Studies of reaction of tetramethylthiourea with hydrogen peroxide: evidence of formation of tetramethylthiourea monoxide as a key intermediate of the reaction

Article abstract of DOI:10.1080/17415993.2017.1321650

The reaction between tetramethylthiourea (TMTU) and hydrogen peroxide was studied by UV–VIS spectroscopy, ESI mass spectrometry, ¹H NMR, cyclic voltammetry and surface-enhanced Raman scattering. We found that the reaction includes two consecutive steps, that is, (i) an oxidation of TMTU to TMTU monoxide (TMTMO) and (ii) further oxidation of TMTU monoxide to tetramethylurea (TMU) and sulfate. The second step is complex and seems to include extrusion of sulfur monoxide (SO). Density functional theory calculations were employed on tetramethylthiourea oxide models in order to underline differences between monoxide and di- and trioxides. Calculations predict that the TMTMO structure can be best explained as an adduct of thiourea with an oxygen atom (═S–>O).

Full text of DOI:10.1080/17415993.2017.1321650

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Studies of reaction of tetramethylthiourea
with hydrogen peroxide: evidence of formation
of tetramethylthiourea monoxide as a key
intermediate of the reaction
Ilia A. Dereven’kov, Pavel A. Ivlev, Denis S. Salnikov, Cristina Bischin, Amr A.
A. Attia, Radu Silaghi-Dumitrescu & Sergei V. Makarov
To cite this article: Ilia A. Dereven’kov, Pavel A. Ivlev, Denis S. Salnikov, Cristina Bischin,
Amr A. A. Attia, Radu Silaghi-Dumitrescu & Sergei V. Makarov (2017): Studies of reaction
of tetramethylthiourea with hydrogen peroxide: evidence of formation of tetramethylthiourea
monoxide as a key intermediate of the reaction, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2017.1321650
To link to this article: http://dx.doi.org/10.1080/17415993.2017.1321650
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Date: 10 May 2017, At: 23:14

JOURNAL OF SULFUR CHEMISTRY, 2017
https://doi.org/10.1080/17415993.2017.1321650
Studies of reaction of tetramethylthiourea with hydrogen
peroxide: evidence of formation of tetramethylthiourea
monoxide as a key intermediate of the reaction
Ilia A. Dereven’kova, Pavel A. Ivleva, Denis S. Salnikova, Cristina Bischinb,
Amr A. A. Attiab, Radu Silaghi-Dumitrescub and Sergei V. Makarova
aDepartment of Food Chemistry, Ivanovo State University of Chemistry and Technology, Ivanovo, Russia;
bDepartamentul de Chimie, Facultatea de Chimie şi Inginerie Chimică, Universitatea Babeş-Bolyai,
Cluj-Napoca, Romania
ABSTRACT
ARTICLE HISTORY
Received 3 December 2016
Accepted 16 April 2017
The reaction between tetramethylthiourea (TMTU) and hydrogen
peroxide was studied by UV–VIS spectroscopy, ESI mass spectrom-
etry, 1H NMR, cyclic voltammetry and surface-enhanced Raman scat-
tering. We found that the reaction includes two consecutive steps,
that is, (i) an oxidation of TMTU to TMTU monoxide (TMTMO) and
(ii) further oxidation of TMTU monoxide to tetramethylurea (TMU)
and sulfate. The second step is complex and seems to include extru-
sion of sulfur monoxide (SO). Density functional theory calculations
were employed on tetramethylthiourea oxide models in order to
underline differences between monoxide and di- and trioxides. Cal-
culations predict that the TMTMO structure can be best explained as
KEYWORDS
Thiourea oxides;
tetramethylthiourea
monoxide; hydrogen
peroxide; oxidation; density
functional theory
=
an adduct of thiourea with an oxygen atom ( S– > O).
1. Introduction
Oxides of thioureas (TUs) represent group of compounds that include mon-, di- and tri-
oxides. Thiourea dioxide (TDO, (NH2)2CSO2) is a well-known chemical, which has a
wide application in chemistry and technology [1–3]. Dioxide and trioxide can be easily
CONTACT Sergei V. Makarov
makarov@isuct.ru; Ilia A. Dereven’kov
derevenkov@gmail.com
Department
of Food Chemistry, Ivanovo State University of Chemistry and Technology, Sheremetevskiy str. 7, 153000 Ivanovo, Russia
Supplemental data for this article can be at doi:10.1080/17415993.2017.1321650
© 2017 Informa UK Limited, trading as Taylor & Francis Group

2
I. A. DEREVEN’KOV ET AL.
synthesized by the reaction of thiourea with hydrogen peroxide or peracetic acid [1–3].
TDO exhibits its strong reducing properties due to the formation of sulfoxylate (SO2H−
or SO22−) in alkaline solutions [4–7]. To date, anaerobic decomposition of TDO in alkaline
aqueous solutions (reaction 1) is the most convenient pathway of sulfoxylate preparation
[4]. Reactivity of SO22− (SO2H−) toward several compounds is documented [6–10]. N-
methylthiourea and N,Nꢀ-dimethylthiourea dioxides have also been prepared and their
behavior in alkaline medium is essentially similar to that of TDO [11–13]. Denk and
coworkers reported a computational study on the nature of the C–S bond in thiourea
S,S-dioxides [14]. In their study, density functional theory (DFT) calculations revealed
elongated C–S bonds and pyramidal-shaped SO2. Such complexes were characterized as
Lewis acid–base moieties of sulfur dioxide and diamino carbenes [14].
Thiourea trioxide (TTO, (NH2)2CSO3) can be produced by further oxidation of TDO
by hydrogen peroxide or peracetic acid [3,15,16]. TTO exhibits much lesser pronounced
reducing properties than TDO [6]. In contrast to TDO, decomposition of TTO in alkaline
solutions results in the primary formation of sulfite (reaction 2) [15].
Thiourea monoxide (TMO, (NH2)2CSO) is the least studied oxide of thiourea. Recently,
a reversed-phase ion-pair high-performance liquid chromatography and mass spectrom-
etry (MS) were used to track and determine intermediate species during the oxidation of
thiourea by hydrogen peroxide [17]. Experimental results illustrated that the four species:
thiourea monoxide, formamidine disulfide, thiourea dioxide and thiourea trioxide were
formed during the oxidation process. An evidence of the formation of thiourea monoxide
as a long-lived product in the course of oxidation of TU with hypochlorite was obtained
by Stanbury and coworkers [18].
Simoyi and coworkers observed the formation of tetramethylthiourea monoxide
(TMTMO) as an intermediate of reactions between tetramethylthiourea (TMTU) and
chlorite [19] or bromate [20]. Monoxides of other thioureas, namely, phenylTU, naph-
thylTU, were registered during their oxygenation by flavin-containing monooxygenases
[21]. Monoxide is also the first product in the oxidation of ethylenethiourea by hydro-
gen peroxide [22]. It is important to note that TMTU is more advantageous for studies of
thiourea monoxides as compared to thioureas with bulk substituents, since TMTU is more
soluble in water.
In this work, the reaction between TMTU and H2O2 in aqueous solutions was investi-
gated and TMTMO was characterized as the main intermediate of this process.
2. Results and discussion
Addition of an excess of H2O2 to TMTU results in changes in UV–VIS spectrum as shown
in Figure 1. A partial decrease of absorbance at 248 nm was observed as well as a new
peak at 313 nm appeared in the course of the first reaction step (Figure 1(a)). Furthermore,

JOURNAL OF SULFUR CHEMISTRY
3
Figure 1. UV–VIS spectra of the first (a) and second (b) step of reaction between TMTU (0.6 mM) and
H2O2 (8.5 mM) at pH 4.5; 25°C.
peaks at 248 and 313 nm completely disappeared and a new absorption band is observed
at 223 nm (Figure 1(b)). A shape of typical kinetic curve at 313 nm (Figure 2) corresponds
to a consecutive reaction with two steps.
In order to identify reaction products and characterize their properties, we performed
1
ESI-MS, H NMR, surface-enhanced Raman scattering (SERS) and cyclic voltammetry
(CV) studies. ESI mass spectrum of mixture of TMTU with excess H2O2 after 20 min shows
peak at m/z = 149.07 corresponding to TMTU monoxide (Figure S1). The closest to that
peak at m/z = 133.08 belongs, probably, either to monodemethylated TMTU monoxide
or to unreacted [TMTU + H+]+. The same mass spectrum was observed earlier for the
reaction between TMTU and ClO−2 and also was ascribed to TMTU monoxide [19].
An incubation of TMTU with H2O2 in water within a longer time leads to the formation
of intense peak at m/z = 117.10, belonging to [tetramethylurea + H+]+. Tetramethylurea
is reported to be the product of oxidation of TMTU by ClO−2 [19]. It is important to

4
I. A. DEREVEN’KOV ET AL.
Figure 2. Typical kinetic trace of reaction between TMTU (0.6 mM) and H2O2 (8.5 mM) at pH 4.5; 25°C
monitored at 313 nm.
1
Figure 3. H NMR spectra of TMTU (solid line), TMTU + D2O2 (dashed line) after 20 min and
TMTU + D2O2 (dashed line) after 2 h (dash-dot line) in D2O. [TMTU]0 = 10 mM and [D2O2]0 = 50 mM.
note that mass spectra indicate an absence of the formation of tetramethylformamidinium
disulfide (M = 264).
1
Initial TMTU exhibits singlet at 2.96 ppm in H NMR corresponding to equivalent
protons of methyl groups in symmetric molecule. Interaction with D2O2 results in the
appearance of three new signals at 3.19, 3.07 and 3.04 ppm after 20 min after mixing
reagents and two signals at 3.18 and 3.06 ppm found in the spectrum after 2 h remain
unchanged after 3 days and probably belong to tetramethylurea (TMU) in D2O solu-
1
tion (Figure 3). H NMR of intermediate compound clearly reflects a loss in symmetry

JOURNAL OF SULFUR CHEMISTRY
5
Figure 4. SERS spectra of TMTU (1), TMTU/H2O2 system (2; 20 min after mixing) (a) and TMTU/H2O2
systems (b): 20 min (2) and 1 h (3) after mixing. Spectra are rescaled for clarity. [TMTU]0 = 10 mM;
[H2O2]0 = 50 mM.
of TMTU after the first oxidation event. Assuming the formation of TMTU monoxide as
the intermediate, its asymmetric structure can be drawn out.
In the SERS spectrum (Figure 4), after adding H2O2 to TMTU solution an increase in
intensity at 1374 cm−1 is observed as well as a weak band at 1348 cm−1 disappeared during
the time corresponding to TMTMO formation. Analysis of Raman spectrum of TMTU
has been performed previously [23] indicating its complex structure. According to pub-
lished data [23] the band at 1370 corresponds to δ(CH3), ν (NCN), ν (NCH3) vibra-
as
as
tions. There is no assignment of 1348 cm−1 band, but all bands in 1334–1359 cm−1

6
I. A. DEREVEN’KOV ET AL.
Figure 5. Cyclic voltammograms of TMTU (15 mM; upper line) and TMTMO (bottom line) generated in
situ by reaction between TMTU (15 mM) and H2O2 (30 mM) at pH 9.2, scan rate 100 mV s−1
.
region correspond to δ(CH3) and ν (H3C–N) vibrations. Thus, the formation of TMTU
as
monoxide strongly affects vibrations of N–C and H3C–N bonds.
The structure of the 1345–1380 cm−1 region is partially recovered after a longer reaction
time corresponding to the formation of TMU, that is, the intensity of the band at 1374 cm−1
is substantially decreased as well as a new weak band at 1351 cm−1 appeared.
It can be proposed that the formation of the asymmetric TMTMO molecule from sym-
=
metric TMTU affects the C–N bond order from N–C–N to N C–N changing frequencies
of their vibrations. The latter can change vibrations of H3C–N bonds resulting in corre-
sponding changes in the SERS spectrum. When an asymmetric TMTMO molecule goes to
more symmetric TMU, vibrations of the NCN frame can be partially recovered reflecting
in the 1345–1380 cm−1 region [24].
Mass spectrum of the decomposed TMTMO (Figure S2) at pH 3.5 (HCl) indicates
new signals at m/z = 132.07, 167.04 and 261.03. We attribute signals at 132.07 and
261.03 to tetramethylformamidinium disulfide, that is, the former relates to its dicationic
form and the latter – to [tetramethylformamidinium disulfide – H+ − 2H]+. A peak at
m/z = 167.07, probably, belongs to [tetramethylformamidinium disulfide – H+ + Cl−]+.
Next, we obtained cyclic voltammograms of TMTU and TMTMO in weakly alkaline
medium. TMTU exhibits an oxidation wave at 660 mV (vs. Ag/AgCl), but in contrast to a
reaction in acetonitrile [25] no coupled reduction wave was found. The oxidation of TMTU
by H2O2 alters redox behavior of the system: no redox waves were observed for TMTMO
(Figure 5) indicating its relative redox inertness.
According to experimental data the following reaction mechanism can be proposed
(Scheme 1). The reaction between TMTU and hydrogen peroxide involves oxygen atom
transfer from both H2O2 and HO−2 species giving TMTU monoxide. Further oxidation of
TMTMO by H2O2 and HO− leads to TMU and sulfate as the final products with inter-
mediary formation of sulfur2monoxide (SO) and sulfur dioxide (sulfite). The formation of

JOURNAL OF SULFUR CHEMISTRY
7
Scheme 1. Reaction between TMTU and hydrogen peroxide.
SO in reaction of TMTU and chlorite or bromate has been proposed earlier [19,20]. Sul-
fur monoxide is unstable and oxidized by hydrogen peroxide to sulfite and sulfate. The
formation of sulfate was demonstrated using barium chloride: white precipitate insolu-
ble in HCl was detected after the addition of BaCl2 to TMTU oxidized by an excess of
H2O2. Indeed, higher oxides were earlier shown to be unavailable by means of oxida-
tion of TMTU by peroxides and alternative pathways of synthesis should be employed
[26,27]. Indeed, Walter and Rohloff have received TMTU trioxide in reaction between
1-chloro-tetramethylformamidinium chloride with silver sulfite [26].
In order to clarify structural features and reactivity of TMTU monoxide in comparison
with higher oxides, we employed DFT calculations on thiourea oxide models as well as on
their methylated versions.
The DFT-derived profiles for C–S bond cleavage (up until ∼ the sum of van der
Waals radii for C and S, 3.1 Å) for TDO and for its tautomer formamidine sulfinic acid
HNH2NCSO2H (FSA) (similar to those already published [28]) are shown in Figure S3
in contrast with those of the monoxide and trioxide. Notably, these two higher oxides
reveal no reasonable pathway for C–S monomolecular bond cleavage. Interestingly, up
until ∼2.3 Å the profiles for FSA and TTO are almost identical; it is at this point that
FSA tautomerizes to TDO – and C–S bond cleavage can be further pursued without fur-
ther significant energetic costs. TMO shows distinctly higher energy costs for C–S bond
cleavage, compared with the other oxides.
For the tetramethylated derivatives of the thiourea oxides, the barriers follow similar
trends compared to the non-methylated analogs (Figure 6), insofar as TMTU monoxide
shows the most resilient C–S bond, followed by TMTU trioxide (TMTTO) – both showing
energy costs too large to allow facile cleavage. In contrast, TMTU dioxide (TMTDO) shows
a very flat potential energy surface – even flatter than for TDO and with the C–S bond
longer by some 0.4 Å than in the non-methylated model – while TMTMO and TMTTO
show equilibrium C–S bond lengths similar to their non-methylated analogs, TMO and
TTO.
The four methyl groups thus appear to exert a unique effect on TDO, but not on TTO
and TMO. The much flatter potential energy curve for C–S elongation in TDO vs. TTO and
TMO may provide the premises for any influence to be exerted much easier in the dioxide
compared with the monoxide or trioxide. The methyl groups in the TMTU oxides may
be expected to manifest themselves in two ways: inductive electronic effects and sterical
conflicts. The latter may be leading to disturbance in the N–C–N π conjugation previously

8
I. A. DEREVEN’KOV ET AL.
Figure 6. B3LYP/6-31G(d,p) profiles for C–S bond cleavage in the tetramethylated versions of TTO, TDO
and TMO.
Figure 7. B3LYP/6-31G(d,p) optimized geometries for key models examined in the present work.
noted to be responsible for the planarity of the H2N–C–NH2 moiety in TDO, but they may
also be repelling the oxygen atoms (and implicitly the SO2 moiety) away from the N–C–N
unit. Indeed, the planarity is lost in all the tetramethylated derivatives, as shown in Figure7.
Also important is the appearance of two NH–O hydrogen bonds in TDO – which in
TMTU dioxide are replaced by a single CH–O interaction. We propose that it is these
hydrogen bonds that add extra strength to the (NH2)2C–SO2 interaction – so much so that
in their absence the C–S bond may be taken to be the sum of the van der Waals radii with
a cost of less than 5 kcal/mol – that is, it is intrinsically weaker than a hydrogen bond. To
this may be added the fact that even in TMTU dioxide there is a weak CH–O interaction
at 2.02 Å, which may contribute a notable proportion to those ∼4 kcal/mol of interac-
tion between the SO2 and the [N(CH3)2]2C moieties. By comparison, in TMTU trioxide,
where the C–S bond is distinctly shorter than in TMTU dioxide, there are two longer CH–O
interactions, at 2.15–2.19 Å.
To verify the above arguments, geometries were optimized for the four possible isomers
of the trimethyl versions of TMO, TDO and TTO (denoted here with the prefix TrM). Per-
haps expectedly, in TrMTU monoxide one of the isomers – the one allowing for a NH–O
hydrogen bond – is 4–5 kcal/mol more stable than the other three. This gives an estimate
of the intrinsic strength of such a hydrogen bond in a thiourea oxide. In the trioxide,

JOURNAL OF SULFUR CHEMISTRY
9
where two such isomers allow for the formation of a hydrogen bond, both of them are
∼4 kcal/mol more stable than the other two. In line with the data discussed above, the C–S
bond lengths in TMO, TrMTU monoxide and TMTU monoxide are reasonably similar to
each other (less than 0.02 Å different), as is also the case for TTO vs. TrMTU trioxide and
TMTU trioxide. The two TrMTU dioxide isomers accomodating NH–O hydrogen bonds
are both ∼5 kcal/mol more stable than the non-hydrogen-bonded counterparts – in line
with the energy differences seen for the TMO and TTO analogs. However, remarkably,
these two hydrogen-bonded TrMTU dioxide isomers also feature C–S bonds 0.2–0.3 Å
shorter than their non-hydrogen-bonded isomer – and thus much closer to TDO than
to TMTU dioxide.
Unexpectedly high lability of the C–S bond in TMTU dioxide can explain a reason
why this oxide is unavailable by means of oxidation of TMTU by H2O2. Probably, a rapid
cleavage of the C–S bond occurs, when oxidation of TMTU approaches TMTU dioxide
state.
In terms of the electronic structure, the Mulliken partial atomic charges listed in Table
S1 are in line with previously reported data on TDO and FSA. There is a negative charge
accumulated on the SO moiety in TMO, of a magnitude 30% smaller than that the one
accumulated on SO2 in TDO as well as on the SO3 in TTO. While the partial atomic charges
on oxygen remain relatively constant in all three oxides at ∼−0.5, the charge on sulfur
varies dramatically, from −0.43 in thiourea to 0.05 in TMO, 0.27 in TDO, and 1.10 in
TTO. The Wiberg partial atomic charges are listed in Table S2 and show a similar trend.
This may be explained by the dative S–>O bonds draining electron density from the sulfur
and arguably turning it into a less-soft center.
In the tetramethylated versions, the magnitude of the SOx charge in TMTU monoxide
and in TMTU dioxide is both distinctly smaller than the charge on SO3 in TTO (by 45%
and 35%, respectively). The individual partial atomic charges on the oxygen and sulfur
atoms follow similar trends to the non-methylated versions.
Figures 8 and S4 show key molecular orbitals in TU. The expected σ (HOMO-3), σ*
(LUMO+2), n (HOMO), and π/π* (HOMO-4, HOMO-2, HOMO-1 and LUMO) are
clearly discernible. The essentially planar N,N–C–S system harbors three electron pairs in
four pz orbitals. While the N–C–N orbitals are efficiently delocalized, mixing with the sul-
fur pz orbital is less efficient, to the extent to which one may regard LUMO and HOMO-1 as
distinct bonding–antibonding partners. The sulfur is well describable as non-hybridized,
in line with similar systems [29].
The C–S–O angle in TMO, at 104°, may be suggestive of an sp3 geometry at the sulfur.
However, the molecular orbitals clearly reveal a non-sp3 electronic structure, since there are
at least two sets of orbitals with ample localization at the sulfur and perpendicular to each
other. With the valence angle distinctly remote from 120°, one can only conclude that the
sulfur is non-hybridized. The 16°-deviation from the expected valence angle at the sulfur
may then be ascribed to a steric conflict between the oxygen and the neighboring hydrogen
– obviously complemented by an attractive electrostatic interaction (hydrogen bond-like,
at 2.03 Å). With this interpretation, one may identify a py pair at the sulfur involved in
σ donation to the non-hybridized oxygen (HOMO-4), an empty S px orbital receiving σ
donation from carbon and thus forming the C–S single bond (HOMO-1), a filled S pz
orbital involved in π interaction with the CN2 moiety, plus the 3s2 sulfur orbital at lower
energies (not shown). The five heavy atoms are all placed in the same plane and available for

10
I. A. DEREVEN’KOV ET AL.
Figure 8. Key frontier molecular orbitals for TU, TMO, TDO and TTO.
extended π conjugation. Figure 8 indeed shows five such molecular orbitals – as resulting
from a combination of the five pz orbitals; four of these are occupied (HOMO-6, HOMO-
3, HOMO-2, HOMO) and one is empty (LUMO) – testifying of four pairs of electrons in
the system, delocalized in a manner reminiscent of the previously invoked Y conjugation
in guanidinium cations – a conjugation showed to add a very low level of stability [30,31].
Possibly of note, the π electron count in TMO is 4n, and of the five π orbitals four are occu-
pied – including an antibonding one – the acyclic equivalent of an antiaromatic case. The
C–N bond lengths are at 1.35 Å, almost identical to thiourea – as is the C–S distance. Thus,
=
overall TMO may be viewed as an adduct of thiourea with an oxygen atom ( S–>O), with
little influence on the molecular geometry of the N2CS unit.
Figure 8 also shows key molecular orbitals for TDO. The HOMO and LUMO are in line
with previously reported DFT data, interpreted to reveal a carbene donating a σ pair into

JOURNAL OF SULFUR CHEMISTRY
11
a sulfur empty p orbital. A notable difference from TMO is that now both oxygen atoms
are outside of the N,N–C–S plane. If one accepts the schematic description for TMO as a σ
donation by the non-hybridized sulfur of TU towards the oxygen atom, then the addition
of one extra oxygen atom to TMO would have only been possible to the pz orbital. The
deviation from such a geometry may be explained as due to the competition between the
two NH–O hydrogen bonds in TDO. A side-effect of these attractions is that both oxygen
atoms have left the N,N–C–S plane in order to attain the shortest H–O distances for both
oxygens. As a consequence, the extended π system only contains four atoms – and hence
four molecular orbitals containing three pairs of electrons: HOMO-8, HOMO-5, HOMO-4
and LUMO.
Figure 8 also shows a qualitatively similar situation in TTO, with HOMO-6, HOMO-7,
HOMO-9 and LUMO making up the π system.
In terms of the energies of the orbitals, a simple analysis (Table S3) of the
HOMO–LUMO gaps reveals TU to be the most stable (125 kcal/mol), followed very closely
by TTO (122 kcal/mol) and then by TDO (105 kcal/mol) and TMO (99 kcal/mol). In terms
of the orbitals connected to the C–S interaction, the differences are even further instruc-
tive: 280 kcal/mol for TU, 222 for TTO, 210 for TMO, and only 133 for TDO. Furthermore,
the σ* orbital energy of TDO is distinctly lower – and hence this LUMO is distinctly more
accessible – than in TU, TMO and TDO (0.34 eV, vs. 2.32, 2.67 and 1.57, respectively).
These data are in good agreement with the fact, described above, that the TDO C–S poten-
tial energy curve is much flatter compared with the other two oxides. The molecular orbital
energy trends in TDO are, importantly, conserved when one reoptimizes TDO enforcing
C–S distances similar to the ones in TMO or TTO, suggesting that the elongated C–S bond
in TDO vs. TTO/TMO is an effect of the differences in electronic structure – particularly
of the lower-energy σ* and subsequently lower σ–σ* gap.
The tetramethylated derivatives feature σ–σ* gaps increased by 9 kcal vs. TU, and
decreased by 5, 18 and 20 kcal/mol vs. TMO, TTO and TDO, respectively, – conserving
the trend of (TM)TDO displaying a much weaker C–S interaction than either TTO or
TMO.
3. Conclusion
This work showed that an oxidation of TMTU by hydrogen peroxide involves the formation
of TMTU monoxide and its further oxidation to tetramethylurea and sulfate with interme-
diary formation of sulfur monoxide. The evidence of the asymmetric structure of TMTU
monoxide was elucidated from 1H NMR studies. DFT calculations predict that the overall
=
TMO structure may be viewed as an adduct of thiourea with an oxygen atom ( S–>O).
DFT calculations predict also high lability of the C–S bond in TMTU dioxide; this explains
why this oxide is unavailable by means of oxidation of TMTU by H2O2.
4. Experimental
4.1. Chemicals
TMTU, hydrogen peroxide, deuterium oxide were purchased from Sigma-Aldrich
and used as received. Concentrations of H2O2 were determined using potassium
permanganate. Other chemicals used throughout this work were of reagent grade.

12
I. A. DEREVEN’KOV ET AL.
Hydrochloric and phosphoric acids, sodium acetate, potassium hydrophosphate and dihy-
drophosphate, sodium tetraborate were used to adjust pH.
4.2. UV measurements
Measurements were performed using a cryothermostated ( 0.1°C) Cary 50 UV–VIS
spectrophotometer using 1 cm quartz cuvettes under anaerobic conditions.
4.3. ESI-MS measurements
The mass spectra were recorded on an LTQ Orbitrap XL-Thermo-Scientific mass-
spectrometer.
4.4. 1H NMR measurements
1
The H NMR spectra were recorded on a Bruker Advance spectrometer operating at
600 MHz, using deuteriated solvents (D2O). Chemical shifts (δ) are given as ppm relative
to the residual solvent peak.
4.5. Surface-enhanced Raman scattering measurements
SERS spectra were recorded using a DeltaNu Advantage 532 Raman spectrometer
(DeltaNu, USA) equipped with a frequency doubled NdYAG laser emitting at 532 nm. The
laser power was 10 mW and the spectral resolution was ∼8 cm−1. The SERS spectra were
recorded by averaging five accumulations, each of 10 s exposure time. For all measure-
ments 25 μL of the sample solution (10 mM) was added to 0.5 mL silver colloid reduced
with hydroxylamine.
4.6. Cyclic voltammetry
CV was performed on an Elins P-4 potentiostat equipped with a three-electrode system,
which included a glass-carbon working electrode (NTF Volta), a platinum wire used as
a counter electrode (NTF Volta) and a silver chloride (EVL-1 M; in KCl 3.5 M) reference
electrode (0.22 V vs. NHE at 20°C). Prior to measurements, the surface of the glass-carbon
electrode was polished with alumina powder. Throughout the experiment, concentrated
buffer solutions (0.1 M) were used as supporting electrolytes.
4.7. DFT calculations
DFT calculations B3LYP/6-31G(d,p) were performed as previously described for related
thiourea dioxide systems, where their good agreement with experiment was verified [28].
Additional calculations were also performed by utilizing the wB97XD DFT functional and
the def2TZVP basis set and the solvation model based on density. The latter methodology
provided qualitatively very similar results thus validating our chosen level of theory for our
model compounds. Additional data can be found in the supplementary information.

JOURNAL OF SULFUR CHEMISTRY
13
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by Russian Foundation for Basic Research, project 16-03-00162 (to
S.V.M.). Computational resources were provided by the high-performance computational facility
of the Babeş-Bolyai University (MADECIP, POSCCE, COD SMIS 48801/1862) co-financed by the
European Regional Development Fund of the European Union.
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