Spectroscopic and structural investigation of interaction of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt with molecular iodine

Article abstract of DOI:10.1016/j.saa.2018.03.069

The interest in the study of heteroaromatic thioamides which are known to exhibit antithyroid activity is stimulated by the variety and an unusual structure their complexes with molecular iodine. The directions of dithiones investigation are diversity eno

Full text of DOI:10.1016/j.saa.2018.03.069

Accepted Manuscript
Spectroscopic and structural investigation of interaction of
5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt
with molecular iodine
Victoria A. Ivolgina, Margarita S. Chernov'yants
PII:
DOI:
Reference:
S1386-1425(18)30277-4
doi:10.1016/j.saa.2018.03.069
SAA 15941
Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy
To appear in:
Received date: 16 November 2017
Revised date:
Accepted
date:
1 February 2018
25 March 2018
Please cite this article as: Victoria A. Ivolgina, Margarita S. Chernov'yants , Spectroscopic
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ACCEPTED MANUSCRIPT
Spectroscopic and structural investigation of interaction of 5-mercapto-3-
phenyl-1,3,4-thiadiazole-2-thione potassium salt with molecular iodine
Victoria A. Ivolgina, Margarita S. Chernov’yants.
Department of Chemistry, Southern Federal University, Zorge St. 7, 344090 Rostov-
on-Don, Russia
Abstract
The interest in the study of heteroaromatic thioamides which are known to exhibit
antithyroid activity is stimulated by the variety and an unusual structure their
complexes with molecular iodine.
The directions of dithiones investigation are diversity enough, however a few works
are devoted to the study them as the potential thyreostatics. The ability of 5-
mercapto-3-phenyl-1,3,4-thiadiazole-2-thion potassium salt to form the outer-sphere
charge-transfer complex in dilute chloroform solution, coordinating 2 iodine
molecules has been studied by UV-vis spectroscopy (lgβ=7.91). The compound of the
5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione)
-
product
of
irreversible oxidation of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium
salthas been isolated and characterized by X-ray diffraction. Intermolecular
interactions between sulfur atoms are observed with very short interatomic distance,
shorter than sum of van der Waals radii. The contact between heterocyclic sulfur and
heterocyclic nitrogen is also slightly short – 3.169 Å (0.053 Å less than vdW radii
sum).
This investigation constitutes a starting point for study of novel antithyroid drugs in
future.

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Keywords: 5-Mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt; 5,5’-
disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione);X-ray diffraction;HRMS;
NMR; UV-vis; Raman; FT-IR study.
1. Introduction
The interest in the study of structure-activity relationship of thioamides against
molecular iodine is stimulated by the interest in the molecular compounds formed
between antithyroid drugs and diiodine, [1-10]since thioamides are known to exhibit
antithyroid activity [10].
It should be noted that the molecular interactions of antithyroid drugs with iodine
have been subjected to many investigations because these drugs may inhibit thyroid
hormone synthesis by forming donor-acceptor complexes with iodine[11].
Reactions of diiodine with heterocycles compounds such as ketones, thiones [12-16]
or selones [17-20] are known to produce various types of iodine compounds,
including charge transfer complexes [21-23], with “spoke structures” (D–I2; D =
donor), “extended spoke structures” (D–I2–I2) [24-26], iodonium salts [27],
monocationic disulfides and dicationic disulfides or diselenides [28-30, 31-
35].Synthesis, spectroscopicand structuralcharacterizationofnovelinteractionproduct
of pirrolidine-2-thione withmoleculariodineformed in the resultof oxidative
desulfurizationhasbeenreported [36].
Challenges related to characterization of the halogen-bonding diversity (Desirajuet
al.,
2013)
and
iodine–iodine
non-covalent
interactions
in
crystalsarethefocusofattentionofmanyresearchersworking in crystalengineering [37].
Recently, much attention has been paid to investigation the properties of heterocyclic
thioamides with an oxygen, nitrogen, sulfur containing moiety for which the σ and π-
donor properties were estimated [38, 39].

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Heteroaromatic compounds azole derivatives are a versatile group of compounds
with a wide range of application. Among them, thiadiazole andits derivatives
areessentiallybiologicalactivecompounds. Theyrevealactions in antihypertensive
[40]andcardioprotectivetreatment [41, 42]. Theyhave a potential activity as G-protein
coupledreceptors [43]. Thiadiazoleenzymeswithactivecysteineresidues [44] (e.g.
bacterialenzymes
[45])
andtheyareconstituentsof
non-steroidal
anti-
inflammatoryagents [46].
Whenstudyingthereactions of thiadiazole-2-thione derivatives withmolecular iodine it
was established that the species of forming products depend on the iodine
concentration, the nature of reaction medium and the type of substitute group. In
chloroform medium thereactionbetween 5-methyl-1,3,4-thiadiazole-2-thione and
iodine producedthecorrespondingcharge-transfer complex 5-methylthiadiazole-2-
thione-I2andadditionofthreemolecules of iodineto two thione molecules produced a
novelcationiccomplexhaving an almost linear S-I+-S moietyand I5 counteranion
[47,48]. When 5-methyl-1,3,4-thiadiazole-2-thione was treated with I2 in water,
thereactionproducedthem monocationcontaining a disulfidebond as a majorproduct.It
is suggested that the high reactivityofthione toward I2 andtherelativelylow IC50value
in the LPO-catalyzediodinationreaction, is stipulated [49]bystrong antithyroidactivity.
Сurrently, chemistry has expanded from molecular to dynamic combinatorial
chemistry (DCC) which is one of the often used methods to generate complex
supramolecular systems and allow one to identify biologically active compounds,
design host-guest systems and study noncovalent interactions. Organic compounds
with two thionic groups, such as dithiones, are reported in dynamic combinatorial
chemistry. S. Otto and others [50, 51] have recently adapted disulfide chemistry for
the generation of dynamic combinatorial library (DCLs) in water using dithiol
building blocks of very different chemical nature to construct the structures aiming at
molecular recognition. B. M. Matysiak and others [52] combined thiol-disulfide
[53,54,55-61] and thio-Michael exchange [62-66] to design antiparallel chemistries.
Furthermore, the use of dithiones as the potential drugs with a various range of
properties has been widespread in industrial application. Oltipraz, 4-methyl-5-

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pyrazinyl-3H-1,2-dithiole-3-thione (OPZ), which was originally developed as an
antischistosomal agent, is a synthetic derivative of the naturally occurring
dithiolthiones and it is currently being evaluated in clinical studies as a
chemopreventive agent for hepatocarcinogenesis [67]. In addition to cancer
chemopreventive activity, OPZ possesses potent antiangiogenic activity [67].
The directions of dithiones investigation are diversity enough. For 2,4-dithiouracil
(DTU), a close pyrimidine analogue of the title compound, the double-proton-transfer
reactions leading to 2,4-pirimidinedithiol form [68]and for 2,6-dithiopurine, a
possible chemopreventive agent, the phototautomeric reactions isolated in Ar and N2
matrix were observed by matrix isolation infrared spectroscopy.
The aim of the present research was to study the reaction of dithione, 5-mercapto-3-
phenyl-1,3,4-thiadiazole-2-thion potassium salt, with molecular iodine in chloroform
and ethanol solutions by UV-vis spectroscopy, Raman spectroscopy and X-ray
diffraction analysis method. To give a comparative evaluation of the solvent influence
on the reactivity and chemical structure of the interaction product of the k-salt of a
potential thyreostatic with molecular iodine.
2. Experimental section
5-Mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt (AlfaAesar) was used
without additional purification. The solvents were purified according to known
procedures [69].
5,5’-Disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione) was synthesized
by mixing of 0.0264 g of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione in 1 ml
ethanol solution and 0.0127 g of molecular iodine in 7.6 ml of chloroform solution
(molar ratio 1:0.5) followed by slow evaporation of the solvent in air to obtain light-
yellow rectangular plate-like crystals. The yield of product was 71 %. The compound
mp (123ºC).
¹H NMR (250 MHz, CDCl3, δ /ppm, J/Hz): δ 7.43-7.53 (m 6H), δ 7.65-7.71 (m
4H).

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ˡ³C (62.9 MHz, CDCl3, δ /ppm): δ 125.6; 129.17; 129.55.
HRMS spectra of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione)
was measured in CH3CN 100 %. The source type was ESI in positive ion polarity.
Infrared spectra in the region 7800-375 cm-1 were obtained in vaseline oil, with
Varian 660 FT-IR spectrophotometer.
The UV-vis absorption spectra of chloroform solutions containing thione and
molecular iodine in different ratios were measured on a Cary 100 (Varian) UV-vis
spectrophotometer in a quartz cell with a 1.0 cm light path in the 250-800 nm range at
22.0 ⁰C. 1.0 × 10 -3 mol/L concentration of thione and the iodine in chloroform were
used as the stock solutions. The precise value of the molar absorption coefficient of
iodine (ε510) was determined from the calibration curve (ε = 899.83 L × mol-1× cm-1).
The concentration of molecular iodine was varied from zero to a 24-fold excess, the
concentration of thione remained constant (2 × 10-5 mol/L).
X-ray crystallographydiffraction study. Crystal data C16H10N4S6 are shown in
Table 1 [70]. Atomic coordinates, bond lengths, bond angles and termal parameters of
5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione) have been deposited
at the Cambridge Crystallographic Data Centre (CCDC) 1575843.
C16H10N4S6 are triclinic, space group P-1:a=8.8166(5)Å, b=13.2398(7)Å,
c=16.1522(8)Å, α=97.1090(10)°,=90.1590(10), γ=93.6000(10)°, V = 1867.2(2) Å3,
Z = 4, M = 450.64, dcalc = 1.603 gcm-3, = 0.121 mm-1. 46366 reflections were
collected at SMART APEX II CCD difractometer ((Mo-K)=0.71073 Å, graphite
monochromator, -scans, 2<58.66) at 120K. The structure was solved by the direct
methods and refined by the full-matrix least-squares procedure in anisotropic
approximation. 10198 independent reflections [Rint = 0.0422] were used in the
refinement procedure that was converged to wR2 = 0.0795 calculated on F2hkl (GOF =
1.056, R1 = 0.0348 calculated on Fhkl using 8499 reflections with I>2(I)). These data
can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif. All
calculations were carried out on an IBM PC AT with the use of the SHELXTL

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program package [71]. The experimental data had been corrected for absorption
effects with SADABS procedure [72].
PLATON [73] and Mercury v.2.3 software [74] were used to prepare material for
publication.
Raman spectra of the 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-
thione) were obtained in the frequency range of 50-1800 cm-1.
The Raman spectra were excited by polarized radiation from an argon laser (λ=514.5
nm)with output power 25 mW and recorded on a single-beam Renshaw unit equipped
with a (NExT) Near-Excitation Tuneable filter to analyze the low frequency spectral
region. The exciting radiation beam focused onto the sampleusing a Leica optical
microscope; the diameter of the focused beam on the sample was 5 µm.

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Table 1
Crystal data and structure refinement for 5,5’-disulfanediylbis(3-phenyl-1,3,4-
thiadiazole-2(3H)-thione).
Identification code
Empirical formula
Formula weight
Temperature
tdak
C16 H10 N4 S6
450.64
120(2) K
Wavelength
0.71073 Å
Crystal system
Space group
Triclinic
P -1
Unit cell dimensions
a = 8.8166(5) Å α= 97.1090(10)°
b = 13.2398(7) Å β= 90.1590(10)°
c = 16.1522(8) Å γ = 93.6000(10)°
3
Volume
1867.15(17) Å
Z
4
Density (calculated)
Absorption coefficient
F(000)
3
1.603 Mg/m
-1
0.741 mm
920
Crystal size
3
0.14 x 0.12 x 0.03 mm
Theta range for data collection
Index ranges
1.88 to 29.33°.
-12≤h≤12, -18≤k≤18, -22≤l≤22
Reflections collected
Independent reflections
Completeness to theta = 29.33°
Absorption correction
Refinement method
46366
10198 [R(int) = 0.0422]
99.5 %
None
2
Full-matrix least-squares on F

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Data / restraints / parameters
10198 / 0 / 469
2
1.056
Goodness-of-fit on F
R1 = 0.0348, wR2 = 0.0726
R1 = 0.0470, wR2 = 0.0795
Final R indices [for 8499 rfln with I>2ϭ(I)]
R indices (all data)
-3
Largest diff. peak and hole
0.441 and -0.318 e.Å
3. Results and discussion
Since the good correlation between the antithyroid activity of heteroaromatic
thioamides in vivo and the charge transfer complex constants with the iodine [75] has
been revealed, it was interesting to evaluate the stability of outer-sphere complex of
5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt with the molecular
iodine. Electronic absorption spectra of chloroform solutions containing 5-mercapto-
3-phenyl-1,3,4-thiadiazole-2-thione potassium salt, molecular iodine, forming
molecular adduct and the product of irreversible oxidation of 5-mercapto-3-phenyl-
1,3,4-thiadiazole-2-thione potassium salt (5,5’-disulfanediylbis(3-phenyl-1,3,4-
thiadiazole-2(3H)-thione)) are presented in Fig. 2. When each solution having been
prepared the spectra were registered after 5 sec. The concentration of molecular
iodine was varied from its absence to 24-fold excess while the concentration of
thioamide remained constant.When the iodine solutions were added to the chloroform
thioamide solutions, the solutions became peach-colored. The 326 nm absorption
band has characterized the 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium
salt(Fig. 2. curve (1)), the 510 nm absorption band (Fig. 2. curves 2-8) has
characterized the molecular iodine and the 335 nm (Fig. 2. curve (9)) has
characterized5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione), which
wasdiscussed above.

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Fig. 2. Electronic absorption spectra of chloroform solutions containing thione
2 ×10-5mol/L and molecular iodine at the concentration: 0 (1), 8.0 ×10-5 (2), 1.2 ×10-4
(3), 1.6 ×10-4 (4), 2.4 ×10-4 (5), 3.6 ×10-4 (6), 4.0×10-4 (7), 4.8×10-4 (8)mol/L in
chloroform,ε (I2) = 899.83 L × mol-1× cm-1, (9) 2 ×10-5mol/L5,5’-disulfanediylbis(3-
phenyl-1,3,4-thiadiazole-2(3H)-thione), l=1.0cm.
The new intensive absorption bands corresponded to the interaction product of
molecular iodine and thione have been observed in the electronic spectrum at 289 nm
and 354 nm, respectively. The number of iodine molecules coordinated to thione and
the stability constant of molecular adduct were evaluated with the use of average
iodine number푛퐼 function which was proposed in our previous works[76-78]. The
2
equilibrium concentration of iodine ([I2]) was calculated from the absorbance of the
individual absorption band at λ (510±5) nm of elemental iodine accordingto the
equation [I2]=A/lεI . For each equilibrium concentration of iodine, the corresponding
2
value of 푛퐼 was calculated according to the Eq. 1:
2
푛퐼 = (С퐼 -[I2])/CHet,
(1)
2
2

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where CHet and С퐼 are the analytical concentrations of 5-mercapto-3-phenyl-1,3,4-
2
thiadiazole-2-thione potassium salt and molecular iodine, respectively. The
experimental data reflect the high coordination saturation of complex (푛퐼 ≥ 1.9).
2
The stability constantsβ1and β2 were calculated by the least squares method
according to Eq.2:
푛
= 훽1+β2 (2−푛 )[퐼2](2)
퐼
퐼
2
2
(1−푛 )[퐼 ]
(1−푛 )
퐼
2
퐼
2
2
lgβ2=7.91, lg 훽1=5.07(ρ =0.999).
The comparative assessment of coordinating ability of the 5-methyl-1,3,4-
thiadiazoline-2-thione [48], shows that the thione coordinates one iodine molecule,
the stability constant of the molecular adduct with iodine in dilute chloroform
solutions (lgβ=2.9±0.1, (ρ =0.993)) is lower than molecular adduct constant stability
of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thion potassium salt with molecular
iodine.Apparently, it can be explained by the presence of two thione groups in the
molecule of heterocycle, that enhances thyreostatic activity of this compound.
Therefore, 5-methyl-1,3,4-thiadiazoline-2-thione will be able to show
pharmacological activity close to the activity of thiouracil in vivo which inhibit the
activity of iodothyroninedeiodinase (ID-SeH), an enzyme responsible for the
monodeiodination of the T4 prohormone to the T3 hormone [16].
The interaction of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione potassium salt
with iodine molecule in 1:0.5 ratio in mixing of ethanol and chloroform solution gave
5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione) according to the
equation:

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N N
S
N
N
+
S
I2
2
S
S
+
S
2
KI
S
S
SK
S
N
N
The crystal structure of reaction product of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-
thione potassium salt with molecular iodine is disulfide of 5-mercapto-3-phenyl-
1,3,4-thiadiazole-2-thion potassium salt Fig.1. The bonds and angles for the crystal
structure of reaction product 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-
thione) with molecular iodine are presented: distances S(4)-C(9) 1.760 Å (1), S(3)-
C(8) 1.7692 Å (2). The S(3)-S(4) bond length 2.0577(6)Å (3), torsion angles C(8)-
S(3)-S(4)-C(9) is 86.15 (8)°.
ORTEP-diagram 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione) is
presented in Fig. 1.
Fig. 1. ORTEP-diagram C16H10N4S6. The thermal ellipsoid at the 50% probability
level.

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Mixing ethanol solution of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thion
potassium salt and chloroform solution of iodine resulted in irreversible oxidation of
the thione with formation of disulfide 5,5’-disulfanediylbis(3-phenyl-1,3,4-
thiadiazole-2(3H)-thione), for which molecular and crystal structure was studied by
X-ray diffraction data.
The molecular structure of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-
thione) with the atom-numbering scheme is shown in Fig. 2 and selected geometric
parameters are given in Table 1.
Connected in such «head-tail» manner molecules of disulfide form infinite chains.
The structure is shown in Fig.3.
The S3-S4 bond length (2.0577(6) Å) is rather short for acyclic disulfide bridge
connecting five-membered heterocycles (common range is 2.013-2.141 Å)[79].
The crystal structure of the interaction product 5-methyl-1,3,4-thiadiazoline-2-
thione with the iodine was formed by the iodonium cations (С3H4N2S2)2I+ and I5
counter anions interconnected by intermolecular hydrogen bonds. 5-Methyl-1,3,4-
thiadiazoline-2-thione forming n-σ complex with the molecular iodine initiates
complete charge transfer in the molecule and generates iodonium salt with 3-center-
10-electron molecular orbital [48].

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Itisshown [80, 81] themechanismofthethiomidesinteractionwiththeiodine (formation
disulfide or iodonium salt) depends upon electrodonor properties of heterocycle and a
number of thiol groups in molecule.
Fig. 3. Packing arrangement of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-
2(3H)-thione)
in
crystal
structure.
Table 2. Selected geometric parameters (Å, °)
Parameter
Bond lengths (Å)
S(3)-C(8)
Value
1.7692(18)
2.0577(6)
1.7601(18)
2.0583(6)
1.7554(18)
S(3)-S(4)
S(4)-C(9)
S(3')-S(4')
S(4')-C(9')

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S(3')-C(8')
1.7683(18)
Bond angles (°)
C(8)-S(3)-S(4)
100.00(6)
99.46(6)
C(9)-S(4)-S(3)
Torsion angles (°)
86.15(8)
C(8)-S(3)-S(4)-C(9)
An asymmetric unit cell of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-
thione contains two molecules (Z'=2) denoted by unprimed (A) and primed (A')
labels. In Figure 1, general view of the first independent molecule (A) is depicted. In
both molecules, benzene and neighbouring thiadiazole rings are not coplanar
(corresponding C-C-N-N torsion angles vary in the range of 37 to 54°). Two
independent molecules adopt somewhat different conformations that is reflected in
different values of the N3-C9-S4-S3 and C2-C1-N1-N2 torsion angles being equal to
-161.0(2) and 54.1(2) ° for the first independent molecule, and -175.7(2) and 37.7(2)
for the second one. The crystal packing is stabilized by close intermolecular S…S
contacts in the range of 3.2 – 3.5 Å and by van-der-Waals interactions (Table 1S). It
is interesting to note that the close contacts are observed between symmetrically
independent molecules (A…A') which are somewhat strongly bound to each other
than molecules of the same symmetrical type (A…A or A'…A', connected by
ordinary van-der-Waals interactions). Similar observations were made earlier for co-
crystals, solvates and crystals with Z'≥2 [82-84]. It can be suggested that the stronger
intermolecular interaction in A…A' molecular pairs is responsible for appearance of
two symmetrically independent molecules.Intermolecular contacts between
S(2)...S(3') atoms 3.201 Å and also S(3)…S(2') atoms 3.445 Å are observed with very
short interatomic distance. There are 0.33 Å and 0.085, respectively, shorter than sum
of van der Waals radii. Intermolecular contacts between S(3)...S(6') atoms 3.267 Å
and S(4)...S(6') atoms 3.587 of another molecule of thione are shorter than sum of

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van der Waals radii, respectively. The contact between heterocyclic sulfur S(1') and
heterocyclic nitrogen N(2) is also slightly short – 3.169 Å (0.053 Å less than vdW
radii sum).
Raman Spectroscopy is a powerful tool for the structural identification compounds.
One band can be seen in the Raman spectrum of the product of irreversible oxidation
of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione. The Raman
spectrum of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione in the ν
(S-S) region shows intense peaks at 505 cm-1.
The FT-IR spectra of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione
shown prominent peaks at the range 1300-1400 cm-1, 900-1300 cm-1, 1590-1700 cm-1
(for C=S, C-N, C=N bond vibrations, respectively).
HR-Mass spectra of 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-thione)
isotope claster are characterized by ESI: m/z, Ir (%) M+nH [C16H10N4S6]: 450.9293
(100), 451.9313 (25), 452.9261 (30), 453.9274 (5), 454.9226 (1.5).
The theoretical calculations are characterized m/z, Ir (%) M+nH [C16H10N4S6]:
450.9302 (100), 451.9334 (23), 452.9262 (30), 453.9294 (5), 454.9219 (1).
4. Conclusions
Therefore, the reaction product of 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thione
potassium salt is presented disulfide with intermolecular interactions between sulfur
atoms and very short interatomic distances, shorter than sum of van der Waals radii.
The contact between heterocyclic sulfur and heterocyclic nitrogen is also slightly
short – 3.169 Å (0.053 Å less than vdW radii sum). Connected in such «head-tail»
manner molecules of disulfide form infinite chains.
The method of UV-vis a

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spectroscopy found that 5-mercapto-3-phenyl-1,3,4-thiadiazole-2-thion potassium
salt in dilute chloroform solutions forms the charge transfer complex of a high
stability (lgβ=7.91) with molecular iodine.
Hence, it was shown, that the formation of 5,5’-disulfanediylbis(3-phenyl-1,3,4-
thiadiazole-2(3H)-thione), the interaction product of the thioamide with iodine in
1mixed of ethanol and chloroform solution, depends on nature of the heteroaromatic
moiety and presence of two thione groups.
Acknowledgements
The X-ray diffraction data were obtained using the equipment of Centre for
molecules composition studies of INEOS RAS.
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Graphical abstract

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Highlights
• The relationship between the nature of the thioamide and thyreostatic activity is
revealed.
• Product of oxidation, 5,5’-disulfanediylbis(3-phenyl-1,3,4-thiadiazole-2(3H)-
thione), has been characterized by molecular spectroscopic methods and X-ray
diffraction.
• In crystal package intermolecular S...S contacts, shorter than sum of van der Waals
radii.