drug that was used for the first time in 1943 as therapy of Graves’ disease [7], and
that is still in use nowadays.
An interesting property of this type of compounds is that they may undergo slow
oxidation to the disulfide dimeric form in acidic media [8]. In turn, structurally
appropriate disulfides may undergo homolytic S–S bond photodissociation into a
pair of radicals exhibiting suitable magnetic and/or optical properties to act as
photoswitches [9, 10].
The molecules studied in our laboratory were 2-thiobenzimidazole (TBI),
1-methyl-2-thioimidazole (MTI), and 1-methyl-2-thiobenzimidazole (MTBI). All
these molecules can exist in two tautomeric forms, thione and thiol, whose structures are represented in Fig. 7.1. DFT(B3LYP)/6-311++G(d,p) calculations
demonstrated that for all molecules, the thione tautomer is more stable than the thiol
form [11, 12]. The relative energy difference between the tautomers increases in the
order MTI < TBI < MTBI (38.8, 44.6 and 49.8 kJ mol
−1 , respectively), indicating that the presence of both benzo and methyl substituents stabilizes the thione
tautomer. In the thiol tautomer, the SH group points toward the imine ring nitrogen
atom (Fig. 7.1), both to minimize repulsions between the sulfhydryl hydrogen atom
and the ortho hydrogen atom or methyl substituent and to maximize the attractive
interaction between the nearly antiparallel bond dipoles associated with the SH and
C=N ring bonds.
Fig. 7.1 Structures of TBI,
MTI, and MTBI tautomeric
forms (thione: left; thiol:
right)
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that is still in use nowadays.
An interesting property of this type of compounds is that they may undergo slow
oxidation to the disulfide dimeric form in acidic media [8]. In turn, structurally
appropriate disulfides may undergo homolytic S–S bond photodissociation into a
pair of radicals exhibiting suitable magnetic and/or optical properties to act as
photoswitches [9, 10].
The molecules studied in our laboratory were 2-thiobenzimidazole (TBI),
1-methyl-2-thioimidazole (MTI), and 1-methyl-2-thiobenzimidazole (MTBI). All
these molecules can exist in two tautomeric forms, thione and thiol, whose structures are represented in Fig. 7.1. DFT(B3LYP)/6-311++G(d,p) calculations
demonstrated that for all molecules, the thione tautomer is more stable than the thiol
form [11, 12]. The relative energy difference between the tautomers increases in the
order MTI < TBI < MTBI (38.8, 44.6 and 49.8 kJ mol
−1 , respectively), indicating that the presence of both benzo and methyl substituents stabilizes the thione
tautomer. In the thiol tautomer, the SH group points toward the imine ring nitrogen
atom (Fig. 7.1), both to minimize repulsions between the sulfhydryl hydrogen atom
and the ortho hydrogen atom or methyl substituent and to maximize the attractive
interaction between the nearly antiparallel bond dipoles associated with the SH and
C=N ring bonds.
Fig. 7.1 Structures of TBI,
MTI, and MTBI tautomeric
forms (thione: left; thiol:
right)
202
R. Fausto et al.