oxidation steps. ) except for the absence of substrate. UV-visible monitoring shows the complete disappearance of the absorption band within the first 30 minutes. However, upon adding the DBT substrate after a waiting period of 30 min, the catalysis started and proceeded the same rate constants as those reported in Table1within experimental error (k1obs =

	1.01(6)•10 -3 ; k2obs = 8.4(5)•10
	Run Substrate cat Substr/cat H2O2/Substr T (°C) k1obs (s -1 )•10 4 k2obs (s -1 )•10 4
	1	BT	1	135	4	75	0.069(1)	2.1(2)
	2	BT	2	100	4	75	8.1(2)	151(96)
	3	BT	2	100	4	65	4.8(1)	100(36)
	4	BT	2	100	4	55	2.56(4)	60(17)
	5	BT	2	100	4	45	1.58(2)	31(6)
	6	DBT	1	100	4	45	0.235(4)	0.34(1)
	7	DBT	2	100	4	45	16(1)	19(2)
	8	DBT	2	100	4	35	9.3(4)	9.5(5)
	9	DBT	2	100	4	25	6.5(3)	6.5(4)
	10	DBT	2	100	4	15	4.0(1)	2.9(1)
	11	DBT	2	100	8	35	9.4(2)	7.7(1)
	12	DBT	2	100	12	35	5.7(2)	4.3(2)
	13	DBT	2	500	4	65	1.92(6)	4.5(3)
	14	DMDBT 2	500	4	65	0.94(2)	2.2(1)

The DBT oxidation experiment with the W catalyst at 35°C was also repeated with a greater H2O2 concentration (twice and three times the amount used in run 8, see runs

11 and 12)

. The result of run 11 is identical to that of run 8 within experimental error. Tripling the H2O2 amount does not increase the rates; on the contrary, a small but noticeable decrease on both rate constants is observed. This change suggests that a lower catalyst concentration is present in run 12. However, this does not appear to result from catalyst decomposition induced by the larger H2O2 excess, because the kinetic model of two consecutive 1 st order reactions still provide an excellent fit of the data and thus indicates that the catalyst does not significantly change in concentration over the time range of the kinetics experiments. It is possible that equilibria are established by the active catalyst with a larger excess of H2O2 to yield inactive or less active metal complexes. At any rate, we can safely conclude that the rate has a first order dependence on the substrate and a zero order dependence on H2O2, thus the slow step of the catalytic cycle involves the substrate activation, whereas the activation of H2O2 must occur in a faster step.

The question of catalyst stability was also addressed by a separate experiment, carried out under the same conditions of run 8 in Table

1

(catalyst 2, 35°C, [1] = 8.0•10 -4 M;

[H2O2]/

[1]

= 400

Table 2 .

 2 Activation parameters for the oxidation of thiophene derivatives catalyzed by 2.

	Reaction	H ‡ /kcal mol -1 S ‡ /e.u.
	BT  BTO	11.4(5)	-26.1(1.6)
	BTO  BTO2	10.8(5)	-21.8(1.6)
	DBT  DBTO	7.7(6)	-33(2)
	DBTO  DBTO2 10.3(9)	-

Table 3 .

 3 Comparison

		of rate constants for the first (k1) and second (k2) oxidation steps of BT
	and DBT with the [Cp*2W2O5] (in MeCN at 25°C) and [(CH3)ReO3] (in MeCN-
	H2O 1:1, 0.1 M HClO4 at 25°C) catalysts.
		[Cp*2W2O5] a	[(CH3)ReO3] b
	k1(BT)/s -1 L mol -1	0.053 c	1.75(3)
	k2(BT)/s -1 L mol -1	1.2 c	1-2
	k1(DBT)/s -1 L mol -1 0.79(4)	21.8(1)
	k2(DBT)/s -1 L mol -1 0.80(5)	0.85(3)
	k1(DBT)/k1(BT)	15	12.5(2)
	k2(DBT)/k2(BT)	0.67	0.42-0.85
	k1(BT)/k2(BT)	4.4•10 -2	0.85-1.75
	k1(DBT)/k2(DBT)	0.99(8)	25.6(9)

a Second order k values for the [Cp*2W2O5]-catalyzed reactions are obtained by dividing the kobs values in Table

We acknowledge financial support from the European Commission through the AQUACHEM program (contract HPRN-CT-2002-00176), COST (D29 Action) for funding a Short Term Scientific Mission (STMS) of CD in Florence, and the Institut Universitaire de France through a senior membership to RP. In addition, we thank the CICT (through project CALMIP) for granting free CPU time and Mrs. Sandrine Vincendeau for technical assistance with the GC measurements.

Supporting Information Available

Kinetics plots, description of data handling, Eyring plots, molecular orbital correlations for the BT, DBT and corresponding sulfoxides (9 pages).


A A Azim

Frédéric Bukiet
email: frederic.bukiet@univ-amu.fr

M Guivarc'h

C Jeanneau

T Giraud

L Pommel

I About

Prof Frédéric Bukiet

An international survey on the use of calcium silicate-based sealers in non surgical endodontic treatment

Keywords: Bioceramic root canal sealer, calcium silicate-based sealer, endodontics, root canal filling, single cone technique

An international survey on the use of calcium silicate-based sealers in non surgical endodontic treatment

Introduction

The primary goal of endodontic treatment is to prevent and to treat apical periodontitis by adequately disinfecting and filling the root canal space [START_REF] Hülsmann | Mechanical preparation of root canals: shaping goals, techniques and means[END_REF]. Since reaching a sterile environment is impossible due to the complexity of the root canal system, filling and sealing of the latter is essential to prevent the passage of residual microorganisms and their by-products into the peri-radicular tissues [START_REF] Vertucci | Root canal morphology and its relationship to endodontic procedures[END_REF]. Several obturation techniques combining gutta-percha and a root canal sealer have been used to seal the root canal space including the "single cone technique" (SCT) [START_REF] Tomson | Contemporary obturation of the root canal system[END_REF]. This technique relies primarily on one gutta-percha cone and more emphasis is placed on the sealer which functions as a root canal filler.

Among the available root filling techniques, SCT is considered to be less technique-sensitive as well as cost-effective [START_REF] Wu | A 1-year follow-up study on leakage of single-cone fillings with RoekoRSA sealer[END_REF]. However, a higher sealer volume inside the root canal space may negatively influence the seal as most available sealers tend to shrink upon setting [START_REF] Ørstavik | Dimensional change following setting of root canal sealer materials[END_REF]. As a result, SCT combined with conventional sealers was deemed inappropriate, and up till now it was recommended to maximize the gutta percha volume and minimize the sealer thickness [START_REF] De-Deus | Polymicrobial leakage of four root canal sealers at two different thicknesses[END_REF] using thermoplasticized gutta-percha obturation techniques. Since Mineral Trioxide Aggregate development, silicate-based materials are widely used in endodontic procedures because of their excellent biological properties [START_REF] Kaur | MTA versus Biodentine: Review of Literature with a Comparative Analysis[END_REF]. This explains the advent of calcium silicate-based sealers also known as bioceramic root canal sealers (BRCS) [START_REF] Camilleri | Will Bioceramics be the Future Root Canal Filling Materials?[END_REF] characterized by handling and viscosity properties optimized for obturation of the root canal space.

Recently, SCT has been updated with BRCS usage considering that the latter do not shrink upon setting [START_REF] Almeida | Are Premixed Calcium Silicate-based Endodontic Sealers Comparable to Conventional Materials? A Systematic Review of In Vitro Studies[END_REF]. On the other hand, thermoplasticized gutta-percha obturation techniques are controversial with this type of sealers [START_REF] Camilleri | Sealers and warm gutta-percha obturation techniques[END_REF][START_REF] Delong | The effect of obturation technique on the push-out bond strength of calcium silicate sealers[END_REF].

Given the increasing BRCS release into the market, an international survey was set up to examine the knowledge and clinical application of these materials by endodontic practitioners (EPs) and general dental practitioners (GDPs) in order to determine if the latter were in accordance with the best available evidence.

Material and methods

A descriptive, cross-sectional and international survey was conducted online in November 2017 with two recalls set 15 days apart. A multiple-choice self-administered questionnaire was sent by e-mail to all members identified as dentists on a web-based educational forum, "Endolit". At the time of the investigation, it represented 2335 practitioners of whom 62.4% were registered on this forum as endodontic specialists, 11.1% as endodontic residents and 26.5% as GDPs. This close-ended questionnaire included 18 questions related to BRCS endodontic use (Fig. 1). All participants were asked to provide socio-demographic data on their age, gender, practice experience, type of practice and geographic region. Other questions focused on dentists' knowledge about BRCS, the way they apply the material during endodontic treatment, as well as their motivation and perception toward BRCS. All participants received a written explanation of the terms of the study prior to their participation and had to give their informed consent to participate in the study without any financial compensation. This survey was approved by the Ethics Committee of Aix-Marseille University, France (reference 2018-06-02-002).

Statistical analysis

Statistical analysis was performed using SPSS Statistics (IBM, Armonk, USA). The participants of the present study were categorized into two groups; General dental practitioners (GDPs) or Endodontic practitioners (EPs). The EPs group included both endodontic specialists and endodontic residents considering that their undergoing specialty training, education and clinical practice are monitored by endodontic specialists. First, the distribution by age (5 classes), gender, years of practice (4 classes) and type of practice (GDPs/EPs) was examined with regard to the following two points: "has heard of BRCS before" and "has already used BRCS". The rest of the analysis was conducted only with the respondents who reported using BRCS at a frequency ranging from "sometimes" to "always" (Fig. 1).

In this part, we were particularly interested in the influence of the type of practice (GDPs VS EPs) on clinical habits with BRCS usage, and the perception about the material. Chi-squared test (χ²) or Fisher's exact test were used, as appropriate, to assess the associations between the variable categories (p-value<0.05).

Results

Characteristics of dentists included in the study

Of the 2335 contacted dentists, 675 practitioners gave their informed consent yielding a response rate of 28.9%. Participants were from: North America (50.8%), Europe (22.8%), Asia/Australia (16.3%), South America (5.9%) and Africa (4.2%). The age of the participants ranged from 23 to 85 years [meanstandard deviation (SD): 43.913; median=41] and years of practice ranged from 0 to 62 years [meanSD: 18.112.9; median=15]; 80.3% of them were EPs and 19.7% GDPs (Table 1).

Knowledge and usage of BRCS

Among the participants (n=675), 94.8% had heard about BRCS before (n=640), which was significantly associated with being in the EPs group (p<0.05) (Table 2). Participants knew about BRCS via: "conferences/course" (57.50%), followed by "manufacturers' speech/advertising" (22.2%), "colleagues' experience" (12.2%), "literature" (4.1%) and "websites/internet" (1.5%).

Among the respondents knowing BRCS, 58.4% had used BRCS at least once (n=374), which was significantly associated with being in the EPs group (p<0.05) (Table 2). These latter were further asked how often they used BRCS in their daily practice (Fig. 1). The distribution of the frequency of BRCS usage was: "always" (22.2%), "frequently" (22.4%), "sometimes" (48.7%) and "never" (6.7%) and couldn't be related to the type of practice (p>0.05) (Table 2). For the subsequent statistical analysis, those describing a BRCS usage ranging from "sometimes" to "always" were identified as "BRCS users" (n=349) and had to answer questions related to their clinical practice with BRCS and reasons for using them. This subgroup represented 51.7% of the overall participants and was composed of 87.4% EPs and 12.6% GDPs.

BRCS clinical practice

Canal drying

Among BRCS users, 69.4% employed paper points alone to dry canals prior to obturation, 19.6% used vacuum and paper points, 10.1% used alcohol before paper points and 0.9% used vacuum alone.

BRCS application

For BRCS application, 51% of BRCS users employed a device helping injection and distribution of the sealer into the root canal (either a Lentulo spiral 8%, a specific injection tip 40.7%, a file 2% or a sonic/ultrasonic system 0.3%). The remaining 49% carried out a simple coating of the master cone with BRCS.

Obturation technique with BRCS Among BRCS users, 63.3% employed SCT for root canal obturation; 16.7% used cold lateral compaction and 46.1% used thermoplasticized gutta-percha obturation technique (either carrier-based obturation or warm vertical compaction). Systematic use of SCT with BRCS was reported by 40.7% of BRCS users. There was a significant association between the obturation method and the type of practice: GDPs tended to use SCT more (p<0.05) while EPs used warm obturation techniques more often (p<0.05) (Fig. 2). BRCS users were also asked about the obturation methods they used with other sealers than BRCS. Our results highlighted that the preferential obturation method significantly changed depending on the type of sealer used, independently of the type of practice. SCT was the most implemented technique with BRCS (p<0.05) while warm vertical compaction was preferentially used with other types of sealers (p<0.05) (Fig. 3). Specific bioceramic nanoparticles preimpregnated/pre-coated gutta-percha cones were used by only 22.1% of the BRCS users. There was no significant association between using these specific cones and the type of practice (p>0.05).

Motivations and perception toward BRCS

The improved biological and physicochemical properties appeared as the main reason for using BRCS, followed by the possibility to fill simultaneously the root canal space and a perforation. These two motivations were not associated with the type of practice. On the other hand, reasons such as the innovative aspect of BRCS, the simplification of clinical procedures, the connection with minimal invasive dentistry (preservation of coronal, pericervical and radicular dental tissue) and the fact that no specific equipment for obturation would be needed all showed significant association with being a GDP (p<0.05) (Table 3).

To the question "Do you think BRCS usage with SCT can be indicated regardless of the root canal anatomy?", 38.4% of the BRCS users answered "Yes", 57.6% answered "No" and 4% had no opinion.

Thinking that BRCS usage with SCT could be indicated regardless of the root canal anatomy was significantly associated with being in the GDPs group (68.2%) rather than in the EPs group (34.1%) (p<0.05).

To the question "Do you think BRCS usage may influence the ability to re-establish apical patency during non-surgical retreatment?", 55.6% of the BRCS users answered "Yes" and it was significantly associated with being in the GDPs group (68.2%) rather than in the EPs group (51.8%) (p<0.05).

Discussion

The present study aimed to gain insight into the current use of BRCS, to discuss the clinical practices reported by endodontic practitioners (EPs) and general dental practitioners (GDPs) and to determine if it was in accordance with the best available evidence.

To our knowledge, this is the first international survey addressing BRCS use in root canal obturation.

Previously conducted surveys on endodontic practices often included one category of practitioners (either GDPs or EPs) and only within a single country [START_REF] Bjørndal | The adoption of new endodontic technology amongst Danish general dental practitioners[END_REF][START_REF] Savani | Current Trends in Endodontic Treatment by General Dental Practitioners: Report of a United States National Survey[END_REF][START_REF] Setzer | A Survey of Cone-beam Computed Tomographic Use among Endodontic Practitioners in the United States[END_REF]. The present survey considered and compared both type of practice and utilized the data-base of a web-based endodontic forum that is available to clinicians world-wide. Despite Endolit being based in the United States, the practitioners registered on this website are from different countries and more than a half of the respondents were not practicing in the United States (55.7%). The number of contacted dentists was consistent (n=2335) and the global response rate achieved (close to 30%) as well as the gender ratio were in line with previously conducted surveys on the dentists' knowledge and type of clinical practice [START_REF] Savani | Current Trends in Endodontic Treatment by General Dental Practitioners: Report of a United States National Survey[END_REF][START_REF] Setzer | A Survey of Cone-beam Computed Tomographic Use among Endodontic Practitioners in the United States[END_REF]. The distribution between EPs and GDPs among respondents (80.3% and 19.7% respectively) was coherent with its distribution in the overall population included in the survey (73.5% of EPs, 26.5% of GDPs).

The results of this survey highlighted a widespread knowledge of BRCS among the respondents (94.8%). Despite the presence of numerous alternative root canal sealers, BRCS was quite popular since 51.7% of the participants used these materials in their clinical practice. Being an EP appeared to be a determining factor in using BRCS (p<0.05). The primary reason for using this type of sealers was their improved biological and physicochemical properties (87.7% of BRCS users), regardless of the type of practice. This finding clearly indicates that most practitioners are aware of BRCS properties.

Indeed it has been shown that BRCS properties are overall similar or better than those of conventional root canal sealers [START_REF] Almeida | Are Premixed Calcium Silicate-based Endodontic Sealers Comparable to Conventional Materials? A Systematic Review of In Vitro Studies[END_REF][START_REF] Donnermeyer | Endodontic sealers based on calcium silicates: a systematic review[END_REF]. Indeed, several studies compared physico-chemical and biological properties of different BRCS formulations such as iRoot SP (Innovative Bioceramix, Vancouver, Canada) / EndoSequence BC (Brasseler, Savannah, GA, USA), BioRoot™ RCS (Septodont, Saint-Maur-des-Fossés, France) or Endoseal MTA (Maruchi, Wonju, Korea) versus widely used root canal sealers such as Pulp Canal Sealer (SybronEndo, Orange, CA, USA) a zinc oxide eugenol-based sealer, or AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany) an epoxy resin-based sealer [START_REF] Almeida | Are Premixed Calcium Silicate-based Endodontic Sealers Comparable to Conventional Materials? A Systematic Review of In Vitro Studies[END_REF][START_REF] Donnermeyer | Endodontic sealers based on calcium silicates: a systematic review[END_REF]. BRCS generally fulfil general endodontic sealer requirements (ISO 6876) regarding radioopacity, film thickness, solubility and flow [START_REF] Almeida | Are Premixed Calcium Silicate-based Endodontic Sealers Comparable to Conventional Materials? A Systematic Review of In Vitro Studies[END_REF][START_REF] Donnermeyer | Endodontic sealers based on calcium silicates: a systematic review[END_REF][START_REF] Jafari | Composition and physicochemical properties of calcium silicate based sealers: A review article[END_REF]. The specific biological properties of BRCS are due to the presence of calcium silicates whose setting reaction leads to hydration byproducts such as hydroxyl and calcium ions and calcium hydroxide followed by a precipitation reaction with calcium phosphate leading to hydroxyapatite formation. This results in dentinal interaction forming a mineral infiltration zone [START_REF] Atmeh | Dentin-cement interfacial interaction: calcium silicates and polyalkenoates[END_REF] with higher tubule penetration and push-out strength properties for iRoot SP [START_REF] Donnermeyer | Endodontic sealers based on calcium silicates: a systematic review[END_REF]. BRCS generally provide a good antimicrobial activity [START_REF] Donnermeyer | Endodontic sealers based on calcium silicates: a systematic review[END_REF] without cell toxicity [START_REF] Camps | Bioactivity of a Calcium Silicate-based Endodontic Cement (BioRoot RCS): Interactions with Human Periodontal Ligament Cells In Vitro[END_REF][START_REF] Giacomino | Comparative Biocompatibility and Osteogenic Potential of Two Bioceramic Sealers[END_REF] and are also reported to be biocompatible inducing periodontal ligament stem cell proliferation and migration [START_REF] Collado-González | Biocompatibility of three new calcium silicate-based endodontic sealers on human periodontal ligament stem cells[END_REF].

Moreover, previous studies have demonstrated BRCS bioactivity on periodontal cells. Indeed their interaction with periodontal ligament cells demonstrated an increased secretion of angiogenic growth factors (VEGF and FGF-2) and the osteogenic factors (BMP-2) [START_REF] Camps | Bioactivity of a Calcium Silicate-based Endodontic Cement (BioRoot RCS): Interactions with Human Periodontal Ligament Cells In Vitro[END_REF]. In addition, in vitro stimulation murine osteoblast precursor cell line by BRCS led to an increased DMP-1 expression and mineral deposition [START_REF] Giacomino | Comparative Biocompatibility and Osteogenic Potential of Two Bioceramic Sealers[END_REF]. Therefore, even if several factors impact the outcome of root canal treatment these biological properties may help the periodontal healing process in case of apical periodontitis.

The attraction toward a "new" product and simplification of the root canal filling procedure appeared as strong arguments in favor of BRCS usage for GDPs (p<0.05). However, our findings showed that the clinical practices still remain controversial. For instance, it is well known that drying the canals is a prerequisite before applying conventional endodontic sealers since moisture can affect their setting and adhesion properties [START_REF] Zmener | Significance of moist root canal dentin with the use of methacrylate-based endodontic sealers: an in vitro coronal dye leakage study[END_REF]. On the contrary, hydration of BRCS is needed to trigger the setting process and to take advantage of their enhanced properties previously mentioned. Surprisingly, our investigation showed that around 10% of BRCS users used alcohol in combination with a paper point to dry the canals, which is known to lead to dentin dehydration [START_REF] Nagas | Dentin moisture conditions affect the adhesion of root canal sealers[END_REF][START_REF] Taşdemir | Bond strength of calcium silicate-based sealers to dentine dried with different techniques[END_REF]. The degree to which such procedures can impact the bond strength of BRCS deserves further investigation especially since different adverse effects have been shown between some root canal irrigants and BRCS [START_REF] Razmi | The Effect of Canal Dryness on Bond Strength of Bioceramic and Epoxy-resin Sealers after Irrigation with Sodium Hypochlorite or Chlorhexidine[END_REF][START_REF] Arias-Moliz | The effect of the final irrigant on the antimicrobial activity of root canal sealers[END_REF].

In a similar manner, changes in BRCS physical properties has been shown to occur when subjected to high temperatures associated with warm vertical obturation techniques [START_REF] Camilleri | Sealers and warm gutta-percha obturation techniques[END_REF][START_REF] Delong | The effect of obturation technique on the push-out bond strength of calcium silicate sealers[END_REF]. Despite this fact, almost half of the respondents (46.1%) including more EPs (p<0.05) implemented thermoplasticized gutta-percha obturation techniques. These findings suggest that many practitioners, a fortiori EPs, may tend to rely on their clinical convenience when using BCRS rather than considering the available evidence or respecting the manufacturers' recommendations. It should be noted that a new BRCS has been recently introduced that is intended to be used with warm gutta-percha techniques (BC HiFlow, Brassler, Savannah, GA, USA) [START_REF] Buchanan | Warm gutta-percha obturation with BC HiFlow TM Sealer[END_REF]. This survey, however, was conducted prior to the release of this product to the dental market.

In a recently published clinical study, the use of SCT with BRCS has shown a high success rate (around 90%) for both initial treatment and retreatment [START_REF] Chybowski | Clinical Outcome of Non-Surgical Root Canal Treatment Using a Single-cone Technique with Endosequence Bioceramic Sealer: A Retrospective Analysis[END_REF]. However, no long-term clinical studies about BRCS usage are available yet. The presence of voids has been observed regardless of the root canal filling technique and may result in the proliferation of residual microorganisms and jeopardize the long-term outcome [START_REF] Hammad | Evaluation of root canal obturation: a three-dimensional in vitro study[END_REF]. Although SCT may be suitable for filling tapered-rounded canals, it can result in more voids in irregularly shaped anatomies compared to other filling techniques, regardless of the type of the sealer [START_REF] Celikten | Evaluation of root canal sealer filling quality using a single-cone technique in oval shaped canals: An In vitro Micro-CT study[END_REF][START_REF] Gordon | An evaluation of .06 tapered gutta-percha cones for filling of .06 taper prepared curved root canals[END_REF][START_REF] Celikten | Micro-CT assessment of the sealing ability of three root canal filling techniques[END_REF][START_REF] Viapiana | Porosity and sealing ability of root fillings with gutta-percha and BioRoot RCS or AH Plus sealers. Evaluation by three ex vivo methods[END_REF]. In the present study, 63.3% of BRCS users implemented SCT for root canal obturation in some of their cases and around 40% used it on every case. Among BRCS users, 38.4% thought that SCT combined with BRCS can be indicated on every case regardless of the root canal configuration, especially among GDPs (p<0.05). EPs, however, tended to adapt the obturation method to the type of sealer. SCT was significantly associated with BRCS usage while warm vertical compaction was the most used obturation technique with sealers other than BRCS (p<0.05). Among the participants, 51% declared employing devices such as an injection tip or a Lentulo spiral for sealer insertion into the root canal. Such practices have been shown to reduce voids in the root canal filling [START_REF] Guinesi | Influence of sealer placement technique on the quality of root canal filling by lateral compaction or single cone[END_REF] and may be recommended.

Sealability of SCT with BRCS partially depends on the interface between the gutta-percha (hydrophobic) and the sealer (hydrophilic). Some manufacturers claim improvement of this interface thanks to the use of nanoparticles bioceramic pre-impregnated gutta-percha cones. However, a recent study concluded that conventional gutta-percha cones usage showed a slightly better interface with BRCS than pre-impregnated ones [START_REF] Eltair | Evaluation of the interface between guttapercha and two types of sealers using scanning electron microscopy (SEM)[END_REF]. Thus, the fact that only 22% of BRCS users implemented these specific pre-coated gutta cones may not affect the obturation quality.

Finally, one of the controversies linked to BRCS usage is their retreatability since the material may become impenetrable given its hardness upon setting [START_REF] Hess | Retreatability of a bioceramic root canal sealing material[END_REF]. Most studies have shown that apical patency can be properly re-established if the master cone fitted to the full working length [START_REF] Hess | Retreatability of a bioceramic root canal sealing material[END_REF][START_REF] Ersev | The efficacy of ProTaper Universal rotary retreatment instrumentation to remove single gutta-percha cones cemented with several endodontic sealers[END_REF][START_REF] Neelakantan | Retreatability of 2 mineral trioxide aggregate-based root canal sealers: a cone-beam computed tomography analysis[END_REF][START_REF] Carpenter | Regaining apical patency after obturation with gutta-percha and a sealer containing mineral trioxide aggregate[END_REF][START_REF] Donnermeyer | Retreatability of three calcium silicatecontaining sealers and one epoxy resin-based root canal sealer with four different root canal instruments[END_REF].

However, the adequacy between the retreatment method and the clinical relevance can be questioned since most non-surgical retreatments are indicated in case of obturation short of the radiographic apex and associated with apical periodontitis [START_REF] Filippo | Apical periodontitis and the technical quality of root canal treatment in an adult sub-population in London[END_REF]. While patency has been reported to be achieved when chloroform is used [START_REF] Oltra | Retreatability of two endodontic sealers, EndoSequence BC Sealer and AH Plus: a micro-computed tomographic comparison[END_REF], other studies reported that it was often impossible to gain apical patency on curved canals when fillings are short of the working length [START_REF] Hess | Retreatability of a bioceramic root canal sealing material[END_REF]. This suggests that BRCS presence beyond the master cone may make endodontic retreatment challenging. The fact that 44.4% of BRCS users considered that these sealers may not influence their ability to re-establish apical patency during retreatment (especially among EPs p<0.05) suggests either that BRCS retreatability may not be considered as a major clinical issue or that practitioners are underestimating this problem. It should also be taken into account that non surgical endodontic retreatment does not only aim to re-establish apical patency but also achieving complete removal of the previous root canal filling materials as well as cleaning and disinfection of the root canal space [START_REF] Rossi-Fedele | Assessment of Root Canal Filling Removal Effectiveness Using Micro-computed Tomography: A Systematic Review[END_REF]. Some limitations should be noted regarding the present survey. Indeed, it utilized a web-based forum primarily dedicated to endodontics. Thus, it can be hypothesized that the GDPs population surveyed may have a particular interest in this specialty. Therefore, our findings should not be generalized to all dentists. As with any survey, another limitation of the study is the self-declaration of the respondents concerning their type of practice. Indeed, the specific requirements to become EPs are location sensitive as well as the recognition of endodontics as an official dental specialty.

Conclusions

This study highlights wide variation in the clinical practices which are not often in accordance with the current literature on BRCS. The participants of this international survey tend to rely on their clinical habits rather than following the manufacturers' recommendations or considering the best available evidence when using BCRS. This inconsistency implies to provide further clarifications on BRCS clinical application which may pave the way to better standardize their use and improve their future evaluation. .

Figures Legends

Figure 1 :Figure 2 :

 12 Figure 1: Survey questionnaire

Figure 3 :

 3 Figure 3: Obturation techniques implemented by BRCS users according to the type of sealer (%) (n=349) CLC, Cold Lateral Compaction; SCT, Single Cone Technique; WV, Warm Vertical. (*) represents significant differences between two groups (p<0.05).

Figure 3

 3 Figure 2

Table 1

 1 Distribution of participants (n=675)

	Tables
	Continent	%
	Africa	4.2
	Asia/Australia	16.3
	Europe	22.8
	North America	50.8
	South America	5.9
	Age (years)
	<30	12.2
	30-39	31.0
	40-49	24.4
	50-59	15.7
	≥60	16.7
	Gender
	Male	72.3
	Female	27.7
	Years of Practice
	0-10	34.5
	11-20	29.3
	21-30	16.9
	≥30	19.3
	Type of practice
	GDPs	19.7
	EPs	80.3

Table 3

 3 Reasons for using BRCS (n=349) We would like to attract your attention on an online study regarding your practice in root canal filling. We would be very grateful if you could give us some of your time by spending a few minutes filling out a questionnaire. Filling the questionnaire does not require any specific knowledge and only refers to your own clinical experience. The time required is about 5 minutes and the data collected is strictly anonymous. There is absolutely no obligation to participate in this study and your decision to contribute will be considered as informed consent. Aware that your time is valuable, we are very grateful for the attention you will give to the completion of this survey. Thank you for your time and assistance.

		GDPs	EPs	Global	P Value
		(%)	(%)	(%)
	Biological and physicochemical properties	88.6	87.5	87.7	p>0.05
	Possibility to fill simultaneously the root canal and a perforation	38.6	36.4	36.7	p>0.05
	Attraction toward a new biomaterial	47.7	30.2	32.4	p<0.05
	Simplification and saving time	47.7	23.9	26.9	p<0.05
	Connection with minimal invasive dentistry	29.5	14.4	16.3	p<0.05
	No specific equipment for obturation	36.4	12.1	15.8	p<0.05

Have you ever heard about Bioceramic root canal sealers (BRCS)?

	 Yes	 No (go to question 13)
	3. How have you first known about BRCS?
	 Through conferences / courses	 Through manufacturers / advertising
	 Through another dentist's experience	 Other
	4. Have you ever used BRCS?
	 Yes	 No (go to question 13)
	5.

At what frequency do you estimate the use of BRCS in your daily practice?

	 Never (go to question 13)	 Sometimes
	 Frequently	 Always (i.e. in every case)
	6.

When using BRCS, how do you generally dry the root canal? 

  Sterile paper points alone  With alcohol before using sterile paper points  With sterile paper points combined with Luer vacuum adapter (or equivalent system)  Other (specify)

7. When using BRCS, how do you generally apply the sealer?

	 Simple gutta cone coating	 Injection tip
	 Lentulo spiral	 Other (specify)

8. When using BRCS, which obturation technique do you use? (multiple answers

	possible)
	 Warm vertical compaction	 Cold lateral compaction	 Carrier-based obturation
	 Single cone technique	 Other (specify)
	9.

What type of gutta percha cones do you currently use with BRCS?

  Biological and physico-chemical properties of this type of sealers  Significant saving time and simplification  No need of special equipment devoted to root canal obturation  Possibility to fill simultaneously the root canal and a root perforation  Connection with minimal invasive endodontics (preservation of coronal, pericervical and radicular dental tissue)

	 Bioceramic nanoparticles pre-coated gutta percha cones 10. What was your motivation to use BRCS in your practice? (multiple answers  Non pre-coated cones possible)  Willingness to try this recent biomaterial  Figure 1 11.

It is generally recommended to use BRCS with single cone technique. Do you think this method can be indicated regardless of the root canal anatomy?

	 Yes	 No
	12.

Do you think BRCS usage may influence the ability to re-establish apical patency during non-surgical retreatment?

	 Yes	 No
	13. If you do not use BRCS, which obturation technique do you use? (multiple
		answers possible)
	 Warm vertical compaction	 Cold lateral compaction	 Carrier-based obturation
	 Single cone technique	 Other (specify)
	14. What is your gender?
	 Male	 Female
	15. How old are you?
	…………….. (years)

16. In which year did you graduate as a dentist? ……………. 17. Do you practice as...

	 Africa	 Asia/Australia	 Europe	 North America	 South America
		SCT		WV	CLC
				GPs	ES

 A general practitioner  An endodontist practitioner  A postgraduate student/resident in endodontics 18. Where do you practice? * * EPs GDPs

Acknowledgment

The authors of this manuscript deny any conflict of interest.

Compliance with ethical standards